History > 2006 > USA > Health (II)

Dr. Sara Gibson,

in her office in Flagstaff, Ariz.,

meets with a patient more than 100 miles away in St. Johns.

Jeff Topping for The New York Times        June 7, 2006

TV Screen, Not Couch, Is Required for This Session

NYT

8.6.2006

http://www.nytimes.com/2006/06/08/us/08teleshrink.html

The New Age

Live Long? Die Young?

Answer Isn’t Just in Genes

August 31, 2006
The New York Times
By GINA KOLATA

Josephine Tesauro never thought she would live so long. At 92, she is straight backed, firm jawed and vibrantly healthy, living alone in an immaculate brick ranch house high on a hill near McKeesport, a Pittsburgh suburb. She works part time in a hospital gift shop and drives her 1995 white Oldsmobile Cutlass Ciera to meetings of her four bridge groups, to church and to the grocery store. She has outlived her husband, who died nine years ago, when he was 84. She has outlived her friends, and she has outlived three of her six brothers.

Mrs. Tesauro does, however, have a living sister, an identical twin. But she and her twin are not so identical anymore. Her sister is incontinent, she has had a hip replacement, and she has a degenerative disorder that destroyed most of her vision. She also has dementia. “She just does not comprehend,” Mrs. Tesauro says.

Even researchers who study aging are fascinated by such stories. How could it be that two people with the same genes, growing up in the same family, living all their lives in the same place, could age so differently?

The scientific view of what determines a life span or how a person ages has swung back and forth. First, a couple of decades ago, the emphasis was on environment, eating right, exercising, getting good medical care. Then the view switched to genes, the idea that you either inherit the right combination of genes that will let you eat fatty steaks and smoke cigars and live to be 100 or you do not. And the notion has stuck, so that these days, many people point to an ancestor or two who lived a long life and assume they have a genetic gift for longevity.

But recent studies find that genes may not be so important in determining how long someone will live and whether a person will get some diseases — except, perhaps, in some exceptionally long-lived families. That means it is generally impossible to predict how long a person will live based on how long the person’s relatives lived.

Life spans, says James W. Vaupel, who directs the Laboratory of Survival and Longevity at the Max Planck Institute for Demographic Research in Rostock, Germany, are nothing like a trait like height, which is strongly inherited.

“How tall your parents are compared to the average height explains 80 to 90 percent of how tall you are compared to the average person,” Dr. Vaupel said. But “only 3 percent of how long you live compared to the average person can be explained by how long your parents lived.”

“You really learn very little about your own life span from your parents’ life spans,” Dr. Vaupel said. “That’s what the evidence shows. Even twins, identical twins, die at different times.” On average, he said, more than 10 years apart.

The likely reason is that life span is determined by such a complex mix of events that there is no accurate predicting for individuals. The factors include genetic predispositions, disease, nutrition, a woman’s health during pregnancy, subtle injuries and accidents and simply chance events, like a randomly occurring mutation in a gene of a cell that ultimately leads to cancer.

The result is that old people can appear to be struck down for many reasons, or for what looks like almost no reason at all, just chance. Some may be more vulnerable than others, and over all, it is clear that the most fragile are likely to die first. But there are still those among the fragile who somehow live on and on. And there are seemingly healthy people who die suddenly.

Some diseases, like early onset Alzheimer’s and early onset heart disease, are more linked to family histories than others, like most cancers and Parkinson’s disease. But predisposition is not a guarantee that an individual will develop the disease. Most, in fact, do not get the disease they are predisposed to. And even getting the disease does not mean a person will die of it.

There are, of course, some valid generalizations. On average, for example, obese men who smoke will die sooner than women who are thin and active and never get near a cigarette. But for individuals, there is no telling who will get what when or who will succumb quickly and who will linger.

“We are pretty good at predicting on a group level,” said Dr. Kaare Christensen, a professor of epidemiology at the University of Southern Denmark. “But we are really bad on the individual level.”

Looking to Twins

James Lyons used to think his life would be short. Mr. Lyons, a retired executive with the Boy Scouts of America, thought of his father, who died at 55. “He had one heart attack. It was six hours from onset to death, and that was it.”

Then there were his first cousins on his father’s side. One died at 57 and another at 50. “He was in a barber chair and had a heart attack,” Mr. Lyons said of the 50-year-old. “He died on the spot.”

“He was a big strapping guy, 6-4, healthy and energetic. Then, boom. One day he was there, and the next day he was gone.”

“I approached my 50’s with trepidation,” said Mr. Lyons, who lives in Lansing, Mich.

But his 50’s came and went, and now he is 75. He is still healthy, and he has lived longer than most of his ancestors. He is baffled as to why.

It seems like common sense. Family members tend to look alike. And many characteristics are strongly inherited — height, weight, a tendency to develop early onset heart disease or to get diabetes. Even personalities run in families. Life span would seem to fit with the rest.

But scientists have been trying for decades to find out if there really is a strong genetic link to life spans and, if so, to what extent.

They turned to studies of families and of parents and children, but data analysis has been difficult and any definitive answer elusive. If a family’s members tend to live to ripe old ages, is that because they share some genes or because they share an environment?

“Is it good socioeconomic status, good health or good genes?” Dr. Christensen asked. “How can you disentangle it?”

His solution, a classic one in science, was to study twins. The idea was to compare identical twins, who share all their genes, with fraternal twins, who share some of them. To do this, Dr. Christensen and his colleagues took advantage of detailed registries that included all the twins in Denmark, Finland and Switzerland born from 1870 to 1910. That study followed the twins until 2004 to 2005, when nearly all had died.

Now, Dr. Christensen and his colleagues have analyzed the data. They restricted themselves to twins of the same sex, which obviated the problem that women tend to live longer than men. That left them with 10,251 pairs of same-sex twins, identical or fraternal. And that was enough for meaningful analyses even at the highest ages. “We were able to disentangle the genetic component,” Dr. Christensen said.

But the genetic influence was much smaller than most people, even most scientists, had assumed. The researchers reported their findings in a recent paper published in Human Genetics. Identical twins were slightly closer in age when they died than were fraternal twins.

But, Dr. Christensen said, even with identical twins, “the vast majority die years apart.”

The investigators also asked when the genetic factor kicked in. One hypothesis, favored by Dr. Christensen, was that the strongest genetic effect was on deaths early in life. He thought that deaths at young ages would reflect things like inherited predispositions to premature heart disease or to fatal cancers.

But there was almost no genetic influence on age of death before 60, suggesting that early death has a large random component — an auto accident, a fall. In fact, the studies of twins found almost no genetic influence on age of death even at older ages, except among people who live to be very old, the late 80’s, the 90’s or even 100. The average age at which people are dying today in the United States is 68.5 for men, and 76.1 for women, according to Arialdi M. Minio of the National Center for Health Statistics. This statistic differs from life expectancy, which estimates how long people born today are expected to live.

Finding Randomness

Even though there may be a tendency in some rare families to live extraordinarily long, the genetic influence that emerged from the studies of twins was significantly less than much of the public and many scientists think it is.

A woman whose sister lived to be 100 has a 4 percent chance of living that long, Dr. Christensen says. That is better than the 1 percent chance for women in general, but still not very great because the absolute numbers, 1 out of 100 or 4 out of 100, are still so small. For men, the odds are much lower. A man whose sister lived to be 100 has just a 0.4 percent chance of living that long. In comparison, men in general have a 0.1 percent chance of reaching 100.

Those data fit well with animal studies, says Caleb Finch, a researcher on aging at the University of Southern California. Genetically identical animals — from worms to flies to mice — living in the same environments die at different times.

The reason is not known, Dr. Finch said.

“It’s random,” he said. “Since we can’t find any regular pattern, that’s the hand wave explanation — randomness.”

And random can mean more than one thing.

“There are two phases of randomness,” Dr. Finch said. “There’s the randomness of life experiences. The unlucky ones, who get an infection, get hit on the head or get mutations that turn a cell into cancer. And there are random events in development.”

Random cell growth and division and random differences in which genes get turned on and how active they are during development can cause identical twins to have different numbers of cells in their kidneys and even different patterns of folds in their brains, Dr. Finch pointed out. And random differences in development early in life can set the stage for deterioration decades later.

But seemingly random events can still come as a shock. That’s how Annmarie Bald felt when her identical twin, Catherine Polk, died in her sleep of a heart attack. It happened seven years ago, when Ms. Polk was 43. To this day, Ms. Bald, of Forked River, N.J., lives in fear that the same thing will happen to her. She nervously sees her doctor every year for a checkup, and every year her doctor tells her the same thing: her heart is fine.

“The question in my mind every day is, ‘How did I end up still here and she’s gone?’ ” Ms. Bald said. “It’s not something you ever get over.”

Yet even diseases commonly thought to be strongly inherited, like many cancers, are not, researchers found. In a paper in The New England Journal of Medicine in 2000, Dr. Paul Lichtenstein of the Karolinska Institute in Stockholm and his colleagues analyzed cancer rates in 44,788 pairs of Nordic twins. They found that only a few cancers — breast, prostate and colorectal — had a noticeable genetic component. And it was not much. If one identical twin got one of those cancers, the chance that the other twin would get it was generally less than 15 percent, about five times the risk for the average person but not a very big risk over all.

Looked at one way, the data say that genes can determine cancer risk. But viewed another way, the data say that the risk for an identical twin of a cancer patient is not even close to 100 percent, as it would be if genes completely determined who would get the disease.

Dr. Robert Hoover of the National Cancer Institute wrote in an accompanying editorial: “There is a low absolute probability that a cancer will develop in a person whose identical twin — a person with an identical genome and many similar exposures — has the same type of cancer. This should also be instructive to some scientists and others interested in individual risk assessment who believe that with enough information, it will be possible to predict accurately who will contract a disease and who will not.”

Alzheimer’s disease also has a genetic component, but genes are far from the only factor in determining who gets the disease, said Margaret Gatz of the University of Southern California and Nancy Pedersen of the Karolinska Institute.

Dr. Gatz and Dr. Pedersen analyzed data from a study of identical and fraternal Swedish twins 65 and older. If one of a pair of identical twins developed Alzheimer’s disease, the other had a 60 percent chance of getting it. If one of a pair of fraternal twins, who are related like other brothers and sisters, got Alzheimer’s, the other had a 30 percent chance of getting it.

But, Dr. Pedersen noted, Alzheimer’s is so common in the elderly that it occurs in 35 percent of people age 80 and older. If genes determine who gets Alzheimer’s at older ages, Dr. Pedersen says, “those genes must be very common, have small effects and probably interact with the environment.”

As for other chronic diseases of the elderly, Parkinson’s has no detectable heritable component, studies repeatedly find. Heart disease appears to be indiscriminate, striking almost everyone eventually, says Dr. Anne Newman of the University of Pittsburgh, who has studied it systematically in a large group of elderly people.

But the general picture is consistent in study after study. A strong family history of even a genetically linked disease does not guarantee a person will get it, and having no family history does not mean a person is protected. Instead, chronic diseases strike almost at random among the elderly, making it perhaps not so surprising that life spans themselves have such a weak genetic link.

Matt McGue, a psychology professor at the University of Minnesota who studies twins, contrasts life spans with personality, which, he says, is about 50 percent heritable, or attention-deficit hyperactivity disorder, which is 70 to 80 percent heritable, or body weight, which is 70 percent heritable.

“I’ve been in this business for a long while, and life span is probably one of the most weakly heritable traits I’ve ever studied,” Dr. McGue said.

Seeking Rare Families

At the National Institute on Aging, the question still hovers: Is it possible to find genetic determinants of exceptional health and longevity?

“If you could identify factors for exceptionally good health, that might allow people to avoid disease,” said Evan Hadley, director of the institute’s geriatrics and clinical gerontology program.

There are two methods to do this, Dr. Hadley said. One is to look at how the genes of centenarians differ from those of the rest of the population. But, he said, that requires that if longevity genes exist, they are common among centenarians. And, so far, such studies have not yielded much that has held up — with one well accepted exception: a gene for a cholesterol-carrying protein that affects risk for heart disease as well as Alzheimer’s disease. Those who have that gene have double the chances of living to 100. But that chance is not much anyway. Only about 2 percent of people born in 1910 could expect to reach 100. The second approach is to look for rare genes in unusually long-lived families. “If there is something in a family, it may be in only one or a few families,” Dr. Hadley said. But it may have a big effect.

So the National Institute on Aging is starting a research project with investigators at three United States medical centers and at Dr. Christensen’s center in Denmark. The plan is to find exceptional families, those in which there is a cluster of very old, closely related members — two sisters in their 90’s, for example — whose children, who would typically be in their 70’s, and grandchildren, can be studied too.

Today, many families have a few members living to advanced ages, but very few families have many of them. And in large families, just by chance, someone may live past 90, but it is unlikely that most of the brothers and sisters will get there. For these families, there does not appear to be a genetic component to life spans.

For now, the study is in a pilot phase, testing a scoring system to define the families who seem to fit the criteria.

“If you are really, really old in a family, that gets you more points,” Dr. Hadley said. “You get more points for being 97 than for being 92. But we also are looking at the whole family structure. If there are just two siblings in a family and both live to 98, that’s very exceptional. But suppose there are eight kids and they all made it to 87. That’s pretty unusual, too.’’

If the researchers find genes in the oldest family members that seem to be associated with protection from a disease like heart disease and with a long life, they will follow the younger members of the family, children in their 60’s and 70’s, asking if the same genes seem to protect them as they age.

Some wonder if the project can succeed, said Dr. Newman, who is directing one study center, at the University of Pittsburgh. “The big debate is, is it possible for there to be a few genes that are protective or is it going to be so complicated that we won’t be able to figure out the genetic factors? Is it going to be that some people are just lucky?”

She is optimistic, reasoning that since some families tend to have early onset of certain diseases, others probably have a genetic predisposition to get diseases like heart disease, cancer and Alzheimer’s so late that most members do not get them at all and live very long and healthy lives.

“This would be the flip side of early onset,” she says.

Mrs. Tesauro is in the pilot study. She had always been healthy and active, a self-described tomboy growing up who played tennis until she was 85. “I just can’t sit still,” she said.

She was a woman who knew her mind, so eager to go to college that she defied her father, who thought it was a waste of money, and worked her way through. She ended up with a master’s degree in education and a career as a high school teacher.

Her twin was different. She was the frilly type, Mrs. Tesauro said, and was not much of a student. She failed a grade in high school and barely graduated. Both Mrs. Tesauro and her sister married and had children.

Mrs. Tesauro was born first, and it is a common belief even among scientists that the twin born first is stronger and lives longer. But when he looked at the Scandinavian data, Dr. Christensen said, he found that birth order made no difference in health or longevity.

The day before visiting Mrs. Tesauro for the first time, the Pittsburgh investigators tried to call her, just to be sure she was still alive and still healthy enough to be interviewed. When they could not reach her, they began to worry.

But all was well. Mrs. Tesauro answered the phone the next morning and explained why they had had such trouble. She was out running errands.

Live Long? Die Young? Answer Isn’t Just in Genes, NYT, 31.8.2006, http://www.nytimes.com/2006/08/31/health/31age.html

Clinton Makes Up

for Lost Time in Battling AIDS

August 29, 2006
The New York Times
By CELIA W. DUGGER

RWINKWAVU, Rwanda — Bill Clinton worked the crowd of AIDS survivors, clasping the outstretched hands of children alive because of the AIDS medicines his foundation donated.

Inside the rural hospital here that he recently helped renovate, where Rwandans were hunted down and killed during the genocide he regrets he didn’t try to stop as president, Mr. Clinton heard people once skeletal from AIDS tell of their resurrections to robust health.

Since he left office more than five years ago at age 54, one of the youngest former presidents ever, Mr. Clinton has made a lasting mark in a cause that he came to only late in his presidency: fighting the AIDS pandemic across Africa and the world.

Few public figures in America have spawned as much speculation about what motivates them as Mr. Clinton. Abroad, even fewer inspire the affectionate reception Mr. Clinton received as he raced across seven African countries in eight days in July. Crowds at roadsides and in hospitals wanted to touch him — and he obliged by shaking hands, kissing babies and hugging people with AIDS.

Here on Mr. Clinton’s fourth visit to Rwanda, it was clear the efforts by his foundation had personal meaning. He said he was sorry his administration failed to intervene during the 1994 genocide. “The United States just blew it in Rwanda,” he said flatly. Paul Kagame, Rwanda’s president, said he had accepted Mr. Clinton’s repeated apologies.

But on this trip, Mr. Clinton seemed anything but a man tormented by guilt. Rather, he reveled in his role as a private citizen championing people with AIDS.

“The reason I do this work I do is that I really care about politics and people and public policy,” he said in one of several interviews, scornfully dismissing questions about whether his global AIDS work is a form of redemption for what he failed to accomplish on the issue as president, or for the Monica Lewinsky scandal. “I’m 60 years old now, and I’m not running for anything, so I don’t have to be polite anymore,” he said. “I think it’s all a bunch of hokum,” he added, calling such speculation psychobabble.

“I have never met anybody who spent all their time talking about everybody’s motives who at the end of their life could talk about very many lives they had saved,” he said.

Mr. Clinton was adamant that he had done all he could about global AIDS with a Congress hostile to foreign aid, though he conceded that his administration fought too long to protect the patent rights of pharmaceutical companies against countries trying to make or import cheaper AIDS medicines.

‘Everyone Was Worried’

After he left office, Mr. Clinton faced some skepticism as he took up the cause of people with AIDS dying faraway deaths in poor countries. His administration, which sought more resources to combat AIDS domestically, had a far weaker claim to leadership on AIDS worldwide.

When doctors specializing in public health met him at the William J. Clinton Foundation in Harlem in the fall of 2002, Howard Hiatt, the former dean of the Harvard School of Public Health, bluntly asked Mr. Clinton why those present should expect that “you’ll be able to accomplish now what you didn’t undertake in your presidency — an attack on this plague?”

“Everyone was worried,” said Richard Marlink, who headed Harvard’s AIDS Institute. “Is this a campaign with photo ops and press releases or a long-term commitment?”

In the years since, doctors at the forefront of AIDS treatment have worked with Mr. Clinton. Dr. Marlink volunteered to help Mr. Clinton’s foundation in South Africa. Dr. Hiatt, who serves on the board of Partners in Health, a nonprofit group that works with Mr. Clinton in Rwanda, said the former president “has really perceived the seriousness of the problem.”

Mr. Clinton and his foundation have undertaken projects with two dozen developing countries, raising money to post nurses in rural clinics in Kenya, mustering experts to train hospital managers in Ethiopia and buying drugs for thousands of sick children, among other things.

His foundation also has negotiated steep cuts in the price of AIDS medicines through deals with drug companies that cover more than 400,000 patients in dozens of countries, helping propel momentum for treatment of the destitute.

Dr. Bernard Pécoul, who led a campaign for access to medicines for Doctors Without Borders from 1998 to 2003, credited Mr. Clinton and his foundation for showing independence from the politically powerful drug industry and helping to accelerate the decline in prices for generic AIDS medicines in developing countries.

“They have been very clever in supporting generic policy in the United States, a country where it’s not easy,” he said. “And sometimes they’ve been even more courageous than the United Nations system, which is under pressure from member states.”

The Clinton foundation’s budget last year was $30 million, raised from private donors. Mr. Clinton, who oversees its operations full time, has plunged into many causes, from childhood obesity to tsunami relief to global warming, but he has made his most substantive contribution on AIDS.

He said Rwanda was one of the first countries he chose to work in because “they had a really good chance to dig out of the hole and I wanted to help them do it.”

For years, he tried to coax Dr. Paul Farmer, known for his work caring for the poor in remote, rural Haiti, to recreate his model of AIDS treatment in Africa, the heart of the epidemic.

Last year, Dr. Farmer and the group he co-founded, Partners in Health, arrived in Rwinkwavu. With support from the Clinton Foundation and others, he has transformed a dilapidated facility that lacked even a doctor into a thriving rural hospital.

More than 1,500 people have been put on AIDS medicines here. Reproducing the pioneering model used in Haiti, Dr. Farmer has community workers, many of them peasants, deliver antiretroviral medicines to people with AIDS every day, minimizing reliance on scarce doctors and nurses.

Like most international leaders and American advocates for people with AIDS in the 1990’s, critics say, Mr. Clinton’s efforts on global AIDS did not match the epic scale of the human tragedy as it unfolded across Africa and millions died and were orphaned.

In recent years, the fight against AIDS has leapt onto the world stage, claimed by Mr. Clinton and his Republican successor, George W. Bush.

There is a measure of irony in this. Since 2003, Mr. Bush has marshaled billions of dollars in American assistance for a global assault on the disease, financing lifesaving treatment for hundreds of thousands of people with AIDS. Yet because of his foreign policies, notably the war in Iraq, he is often met by protests when he travels abroad, while Mr. Clinton is warmly embraced across the developing world.

“George Bush has actually delivered more resources, but Clinton is ten times more popular in Africa,” said Princeton Lyman, who was American ambassador to South Africa under Mr. Clinton. “That’s because, just like he does everywhere, he portrays that sense that he cares.”

On his recent tour of Africa — his fifth since 2001 — Mr. Clinton showed a remarkable ability to establish a human connection with people he met.

In Johannesburg, Mr. Clinton and a frail Nelson Mandela, about to turn 88, clutched each other’s hands like a long-lost son and his beloved father.

En route to the airport in Lilongwe, Malawi, where crowds of people strained to catch a glimpse of him, Mr. Clinton suddenly halted the motorcade, conducted an impromptu interview in the middle of the road, then plunged into a throng of young men reaching out to touch him.

At a hospital in Mafeteng, Lesotho, Mr. Clinton strolled into a sunny courtyard with 6-year-old Arriet Moeketsi, a little girl in a polka-dot dress. Arriet, who takes AIDS medicines donated by Mr. Clinton’s foundation, trustingly leaned her face against the former president and never let go of his hands during a prolonged news conference.

Bill and Melinda Gates, the billionaire philanthropists, watched. Mr. Clinton had visited an AIDS project of theirs in Durban, South Africa, and they had come to Lesotho to see his work. When Mr. Clinton left the hospital with Arriet, a Clinton volunteer asked the Gateses to stay back so photographers could follow him.

The world’s wealthiest couple seemed to take no offense. The two Bills, as they have been dubbed, have taken to doing high-profile AIDS advocacy events together, with Mr. Clinton bringing star power and Mr. Gates his deep pockets.

“He plays a unique role in shining a light on the problem,” said Mr. Gates, after he made it into the courtyard.

Mr. Clinton has come a long way on global AIDS. For most of his presidency, his trade office fought to protect the patent rights of pharmaceutical companies against attempts by developing countries to make or import cheaper generic medicines. “I think it was wrong,” he now says of that approach.

During the first six years of his presidency, federal spending to fight AIDS worldwide stagnated at paltry levels, never topping $141 million.

But by his last budget, spending more than tripled to $540 million, but Mr. Clinton says that was far from enough. Even so, he contends that no one could have done better.

The Role of Congress

The Democrats controlled Congress for only his first two years in office, he pointed out, when “everybody’s obsession” was the AIDS problem in America. After that, the Republican-dominated Congress that later supported Mr. Bush’s $15 billion, five-year global AIDS plan fiercely resisted spending on foreign assistance.

“Have you forgotten what I had in the Congress?” he asked. “That the Republican Congress spent all their time trying to trash me?

“And the only reason they gave money to George Bush for AIDS is they wanted to have something they looked progressive on since they were cutting taxes for rich people like me,” he said.

Michael Gerson, who was a senior adviser to Mr. Bush on global health issues, noted that the Republican Congress was, in fact, open to persuasion that global AIDS was a spending priority. But he also said the issue had ripened by the time Mr. Bush was president. The price of antiretroviral drugs fell after Mr. Clinton left office, helping change the view that it was too costly and difficult to treat people in poor countries.

But Mr. Gerson also said of the Clinton record: “I don’t believe they were visionary or pushed the system. I don’t think they were thinking big.”

The debate over whether Mr. Clinton missed a political opportunity to lead the charge on global AIDS years before Mr. Bush seized it is far from over.

Greg Behrman, the author of “The Invisible People: How the U.S. Has Slept Through the Global AIDS Pandemic, the Greatest Humanitarian Catastrophe of Our Time,” offers a split verdict.

“There are two acts here,” he said. “Clinton’s post-presidential leadership has been extraordinary. As president, though, the record is clear. Clinton was not a leader on global AIDS and the consequences have been devastating.”

After he left office, Mr. Clinton considered his future with a keen eye on history, analyzing what former presidents had done.

He concluded that another former Southern governor, Jimmy Carter, a Nobel Peace Prize winner who is now recognized for his work on human rights, democracy and neglected diseases, was “the only person who’d done anything that remotely resembled what I thought I could do.”

From the start, Mr. Clinton had a host of issues on his agenda, but quickly found himself drawn into AIDS. He turned to his old friend Ira Magaziner, a fellow Rhodes scholar and corporate consultant who had managed the Clintons’ failed health care reform effort. Mr. Magaziner has since led the foundation’s AIDS program.

The two men discovered in 2002 that the Bahamas was paying $3,500 per person a year for generic AIDS drugs. “I said, ‘Ira, please find out why in the hell these people are paying $3,500 for $500 drugs,’ ” Mr. Clinton said.

They learned the Bahamas was buying through middlemen, so the foundation helped the country purchase directly from Cipla, the Indian generic-drug manufacturer. “So our first victory was a lay-down,” Mr. Clinton said. “All of a sudden, they could treat six times as many people for the same amount of money.”

Opportunities proliferated, and Mr. Clinton’s enthusiasm grew.

His name opened doors with generic drug makers. With growing demand for AIDS drugs already on the horizon, as well as the economies of scale that come with that, Mr. Magaziner took a team of volunteer consultants to India in 2003 to negotiate for lower prices. Companies opened their books.

“The name Clinton in India holds more charisma and credibility than any other American name,” said Dr. Yusuf K. Hamied, Cipla’s chairman.

Through cost cutting, spurred by breakthrough talks with companies that supplied ingredients to the drug makers, the team got deals. Cipla, for example, halved the price of the most common AIDS triple-drug therapy, already declining due to competition, to $140 a person per year.

Similarly, Mr. Clinton was able to use his relationships with political leaders, like President Thabo Mbeki of South Africa, who had questioned whether H.I.V. caused AIDS. The country had not begun treating its people for the disease, though almost five million had been infected. “He was getting killed in the global press about it,” Mr. Clinton recalled.

Mr. Clinton, who knew him from his own time as president, met with Mr. Mbeki in 2003 as one politician to another. “I said, ‘You know, I really want to help you, and as you know, I may be the only one of those involved in this work who’s never been publicly critical of you,’ ” Mr. Clinton said he told Mr. Mbeki. “ ‘But this is something you have to do.’ ”

Mr. Mbeki soon invited Mr. Clinton’s foundation to help the country write a comprehensive treatment plan. South Africa now has more than 130,000 people on antiretroviral drugs, still far short of what critics say is needed.

Since 2004, Mr. Clinton has campaigned to raise the profile of children with AIDS. A scant 20,000 children in the developing world were then getting drug treatment, while more than 500,000 a year were dying. The Clinton foundation has raised $4.4 million to buy drugs for 13,000 children, train health workers, renovate pediatric wings and pay for lab tests.

“Children are alive in numbers we couldn’t have imagined a couple of years ago because of what he’s done,” said Peter McDermott, chief of H.I.V. and AIDS programs at Unicef.

Mr. Clinton’s ambitions seem to grow daily, and his foundation is now branching out in Africa from AIDS into poverty. As he relaxed one recent evening in a sumptuous, $2,260-a-night suite in Johannesburg, with zebra skin rugs underfoot (the lodgings provided to him gratis by a rich South African businessman who owned the hotel), he got excited just thinking about fertilizer.

Mr. Magaziner has people riding trains and trucks that carry fertilizer to figure out why a commodity that should enable farmers to grow more food and avoid hunger costs so much in Africa.

“You follow the trail!” Mr. Clinton said.

Mr. Clinton was joined on his trip by Sir Tom Hunter, a Scottish entrepreneur who has promised to spend $100 million of his fortune in collaboration with the foundation, much of it on economic development.

“Tom, where’s Tom?” Mr. Clinton called out excitedly as he chatted with representatives of a nonprofit group that promotes solar-powered lights during an event here in Rwinkwavu.

What if Rwanda could manufacture such lights locally? Mr. Clinton mused. Why not electrify villages so children can study at night? “It might be possible to get a factory here that would serve all of central Africa!”

    Clinton Makes Up for Lost Time in Battling AIDS, NYT, 29.8.2006, http://www.nytimes.com/2006/08/29/health/29clinton.html

Philadelphia yanks HIV ads

showing black men in gun's cross hairs

Posted 8/8/2006 4:44 PM ET
AP
USA Today

PHILADELPHIA (AP) — Health officials yanked public service advertisements urging HIV testing after a gay advocacy group expressed concerns about images depicting young black men in a gun's cross hairs.

"Putting the face of a black man in the cross hairs of a gun paints a damaging message about violence and black men," Lee Carson, chairman of the Black Gay Men's Leadership Council, wrote in a letter to the city's interim health commissioner last month.

The $236,000 campaign, which ended abruptly Monday, was geared at gay and bisexual men and featured the tagline, "Have YOU been hit?"

"Given the violence perpetrated against gay men, it is not farfetched to see how this campaign fosters violence," Carson wrote to interim Health Commissioner Carmen Paris.

Paris said she "inherited" the campaign and only recently saw the ads. She added, "The right thing to do, of course, is not to promote any message that could be perceived as promoting violence."

The campaign was launched May 19 with ads on buses, television, postcards and a website. The ads were no longer posted on the website Tuesday.

Zigzag Net Inc., the Philadelphia-based marketing company that developed the campaign, spent months setting up two focus groups to evaluate the most effective themes.

"We are aware of objections to the campaign," project manager Aaron McLean said. "However, we acted under the explicit direction of the city Health Department. The response in the focus groups was very positive."

    Philadelphia yanks HIV ads showing black men in gun's cross hairs, UT, 8.8.2006, http://www.usatoday.com/news/health/2006-08-08-hivads_x.htm

Doctors: Separation of Twins Going Well

August 8, 2006
By THE ASSOCIATED PRESS
Filed at 2:22 a.m. ET
The New York Times

SALT LAKE CITY (AP) -- Doctors have successfully separated 4-year-old twin sisters born fused at the midsection, with just one kidney and one set of legs, and were continuing with reconstruction surgery.

The parents broke into tears when doctors announced that the separation had been completed at 10:50 p.m., and, at 11 p.m., one -- Kendra Herrin -- was moved to a separate operating room.

''It's just a new beginning -- and the end of a really good one,'' father Jake Herrin said.

Reconstruction was expected to take another 4 1/2 hours.

Doctors at Primary Children's Hospital said it was the first known surgical attempt to separate twins with a shared kidney.

Kendra and Maliyah Herrin were rolled into the operating room at 7:15 a.m. after a tearful goodbye from their parents.

''It was very emotional,'' said their father, Jake Herrin. ''They were more brave than us.''

The operation was expected to last 12 to 24 hours, during which surgeons planned to give each girl one leg and Kendra the kidney. Maliyah will be put on dialysis for three to six months until she is strong enough for a transplant of a kidney from her mother, Erin Herrin.

Surgeons also divided the girls' single liver and separated their intestines.

The twins were stable through the first 12 hours of the operation, the doctors said earlier.

''Going great, no problems whatsoever,'' said Dr. Rebecka Meyers, the hospital's chief of pediatric surgery. She said the procedures surgeons performed on the twins are commonly done in many patients -- just not those who are attached to each other.

''What's unusual is doing them all in one single surgery, in two separate girls, followed by the physical separation of the children,'' hospital spokeswoman Bonnie Midget said.

The surgery included successfully separating the intestines, divided and reconstructed the twins' two bladders.

Surrounded by family and close friends, the girls' parents were being updated hourly by the surgical team's lead nurse and tried to stay upbeat.

''We know going into this surgery that angels are watching over our children, we feel it,'' Erin Herrin said.

Jake Herrin said they were grateful for messages posted on the North Salt Lake family's Web site from well-wishers around the world.

The blue-eyed, sandy-haired girls were born locked in an embrace, practically face to face. Conjoined twins occur about once in every 50,000 to 100,000 births. Only about 20 percent survive to become viable candidates for separation.

Monday's surgical team included six surgeons, two anesthesiologists, one radiologist, two urologists and 25 to 30 support staff members.

------

On the Net:

www.Herrintwins.com

    Doctors: Separation of Twins Going Well, NYT, 8.8.2006, http://www.nytimes.com/aponline/us/AP-Conjoined-Twins.html

Aging face of HIV poses new challenges

Updated 8/4/2006 9:35 PM ET
AP
USA Today

NEW YORK (AP) — Pat Shelton has had the AIDS virus for at least 15 years, and also struggles with hepatitis C and high blood pressure. But what is bothering her most on this sultry summer day are hot flashes.

"I've gone through hell with my menopause," said Shelton, an elegant woman who recently swapped her dreadlocks for a close-cropped look while trying to stay cool. "It's kicking me. But HIV, I've been very blessed. I don't know why."

The 53-year-old Shelton, whose drug regimen has kept her HIV from developing into full-blown AIDS, in many ways represents the changing face of the HIV population in New York and around the country: They are getting older and presenting new challenges to health care providers.

In New York City, the epicenter of AIDS in the United States, 30% of the 100,000 people with HIV are over 50, and 70% are over 40, according to the city health department. Nationwide, 27% of people with AIDS are now over 50, the Centers for Disease Control reported.

"Here is a group of people who, yes, they have HIV, but they're going to get other illnesses," said Stephen Karpiak, the associate director of research for the AIDS Community Research Initiative of America (ACRIA). "And we don't know the interaction of all the drugs. There are God knows how many hundreds of drugs used by folks for cardiac issues, osteoporosis, arthritis — we don't know those interactions at all.

"No one's ever looked at them. Someone needs to do trials."

Karpiak's agency conducted a study, released this week, that examined the many challenges faced by people with the AIDS virus.

The AIDS service organizations that arose after the epidemic hit in the 1980s were designed to provide care and counseling to people facing shortened life spans. While there's still no cure for AIDS, anti-retroviral drugs have made it a manageable illness for many patients and prolonged their lives beyond what once seemed possible.

As this group ages, they fall prey to a host of conditions that require medicines that may interfere with the effectiveness of AIDS drugs.

And that's if the condition gets diagnosed at all. AIDS patients typically see infectious disease specialists who may not have their antennae out for unrelated diseases, Karpiak said.

They don't look for age-related problems, he said. "That is not their profession."

Conversely, doctors unfamiliar with AIDS may not suspect that older patients have the disease.

Because AIDS arose in the United States among gay men, a stigmatized group, it remains more ostracized than other diseases. Fearing rejection, people with AIDS often isolate themselves. Isolation becomes more of a problem with age, said Karpiak, who noted that 70% of the people in the study live alone.

"This is an isolated, stigmatized group of people who have been largely neglected by their churches, by their communities," he said. "Half have not told their families. ... And as you age, you need those people for emotional and everyday support."

Without friends and family, Karpiak said, older people with HIV turn to home health aides. That creates the potential of overburdening the system as the number of HIV positive people over 50 continues to rise.

Marjorie Hill of Gay Men's Health Crisis, one of the nation's largest AIDS service organizations, said 33% of the agency's 15,000 clients are over 50 — up from 25% two or three years ago.

Among the organization's tailored services are meals and exercise classes better suited for older clients.

In addition, Hill said, a public service campaign featuring older people — unlike the subway and magazine ads that typically show images of handsome young men — is in the works.

"We are actively fundraising to develop a campaign targeting persons over 50 with prevention and education," she said.

Shelton, a former drug user who tested positive for HIV in 1991, has been an AIDS peer educator since 1998. She is trained to give support but gets support herself at Copacetic Women, a group for women with HIV over 50.

"I really don't feel too comfortable sitting in a group with people my children's age," she said. "They're not really going to open up or listen to what I really have to say. ... We have concerns and health problems that the doctors are not taking care of. We needed a safe haven."

On the Net: http://www.acria.org

    Aging face of HIV poses new challenges, UT, 4.8.2006, http://www.usatoday.com/news/health/2006-08-04-aids-aging_x.htm

Kerry Proposes Universal Coverage by 2012

July 31, 2006
By THE ASSOCIATED PRESS
Filed at 1:51 p.m. ET
The New York Times

BOSTON (AP) -- Sen. John Kerry on Monday proposed requiring all Americans to have health insurance by 2012, ''with the federal government guaranteeing that they have the means to afford it.''

The Massachusetts Democrat, whose name is figuring prominently in 2008 White House speculation, repeated his 2004 presidential campaign call for expanding the federal Medicaid program to cover children. He also proposed creating a program to cover catastrophic cases so an employer providing insurance doesn't have to pass the cost to his other workers, and; offering Americans the ability to buy into the same insurance program used by federal workers such as members of Congress.

Kerry proposes to pay for the program by repealing tax cuts enacted during the Bush administration that benefit those earning over $200,000 annually. He did not immediately elaborate on how he would enact his insurance mandate, but one aid said he would do so with a requirement written into the legislation spelling out that the government covers anyone who is uninsured.

''One of my biggest regrets is that fear talk trumped the health care walk, and that we are less safe abroad and less healthy at home because of that,'' Kerry told a crowd of several hundred during a midday speech at Faneuil Hall. The senator had previously delivered two other speeches at the Revolutionary War meeting house laying the ground work for a second presidential campaign.

The senator also promoted his health care proposal in a Boston Globe op-ed piece published Monday morning, and during an appearance on Don Imus's national radio program.

Kerry conceded his health care proposal is virtually the same as the program he outlined during his failed campaign. However, he said that continuity was a measure of his commitment to his health care ideals.

''Every day since the election, the health care crisis has grown steadily worse,'' Kerry said. ''The president has stuck to his guns -- or, more accurately, his empty holster -- and done nothing beyond trotting out the conservative hobby horse of health savings accounts.''

The senator said his plan will lead to universal coverage by 2012, ''but if we're not there by 2012, we will require that all Americans have health insurance, with the federal government guaranteeing they have the means to afford it.''

The Republican National Committee, which typically responds to political criticism of the president, said Kerry's critique ignored the prescription drug program enacted by the Bush administration.

''It's unfortunate that John Kerry's bitterness over losing the election clouds his ability to recognize the president's prescription drug plan is providing millions of seniors with more affordable medicine,'' said RNC spokeswoman Tracey Schmitt.

Whatever his criticism, Kerry faces the reality that the governor of his home state -- Republican Mitt Romney, himself a potential 2008 presidential candidate -- has not only talked about but enacted a sweeping health care overhaul designed to bring universal coverage to Massachusetts. Last week, Michael Leavitt, secretary of the U.S. Department of Health and Human services, called the program ''a model'' for the nation.

Romney negotiated the plan with a Democratic Legislature, and in cooperation with Sen. Edward M. Kennedy, D-Mass., Kerry's senior colleague.

Under Romney's plan, which the federal government is assisting with $385 million annually, Medicaid will be expanded for 100,000 people, the government will cover premium costs for another 200,000 who buy private programs, while an additional 200,000 will be required to buy insurance from low-cost policies offered by private companies working in tandem with the government.

Romney signed the bill into law in April on the same Faneuil Hall stage where Kerry planned his remarks.

    Kerry Proposes Universal Coverage by 2012, NYT, 31.7.2006, http://www.nytimes.com/aponline/us/AP-Kerry-Health-Care.html

F.D.A. Plans to Consider Morning-After Pill

July 31, 2006
The New York Times
By JEREMY W. PETERS

The Food and Drug Administration said today it is considering approval of the morning-after pill for sale without a prescription, a surprise move on an issue that has ensnared the agency in debate for years.

Discussions between the government and Barr Laboratories, which manufactures the drug, known as Plan B, are set to begin immediately and could be completed “in a matter of weeks,” the agency said in a statement.

The move could end a standoff between the Bush administration and Democrats on Capitol Hill.

The decision to move forward with consideration of the pill, now available by prescription, comes just as President Bush’s nominee to lead the F.D.A., Dr. Andrew C. von Eschenbach, prepares to go before the Senate for his confirmation hearings. Those hearings are to begin on Tuesday.

Approval of the nomination has been in doubt since Senators Hillary Rodham Clinton of New York and Patty Murray of Washington, both Democrats who support over-the-counter sales of Plan B, said they would block any vote on Dr. von Eschenbach until the agency makes a decision.

Barr’s application for over-the-counter approval of Plan B has been pending before the F.D.A. for three years and has sparked considerable discord within the agency. It has also become a proxy fight in the debate between foes and supporters of abortion rights.

In December 2003, an F.D.A. advisory committee voted 23 to 4 to approve Barr’s application with no age restrictions. Six months later, however, a top agency official rejected the application, citing concerns that the pill would be available to young teenagers.

Barr resubmitted its application, this time seeking approval to sell the drug only to those 16 and older.

Internal F.D.A. documents show that agency officials suggested to Barr that it rewrite its application to allow over-the-counter sales to adult women while still requiring younger teenagers to get a prescription. Barr did that, but in January 2005, the statutory deadline for an F.D.A. decision passed without a decision.

In a letter to Barr today, Dr. von Eschenbach indicated the F.D.A. would not approve Plan B for over-the-counter sale for girls under 18. “We believe that the appropriate age for OTC access is 18,” he wrote.

While the F.D.A. has insisted that its decisions to reject or delay the Plan B application were the result of scientific or regulatory concerns, a Congressional investigation found last year that top agency officials decided at one point to reject the application before its staff’s scientific review was even complete.

Dr. Susan Wood resigned in August as director of the F.D.A.’s office of women’s health to protest what she said was political interference in the agency’s scientific deliberations.

    F.D.A. Plans to Consider Morning-After Pill, NYT, 31.7.2006, http://www.nytimes.com/2006/07/31/giving/31cnd-pill.html?hp&ex=1154404800&en=3df0f0cc0e529b01&ei=5094&partner=homepage

The New Age

So Big and Healthy Nowadays That Grandpa Wouldn’t Even Know You

July 30, 2006
The New York Times
By GINA KOLATA

Valentin Keller enlisted in an all-German unit of the Union Army in Hamilton, Ohio, in 1862. He was 26, a small, slender man, 5 feet 4 inches tall, who had just become a naturalized citizen. He listed his occupation as tailor.

A year later, Keller was honorably discharged, sick and broken. He had a lung ailment and was so crippled from arthritis in his hips that he could barely walk.

His pension record tells of his suffering. “His rheumatism is so that he is unable to walk without the aid of crutches and then only with great pain,” it says. His lungs and his joints never got better, and Keller never worked again.

He died at age 41 of “dropsy,” which probably meant that he had congestive heart failure, a condition not associated with his time in the Army. His 39-year-old wife, Otilia, died a month before him of what her death certificate said was “exhaustion.”

People of Valentin Keller’s era, like those before and after them, expected to develop chronic diseases by their 40’s or 50’s. Keller’s descendants had lung problems, they had heart problems, they had liver problems. They died in their 50’s or 60’s.

Now, though, life has changed. The family’s baby boomers are reaching middle age and beyond and are doing fine.

“I feel good,” says Keller’s great-great-great-grandson Craig Keller. At 45, Mr. Keller says he has no health problems, nor does his 45-year-old wife, Sandy.

The Keller family illustrates what may prove to be one of the most striking shifts in human existence — a change from small, relatively weak and sickly people to humans who are so big and robust that their ancestors seem almost unrecognizable.

New research from around the world has begun to reveal a picture of humans today that is so different from what it was in the past that scientists say they are startled. Over the past 100 years, says one researcher, Robert W. Fogel of the University of Chicago, humans in the industrialized world have undergone “a form of evolution that is unique not only to humankind, but unique among the 7,000 or so generations of humans who have ever inhabited the earth.”

The difference does not involve changes in genes, as far as is known, but changes in the human form. It shows up in several ways, from those that are well known and almost taken for granted, like greater heights and longer lives, to ones that are emerging only from comparisons of health records.

The biggest surprise emerging from the new studies is that many chronic ailments like heart disease, lung disease and arthritis are occurring an average of 10 to 25 years later than they used to. There is also less disability among older people today, according to a federal study that directly measures it. And that is not just because medical treatments like cataract surgery keep people functioning. Human bodies are simply not breaking down the way they did before.

Even the human mind seems improved. The average I.Q. has been increasing for decades, and at least one study found that a person’s chances of having dementia in old age appeared to have fallen in recent years.

The proposed reasons are as unexpected as the changes themselves. Improved medical care is only part of the explanation; studies suggest that the effects seem to have been set in motion by events early in life, even in the womb, that show up in middle and old age.

“What happens before the age of 2 has a permanent, lasting effect on your health, and that includes aging,” said Dr. David J. P. Barker, a professor of medicine at Oregon Health and Science University in Portland and a professor of epidemiology at the University of Southampton in England.

Each event can touch off others. Less cardiovascular disease, for example, can mean less dementia in old age. The reason is that cardiovascular disease can precipitate mini-strokes, which can cause dementia. Cardiovascular disease is also a suspected risk factor for Alzheimer’s disease.

The effects are not just in the United States. Large and careful studies from Finland, Britain, France, Sweden and the Netherlands all confirm that the same things have happened there; they are also beginning to show up in the underdeveloped world.

Of course, there were people in previous generations who lived long and healthy lives, and there are people today whose lives are cut short by disease or who suffer for years with chronic ailments. But on average, the changes, researchers say, are huge.

Even more obvious differences surprise scientists by the extent of the change.

In 1900, 13 percent of people who were 65 could expect to see 85. Now, nearly half of 65-year-olds can expect to live that long.

People even look different today. American men, for example, are nearly 3 inches taller than they were 100 years ago and about 50 pounds heavier.

“We’ve been transformed,” Dr. Fogel said.

What next? scientists ask. Today’s middle-aged people are the first generation to grow up with childhood vaccines and with antibiotics. Early life for them was much better than it was for their parents, whose early life, in turn, was much better than it was for their parents.

And if good health and nutrition early in life are major factors in determining health in middle and old age, that bodes well for middle-aged people today. Investigators predict that they may live longer and with less pain and misery than any previous generation.

“Will old age for today’s baby boomers be anything like the old age we think we know?” Dr. Barker asked. “The answer is no.”

Trying to Change a Pattern

Craig Keller does not know what to expect of his old age. But he is optimistic by nature, and he knows he has already lived past the life span of his beleaguered ancestor Valentin. He is 5-foot-9, 200 pounds and exuberantly healthy.

He grew up in Hamilton, the same town on the Kentucky border where Valentin lived, worshiped and was buried. And he still lives there, working as a court bailiff, married to Sandy, whom he met when they were in second grade. Now, married 25 years, the Kellers have two grown daughters, a lively black dog and no complaints.

Craig and Sandy Keller had all the advantages of middle-class Americans of their age: childhood vaccines, plenty of food, antibiotics when they fell ill. Now, wanting to stay healthy, they walk in the evenings, try to eat well and rely on their strong faith, which, they say, makes a big difference to their health. And they enjoy life.

Mr. Keller pulls his wife’s tan Chevy Malibu into the driveway of his small, immaculate house on a sidewalk-lined street. It is the same house that he grew up in; he and Mrs. Keller bought it from Mr. Keller’s parents 22 years ago. While Mrs. Keller brings out a snack of a homemade cheese ball, crackers, sandwiches, fruit salad and brownies, Mr. Keller settles in to marvel at the contrast between his comfortable life and the lives of his ancestors.

For him, the idea of falling ill in his late 20’s and never working again is unimaginable. He knows, though, that he is nearing the age when many of his ancestors died. His father, Carl D. Keller, a lifelong smoker, developed prostate cancer, then emphysema, and then lung cancer, which killed him at age 65. His father’s father, Carl W. Keller, also a smoker, died of cancer of the esophagus just after he turned 69. His grandfather on his mother’s side died of cirrhosis of the liver at 55; his grandmother died at 56 of breast cancer.

“They never got out of their 50’s and 60’s,” Mr. Keller said. “So that’s kind of in the back of your mind.” He worries about his lungs, given his family history. He had pneumonia once and has had bronchitis.

But, Mr. Keller reasons, he is so physically different from his ancestors — he has never smoked and is so much healthier, so much better fed — that he really thinks he will break the spell.

And if exercise is good for health, the Kellers certainly have exercised. Mr. Keller displays a bookcase in their basement, crammed with athletic trophies. Mrs. Keller’s are from baton twirling, Mr. Keller’s are from baseball, basketball, softball and soccer. Their daughters, 19-year-old Rachel and 22-year-old Kristy, got theirs cheerleading.

Mrs. Keller said that when she was her daughters’ age, “I didn’t think about my health very much.”

“But later in my 30’s and toward my 40’s,” she said, “I started to think about it. You try to eat right, you try to exercise. And you do see your parents with illnesses. And you wonder about yourself. My mom had a quadruple bypass when she was 75, and she had to have a pacemaker after that. She’s now in her 80’s, but you do wonder.”

Was it genetic destiny or health habits that caused her mother’s heart disease? Mrs. Keller asks herself. Her mother smoked for more than a decade, finally quitting with great difficulty before Mrs. Keller was born. “She said the Lord helped her,” Mrs. Keller said.

Mrs. Keller has never smoked. Concerned about heart disease, she had her cholesterol level tested a few years ago and now takes medication to lower it. She walks at lunch with the women in her office and after dinner with her husband.

Her daughter Rachel, petite and quiet with a quick smile, is already thinking about her family’s medical history. She worries about heart disease, worries about lung disease. She has already had her cholesterol level measured — it was normal. And she is shocked when people her age start smoking.

“In high school, none of my friends smoked,” she said. “They came back from their first year in college, and all of them did.”

“It’s hard to think about getting old when you’re young,” Rachel added. “But when you see your family members — my grandpa died of lung cancer, my grandparents on both sides had cancer. So it’s on my mind a lot of times.”

But still, the future is so distant it is almost unfathomable to her. “I wonder what we’re going to be like when we’re old,” she mused.

Lives Plagued by Illness

Scientists used to say that the reason people are living so long these days is that medicine is keeping them alive, though debilitated. But studies like one Dr. Fogel directs, using records of of Union Army veterans, have led many to rethink that notion.

The study involves a random sample of about 50,000 Union Army veterans. Dr. Fogel compared those men, the first generation to reach age 65 in the 20th century, with people born more recently.

The researchers focused on common diseases that are diagnosed in pretty much the same way now as they were in the last century. So they looked at ailments like arthritis, back pain and various kinds of heart disease that can be detected by listening to the heart.

The first surprise was just how sick people were, and for how long.

Instead of inferring health from causes of death on death certificates, Dr. Fogel and his colleagues looked at health throughout life. They used the daily military history of each regiment in which each veteran served, which showed who was sick and for how long; census manuscripts; public health records; pension records; doctors’ certificates showing the results of periodic examinations of the pensioners; and death certificates.

They discovered that almost everyone of the Civil War generation was plagued by life-sapping illnesses, suffering for decades. And these were not some unusual subset of American men — 65 percent of the male population ages 18 to 25 signed up to serve in the Union Army. “They presumably thought they were fit enough to serve,” Dr. Fogel said.

Even teenagers were ill. Eighty percent of the male population ages 16 to 19 tried to sign up for the Union Army in 1861, but one out of six was rejected because he was deemed disabled.

And the Union Army was not very picky. “Incontinence of urine alone is not grounds for dismissal,” said Dora Costa, an M.I.T. economist who works with Dr. Fogel, quoting from the regulations. A man who was blind in his right eye was disqualified from serving because that was his musket eye. But, Dr. Costa said, “blindness in the left eye was O.K.”

After the war ended, as the veterans entered middle age, they were rarely spared chronic ailments.

“In the pension records there were descriptions of hernias as big as grapefruits,” Dr. Costa said. “They were held in by a truss. These guys were continuing to work although they clearly were in a lot of pain. They just had to cope.”

Eighty percent had heart disease by the time they were 60, compared with less than 50 percent today. By ages 65 to 74, 55 percent of the Union Army veterans had back problems. The comparable figure today is 35 percent.

The steadily improving health of recent generations shows up in population after population and country after country. But these findings raise a fundamental question, Dr. Costa said.

“The question is, O.K., there are these differences, and yes, they are big. But why?” she said.

“That’s the million-dollar question,” said David M. Cutler, a health economist at Harvard. “Maybe it’s the trillion-dollar question. And there is not a received answer that everybody agrees with.”

Outgrowing the Past

Don Hotchkiss, a civil engineer in Las Vegas and a descendant of Civil War veterans, is an avid Civil War re-enactor. Early on, he and his brother tried to sleep in an exact replica of one of the old tents.

It was too small, Mr. Hotchkiss said. He is six feet tall and stocky. His brother, a police officer in Phoenix, is thinner, but 6-foot-2. The tents were made for men who were average size then. “In the past 145 years, we’ve ballooned up,” Mr. Hotchkiss said.

At a recent meeting of a Las Vegas chapter of the Sons of Confederate Veterans, eight burly men crowded into a library meeting room. All had experienced the equivalent of the Civil War tent problem.

“At the re-enactments, all the directors, all the costume directors say the re-enactors are just too darn big,” said George McClendon, a hefty 67-year-old retired airline pilot.

Mr. McClendon is right. Men living in the Civil War era had an average height of 5-foot-7 and weighed an average of 147 pounds. That translates into a body mass index of 23, well within the range deemed “normal.” Today, men average 5-foot-9½ and weigh an average of 191 pounds, giving them an average body mass index of 28.2, overweight and edging toward obesity.

Those changes, along with the great improvements in general health and life expectancy in recent years, intrigued Dr. Costa. Common chronic diseases — respiratory problems, valvular heart disease, arteriosclerosis, and joint and back problems — have been declining by about 0.7 percent a year since the turn of the 20th century. And when they do occur, they emerge at older ages and are less severe.

The reasons, she and others are finding, seem to have a lot to do with conditions early in life. Poor nutrition in early years is associated with short stature and lifelong ill health, and until recently, food was expensive in the United States and Europe.


Dr. Fogel and Dr. Costa looked at data on height and body mass index among Union Army veterans who were 65 and older in 1910 and veterans of World War II who were that age in the 1980’s. Their data relating size to health led them to a prediction: the World War II veterans should have had 35 percent less chronic disease than the Union Army veterans. That, they said, is exactly what happened.

They also found that diseases early in life left people predisposed to chronic illnesses when they grew older.

“Suppose you were a survivor of typhoid or tuberculosis,” Dr. Fogel said. “What would that do to aging?” It turned out, he said, that the number of chronic illnesses at age 50 was much higher in that group. “Something is being undermined,” he said. “Even the cancer rates were higher. Ye gods. We never would have suspected that.”

Men who had respiratory infections or measles tended to develop chronic lung disease decades later. Malaria often led to arthritis. Men who survived rheumatic fever later developed diseased heart valves.

And stressful occupations added to the burden on the body.

People would work until they died or were so disabled that they could not continue, Dr. Fogel said. “In 1890, nearly everyone died on the job, and if they lived long enough not to die on the job, the average age of retirement was 85,” he said. Now the average age is 62.

A century ago, most people were farmers, laborers or artisans who were exposed constantly to dust and fumes, Dr. Costa said. “I think there is just this long-term scarring.”

Searching for Answers

Dr. Barker of Oregon Health and Science University is intrigued by the puzzle of who gets what illness, and when.

“Why do some people get heart disease and strokes and others don’t?” he said. “It’s very clear that current ideas about adult lifestyles go only a small way toward explaining this. You can say that it’s genes if you want to cease thinking about it. Or you can say, When do people become vulnerable during development? Once you have that thought, it opens up a whole new world.”

It is a world that obsesses Dr. Barker. Animal studies and data that he and others have been gathering have convinced him that health in middle age can be determined in fetal life and in the first two years after birth.

His work has been controversial. Some say that other factors, like poverty, may really be responsible. But Dr. Barker has also won over many scientists.

In one study, he examined health records of 8,760 people born in Helsinki from 1933 to 1944. Those whose birth weight was below about six and a half pounds and who were thin for the first two years of life, with a body mass index of 17 or less, had more heart disease as adults.

Another study, of 15,000 Swedish men and women born from 1915 to 1929, found the same thing. So did a study of babies born to women who were pregnant during the Dutch famine, known as the Hunger Winter, in World War II.

That famine lasted from November 1944 until May 1945. Women were eating as little as 400 to 800 calories a day, and a sixth of their babies died before birth or shortly afterward. But those who survived seemed fine, says Tessa J. Roseboom, an epidemiologist at the University of Amsterdam, who studied 2,254 people born at one Dutch hospital before, during and after the famine. Even their birth weights were normal.

But now those babies are reaching late middle age, and they are starting to get chronic diseases at a much higher rate than normal, Dr. Roseboom is finding. Their heart disease rate is almost triple that of people born before or after the famine. They have more diabetes. They have more kidney disease.

That is no surprise, Dr. Barker says. Much of the body is complete before birth, he explains, so a baby born to a pregnant woman who is starved or ill may start life with a predisposition to diseases that do not emerge until middle age.

The middle-aged people born during the famine also say they just do not feel well. Twice as many rated their health as poor, 10 percent compared with 5 percent of those born before or after the famine.

“We asked them whether they felt healthy,” Dr. Roseboom said. “The answer to that tends to be highly predictive of future mortality.”

But not everyone was convinced by what has come to be known as the Barker hypothesis, the idea that events very early in life affect health and well-being in middle and old age. One who looked askance was Douglas V. Almond, an economist at Columbia University.

Dr. Almond had a problem with the studies. They were not of randomly selected populations, he said, making it hard to know if other factors had contributed to the health effects. He wanted to see a rigorous test — a sickness or a deprivation that affected everyone, rich and poor, educated and not, and then went away. Then he realized there had been such an event: the 1918 flu.

The flu pandemic arrived in the United States in October 1918 and was gone by January 1919, afflicting a third of the pregnant women in the United States. What happened to their children? Dr. Almond asked.

He compared two populations: those whose mothers were pregnant during the flu epidemic and those whose mothers were pregnant shortly before or shortly after the epidemic.

To his astonishment, Dr. Almond found that the children of women who were pregnant during the influenza epidemic had more illness, especially diabetes, for which the incidence was 20 percent higher by age 61. They also got less education — they were 15 percent less likely to graduate from high school. The men’s incomes were 5 percent to 7 percent lower, and the families were more likely to receive public assistance.

The effects, Dr. Almond said, occurred in whites and nonwhites, in rich and poor, in men and women. He convinced himself, he said, that there was something to the Barker hypothesis.

Craig Keller hopes it is true. He looks back at the hard life of his ancestors, even those of his great-grandfather and his grandfather, working as painters, exposed to fumes. And, of course, there was poor Valentin Keller, his Civil War ancestor, his health ruined by the time he was 30.

Today, Mr. Keller says, he is big and healthy, almost despite himself. He would like to think it is because he tries to live well, but he is not so sure, especially when he hears about what Dr. Barker and Dr. Fogel and the others have found. Maybe it was his good fortune to have been born to a healthy mother and to be well fed and vaccinated.

“I don’t know if we have as much control as we think we do,” he said.

    So Big and Healthy Nowadays That Grandpa Wouldn’t Even Know You, NYT, 30.7.2006, http://www.nytimes.com/2006/07/30/health/30age.html?hp&ex=1154232000&en=a8f44bc2e9318699&ei=5094&partner=homepage

Living Large and Healthy, but How Long Can It Go On?

July 30, 2006
The New York Times
By GINA KOLATA

Longer life. Less disease. Less disability. The trends have continued for more than a century as humans have become bigger, stronger and healthier. But can they — will they — keep going? Or is there some countertrend, obesity or an overuse of medications, perhaps, that will turn the statistics around?

The questions are serious, but, researchers say, for now there are no easy answers, only lessons in humility as, over and over again in recent years, scientists have seen their best predictions overthrown.

Life expectancy, for example, has been a real surprise, says Eileen M. Crimmins, a professor of gerontology and demographic research at the University of Southern California. “When I came of age as a professional, 25 years ago, basically the idea was three score years and 10 is what you get,” Dr. Crimmins said. Life span was “this rock, and you can’t touch it.”

“But,” she added, “then we started noticing that in fact mortality is plummeting.”

Will it continue much longer?

“It is an extremely controversial area, and the answer is, We don’t know,” said Dr. Richard J. Hodes, director of the National Institute on Aging.

Some worry, for example, that today’s fat children will grow up to be tomorrow’s heart disease and diabetes patients, destroying the nation’s gains in health and well-being.

“It is very legitimate to be concerned about levels of overweight and obesity in kids,” said David Williamson, a senior biomedical research scientist at the Centers for Disease Control and Prevention. “But at the same time, those levels of obesity are overlaid on improvements in health in children, which also affect long-term health and longevity.”

An Uncertain Future

The mixed picture has led to disparate views about what is likely to occur.

S. Jay Olshansky, a professor of epidemiology and biostatistics at the University of Illinois at Chicago, predicted in The New England Journal of Medicine that obesity would lead to so much diabetes and heart disease that life expectancy would “level off or even decline within the first half of this century.”

Dr. Olshansky was countered by Samuel H. Preston, a professor of demography at the University of Pennsylvania. Dr. Preston cited the population’s overall better health, from childhood on, and said that obesity had already been factored into national projections of life spans and that the projections were that life spans would continue to increase.

Dana Goldman, director and corporate chairman of health economics at the RAND Corporation, looked at the obesity question from another perspective: disability. In a recent paper in Health Affairs, Dr. Goldman and his colleagues reported that disability rates among young people had begun to increase, although they continued to decline for the elderly. He suspects it is because of obesity and says it does not auger well.

He said in a telephone interview that the increased number of disabled involved less than 1 percent of young people. That means it is possible that he is seeing a spurious trend resulting from minor changes in reporting practices.

“I think of this as the ‘storm clouds on the horizon’ phenomenon,” Dr. Goldman said.

Others remain circumspect. Perhaps obesity will lead to increased disability, some say. While disability is declining over all, said Dr. Richard M. Suzman, director of the office of behavioral and social research programs at the National Institute on Aging, “if you hadn’t had the increase in obesity, would disability have gone down much faster?”

The problem for now, Dr. Williamson says, is that there is so much concern over obesity that other factors may be ignored.

He tells of a recent episode that illustrates his point, when he went with some Italian colleagues to see a photography exhibit.

“We were looking at pictures of Pennsylvania coal miners in the late 1800’s and early 1900’s,” Dr. Williamson said. “A lot of these people were kids.”

“The Italians said to me, ‘Oh, look. These kids were so thin.’ ”

“I said, ‘Well, hell yes they were thin. But were they healthy?’ ” It is likely that they were poor, malnourished and sick from the coal dust, he added. No wonder they were thin.

“It really got me thinking about, gosh, have we gotten so out of touch?” Dr. Williamson said. Obesity, he said, is a very legitimate concern, but it is not the only health risk. And being thin does not necessarily equate with being healthy.

    Living Large and Healthy, but How Long Can It Go On?, NYT, 30.7.2006, http://www.nytimes.com/2006/07/30/health/30ageside.html

Senate Removes Abortion Option for Young Girls

July 26, 2006
The New York Times
By CARL HULSE

WASHINGTON, July 25 — The Senate passed legislation Tuesday that would make it a federal crime to help an under-age girl escape parental notification laws by crossing state lines to obtain an abortion.

The bill was approved on a 65-to-34 vote, with 14 Democrats joining 51 Republicans in favor.

A similar measure passed the House last year, and President Bush said he would sign the legislation if the two chambers could work out their differences and send a final bill to him.

In a statement, Mr. Bush said that “transporting minors across state lines to bypass parental consent laws regarding abortion undermines state law and jeopardizes the lives of young women.”

Critics questioned the necessity of the measure, saying it would apply to only a small number of cases and could result in criminal charges against close relatives or clergy members who interceded to help in a time of personal crisis.

Proponents of the bill, acknowledging that it was unknown how often such incidents occurred, said abortion clinics in states without such parental involvement laws had advertised that no consent was needed in an effort to appeal to those interested in avoiding such requirements.

“If they are advertising, then it obviously at least happens,” said Senator John Ensign, the Nevada Republican who wrote the measure. “If it is happening 20 times a year, it is still worth doing to protect those parental rights and to protect those children from being in these kinds of situations.”

The legislation is the latest in a push by anti-abortion forces to seek incremental changes in federal laws rather than press for a broad rollback of abortion rights.

The measure also provided Republicans another opportunity to reassure their social conservative base that its concerns were being addressed in an election year. And it gave them a chance to force Democrats to take a position on an issue some would prefer to avoid out of concern over alienating abortion-rights advocates on one hand or Democratic centrists on the other.

Twenty-nine Democrats, four Republicans and one independent voted against the bill. Polls have shown consistently that notification requirements are popular with parents. Advocates of the bill said most Americans shared the view that parents should be consulted when it comes to such a consequential matter in the life of a teenager.

“What opponents of this bill forget is that no parent wants anyone to take their children across state lines — or even across the street — without their permission,” said Senator Mitch McConnell of Kentucky, the No. 2 Republican in the Senate.

Opponents said cases would inevitably arise in which a girl had been victimized by a relative, or in which parents were not available or did not have the girl’s best interest in mind. In those cases, they said, the legislation will pose a hardship or worse.

“Life is not always the way we wish it to be,” said Senator Hillary Rodham Clinton, Democrat of New York, who opposed the bill. “Sometimes tragedies happen, and sometimes families are not just negligent but abusive, and sometimes young girls are taken advantage of by members of their family, people in whom they should be able to trust.”

Others were pushing the measure to provide an opportunity for some lawmakers who are against abortion to make political amends after voting last week to support expanding federal research using embryonic stem cells. They said the measure could penalize close relatives trying to come to the aid of a child in trouble, who was the victim of incest or feared a physically violent response to the revelation of a pregnancy.

“I don’t think the American people support throwing Grandma in jail because she embraced her granddaughter and said, ‘Oh my God, I’m worried that your dad may hurt you if you tell the truth,’ ” said Senator Barbara Boxer, Democrat of California.

Under the legislation, known officially as the Child Custody Protection Act, those found guilty of violating it would be subject to a fine and up to a year in jail. Douglas Johnson, the legislative director of the National Right to Life Committee, said the provisions would apply to 26 states that have enforceable laws requiring minor girls to notify or receive the consent of their parents or seek approval from a judge before seeking an abortion.

Mr. Johnson said there “is evidence of widespread circumvention of these state notification laws,” though the frequency varies around the nation depending on the proximity of states without such restrictions. He said anecdotal accounts suggested that many cases involved under-age girls and older men.

Those challenging the measure said they believed that the number of those who went out of state specifically to avoid parental notification laws was low. They said Congress should instead focus on sex education and counseling. A proposal to create new pregnancy prevention grants was defeated on a 51-to-48 vote.

“The American public wants teen pregnancy prevented, not punished,” said Nancy Keenan, president of Naral Pro-Choice America. “This bill does nothing to protect young people or promote communication between teens and their parents.”

To stem criticism that the measure protected fathers guilty of incest, Republicans joined Democrats in approving an amendment that says a parent who has committed incest and transports a minor out of state for an abortion will also face a fine and jail time.

The chief difference between the House and Senate bills is that the House measure requires an out-of-state doctor to provide 24 hours’ notice to a girl’s parents or face criminal penalties. Parents can also sue the person performing the abortion.

Despite the strong vote for the measure, the Democratic leadership objected Tuesday night to a Republican call to appoint negotiators to begin reconciling the House and Senate bills, showing that Democrats were not going to make it easy to reach a final deal.

    Senate Removes Abortion Option for Young Girls, NYT, 26.7.2006, http://www.nytimes.com/2006/07/26/washington/26abort.html?hp&ex=1153972800&en=8f98475eee481bc4&ei=5094&partner=homepage

Scientists Say They’ve Found a Code Beyond Genetics in DNA

July 25, 2006
The New York Times
By NICHOLAS WADE

Researchers believe they have found a second code in DNA in addition to the genetic code.

The genetic code specifies all the proteins that a cell makes. The second code, superimposed on the first, sets the placement of the nucleosomes, miniature protein spools around which the DNA is looped. The spools both protect and control access to the DNA itself.

The discovery, if confirmed, could open new insights into the higher order control of the genes, like the critical but still mysterious process by which each type of human cell is allowed to activate the genes it needs but cannot access the genes used by other types of cell.

The new code is described in the current issue of Nature by Eran Segal of the Weizmann Institute in Israel and Jonathan Widom of Northwestern University in Illinois and their colleagues.

There are about 30 million nucleosomes in each human cell. So many are needed because the DNA strand wraps around each one only 1.65 times, in a twist containing 147 of its units, and the DNA molecule in a single chromosome can be up to 225 million units in length.

Biologists have suspected for years that some positions on the DNA, notably those where it bends most easily, might be more favorable for nucleosomes than others, but no overall pattern was apparent. Drs. Segal and Widom analyzed the sequence at some 200 sites in the yeast genome where nucleosomes are known to bind, and discovered that there is indeed a hidden pattern.

Knowing the pattern, they were able to predict the placement of about 50 percent of the nucleosomes in other organisms.

The pattern is a combination of sequences that makes it easier for the DNA to bend itself and wrap tightly around a nucleosome. But the pattern requires only some of the sequences to be present in each nucleosome binding site, so it is not obvious. The looseness of its requirements is presumably the reason it does not conflict with the genetic code, which also has a little bit of redundancy or wiggle room built into it.

Having the sequence of units in DNA determine the placement of nucleosomes would explain a puzzling feature of transcription factors, the proteins that activate genes. The transcription factors recognize short sequences of DNA, about six to eight units in length, which lie just in front of the gene to be transcribed.

But these short sequences occur so often in the DNA that the transcription factors, it seemed, must often bind to the wrong ones. Dr. Segal, a computational biologist, believes that the wrong sites are in fact inaccessible because they lie in the part of the DNA wrapped around a nucleosome. The transcription factors can only see sites in the naked DNA that lies between two nucleosomes.

The nucleosomes frequently move around, letting the DNA float free when a gene has to be transcribed. Given this constant flux, Dr. Segal said he was surprised they could predict as many as half of the preferred nucleosome positions. But having broken the code, “We think that for the first time we have a real quantitative handle” on exploring how the nucleosomes and other proteins interact to control the DNA, he said.

The other 50 percent of the positions may be determined by competition between the nucleosomes and other proteins, Dr. Segal suggested.

Several experts said the new result was plausible because it generalized the longstanding idea that DNA is more bendable at certain sequences, which should therefore favor nucleosome positioning.

“I think it’s really interesting,” said Bradley Bernstein, a biologist at Massachusetts General Hospital.

Jerry Workman of the Stowers Institute in Kansas City said the detection of the nucleosome code was “a profound insight if true,” because it would explain many aspects of how the DNA is controlled.

The nucleosome is made up of proteins known as histones, which are among the most highly conserved in evolution, meaning that they change very little from one species to another. A histone of peas and cows differs in just 2 of its 102 amino acid units. The conservation is usually attributed to the precise fit required between the histones and the DNA wound around them. But another reason, Dr. Segal suggested, could be that any change would interfere with the nucleosomes’ ability to find their assigned positions on the DNA.

In the genetic code, sets of three DNA units specify various kinds of amino acid, the units of proteins. A curious feature of the code is that it is redundant, meaning that a given amino acid can be defined by any of several different triplets. Biologists have long speculated that the redundancy may have been designed so as to coexist with some other kind of code, and this, Dr. Segal said, could be the nucleosome code.

    Scientists Say They’ve Found a Code Beyond Genetics in DNA, NYT, 25.7.2006, http://www.nytimes.com/2006/07/25/science/25dna.html

Stem Cell Work Gets States’ Aid After Bush Veto

July 25, 2006
The New York Times
By JODI RUDOREN

CHICAGO, July 24 — President Bush’s veto of legislation to expand federally financed embryonic stem cell research has had the unintended consequence of drawing state money into the contentious field and has highlighted the issue in election campaigns across the country.

Two governors seized the political moment Thursday, the day after the veto, to raise their ante for stem cell research.

Gov. Arnold Schwarzenegger of California, a Republican who helped Mr. Bush win a second term but has long disagreed with him on this research, cited the veto as he lent $150 million from the state’s general fund to pay for grants to stem cell scientists. In Illinois, Gov. Rod R. Blagojevich, a Democrat opposed to most every White House initiative, offered $5 million for similar grants in his state.

Before the announcements, the only money available was $72 million that five states had allocated for the research and $90 million that the National Institutes of Health had provided since 2001 for work on a restricted number of stem cell lines.

Several other governors, including one Republican, M. Jodi Rell of Connecticut, denounced the president’s veto, his first, in a sign of the political potency of the stem cell debate.

Within hours, too, the issue sprang to the forefront of some crucial campaigns, including ones for governor, senator and representative in Colorado, Florida, Maryland, Missouri and Tennessee.

In many cases, Republican moderates, mindful of consistent polls showing public support for expanded stem cell research and expecting the promised attacks from Democrats, sought to distinguish their positions from their president’s.

For Mr. Schwarzenegger, who is running for re-election in a state dominated by Democrats, support for stem cell research has helped position him as a centrist, but his Democratic opponent, Phil Angelides, the state treasurer, tried to one-up him by taking credit for the loan.

Sean Tipton, president of the Coalition for the Advancement of Medical Research, the lead lobbyist for the bill Mr. Bush vetoed, said, “In terms of actually getting some resources to the scientists, it turns out like it may be a good week.”

“I also think there’s symbolic significance,” Mr. Tipton said. “It sends a strong signal to patients that there are some politicians that care about them and want to see them taken care of.”

Tony Snow, the White House press secretary, said of the president, “While he recognizes that states have the legal power to use their own funds for embryonic stem cell research, he hopes researchers and entrepreneurs will focus on developing effective cures,” including those “that don’t involve controversial practices.”

Douglas Johnson of the National Right to Life Committee dismissed the initiatives in Illinois and California as a “public relations gimmick” to divert attention from a debate over whether scientists should be allowed to create embryos through cloning.

“It’s regrettable,” Mr. Johnson said, “but it’s really a matter of their trying to focus public attention on an issue that is significant but is not really the front line of this battle.”

In Florida, stem cell research is a rare point of contention between two Republicans vying to succeed the president’s brother Jeb as governor. But when one of them, Attorney General Charlie Crist, announced that he “respectfully” disagreed with the veto, his rival Tom Gallagher, the chief financial officer, accused Mr. Crist of taking “every opportunity to disagree with the governor and the mainstream of the party.”

Meanwhile, Rod Smith, the Florida state senator who is the Democratic candidate for governor, promised, “When I become governor, we are absolutely going to do stem cell research and we are going to fund it in this state.”

In Maryland, Democratic hopefuls in the governor’s race responded to the veto with visits to the homes of quadriplegics and patients with Parkinson’s disease who could benefit from stem cell research, while the Republican incumbent, Gov. Robert L. Ehrlich Jr., pointed to his support of the research as evidence that he did not “govern from the right or the left but the center, where most of us are.”

In Colorado, Representative Diana DeGette, a Democrat and a sponsor of the vetoed legislation, staged a protest rally on Friday when the president visited her district for a $1,000-a-plate luncheon on behalf of Rick O’Donnell, a Republican who supports his position.

Nowhere is the issue hotter than in Missouri, where voters in November are likely to face a ballot initiative supporting stem cell research, and where Senator Jim Talent, a Republican who is seeking re-election, opposes it. Mr. Talent’s Democratic challenger, Claire McCaskill, the state auditor, highlighted the issue last week when she delivered the Democrats’ radio address and then initiated a conference call with national reporters to spotlight her support.

The moves in California and Illinois continue the patchwork pattern of public financing for stem cell research since 2001, when Mr. Bush announced his policy restricting how federal money could be used in the arena.

More than 100 bills have been considered over the past two years by dozens of state legislatures, with one, South Dakota’s, banning such research altogether and five — in California, Connecticut, Illinois, Maryland and New Jersey — allocating state resources to the effort. Other states, including Indiana, Massachusetts, Virginia and Wisconsin, have taken steps to support stem cell science without directly paying for research, while Arizona, North Carolina and Virginia have formed groups to study their state’s role in the emerging field.

Mr. Schwarzenegger’s announcement on Thursday of the $150 million loan will provide the single largest public pot yet available.

“I think with one stroke, the president energized” the program, said Zach W. Hall, the president of the California Institute for Regenerative Medicine, which had an anemic $14 million to spread among 16 training grants before the veto, and which will soon be flush. “It’s not what we would have wanted, but it did have that beneficent side effect.”

For California, the $150 million is half the $300 million per year that would be provided under a decade-long, $3 billion bond issue that 59 percent of voters approved in 2004. Taxpayer groups sued to block the bonds and appealed a verdict in May that favored the state. At the same time, “bond anticipation notes” floated in the interim found little favor in the market. The $150 million loan is intended to fill that shortfall and would be repaid by bond proceeds, presuming the state prevails in court.

“Arnold is supposed to be a Republican, so I don’t understand his thinking here with President Bush. It seems like he’s going against the party line,” said Dana Cody, executive director of the Life Legal Defense Foundation, one of the groups suing the state. “It’s very inconsistent with the governor’s platform, if you will, of ‘we’re tired of being taxed.’ That’s $150 million coming out of the taxpayers’ pocket for something that is questionable at best because of the litigation.”

Asked at a news conference in Sacramento on Friday about the political implications of making such a forceful public move to oppose the president he has previously supported, Mr. Schwarzenegger said, “You don’t have to agree with someone on every issue.”

“It doesn’t matter to me what the president thinks about it, or what any party thinks about it,” the governor added. “I always try to do what’s best for the people of California.”

In Illinois, the $5 million would come out of the administrative budget in the Department of Healthcare and Family Services, and would be added to $10 million in grants awarded in April to hospitals and universities. A five-year, $100 million investment that Mr. Blagojevich pushed has been stalled in the Legislature.

Mr. Blagojevich, who was vacationing in Michigan when the new money was announced via a news release, declined an interview request, through a spokeswoman, Abby Ottenhoff.

“It was after the veto that the governor determined there were no more options,” Ms. Ottenhoff said. “This research is too important to put on hold until there is a new leader in the White House.”

Even with the limitations on federal financing, the overall financing available for stem cell research could be described as fairly robust, given that the research is still at a basic stage and that in addition to state money, philanthropies like the Howard Hughes Medical Institute have made contributions. Moreover, in the private sector, biotech companies like Geron, Advanced Cell Technology and Athersys conduct research on embryonic or adult stem cells.

While stem cell scientists applauded the states’ efforts, they cautioned that such an approach was not ideal.

“In the long term, I don’t think it’s a good idea to have individual states trying to mount efforts which are going to be more piecemeal, less effective and take more time than a federal effort,” said Douglas A. Melton, co-director of the Stem Cell Institute at Harvard University. “I don’t think states should mount their own militias either.”

Dr. Arnold Kriegstein, director of the Institute for Regeneration Medicine at the University of California, San Francisco, said that the $150 million was “absolutely a boon,” but that “if you’re an investigator in another state, besides Illinois or California, I think you’d be very frustrated right now.”

Candace Coffee, a Los Angeles resident who has suffered partial blindness, paralysis and constant headaches from Devic’s disease, appeared with Governor Schwarzenegger on Friday at his news conference.

“President Bush’s veto stole my hope,” Ms. Coffee said. “But just as quickly as our hope was stolen, it was renewed.”

    Stem Cell Work Gets States’ Aid After Bush Veto, NYT, 25.7.2006, http://www.nytimes.com/2006/07/25/us/25stem.html?hp&ex=1153886400&en=0a4ddc283632d4a8&ei=5094&partner=homepage

Catholic Group Urges Candidates to Return Cash

July 25, 2006
The New York Times
By STEPHANIE STROM

The Missouri Catholic Conference is urging candidates for state offices to return contributions from a nonprofit organization that advocates for stem cell research and other medical analysis and testing.

The request has inspired a complaint to the Internal Revenue Service, arguing that it violates prohibitions on political activity by nonprofit organizations.

“It constitutes illegal political interference,” said Marcus S. Owens, a tax lawyer, who filed the complaint on behalf of a client he declined to identify.

The Missouri conference sent the request to more than 50 candidates for state offices who received donations from the organization, Supporters of Health Research and Treatments.

Lawrence A. Weber, executive director and general counsel of the Missouri conference, said he heard about the complaint over the weekend but did not see Mr. Owens’s letter until a reporter faxed it to him on Monday.

“Obviously, it’s something we take seriously and are in the process of looking into,” Mr. Weber said.

Representatives for Supporters of Health Research could not be reached.

Missouri legislators are considering an amendment to the State Constitution that would ban human cloning but would prohibit the state and local governments from discouraging stem cell research, which is allowed under federal law.

The Missouri conference opposes that amendment. In April, Mr. Weber sent a letter to several dozen state legislators who were reported to have received campaign contributions from Supporters of Health Research.

“The Missouri Catholic Conference is committed to informing Missouri voters about campaign contributions promoting human cloning and embryonic stem cell research,” Mr. Weber wrote, “and will report to Missouri voters regarding candidates who choose to associate themselves with this and similar organizations that promote such unethical practices.”

He added that if candidates returned contributions from Supporters of Health Research, the conference would report that to diocesan newspapers so long as documentation was provided.

This month, the St. Louis Review Online, a diocesan Web site, reported that eight candidates had returned money to organizations that support stem cell research. On Monday, Mr. Weber said that “quite a few” candidates had returned such contributions.

State Representative Jim Guest, a Republican from northwest Missouri, said he was stunned by the letter’s tone. “I’m not sure if extortion is the right word,” Mr. Guest said, “but they basically threatened me if I didn’t return the money, and that’s certainly stepping across the line.”

Mr. Guest has not returned the money. “I was going to work for the issue anyway, but it almost made me feel like working harder,” he said.

    Catholic Group Urges Candidates to Return Cash, NYT, 25.7.2006, http://www.nytimes.com/2006/07/25/washington/25threat.html?_r=1&oref=slogin

Senate to Pass Parental Notification Law

July 25, 2006
By THE ASSOCIATED PRESS
Filed at 3:44 a.m. ET
The New York Times

WASHINGTON (AP) -- A pregnant 14-year-old from Lancaster, Pa., decides to keep and raise her baby. Her boyfriend's parents drive her to a New Jersey abortion clinic to get around her home state's parental notification law. They then refuse to take her home until she ends her pregnancy.

It happened -- and a national parental notification law could have stopped it, the girl's mother, Marcia Carroll, told a House panel last year.

A year after the House passed the measure, a similar version is heading toward Senate approval Tuesday with widespread public support.

Opponents, however, say the legislation would cut off an escape route for pregnant teens with abusive parents and punish confidants who might try to help them.

''We should not criminalize the grandparents or clergy members to whom a teen in trouble might turn for help,'' said Sen. Dianne Feinstein, D-Calif., who will introduce an amendment to protect such confidants from prosecution.

No one knows exactly how many girls try to cross state lines to end pregnancies to circumvent parental notification and consent laws back home.

Polls suggest there is widespread public backing for the bill, with almost three-quarters of respondents saying a parent has the right to give consent before a child under 18 has an abortion.

''This is clearly not an issue divided on pro-life or pro-choice lines,'' said Sen. John Ensign, R-Nev., the bill's original sponsor. ''There is broad and consistent support to preserve the rights of parents.''

Under the bill, anyone who helps a pregnant minor cross state lines to obtain an abortion without the knowledge of her parents could be punished by unspecified fines and up to a year in prison. The girl and her parents would not be vulnerable to criminal penalties. The measure contains an exception for those who help underage girls get such abortions to avoid life-threatening conditions.

Democrats will present several other amendments, including one that would add exceptions for anyone helping girls to end pregnancies resulting from rape or incest.

The states without parental notification or consent laws are: Washington, Oregon, New York, Vermont, Rhode Island, and Connecticut, plus the District of Columbia.

The bill passed the House 270-157 in April 2005 after lawmakers rejected an amendment similar to Feinstein's.

The bills are S. 403 and H.R. 748.

------

On the Net:

Congress: http://thomas.loc.gov

    Senate to Pass Parental Notification Law, NYT, 25.7.2006, http://www.nytimes.com/aponline/us/AP-Interstate-Abortion.html

HCA Buyout Highlights Era of Going Private

July 25, 2006
The New York Times
By ANDREW ROSS SORKIN

In April, investment bankers from Merrill Lynch paid one of their regular visits to HCA, the hospital company. Instead of the usual pitch to sell HCA some more hospitals, the bankers had a more audacious proposal: Assemble a group of private investors to acquire the company for more than $30 billion.

Yesterday, HCA agreed to do just that, to sell itself to three private-equity firms and the family of Senator Bill Frist, the Senate majority leader, whose father, the late Dr. Thomas Frist Sr., and his brother, Dr. Thomas F. Frist Jr., founded HCA.

The deal, including debt, is the largest leveraged buyout, eclipsing the $30.6 billion takeover of RJR Nabisco in 1989.

If that 1980’s deal came to define an era — as depicted in the book “Barbarians at the Gate’’ — and helped usher in the modern private-equity industry, the deal yesterday crowns private equity’s ascension to the top of finance: the “barbarians’’ now rule the deal world.

Private-equity firms like Kohlberg Kravis Roberts, which came to fame in the RJR buyout, and others largely unknown outside Wall Street now possess more than $2 trillion in buying power. In addition to Kohlberg Kravis, the new brand names of finance are Bain Capital, Blackstone Group, Carlyle Group and Texas Pacific Group. The companies they own include Toys “R’’ Us and Hertz.

The deal-making prowess of the big private-equity firms means that they have become Wall Street’s most important clients. Beyond Wall Street, the role of private equity as an investor has reshaped industries from energy to retailing to Hollywood.

The buyout spree is expected to run on. Some big public companies, fed up with scrutiny from investors and regulators, are now selling themselves to private-equity firms. And private equity is increasingly able to take on bigger deals. Firms raised more than $260 billion worldwide just this year from big money managers like pension funds and university endowments. This month, Blackstone Group raised $15.6 billion, creating the world’s largest private-equity fund.

“I get calls all the time from C.E.O.’s,’’ said Cristóbal I. Conde, chief executive of SunGard Data Systems, which was acquired by a group of private-equity firms last year for $11.3 billion. “They think they need to consider going private. They can’t ignore the possibility anymore.”

Private-equity firms use the money they have raised and borrow more to buy businesses. The firms borrow against the value of the asset and the cash flow of the company they are acquiring, often allowing the firms to invest only a small sum of equity in a large transaction.

In the HCA deal, the three private-equity firms — Bain, Kohlberg Kravis and Merrill Lynch’s buyout unit — and the Frist family are investing only $5.5 billion in cash. The rest of the $31.6 billion price tag is being financed by debt, which the firms will hope to pay down, like a mortgage payment, using HCA’s income.

Aided by relatively cheap borrowing costs, private-equity firms have gone on a shopping spree. This year they have bought some of the world’s best-known brands, worth more than $347 billion, twice last year’s pace and roughly equal to the gross domestic product of Belgium. Private-equity firms spent $12.3 billion for Univision last month; $22 billion for Kinder Morgan in May; as much as $14 billion for General Motors’ finance unit, G.M.A.C., in April; and $17.4 billion for Albertsons, the grocery chain, in January.

Not only has the size and breadth of private equity deals mushroomed, but the tactics of the firms when they win control of companies have changed substantially. For years, private-equity firms had reputations as corporate raiders that would come into companies and slash and burn jobs to reduce costs. Today, cutting costs is not private equity’s only approach. Indeed, since SunGard agreed to be acquired, it has added 3,000 jobs.

Many of the recent successes of private-equity firms have been tied to their abilities to pile more debt on the businesses than many public investors feel comfortable with.

“The rise of private equity has been a function of the confidence that the equity markets and debt markets have in the management of these firms,” said David M. Rubenstein, the co-founder of Carlyle Group, who is currently working on a book tentatively titled “Beyond Wall Street.”

Mr. Conde of SunGard said: “When you’re running a public company so much of your credibility is linked to the volatility of your earnings. Whether you’re up by a penny or you’re down by a penny is a big deal. As a private company, we can tolerate more volatility.”

The rise of private equity, however, raises questions for public investors, who have often sold businesses only to see them resold, at enormous profits, just years later by the private firms. Hertz, for example, which was acquired late last year from Ford by a group of private-equity firms, is now seeking a public listing less than eight months after the original deal was reached. The equity firms increased Hertz’s debt, paid themselves a $1 billion special dividend, and made some performance improvements.

H. J. Heinz is under attack by some shareholders for selling Weight Watchers in 1999 for $735 million. The firms that bought Weight Watchers retooled the business; after becoming a private company and being taken public, it is worth $4.2 billion.

At a meeting at the World Economic Forum in Davos, Switzerland, this year, Daniel Loeb, an outspoken hedge fund manager, questioned whether private-equity firms “are appropriating profits that should belong to public shareholders.”

With profit opportunities so rich, Wall Street firms are getting into the business themselves. Merrill Lynch, which had acted as a longtime adviser to HCA, switched sides to become a buyer after persuading the company to sell itself. Goldman Sachs has also become heavily involved in the private-equity business.

Yet while private equity has been known as “fast money” for flipping businesses, increasingly the firms are looking to hold assets for longer periods. “Now that private equity has become institutionalized, it has allowed us to have a longer timeframe,” said Stephen Pagliuca of Bain Capital, one of the buyers of HCA who added that he might hold the company for more than the typical five years.

Still, it remains possible that the private-equity market could be a bubble, a fact Mr. Rubenstein of Carlyle Group readily acknowledges. “We may be at the top, but we won’t know for a few years.”

The Kohlberg Kravis deal for RJR Nabisco — first announced in October 1988 and then won months later — proved to be the top of the market and a very difficult deal for the firm, which eked out only a modest profit after years of struggle.

In an odd twist, two of the firms that agreed yesterday to acquire HCA — Bain and Kohlberg Kravis — had passed on buying HCA in 1988, when it took itself private. HCA went public again in 1992 — and may very well do so again in a few years when its private-equity investors look to cash out.

    HCA Buyout Highlights Era of Going Private, NYT, 25.7.2006,http://www.nytimes.com/2006/07/25/business/25buyout.html?hp&ex=1153886400&en=1825fbcb9615f95b&ei=5094&partner=homepage

Hospital Giant HCA Is Close to a Record Buyout

July 24, 2006
The New York Times
By ANDREW ROSS SORKIN

HCA, the nation’s largest for-profit hospital operator, was close to a deal last night to sell itself to a consortium of private equity investors for about $21 billion, people involved in the talks said. The investors would also take on about $10.6 billion of HCA’s debt, making the deal the largest leveraged buyout in history.

The buyout group is led by Thomas Frist Sr., the founder of HCA, and his son, Thomas F. Frist Jr., who are, respectively, the father and brother of Senator Bill Frist, the majority leader. The other investors are Bain Capital, Kohlberg Kravis Roberts & Company and Merrill Lynch’s private equity arm, these people said.

With a value of $31.6 billion the deal would be even larger than Kohlberg Kravis Roberts’ $25 billion acquisition of RJR Nabisco in 1989. HCA is planning to vote on the transaction early today and to announce a deal shortly afterwards.

The potential deal for HCA appears to be driven by trends both on Wall Street and in the health care industry. For one thing, the private equity business — in which investment companies pool capital from investors in order to buy companies and then sell them or take them public — is swimming in cash. And it is eager to invest in a company like HCA, which generates significant revenue and is perceived, based on its stock price, as being undervalued by investors.

As a public company, HCA, like many other for-profit hospital companies, has seen its stock perform poorly in recent years as the whole industry has struggled with increasing amounts of bad debt as more and more people do not pay their bills because they do not have sufficient health insurance or any coverage.

Separately, several enormous acquisitions by private equity firms have taken place recently: last month, a group of investors bought Univision for $12.3 billion; in May, a group of investors bid $22 billion for Kinder Morgan Inc.; in April, another group agreed to buy General Motors’ GMAC unit for as much as $14 billion.

These super-sized buyouts are being spurred by an infusion of billions of dollars of cash to private equity funds. Earlier this month, Blackstone Group said it had lined up $15.6 billion in commitments for its latest buyout vehicle, forming the world’s largest private equity fund.

HCA was taken private in the late 1980’s by the company’s management, which at the time thought it was undervalued. The move turned out to be a success, and HCA went public again a few years later.

The deal would be a huge boon for Wall Street bankers and lawyers who have been toiling away on the transaction for months. Credit Suisse, Morgan Stanley and Shearman & Sterling are advising HCA while Merrill, Bank of America Corporation, Citigroup Inc., J. P. Morgan Chase and Simpson Thacher & Bartlett are financing and working for the buying group.

HCA is the nation’s largest for-profit hospital chain, with 2005 revenues of roughly $25 billion. Headquartered in Nashville, Tenn., the company operates some 180 hospitals and nearly 100 surgery centers. After merging with Columbia Hospital Corporation in 1994, HCA became the subject of a widespread federal Medicare fraud invesigation, which it later settled for $1.7 billion. Thomas Frist Jr., who had left HCA’s management before the fraud charges, eventually returned as chief executive in 1997. He stepped down as chairman in 2002 and remains on the company’s board of directors.

Senator Frist’s ties to the company have drawn criticism over the years as he has been active in the Senate on a variety of health-care inititiaves that have the potential to affect the large hospital company. Last fall, the Securities and Exchange Commission began an investigation into his decision to sell stock, once estimated at more than $10 million, which was held in a trust.

Senator Frist sold the stock in June, just as the price of HCA stock peaked and shortly before it fell the following month. The sale was disclosed in September, and Senator Frist has said he is cooperating fully with the investigation. He has maintained that the timing of the sale was the result of a decision to divest his holdings in the company.

Under the terms of the deal now under discussion, the investor consortium would pay about $51 a share, about a 15 percent premium to HCA’s trading price early last week when word spread that the negotiations had faltered, people involved in the talks said. In addition, the buyout group would assume $10.6 billion of HCA’s debt.

The investor consortium is expected to pay about $6 billion in equity and raise about $15 billion in debt. With the high-yield bond market tightening, however, raising that amount of debt could be a challenge.

There is also the possibility that another group could emerge with a rival offer. HCA has included a provision in its deal with the invetsor consortium that allows it to actively seek a higher offer. Firms like Blackstone Group and Apollo Group could look to get involved as could rival hospital groups.

Reed Abelson contributed reporting for this article.

    Hospital Giant HCA Is Close to a Record Buyout, NYT, 24.7.2006, http://www.nytimes.com/2006/07/24/business/24hospital.html?hp&ex=1153800000&en=d152186ab717605d&ei=5094&partner=homepage

Indictment of Doctor Tests Drug Marketing Rules

July 22, 2006
The New York Times
By ALEX BERENSON

At first, Dr. Peter Gleason thought his arrest was a joke.

In the early afternoon of Monday, March 6, half a dozen men in suits surrounded Dr. Gleason, a Maryland psychiatrist, at a train station on Long Island and handcuffed him.

“I said, ‘Well, this is a gag,’ ” Dr. Gleason recalled in a recent interview. “They said, ‘No, this isn’t.’ ”

Dr. Gleason, 53, was taken aback because he was arrested, and later charged, for doing something that has become common among doctors: promoting a drug for purposes other than those approved by the federal government.

But prosecutors say that Dr. Gleason went too far. At hundreds of speeches and seminars where he was rewarded with generous fees, Dr. Gleason advised other physicians that a powerful drug for narcolepsy could be prescribed for depression and pain relief. In doing so, he conspired with the drug’s manufacturer to recommend it for potentially dangerous uses, the prosecutors claim.

The case has put the spotlight on the murky financial relationships between drug companies and the physicians they use to promote their medicines. Companies cannot directly advertise drugs for purposes not approved by the Food and Drug Administration. But getting drugs prescribed for unapproved uses can increase a drug’s sales, so companies often skirt the rules by sponsoring seminars where doctors are paid to make presentations promoting their drugs, including the “off label” uses.

For doctors, these and other payments they receive for discussing drugs can be very lucrative. Dr. Gleason acknowledges that he received more than $100,000 last year alone from Jazz Pharmaceuticals, which makes Xyrem, the narcolepsy drug he has promoted.

His case could establish limits on what doctors can do to help companies sell their drugs. But any precedent could be complicated by the history of Xyrem, which differs in one important way from other drugs. Because the active ingredient in Xyrem is gamma hydroxybutyrate, or GHB, an illegal street drug with a history of use in date rape and of overdose hazards, Xyrem is listed as a federally controlled substance, with distribution tightly monitored.

Some doctors who have researched Xyrem say that Dr. Gleason, in his enthusiasm for the drug, may have understated its very real risks. Still, at least one former F.D.A. official says that the government appears to be overreaching in going after Dr. Gleason and may chill a common and legitimate form of medical discussion. “This is a very, very scary development,” said Daniel E. Troy, a partner at Sidley Austin and the former chief counsel of the F.D.A.

Dr. Steven Nissen, the interim chairman of cardiovascular medicine at the Cleveland Clinic, said the case could “have a chilling effect on physicians, because when we give lectures, we assume that giving an opinion about the use of a drug is not going to get us into legal difficulty.” The F.D.A. and federal lawyers, he said, need to restrict criminal prosecutions to especially egregious cases of off-label promotion.

Continuing to Practice

Dr. Gleason, who is now free on bail and continues to practice medicine, insists that he is not guilty of conspiracy. He says that he was charged only after he refused to help the government build a case against the drug’s maker, Jazz Pharmaceuticals — a sequence of events that court documents seem to support.

Dr. Gleason freely acknowledges that in meetings with other doctors, he advocated Xyrem as a treatment for many conditions, including depression and fibromyalgia, a poorly understood pain disorder.

In a news release about the indictment, an assistant F.B.I. director compared Dr. Gleason to a “carnival snake-oil salesman.”

But the doctor says that based on his own experience giving Xyrem to patients, he believes everything he said about the drug and that his right to express his views are protected by both F.D.A. rules and the First Amendment.

Some lawyers who have reviewed Dr. Gleason’s case, but are not representing him, say they agree.

Dr. Gleason has been trapped in the complex rules that cover what doctors and drug manufacturers are allowed to say about prescription drugs, according to Harvey A. Silverglate, a lawyer in Boston who specializes in civil liberties cases.

“What they are doing is criminalizing conduct that is not clearly criminal,” said Mr. Silverglate, who is not involved in Dr. Gleason’s defense.

Neither the F.D.A. nor the United States attorney’s office in Brooklyn, which indicted Dr. Gleason, would comment on the case. Nor would David Loftus, a public defender who took over the case after Dr. Gleason determined he could not afford a private lawyer. Jazz Pharmaceuticals, which has not been charged, also declined to comment.

F.D.A. rules allow doctors to prescribe federally approved drugs for any purpose, even if it is not indicated on the medicine’s label. But drug companies are tightly constrained in what they can say about their medicines. Companies can promote drugs only for their federally approved purposes — their so-called “on label” use.

“Off label” promotion by drug companies is illegal, and since 2000 drug makers have paid large fines to settle federal criminal cases over off-label prescriptions.

Pfizer, for example, paid $430 million in 2004 to settle allegations that it had promoted Neurontin, an anti-epilepsy medicine, for pain and bipolar disorder.

Despite the F.D.A.’s constraints on drug makers, though, the companies are allowed to hire independent doctors to talk to other physicians about their medicines. Companies can also sponsor “continuing medical education” sessions, ranging from lunches to weeklong conferences, where specialist doctors tell other physicians about the latest developments in their fields — including off-label uses for drugs already on the market. For such speaking engagements, doctors can receive $3,000 or more a day from the companies.

In other words, the F.D.A. rules allow drug makers to pay independent doctors to discuss medicines in ways that might be illegal for the companies themselves. Beyond the federal rules, guidelines by doctors’ groups give physicians wide latitude to talk about off-label use.

The American Medical Association considers continuing-education sessions valuable and believes that doctors should be free to prescribe drugs for off-label use, according to Dr. Edward Langston, a member of the A.M.A. board.

In general, though, he said, the A.M.A. believes doctors should rely on peer-reviewed research, not anecdotal evidence, when they write off-label prescriptions.

The Accreditation Council for Continuing Medical Education, which oversees the groups that create medical education sessions, loosened its rules in 2004 so that speakers would not have to disclose whether a recommended use is on-label or off-label, said Dr. Murray Kopelow, the council’s chief executive.

“The A.C.C.M.E. abandoned the distinction between off-label and on-label,’’ Dr. Kopelow said. Instead speakers should make recommendations based on accepted medical and scientific evidence, he added.

Dr. Gleason acknowledges that he did not follow those evidence-based guidelines when discussing Xyrem in hundreds of speeches and seminars from 2003 to 2006. The talks were paid for by the original maker of Xyrem, a company called Orphan Medical. Orphan was acquired by Jazz Pharmaceuticals in June 2005.

In one seminar cited in the federal indictment, a session last August in Denver, Dr. Gleason told doctors that “table salt is more dangerous” than Xyrem — a statement scoffed at by other experts on the drug.

An Aid to Sleep Quality

Xyrem’s active ingredient GHB is a fast-acting central nervous system depressant developed as an anesthetic in the 1960’s. The drug improves sleep quality, enabling narcoleptics to stay awake the next day, according to physicians who specialize in treating sleep disorders. But because GHB can suppress breathing, overdoses can cause coma or death.

“It has the potential to do a lot of good if it’s used properly, the potential to do a lot of harm if it’s used improperly,” said Dr. Martin Scharf, the director of the Tri-State Sleep Disorders Clinic in Cincinnati, who said he had studied GHB in hundreds of patients since the early 1980’s.

In 2000, after highly publicized cases in which young women died or were raped after GHB was slipped into their drinks, Congress designated the drug a Schedule I controlled substance, in the same class as heroin.

But by then, doctors had shown that GHB could treat cataplexy, a variant of narcolepsy that causes people to suffer temporary paralysis. After lobbying from doctors and Orphan Medical, Congress said that if the F.D.A. chose to approve prescription GHB, it would be designated as a Schedule III controlled substance, legal for medical use, like the painkiller Vicodin or steroids.

In 2002, after Orphan presented clinical trial data showing GHB’s effectiveness against cataplexy, the F.D.A. approved the drug, under the brand name Xyrem, as a cataplexy treatment. In 2005, the agency approved Xyrem for the treatment of all forms of narcolepsy.

To help persuade the F.D.A. to approve Xyrem, Orphan Medical agreed to make the drug available only from a single pharmacy in Missouri, which ships it to patients nationally. No other prescription drug, even other Schedule III medicines, is so tightly controlled. For now, Xyrem, which costs more than $600 a month, is a niche product, with sales of about $25 million last year.

Dr. Gleason said he had been interested in Xyrem even before the drug was officially approved because he believed that other medicines for insomnia and depression were addictive or had serious side effects. “I immediately just started prescribing this stuff in 2002,” he said.

He prescribed the drug to about 100 of the patients he saw in his private practice in Maryland, almost always for off-label conditions like insomnia and severe depression. Xyrem seemed to work better than existing treatments, he said.

By early 2003, a sales representative for Orphan Medical, noting Dr. Gleason’s high rate of prescriptions, asked him if he would give talks to other doctors about Xyrem.

“I started doing those, and I started getting requested a lot,” Dr. Gleason said. He received $450 to visit a doctor in the office, $750 for speaking at a luncheon and $1,500 for a dinner speech. He made as much as $3,000 a day, he said.

Although he continued to see some patients, the Xyrem talks gradually became his primary source of income.

In April 2005, after a tip from a whistleblower inside Orphan Medical, the government began investigating Dr. Gleason and the company, according to an affidavit that Darren Petri, a criminal investigator for the F.D.A., filed in February in support of an arrest warrant for Dr. Gleason.

The affidavit says that a cooperating witness repeatedly taped Dr. Gleason as he discussed Xyrem, including the Denver talk where he compared Xyrem to table salt and a meeting in November where he said Xyrem was safe for children.

The indictment also charges that Dr. Gleason committed fraud against insurance companies by advising doctors to leave blank an area on the Xyrem prescription form that asked for a disease diagnosis. Dr. Gleason acknowledges that he told doctors not to offer a diagnosis but says he never told them to lie if they were asked for one.

Dr. Gleason says he did not know he was under investigation when he went to Great Neck, N.Y., on March 5 to talk to doctors about Xyrem during a lunch meeting at the office of Dr. Richard Blanck, a neurologist. The meeting had been arranged by a Jazz Pharmaceuticals salesman, Al Caronia, Dr. Gleason said.

An Unexpected Arrest

Dr. Blanck confirmed the meeting and said Dr. Gleason’s comments seemed typical for a sales presentation sponsored by a drug company. Mr. Caronia did not return calls seeking comment.

Afterward, Dr. Gleason says that Mr. Caronia drove him to the Long Island Rail Road station in the village center, to begin his journey home. When he stepped out of the car, Dr. Gleason says, Mr. Petri and other investigators surrounded him, bundled him into a sport utility vehicle and drove him to the Great Neck police station.

Mr. Caronia was not arrested.

The federal agents said he would have to cooperate in their investigation into Jazz Pharmaceuticals, Dr. Gleason contends. “They said, ‘Who in this company roped you into this conspiracy?’ ’’

Insisting that he had broken no laws, Dr. Gleason said he tried to persuade Mr. Petri and the others that his views on Xyrem were scientifically based. He was released later that day.

Dr. Gleason’s account is at least partly supported by a letter on March 13 from Geoffrey Kaiser, an assistant United States attorney, to Lois Bloom, the federal magistrate judge overseeing the case. In the letter, Mr. Kaiser asks that the case be kept quiet because Mr. Gleason may “be willing to cooperate with this office in its broader investigation.”

On Bail and Short on Work

The same day, Dr. Gleason was arraigned in Federal District Court in Brooklyn, where he was released on a $150,000 bond.

It was not until three weeks later, on April 5, that the federal attorney’s office announced Dr. Gleason’s arrest, with the news release comparing him to a snake-oil salesman. As he awaits further hearings and trial, Dr. Gleason, who is divorced, is supporting himself by working as an in-house doctor on short-term contracts. For a brief period, he worked at a Maryland state hospital, before being let go. He said the hospital told him he had been fired because of the indictment; a spokesman for the hospital declined to comment.

Now he is filling in at various hospitals in Western states, which he did not want to identify for fear of losing the work.

As for his former benefactor, Jazz, Dr. Gleason says the company told him it was now cooperating with the investigation and that he would have to face the indictment on his own.

“They’re just cutting me loose,” he said.

For all that, Dr. Gleason said he still believed in Xyrem. “The only thing symmetrical with the efficacy and safety of GHB is the hysteria about it.”

Those sorts of claims discomfort even other doctors and researchers who agree that the drug may be useful.

“He is a very smart man, and I believe he is extremely well intentioned,” Dr. Scharf said. “But this is not candy. It’s not a cure-all.”

    Indictment of Doctor Tests Drug Marketing Rules, NYT, 22.7.2006, http://www.nytimes.com/2006/07/22/business/22drugdoc.html?hp&ex=1153627200&en=c30b0a9f04a0d5c0&ei=5094&partner=homepage

Schwarzenegger gives $150M stem cell loan

Updated 7/22/2006 1:49 PM ET
AP
USA Today

SACRAMENTO (AP) — A day after President Bush vetoed expanded federal funding of embryonic stem cell research, Gov. Arnold Schwarzenegger on Thursday authorized a $150 million loan to fund California's stem cell institute, which has been stalled by lawsuits.

Schwarzenegger, a Republican who has been trying to put distance between himself and the unpopular president as he seeks re-election this year, said the state cannot afford to wait to fund the science associated with stem cells.

"I remain committed to advancing stem cell research in California, in the promise it holds for millions of our citizens who suffer from chronic diseases and injuries that could be helped as a result of stem cell research," Schwarzenegger said in a letter to his finance director.

The state's voters created the California Institute for Regenerative Medicine in 2004 when they passed a ballot measure that authorized $3 billion over 10 years for stem cell research.

Lawyers with ties to anti-abortion and anti-tax groups have sued, arguing that the institute is unconstitutional.

On April 21, a Superior Court judge ruled the institute was a legitimate state agency. But if opponents continue to contest the agency in court, they could hold up the institute's financing until at least next year.

Elsewhere, Illinois Gov. Rod Blagojevich, a Democrat, announced Thursday that he is diverting $5 million from the state budget for stem cell research, despite repeated objections from state legislators.

"Investing in research that can save lives and prevent serious illnesses is more than a sound public health strategy, it's our moral obligation," he said.

The money will come out of administrative funds already set aside for the state Department of health care and Family Services, Blagojevich said.

Last year Blagojevich used an executive order to spend $10 million for stem cell research, a move that caught many state lawmakers off guard. Illinois lawmakers have previously voted against stem cell research, and this spring they did not take up the governor's proposal for $100 million in funding over five years.

Legislators of both political parties criticized his move Thursday.

"Any time this happens, it's not good for the process when you circumvent the legislative body and the voice of the people," said Democratic Rep. John Bradley.

Embryonic stem cells are building blocks that turn into different types of tissue. Scientists hope to use them someday to regenerate damaged organs or other body parts and cure diseases. Some oppose such research because it entails the destruction of human embryos.

    Schwarzenegger gives $150M stem cell loan, UT, 22.7.2006, http://www.usatoday.com/news/nation/2006-07-22-california-stem-cells_x.htm

Jimmy Margulies        New Jersey -- The Record        Cagle        20.7.2006
http://cagle.msnbc.com/politicalcartoons/PCcartoons/margulies.asp

First Bush Veto Maintains Limits on Stem Cell Use

July 20, 2006
The New York Times
By SHERYL GAY STOLBERG

WASHINGTON, July 19 — President Bush on Wednesday rejected legislation to expand federally supported embryonic stem cell research, exercising his first veto while putting himself at odds with many members of his own party and what polls say is a majority of the public.

By defying the Republican-controlled Congress, which had sent him legislation that would have overturned research restrictions he imposed five years ago, Mr. Bush re-inserted himself forcefully into a moral, scientific and political debate in which Republicans are increasingly finding common ground with Democrats.

The president laid out his reasoning in a written message to the House of Representatives, then announced his decision in the East Room of the White House, surrounded by babies born through in vitro fertilization using so-called “adopted embryos.’’

As the infants gurgled and fidgeted in their parents’ arms, Mr. Bush said the bill violated his principles on the sanctity of human life by encouraging the destruction of embryos left over from fertilization procedures. Proponents of the measure have argued that such embryos would be destroyed anyway.

“I felt like crossing this line would be a mistake, and once crossed we would find it almost impossible to turn back,’’ Mr. Bush said. “Crossing the line would needlessly encourage a conflict between science and ethics that can only do damage to both, and to our nation as a whole.’’

Until Wednesday, Mr. Bush was among just seven presidents — all of whom served before 1881 — who had never vetoed a piece of legislation. Four served only partial terms; the other three were John Adams, Thomas Jefferson and John Quincy Adams.

Within hours of the East Room ceremony, the House hurriedly took up a measure to override the veto, but the vote, 235 to 193, fell 51 short of the two-thirds majority required. Fifty-one Republicans, 183 Democrats and 1 independent voted to override, while 4 Democrats joined 179 Republicans in voting to keep the veto intact.

The vote put an end to the bill’s prospects for the year, but not to the stem cell debate, which has escalated into a major issue on Capitol Hill, with Democrats and Republicans alike predicting electoral repercussions in November.

“This is not some wedge issue; this is the soul of America,’’ said Representative Diana DeGette, Democrat of Colorado, who sponsored the bill Mr. Bush vetoed. “And this is a colossal mistake on the part of the president.’’

But beyond the principles involved, the White House had clearly calculated that it would have been more of a political mistake to sign the bill. Social conservatives, the heart of Mr. Bush’s base, had demanded the president keep his promise to veto any measure that altered the careful compromise he articulated in 2001. With Mr. Bush’s approval ratings hovering at about 40 percent, conservatives are more critical than ever to the president, and he cannot afford to arouse their ire.

“This is a profound moral issue,’’ said Representative Mike Pence, Republican of Indiana, after the White House ceremony. “The issue is whether or not it is morally right to use the taxpayer dollars of millions of pro-life Americans who find this research morally objectionable.’’

Yet the ground is shifting in the debate, and even Mr. Pence conceded that opponents of the research were ‘’losing the argument with the American people.’’ Republicans, even those like Mr. Bush who oppose abortion, are wrestling with whether embryos that are no bigger than a typographical period but regarded by some as human beings should be destroyed to save lives.

The issue reflects the complex nature of the politics of abortion and medical research in the United States today and is in some ways the flip side of the Democrats’ quandary over abortion. Just as medical advances like ultrasound imaging have spurred greater opposition to abortion, leading some Democrats to recalibrate their views, the promise of embryonic stem cell research has pushed some Republicans toward positions in which black-and-white beliefs about the sanctity of life have given way to more nuanced and ethically complex stances.

As baby boomers have aged, demanding the best medical treatments for themselves and their elderly parents, the public clamor for stem cell research has grown more intense. According to the Pew Research Center, a nonpartisan polling organization that tracks the issue, roughly two-thirds of all Democrats and independents favor embryonic stem cell research, while nearly half of all Republicans do.

That leaves Mr. Bush — who has not used his veto partly because Republicans have controlled both houses of Congress for nearly all of his presidency — at odds with many leaders of his own party. They include staunch abortion opponents like Senators Orrin G. Hatch of Utah, Gordon H. Smith of Oregon and the Senate majority leader, Bill Frist of Tennessee. Already, some Republicans who opposed Mr. Bush on the stem cell issue are looking to the presidential elections of 2008.

“When there’s another election, another chapter of democracy opens,’’ Mr. Smith said in an interview. “Most of the candidates who have a shot at winning are in favor of stem cell research. This represents a delay en route, but I know where we’re going, and it’s where the American people want to go.’’

As the White House prepared for the East Room ceremony, advocates for patients who support stem cell research flooded the switchboard with calls urging Mr. Bush not to veto the bill.

“We were really hoping, because so many of the American people supported this research, that the president would take this opportunity to take a really big deep breath and reconsider,” said Kathy Lewis, president of the Christopher Reeve Paralysis Foundation, named for the late actor who was an outspoken advocate for the science.

In a sense, the issue has come full circle for Mr. Bush. The president devoted his first prime-time television address to the issue, becoming the first president to open the door to federal financing for the science.

Under the policy, which Mr. Bush announced on Aug. 9, 2001, the federal government pays for studies on stem cell colonies, or lines, created before that date, so that the government does not encourage the destruction of additional embryos. Mr. Bush said Wednesday that his administration had made more than $90 million available for such work.

The bill Mr. Bush vetoed would have allowed taxpayer-financed research on lines derived from embryos slated for destruction by fertility clinics. Mr. Bush also signed a “fetal farming” measure, barring trafficking in embryos and fetuses with the intent of harvesting body parts.

“These boys and girls are not spare parts,” the president said in a speech that was interrupted repeatedly by hoots of applause, and twice by standing ovations. “They remind us of what is lost when embryos are destroyed in the name of research.’’

In one respect, the veto plays to Mr. Bush’s personal strengths, reinforcing the perception that he is someone who makes up his mind and sticks to it, ignoring the polls. But Democrats are determined to make the veto a central theme of their fall election campaigns, hooking it in with another hugely divisive medical issue — the Terri Schiavo right-to-die case — to argue that Republicans are beholden to the religious right.

Within hours of the veto, the Senate Democratic leader, Harry Reid of Nevada, sent out a fund-raising letter asserting that Mr. Bush had decided that curing diseases “was not as important as catering to his right-wing base.” Representative Edward J. Markey, Democrat of Massachusetts, put it this way: “This will be remembered as a Luddite moment in American history.”

Even Republicans concede the president’s action could hurt their candidates, particularly moderates like Representative Christopher Shays of Connecticut, who face tough re-election contests.

“It paints us in a corner as more and more single issue, and more and more unreasonable,” said Ed Rollins, a Republican strategist. “This is the line that the president certainly doesn’t want Republicans to cross, but I think an awful lot of Republicans say this goes across common sense, this research has the potential of saving my father, my mother, or a friend, or curing cancer.”

    First Bush Veto Maintains Limits on Stem Cell Use, NYT, 20.7.2006, http://www.nytimes.com/2006/07/20/washington/20bush.html?hp&ex=1153454400&en=5bd39aa1c9072bd1&ei=5094&partner=homepage

Just Another Face in the Crowd, Indistinguishable Even if It’s Your Own

July 18, 2006
The New York Times
By NICHOLAS BAKALAR

Some people never forget a face. Heather Sellers never remembers one.

She finds it almost impossible to recognize people simply by looking at them. She remembers the books she reads as well as anyone else, but movies and TV shows are impossible to follow because all of the actors’ faces seem so similar. She can recall a name or a telephone number with ease, but she is unable to remember her own face well enough to pick it out in a group photograph.

Dr. Sellers, a professor of English at Hope College in Holland, Mich., has a disorder called prosopagnosia, or face blindness, and she has had it since birth. “I see faces that are human,” she said, “but they all look more or less the same. It’s like looking at a bunch of golden retrievers: some may seem a little older or smaller or bigger, but essentially they all look alike.”

Face blindness can be a rare result of a stroke or a brain injury, but a study published in the July issue of The American Journal of Medical Genetics Part A is the first report of the prevalence of a congenital or developmental form of the disorder.

The researchers say the phenomenon is much more common than previously believed: they found that 2.47 percent of 689 randomly selected students in Münster, Germany, had the disorder.

Dr. Thomas Grüter, a co-author of the paper, said there were reasons to believe that the condition was equally common in other populations. “First,” he said, “our population was not selected in terms of cognition deficits. And second, a study done by Harvard University with a different diagnostic approach yielded very similar figures.”

Dr. Grüter is himself prosopagnosic. His wife and co-author, Dr. Martina Grüter of the Institute for Human Genetics at the University of Münster, did not realize he was face blind until she had known him more than 20 years. The reason, she says, is he was so good at compensating for his deficits.

“How do you recognize a face?” she asked. “For most people, this is a silly question. You just do. But people who have prosopagnosia can tell you exactly why they recognize a person. Thomas consciously looks for the details that others notice unconsciously.”

Dr. Thomas Grüter’s experience in this respect is typical of people with face blindness. They develop alternate strategies for identifying people — they remember their clothes, mannerisms, gait, hairstyle or voice, and by using such techniques, many can compensate quite well.

This may be one reason why cases of prosopagnosia have so rarely been reported — people simply do not know they have it. For face-blind people, adaptations like these are the only choice; there is no known cure.

“Until very recently, not remembering faces was not considered to be a medical condition,” Dr. Thomas Grüter said. “It was not even known to most physicians as such. The term ‘prosopagnosia’ was not taught to students of medicine or psychology.” Most people “would consider it a bad habit,” he said, “much like forgetting the names of people you are introduced to, or being unable to find your way around town.”

Dr. Martina Grüter said many considered her husband and his father, who is also face blind, to be simply “absent-minded professors” who occasionally may not recognize someone because they are preoccupied with higher thoughts.

People with face blindness can typically understand facially expressed emotions — they know whether a face is happy or sad, angry or puzzled. They can detect subtle facial cues, determine gender and even agree with everyone else about which faces are attractive and which are not. In other words, they see the face clearly, they just do not know whose face they are looking at, and cannot remember it once they stop looking.

Even familiar faces can be unrecognizable. Dr. Sellers, for example, said she could summon no picture in her mind of her own mother’s face.

Dr. Sellers discovered her own problem only a year ago, at the age of 40. She was doing research for a novel involving a character with schizophrenia. “I kept coming across the term ‘face recognition,’ ” she said. “It kept ringing a bell, although the phenomenon is quite different for people with schizophrenia. But once I had the term, I searched for it on the Internet. The minute I knew the concept of face blindness existed, I knew I had it.”

The phenomenon has been investigated with functional MRI brain scans, a form of imaging that shows in real time which parts of the brain are active, and it is known that a part of the brain called the fusiform gyrus responds much more strongly to faces than to other objects.

Researchers have detected differing responses in this part of the brain among people with face blindness compared with normal subjects.

“If you show a normal person two different faces in a row,” said Bradley Duchaine, a lecturer in psychology at University College London, “their brain response is different with each one. With some prosopagnosics, you don’t see this different response. It looks like something is not working in those areas of the brain involved with faces.”

Dr. Duchaine and Ken Nakayama, a psychology professor at Harvard, published a review of developmental prosopagnosia in the April issue of Current Opinion in Neurobiology. They run a Web site devoted to the disorder (www.faceblind.org).

Face blindness differs from pervasive cognitive disorders like autism because it usually involves only one specific symptom. Still, face blindness is sometimes accompanied by other problems, especially difficulty in finding one’s way around or, for example, distinguishing one car or dog from another.

Although the specific gene for the disorder has not been found, evidence is mounting that the trait is inherited. “All pedigrees that we’ve been able to establish so far were compatible with autosomal dominant inheritance,” Dr. Thomas Grüter said.

If this turns out to be true, it means that everyone with the disorder will have at least one affected parent, that men and women will be equally likely to inherit the trait, and that the risk for each child of an affected parent will be one in two.

“But we haven’t found the gene, yet,” Dr. Grüter said, “so we can’t be 100 percent sure.”

    Just Another Face in the Crowd, Indistinguishable Even if It’s Your Own, NYT, 18.7.2006, http://www.nytimes.com/2006/07/18/health/psychology/18face.html?ex=1153454400&en=6c7782d3879488df&ei=5087%0A

Editorial

Standing Up for Stem Cell Research

July 18, 2006
The New York Times

The Senate is poised to vote today on a bill that would greatly expand the number of embryonic stem cell lines that can be used in federally financed medical research. This is actually an extremely modest proposal that would allow the new stem cell lines to be derived only from surplus embryos otherwise slated for destruction at fertility clinics. Passage of this bill, which has already been approved by the House, is the very least the Senate should do to spur advancement of one of the most promising fields of biomedical research. A two-thirds majority of each house will be needed to overcome a likely veto from President Bush.

Under current administration policy, scientists can use federal money for research only on some 22 stem cell lines that already existed when President Bush announced his policy in August 2001. Those lines were extracted from microscopic embryos, no bigger than the period at the end of this sentence, that were inevitably destroyed in the process. Mr. Bush was willing to accept that fait accompli in the interest of advancing science but said he did not want to encourage any further destruction of embryos by financing research on additional lines.

That stance has increasingly hobbled embryonic stem cell research because many of the existing lines are deteriorating, contaminated or suffer from technical problems that limit their usefulness. The new proposal would make thousands of surplus embryos from fertility clinics available for federally funded research, a change that would be welcomed by most Americans but is opposed by a minority of religious conservatives.

Our concern with the bill is how limited its reach would be. It would not allow federal financing of the most promising field of research, known as therapeutic or research cloning. Therapeutic cloning involves the creation of embryos genetically matched to patients with specific diseases so that scientists can extract their stem cells and then study how the diseases develop and how best to treat them. The microscopic entities used in these studies may be called embryos but they have none of the attributes of humanity and, sitting outside the womb, no chance of developing into babies. It is no more immoral to create and destroy embryos for therapeutic purposes than to create and destroy surplus embryos for fertility purposes.

But for now the best hope lies with passage of the bill merely allowing use of surplus fertility clinic embryos. If it passes in the Senate, it seems almost certain to draw a veto from Mr. Bush, his first in six years in office. Then it will be up to the House and the Senate to summon the will to override the veto. If they fail to push through this very limited change in federal policy, voters will need to hold all recalcitrant legislators accountable for slowing research that holds great medical potential.

    Standing Up for Stem Cell Research, NYT, 18.7.2006, http://www.nytimes.com/2006/07/18/opinion/18tue1.html

FACTBOX-Stem cells offer therapeutic promise

Mon Jul 17, 2006 5:11 PM ET
Reuters

(Reuters) - The U.S. Senate is expected to pass three stem cell bills on Tuesday, including one that would broaden federal funding of embryonic stem cell research.

Following are some facts about stem cells.

* Stem cells are the body's master cells, the source of all cells and tissue, such as brain, blood, heart, bones, muscles and skin.

* Embryonic stem cells come from days-old embryos and can produce virtually any other type of cell in the body. The very earliest embryonic stem cells, up to five days old, can each give rise to an entire organism.

* Adult stem cells are harbored in mature tissue -- in the bodies of children as well as adults. They are more specialized than embryonic cells and give rise to specific cell types, although they may be coaxed into a broader range of cell types under the right conditions.

* Scientists generally harvest embryonic stem cells from embryos left over after in-vitro fertilization attempts at fertility clinics. These "test-tube baby" techniques, used to help infertile couples have a baby, involve fertilizing a woman's egg cells with a man's sperm cells in a laboratory dish.

Several embryos are created at a time, and not all are implanted into the mother's womb to create live births. Embryos left over are usually discarded by the fertility clinic. These can serve as a source of stem cells, a process that involves removing the blastocyst's inner cells and destroying the embryo.

* Scientists hope to harness the transformational qualities of stem cells to provide treatments for a variety of diseases affecting millions of people worldwide. Because stem cells can turn into many other cell types with the right prompting, doctors may be able to replace tissues and organs damaged by disease or injury to restore healthy function.

For example, in people with Parkinson's disease, injecting stem cells into the area of the brain that controls muscle movement, where the disease kills nerve cells, might regenerate the neurons.

* They also hope to use stem cells to understand the biology of diseases including cancer and genetic disorders.

* The issue is controversial because some people believe the destruction of any embryo is wrong. Leaders of the Roman Catholic Church and some other religious and conservative political figures hold this view, although some opponents of abortion rights support embryonic stem cell research.

Opponents of embryonic stem cell research believe adult stem cell research should be pursued instead.

    FACTBOX-Stem cells offer therapeutic promise, R, 17.7.2006, http://today.reuters.com/news/newsArticle.aspx?type=newsOne&storyid=2006-07-17T211021Z_01_N17298752_RTRUKOT_0_TEXT0.xml&WTmodLoc=NewsArt-L1-RelatedNews-1

 

The Quest for the $1,000 Human Genome        NYT        18.7.2006

http://www.nytimes.com/2006/07/18/science/18dna.htm

The Quest for the $1,000 Human Genome

July 18, 2006
The New York Times
By NICHOLAS WADE

As part of an intensive effort to develop a new generation of machines that will sequence DNA at a vastly reduced cost, scientists are decoding a new human genome — that of James D. Watson, the co-discoverer of the structure of DNA and the first director of the National Institutes of Health’s human genome project.

Decoding a person’s genome is at present far too costly to be a feasible medical procedure. But the goal now being pursued by the N.I.H. and by several manufacturers, including the company decoding Dr. Watson’s DNA, is to drive the costs of decoding a human genome down to as little as $1,000. At that price, it could be worth decoding people’s genomes in certain medical situations and, one day, even routinely at birth.

Low-cost decoding may bring the genomic age to the doctor’s office, but it will also raise quandaries about how to safeguard and interpret such a wealth of delicate and far-reaching personal information.

The first human genome decoding, completed by a public consortium of universities in 2003, cost more than $500 million. With the same technology, dependent on DNA sequencing machines made by Applied Biosystems, a human genome could probably now be decoded for $10 million to $15 million, experts say.

Much greater efficiency is expected from the new generation of DNA sequencing machines, based on different, highly miniaturized technologies. One machine, made by 454 Life Sciences, has been on the market since March 2005. Another, made by Solexa, will start shipping this summer. Applied Biosystems will start marketing its own next-generation machine next year.

Last month, at a training course organized by the Cold Spring Harbor Laboratory on Long Island, researchers were learning how to use the DNA decoding machines made by 454 Life Sciences. Looking like a hybrid between a washing machine and a giant iPod, the machines cost $500,000 each, not counting the computer software needed to analyze the results.

At their heart lies a plate of light-sensitive chips, the same as those used in telescopes for detecting faint light from distant stars. On top of the plate sits a glass slide pitted with thousands of tiny wells, each containing a fragment of the DNA to be decoded.

As each unit of DNA is analyzed in a well, a flash of light is generated by luciferase, the enzyme that fireflies use to make themselves glow. The telescope plate records the twinkling lights from each well and, at the end of the run, which lasts four or five hours, the sequence of units in each well’s DNA fragment has been recorded. The fragments are about 100 units in length, and from their overlaps a computer can then be set to piece together the entire genome they come from.

In the training course, the project was to analyze DNA from a Tasmanian devil, a marsupial afflicted with a mysterious malady called devil facial tumor disease. The researchers found that the genome was laden with a virus that had integrated its sequence into the devil’s DNA.

The 454 machine can assemble small genomes like those of bacteria, which perhaps accounted for the presence at the course of three scientists from the Department of Homeland Security. But the human genome is about 600 times larger than a bacterium’s and includes many repetitive sequences that, like identical pieces in a jigsaw puzzle, make the solution much harder.

At the Cold Spring Harbor course, researchers heard Dr. Watson, the laboratory’s chancellor, say that 454 Life Sciences had asked to sequence his genome with their new machine. Only two human genomes have been sequenced to date. The genome sequenced by the public consortium was a mosaic of DNA from several anonymous people. The consortium’s rival, Celera Genomics, prepared a draft sequence, most of it from the genome of its former president, Dr. J. Craig Venter.

Dr. Watson told the students that he had given the company permission to publish the sequence of his genome, “provided they didn’t release to the world that I have some disease I don’t want to know about.”

Genomic information can already reveal a lot and will reveal much more as the roles of new genes are discovered.

“I think that personal genetic information should ordinarily be kept secret,” Dr. Watson said. “But I have said that 454 can put mine out there, even though it’s saying something about my sons.”

So far, however, 454 Life Sciences has not published Dr. Watson’s genome, and it is not clear how much progress the company has made. Christopher K. McLeod, its chief executive, said, “Technically, we’ve done a lot of good work on it.” But, he added, “I don’t think we want to discuss where we are.”

Mr. McLeod expressed reservations about releasing personal genetic information, despite having Dr. Watson’s permission to do so. “Jim feels there are certain things he’d be comfortable releasing,” he said. “I’m not sure we would agree.”

Another factor may be that the company is developing a more powerful model of its machine that will be able to read DNA fragments that are 200 or even 400 units in length. These longer-read lengths should make it more feasible to decode large genomes, like those of people.

The 454 machine is at present being bought chiefly by researchers and by the large genome sequencing centers established by the public consortium. But it has begun to show promise for the clinic. One new use is in screening tumors for genes known to be mutated in cancer, a task that existing machines do not do well. Spotting which mutation has occurred in a patient’s tumor can help in the choice of chemotherapy.

Although the 454 model is the only next-generation DNA sequencing machine on the market, it will be joined this summer by the machine from Solexa. The Solexa instrument, which will cost $400,000, works on somewhat similar principles but uses fluorescent dyes to visualize the structure of DNA. And next year Applied Biosystems will introduce its next-generation machine, based on a technology developed by George Church of Harvard, said Dennis A. Gilbert, the company’s chief scientific officer.

Each of the manufacturers claims special advantages for its technology, ensuring that researchers will have a rich choice.

David Bentley, Solexa’s chief scientist, said that the company’s DNA sequencing machine had already decoded several bacterial genomes and that he was planning to sequence a human genome — that of an anonymous man from the Yoruba people of Nigeria. An African genome was chosen because there is greater genetic diversity in African populations, Dr. Bentley said.

The demand for whole genome sequencing is a long way off, in Dr. Bentley’s view, but not so distant that it is too early to think about the consequences of generating such information. He advocates that two people should control access to a person’s genome sequence — the patient and the physician.

Why not the patient alone? Dr. Bentley said genomes would be so difficult to analyze correctly that interpretation should stay within the medical profession. Otherwise, freelance services will spring up, offering to predict whether a person will get heart disease or their age of death. This potential for misinformation “would have a huge adverse impact on the medical use of genetic information,” Dr. Bentley said.

A recent example of genetic misinformation occurred last month when a DNA testing genealogy company, Oxford Ancestors, told Thomas R. Robinson, an accountant at the University of Miami, that he was a descendant of Genghis Khan. Only because Mr. Robinson sought a second opinion did he find that the information was incorrect.

Technology, not medicine, is the immediate force behind the quest for the $1,000 human genome. The new decoding machines are being developed because they are possible, not because hospitals are demanding them. But the makers expect that demand will grow as researchers develop new uses.

“As we drop the price and increase the capability, there are applications that couldn’t be done before,” like a researcher being able to screen a thousand patients for cancer mutations, Dr. Gilbert said.

At present, only a handful of genes are monitored by doctors in clinical practice, and specific tests for these genes make it unnecessary to decode a person’s entire genome. But at some point, the new machines or their successors may make genome decoding a routine medical test.

Already, every newborn baby endures its heel being pricked to draw a few drops of blood, which are tested for a handful of enzymic deficiencies. But when genomes can be decoded for $1,000, a baby may arrive home like a new computer, with its complete genetic operating instructions on a DVD.

    The Quest for the $1,000 Human Genome, NYT, 18.7.2006, http://www.nytimes.com/2006/07/18/science/18dna.html

Paralyzed Man Uses Thoughts to Move a Cursor

July 13, 2006
The New York Times
By ANDREW POLLACK

A paralyzed man with a small sensor implanted in his brain was able to control a computer, a television set and a robot using only his thoughts, scientists reported yesterday.

Those results offer hope that in the future, people with spinal cord injuries, Lou Gehrig’s disease or other conditions that impair movement may be able to communicate or better control their world.

“If your brain can do it, we can tap into it,” said John P. Donoghue, a professor of neuroscience at Brown University who has led development of the system and was the senior author of a report on it being published in today’s issue of the journal Nature.

In a variety of experiments, the first person to receive the implant, Matthew Nagle, moved a cursor, opened e-mail, played a simple video game called Pong and drew a crude circle on the screen. He could change the channel or volume on a television set, move a robot arm somewhat, and open and close a prosthetic hand.

Although his cursor control was sometimes wobbly, the basic movements were not hard to learn.

“I pretty much had that mastered in four days,” Mr. Nagle, 26, said in a telephone interview from the New England Sinai Hospital and Rehabilitation Center in Stoughton, Mass. He said the implant did not cause any pain.

Mr. Nagle, a former high school football star in Weymouth, Mass., was paralyzed below the shoulders after being stabbed in the neck during a melee at a beach in July 2001. He said he had not been involved in starting the brawl and did not even know what had sparked it. The man who stabbed him is now serving 10 years in prison, he said.

Implants like the one he received had previously worked in monkeys. There have also been some tests of a simpler sensor implant in people, as well as systems using electrodes outside the scalp. And Mr. Nagle has talked before about his experience.

But the paper in Nature is the first peer-reviewed publication of an experiment in people with a more sophisticated implant, able to monitor many more brain neurons than earlier devices. The paper helps “shift the notion of such ‘implantable neuromotor prosthetics’ from science fiction towards reality,” Stephen H. Scott, professor of anatomy and cell biology at Queen’s University in Ontario, wrote in a commentary in the journal.

The sensor measures 4 millimeters by 4 millimeters — less than a fifth of an inch long and wide — and contains 100 tiny electrodes. The device was implanted in the area of Mr. Nagle’s motor cortex responsible for arm movement and was connected to a pedestal that protruded from the top of his skull.

When the device was to be used, technicians plugged a cable connected to a computer into the pedestal. So Mr. Nagle was directly wired to a computer, somewhat like a character in the “Matrix” movies.

Mr. Nagle would then imagine moving his arm to hit various targets. The implanted sensor eavesdropped on the electrical signals emitted by neurons in his motor cortex as they controlled the imaginary arm movement.

Obstacles must be overcome, though, before brain implants become practical. For one thing, the electrodes’ ability to detect brain signals begins to deteriorate after several months, for reasons not fully understood. In addition, the implant would ideally transmit signals wirelessly out of the brain, doing away with the permanent hole in the head and the accompanying risk of infection. Further, the testing involving Mr. Nagle required recalibration of the system each day, a task that took technicians about half an hour.

Still, scientists said the study was particularly important because it showed that the neurons in Mr. Nagle’s motor cortex were still active years after they had last had a role to play in moving his arms.

The implant system, known as the BrainGate, is being developed by Cyberkinetics Neurotechnology Systems Inc. of Foxborough, Mass. The company is now testing the system in three other people, who remain anonymous: one with a spinal cord injury, one with Lou Gehrig’s disease and one who had a brain stem stroke.

Timothy R. Surgenor, president and chief executive, said Cyberkinetics hoped to have an implant approved for marketing as early as 2008 or 2009. Dr. Donoghue, the chief developer, is co-founder and chief scientist of Cyberkinetics. Some of the paper’s other authors work at the company, while still others are from academic or medical institutions including Massachusetts General Hospital.

Like his performance in other tasks, Mr. Nagle’s control of the computer cursor was not particularly smooth. When his goal was to guide the cursor from the center of the screen to a target on the perimeter, he hit the target 73 to 95 percent of the time. When he did, it took 2.5 seconds on average, but sometimes much longer. And the second patient tested with the implant had worse control than he, the paper said.

By contrast, healthy people moving the cursor by hand hit the target almost every time, and in only one second.

Dr. Jonathan R. Wolpaw, a researcher at the New York State Department of Health, said the BrainGate performance did not appear to be substantially better than that of a noninvasive system he is developing using electroencephalography, in which electrodes are placed outside the scalp.

“If you are going to have something implanted into your brain,” Dr. Wolpaw said, “you’d probably want it to be a lot better.”

Dr. Donoghue and other proponents of the implants say they have the potential to be a lot better, because they are much closer to the relevant neurons than are the scalp electrodes, which get signals from millions of neurons all over the brain.

One way to improve implant performance was suggested by another paper in the same issue of Nature. In a study involving monkeys, Krishna V. Shenoy and colleagues at Stanford University eavesdropped not on the neurons controlling arm movement but on those expressing the intention to move, which occurs earlier and would make the system work faster.

“Instead of sliding the cursor out to the target, we can just predict which target would be hit and the cursor simply leaps there,” said Dr. Shenoy, an assistant professor of electrical engineering and neurosciences. He said the system could operate at the equivalent of typing 15 words a minute, about four times as fast as the devices produced by Cyberkinetics and Dr. Wolpaw.

After more than a year, Mr. Nagle had his implant removed so he could undergo another operation, which allowed him to breathe without a ventilator. He can control a computer by voice, so he does not really need the implant. But he said he was happy he had volunteered for the experiment.

“It gave a lot of people hope,” he said.

    Paralyzed Man Uses Thoughts to Move a Cursor, NYT, 13.7.2006, http://www.nytimes.com/2006/07/13/science/13brain.html

F.D.A. Backs AIDS Pill to Be Taken Once a Day

July 13, 2006
The New York Times
By ANDREW POLLACK

The first drug that allows AIDS to be treated by taking one pill a day won federal approval yesterday, a development that government officials said would both simplify and improve treatment of the disease.

The drug, called Atripla, is a combination of three once-a-day drugs that are already on the market — Sustiva from Bristol-Myers Squibb, and Viread and Emtriva from Gilead Sciences.

Only a decade ago, when cocktails of AIDS drugs began to be used, patients sometimes had to take two dozen or more pills a day.

Atripla, which will be available this week or next, will have a wholesale price of $1,150 a month, equal to the sum of the prices of its components, James Loduca, a spokesman for Gilead, said.

Both Gilead and Bristol-Myers will market the drug.

The approval by the Food and Drug Administration yesterday, which was expected, came well before the October deadline for the agency to act. F.D.A. officials said they moved quickly because a once-a-day treatment would help people take their medicines faithfully. That would prevent the AIDS virus from gaining resistance to the drugs.

“It’s one thing to have medicine available, but it will only be effective when people can indeed take it as they are supposed to,” Dr. Murray M. Lumpkin, an F.D.A. deputy commissioner, said at a news conference in Washington. Dr. Lumpkin said a once-a-day treatment would be particularly important for developing countries, where access to health care is more limited.

Yet no announcement was made yesterday about when the drug would be available overseas and for what price. An agreement must first be reached with Merck & Company, which sells Sustiva, also known as efavirenz, in developing countries under the name Stocrin.

Jeffrey Sturchio, vice president for external affairs at Merck, said his company had “reached agreement on all the issues with Gilead.” He said it was now a matter of formalizing the agreement and then applying for approval in various countries.

He predicted that Atripla would be available in some poor countries in the next several months at a price that would be roughly the sum of the heavily discounted prices at which the component drugs are now sold in those places.

Gilead, based in Foster City, Calif., has become one of the most successful biotechnology companies, based on its AIDS drugs, which accounted for $1.4 billion of its $2 billion in revenue last year. One of its big sellers is Truvada, a once-a-day combination of Viread, also known as tenofovir, and Emtriva, also known as emtricitabine. Truvada is usually taken with another drug, like Bristol-Myers’s Sustiva.

Yaron Werber, an analyst at Citigroup, which counts Gilead as a client, said that adding the Bristol-Myers drug into a three-drug combination pill would allow Gilead to take market share from GlaxoSmithKline, which sells a popular two-drug combination called Combivir.

“I think the drug will do exceptionally well,” Mr. Werber said of Atripla. “The drug is now the most convenient on the market and it’s probably also the most potent.”

    F.D.A. Backs AIDS Pill to Be Taken Once a Day, NYT, 13.7.2006, http://www.nytimes.com/2006/07/13/business/13drug.html

New Medicine for AIDS Is One Pill, Once a Day

July 9, 2006
The New York Times
By ANDREW POLLACK

The first complete treatment for AIDS that is taken once a day as a single pill is expected to be available soon.

The pill, which combines three drugs made by two companies, would be a milestone in improving the simplicity of treatment for the disease, experts say. It should make it easier for people to take their medicine regularly, which is important for keeping the virus that causes the disease in check.

Only a decade ago, when cocktails of AIDS drugs were first used, patients often had to take two or three dozen pills a day, some with food, some without, some so frequently patients had to get up in the middle of the night. Since then, the regimens have been whittled down to as few as two pills a day, and now, one.

"Going down to one pill a day is amazing," said Keith Folger of Washington, who started on 36 pills a day about 11 years ago and expects to switch to the new pill when it becomes available.

Mr. Folger, who is just leaving a job as director of community mobilization for the National Association of People With AIDS, said the pill would be "remarkable, especially for people who are starting on medication for the first time and are sort of freaked out that they will have to take pills for the rest of their lives."

The new drug is a combination of drugs already on the market — Sustiva, sold by Bristol-Myers Squibb, and Truvada, sold by Gilead Sciences. Truvada is a combination of two Gilead drugs, Viread and Emtriva.

The Food and Drug Administration is expected to approve the new drug as soon as this week. The agency has until October to act but is expected to do so much sooner, partly because the government has been encouraging companies to do just this sort of collaboration to come up with simpler AIDS drugs.

The companies have not revealed the new drug's name or its price, though they have suggested it will cost roughly the same as Sustiva and Truvada bought separately, which is about $1,200 a month.

There are already other AIDS pills that combine three drugs. One, made by a company in India, was recently approved by the F.D.A. for use in developing countries. But those other three-in-one pills generally contain older drugs and are taken twice a day.

The drugs in the new pill already constitute the most widely prescribed regimen in the United States and one of the most effective.

Doctors and securities analysts expect most people now taking Sustiva and Truvada separately to switch to the new pill.

It is somewhat less certain how many people taking other drug combinations will switch. Some of them will not because the virus in their bodies is already resistant to one of the drugs in the new pill or because they cannot tolerate side effects. Sustiva, also known as efavirenz, can cause unsettlingly vivid dreams and birth defects.

In addition, the new salmon-colored pill is about 1,500 milligrams, the size of a large vitamin pill, and some people may find it difficult to swallow.

Going to a single pill could be especially important in poor countries, where patients have less access to medical care and more people are illiterate or uneducated. The vast majority of the nearly 40 million people in the world infected by H.I.V., the virus that causes AIDS, are in developing nations. In the United States there are about 1.1 million.

Bristol-Myers and Gilead say they will make the new pill available at a sharply reduced price for developing nations, but details are still being worked out. They are negotiating with Merck & Company, which sells efavirenz in those countries under the name stocrin.

A once-daily treatment did not become feasible until a few years ago, with the development of individual drugs that needed to be taken only once a day.

Still, no one company controlled all the drugs needed for an effective combination. It is rare for rivals to collaborate, though it has been done. Merck and Schering-Plough, for instance, have put two of their drugs into a combination cholesterol treatment called Vytorin.

Executives at Bristol-Myers, discussing in 2003 how to increase sales of Sustiva, came up with the idea of approaching Gilead, which already had two once-a-day pills, Viread, also known as tenofovir, and Emtriva, or emtracitabine. Gilead, based in Foster City, Calif., is now the largest supplier of H.I.V. drugs.

Talks were given further urgency when the F.D.A. summoned the two companies and Merck to a meeting in Washington in April 2004. The government was trying to encourage development of simpler pills as part of the president's plan to provide antiviral treatments to poor countries. The next month, the three companies announced their plan.

But carrying it out was not easy. Simply combining the three chemicals produced a mixture that melted easily.

"We made the first formulation and went out for lunch, and when we came back from lunch we had glue on our hands," said Reza Oliyai, a Gilead scientist. The eventual solution was to keep Truvada and Sustiva in separate layers.

It also took about a year to find a formulation that would produce the same level of the three drugs in a patient's blood as the three drugs taken separately, which is the main requirement for approval of a combination drug. Gilead tested five different formulations in healthy volunteers.

The failure of patients to take their drugs faithfully is a major problem, experts say, because it allows H.I.V. to develop resistance to the drugs.

Still, it is unclear exactly how much better people with H.I.V. will stick to a once-daily regimen compared with one requiring two pills a day.

Bob Huff, who edits a newsletter on new treatments for the Gay Men's Health Crisis, a patient advocacy group in New York, said a drug's potency and side effects were more important to patients than convenience.

Still, he said, "For some people it's just what they need to make treatment doable." A single pill may also mean a single insurance co-payment, he said, instead of two or three now that can cost people $100 a month.

Michael Weinstein, president of the AIDS Healthcare Foundation, a Los Angeles organization that runs clinics in the United States and abroad, said other problems besides inconvenience — like drug addiction, depression and mental illness — kept people from sticking to their AIDS drugs.

Still, Mr. Weinstein called the new pill a "high-water mark" for simplicity and the way it was developed. "To have two companies collaborating — that's going to be significant for the future if it sets an example."

While other companies are expected to try to develop once-daily treatments, no other existing drugs can yet be as readily combined, said Dr. Calvin Cohen, research director for the Community Research Initiative of New England, a nonprofit organization that does clinical trials of H.I.V. drugs and provides patient education.

Dr. Cohen, an adviser to Gilead, Bristol-Myers and other drug manufacturers, said there was already some concern among AIDS experts that having a once-a-day treatment would make people lose their fear of H.I.V. "We still want people to respect that prevention of the disease is better than treatment," he said.

    New Medicine for AIDS Is One Pill, Once a Day, NYT, 9.7.2006, http://www.nytimes.com/2006/07/09/health/09aids.html

New AIDS Pill to Treat People in Poor Countries

July 6, 2006
The New York Times
By DONALD G. McNEIL Jr.

The Food and Drug Administration has approved the first 3-in-1 antiretroviral pill for use by the American-sponsored plan for AIDS treatment, something that the White House's acting global AIDS coordinator said yesterday should greatly improve treatment for AIDS patients in poor countries.

Although it is not yet clear how much money it will save, having patients take only one pill twice a day "should facilitate better therapies and better adherence," said the coordinator, Dr. Mark R. Dybul.

The agency posted the approval of the drug on its Web site on Friday evening. It approved the 3-in-1 pill, made by an Indian generic drug company, for patients in countries helped by the President's Emergency Plan for AIDS Relief.

Under that plan, the United States is now the largest provider of antiretroviral drugs in the world, paying for treatment for 561,000 patients in Africa, Asia and the Caribbean.

The Global Fund for AIDS, Malaria and Tuberculosis, the second-largest provider, pays for about 541,000 patients, Dr. Dybul said, although there is some overlap in countries where both agencies work. (The United States also pays one-third of the Global Fund's budget.)

The new pill, made by Aurobindo Pharma of Hyderabad, India, combines three common first-line drugs, AZT, 3TC and NVP, which are also known as zidovudine, lamivudine and nevirapine and sold in the United States as Retrovir, Epivir and Viramune.

Dr. Dybul said he was also pleased that the new pill did not contain D4T, also known as stavudine and Zerit, which is another common first-line drug, but somewhat more toxic than the others.

In poor countries, where it is harder to do frequent blood and liver tests, toxicity can be harder to control.

The plan Dr. Dybul runs, known as Pepfar, was created after President Bush's announcement in his 2003 State of the Union address that he would spend $15 billion over five years to fight AIDS.

At the time, many Bush administration critics feared the money would be reserved for expensive American and European brand-name drugs. But, defying those expectations, the program in May 2004 began buying generics and now pays for 24 generic formulations, including liquid solutions for infants. Also, the major Western companies dropped their prices for poor countries, sometimes as low as the prices of generics.

However, rather than subscribing to the World Health Organization's drug-approval process, the president's program requires separate F.D.A. approval, which has caused delays, even though the agency created a fast-track process and waived its large fees.

No one from Aurobindo could be reached for comment yesterday, but the company's Web site carried an announcement, dated Monday, saying it was "delighted to share" that its drug had won F.D.A. approval.

The first 3-in-1 antiretroviral pill was triomune, from Cipla, another Indian generic company. It won World Health Organization approval in 2002 and is used by nearly 400,000 patients whose drugs are bought by Unicef, Doctors Without Borders and other donors.

Dr. Yusuf K. Hamied, the company's chairman, said yesterday that he hoped for F.D.A. approval shortly for several Cipla products, including triomune. "Pepfar came on us out of the blue," he said. "We were concentrating more on the W.H.O., and we were a little slow catching up." Nonetheless, he praised his rival Aurobindo, calling it "a totally kosher company," and adding, "As an Indian, I'm proud of them."

    New AIDS Pill to Treat People in Poor Countries, NYT, 6.7.2006, http://www.nytimes.com/2006/07/06/world/06aids.html

Mute 19 Years,

He Helps Reveal Brain's Mysteries

July 4, 2006
The New York Times
By BENEDICT CAREY

HARRIET, Ark., July 2 — Terry Wallis spends almost all of his waking hours in bed, listening to country-western music in a cramped, two-room bungalow down a gravel road off State Highway 263.

Mr. Wallis, 42, wears an open, curious expression and speaks in a slurred but coherent voice. He volleys a visitor's pleased-to-meet-you with, "Glad to be met," and can speak haltingly of his family's plans to light fireworks at his brother's house nearby.

For his family, each word is a miracle. For 19 years — until June 11, 2003 — Mr. Wallis lay mute and virtually unresponsive in a state of minimal consciousness, the result of a head injury suffered in a traffic accident. Since his abrupt recovery — his first word was "Mom," uttered at the sight of his mother — he has continued to improve, speaking more, remembering more.

But Mr. Wallis' return to the world, and the progress he has made, have also been a kind of miracle for scientists: an unprecedented opportunity to study, using advanced scanning technology, how the human brain can suddenly recover from such severe, long-lasting injury.

In a paper being published Monday, researchers are reporting that they have found strong evidence that Mr. Wallis's brain is healing itself by forming new neural connections since 2003.

The paper, appearing in The Journal of Clinical Investigation, includes a series of images of Mr. Wallis's brain, the first such pictures ever taken from a late-recovering patient.

The new findings raise the hope that doctors will eventually have the ability to determine which patients with severe brain damage have the best chance of recovering. They might also help settle disputes in cases like that of Terri Schiavo, the Florida woman who was removed from life support and died last year after a bitter national debate over patients' rights. Ms. Schiavo suffered more profound brain damage than Mr. Wallis and did not show signs of responsive awareness, according to neurologists who examined her.

"We read about these widely publicized cases of miraculous recovery every few years, but none of them — not one — has ever been followed up scientifically until now," said Dr. Nicholas Schiff, a neuroscientist at Weill Cornell Medical College in Manhattan and the senior author of the new imaging study.

An estimated 100,000 to 200,000 Americans subsist in states of partial or minimal consciousness, cut off from those around them.

On Saturday, Mr. Wallis said he felt good, but he showed no memory of the study. After prompting from his mother, he did remember the trip back from the researchers' laboratory in New York.

"Gasoline," he said, referring to a stop the airplane made to refuel. "We stopped for gasoline."

His mother, Angilee Wallis, said: "He is starting to learn things now. That right there is new."

In recent weeks, she said, he has also shown hints of self-awareness, alluding to his disabled condition for the first time.

Mrs. Wallis, 58, and her husband Jerry, 62, live with and care for their son in a white clapboard cabin, with a small concrete porch surrounded on all sides by acres of trees. Their house, between Harriet and Big Flat, is among a scattering of such hidden homes, sheds and dirt roads a couple of miles from a highway intersection anchored by two liquor stores. The nearest decent grocery store is 30 minutes away, in Mountain View, Ark.

For the Wallis family, Terry's accident, his long years of mental absence and his return have been a story of celebrity as well as recovery, of how media attention can strike like a flash flood and just as quickly dry up, leaving families to figure out what all the attention meant, if anything — and whether it was worth it.

He was a lanky 19-year-old in 1984, with a gift for elaborate pranks and engine work, when he and two friends skidded off a small bridge in a pickup, landing upside down in a dry riverbed. The family never figured out exactly what happened. The crash left their son unresponsive, breathing but immobilized, there but not there, said his father.

Terry Wallis showed no improvement in the first year, and doctors soon pronounced him to be in a persistent vegetative state, and gave him virtually no chance of recovery, his parents said.

About 52 percent of people with traumatic wounds to the head, most often from car accidents, recover some awareness in the first year after the injury, studies find; very few do so afterward. Only 15 percent of people who suffer brain damage from oxygen deprivation — like Terri Schiavo, whose heart stopped temporarily — recover some awareness within the first three months. A 1994 review of more than 700 vegetative patients found that none had done so after two years.

But at some point after his accident, probably within months, Mr. Wallis, a mechanic before his injury, entered what is called a minimally conscious state, Dr. Schiff said. The diagnosis, established formally in 2002, is given to people who are severely brain damaged but occasionally responsive. In their good moments, they can track objects with their eyes, respond to commands by blinking, grunting or making small movements. They may spend the rest of their lives in this condition, but it is a necessary intermediate step if they are ever to regain some awareness, neurologists say.

Mr. Wallis spent the second 19 years of his life at a nursing home in Mountain View, and family members who visited said they saw plenty of hints of awareness along the way. He seemed to brighten when they walked in his room. Something in his face would tighten when he was impatient or hungry.

None of which made the day he said "Mom" any less thrilling. Ms. Wallis, her voice unsteady, quickly put out the word to the extended family.

Later, the patient had another visitor, a striking blonde woman: his 19-year-old daughter, Amber, who had been 6 weeks old at the time of his accident. "I was so nervous driving over there," she said. "I was looking in the rearview mirror to check my hair, I swear, I was so worried he wouldn't recognize me."

When finally he did, she said, the first sentence he uttered was, " 'You're beautiful,' and he told me he loved me."

He was suddenly speaking; it was a transformation. He was still disabled, barely able to move or speak, but he was recognizable as Terry.

The months that followed brought a swarm of other emotions. Mr. Wallis, now considered clinically recovered but still in need of around-the-clock attention, was moved into his parents' home, shifting much of the financial burden of his care from Medicaid to them.

And the world came knocking. A camera crew from Japan arrived and spent two weeks doing daily interviews and filming. Another crew visited from England. There were talk show appearances, agents, documentary makers, forcing Mrs. Wallis to take time away from her job at a local shirt factory to help her husband, a mechanic and farmer, play host.

But the attention soon dissipated, and a fund his parents established for their son's care — the Terry Wallis Special Needs Trust — attracted few substantial contributions, they said.

Their son still needed to be fed, washed, exercised and turned in his bed every two hours, night and day. His daughter took two regular shifts a day to tend to him, and another aide began working with the family.

But in some ways it was like living with a child who never grows up or leaves home: there, out back in the trees, was his old gray Ford van, untouched since 1984; out front was an aluminum boat his father had bought for him, overturned, unused.

In 2004, Dr. Schiff contacted the family, asking if they would allow their son to be studied. He helped arrange to have the Wallises flown to New York in April of that year, and again 18 months later, for brain scanning. A research team from New York, New Jersey and New Zealand spent more than a year analyzing the results, comparing them to images from healthy brains and from another minimally conscious patient who had not recovered.

Using a novel technique, they saw evidence of new growth in the midline cerebellum, an area involved in motor control, as Mr. Wallis gained strength and range in his limbs. Another area of new growth, located along the back of the brain, is believed by some experts to be a central switching center for conscious awareness.

The daily exercises, the interactions with his parents, his regular dose of antidepressant medication: any or all of these might have spurred brain cells to grow more connections, the researchers said.

"The big missed opportunity is that we didn't know this guy would spontaneously emerge, and we didn't get to monitor him before then" to find out what preceded it, Dr. Schiff said.

To answer that kind of question in a systematic way, researchers will need to follow more minimally conscious patients for longer periods, experts say. But there is no national system to track such patients, they say, no central database like that which exists for other diseases.

"We don't see these people. They exist outside of our gaze. We don't even know where they live," said Dr. Joseph Fins, chief of the medical ethics division of New York Presbyterian Hospital-Weill Cornell Medical Center.

Mr. Wallis, it was clear over the weekend, continues to live for the day. He has a granddaughter now, Amber's child, Victoria, and the 2-year-old does not seem bothered by the pale man with the dark mustache and the inward-turned arms. He does not feel any physical pain, he told his parents, and he has no real sense of time. He also said recently that he was "proud" to be alive.

"It is good to know all that," said his father, sitting on the porch on Saturday evening.

"It's good to hear him say that, because if he didn't say so, you'd just have no way to know."

    Mute 19 Years, He Helps Reveal Brain's Mysteries, NYT, 4.7.2006, http://www.nytimes.com/2006/07/04/health/psychology/04coma.html

A Warning on Hazards of Secondhand Smoke

June 28, 2006
The New York Times
By JOHN O'NEIL

The evidence is now "indisputable" that secondhand smoke is an "alarming" public health hazard, responsible for tens of thousands of premature deaths among nonsmokers each year, Surgeon General Richard H. Carmona said yesterday.

Dr. Carmona warned that measures like no-smoking sections did not provide adequate protection, adding, "Smoke-free environments are the only approach that protects nonsmokers from the dangers of secondhand smoke."

He did not call for a federal ban on smoking in workplaces, bars or restaurants, a step that has been taken by a growing number of cities and states over the objections of business owners and of groups skeptical about the dangers of secondhand smoke. He said he saw his role as providing the public and Congress with definitive information on the subject.

"I am here to say the debate is over: the science is clear," Dr. Carmona said at a televised news conference, where he released a report updating the original surgeon general's study of secondhand smoke in 1986. Since then, hundreds of studies have indicated that the harm caused by secondhand smoke is far greater than earlier believed, he said. The report includes these findings:

¶There is no safe level of secondhand smoke, and even brief exposure can cause harm, especially for people suffering from heart or respiratory diseases.

¶For nonsmoking adults, exposure raises the risk of heart disease by 25 percent to 30 percent and of cancer by 20 percent to 30 percent. It accounted for 46,000 premature deaths from heart disease and 3,000 premature deaths from cancer last year.

¶Secondhand smoke is a cause of sudden infant death syndrome, or SIDS, accounting for 430 deaths last year. The risk is elevated for children whose mothers were exposed during pregnancy and for children exposed in their homes after birth.

¶The impact on the health and development of children is more severe than previously thought. "Children are especially vulnerable to the poisons in secondhand smoke," Dr. Carmona said.

¶Efforts to minimize the effect of secondhand smoke by separating smokers and nonsmokers are ineffective, as are ventilation systems in a shared space.

¶While exposure has declined, as many as 60 percent of nonsmokers show biological evidence of encountering secondhand smoke, and 22 percent of children are exposed to secondhand smoke in their homes.

Studies conducted by the Centers for Disease Control show that great progress has been made in reducing exposure, Dr. Carmona said. The amount of cotinine — the form nicotine takes after being metabolized — in blood samples fell by 75 percent among adults, according to specimens taken from 1999 to 2002 that were compared with samples taken a decade earlier.

But Dr. Carmona said more needed to be done, particularly to protect children. He urged parents who smoke not only to quit, but also to move their smoking outside while trying to quit. "Make the home a smoke-free environment," he said.

Tobacco companies say the risks of secondhand smoke are unproved and overstated. In a statement on its Web site, R. J. Reynolds says, "It seems unlikely that secondhand smoke presents any significant harm to otherwise healthy nonsmoking adults; and, given the extensive smoking bans and restrictions that have already been enacted, nonsmokers can easily avoid exposure to secondhand smoke."

A spokesman for the company, David Howard, said yesterday, "Bottom line, we believe adults should be able to patronize establishments that permit smoking if they choose to do so," according to The Associated Press.

Dr. Cheryl G. Healton, the president and chief executive of the American Legacy Foundation, a nonprofit group created to use settlement money from tobacco companies to educate young people about the dangers of tobacco, called the surgeon general's report "groundbreaking" even though much of its information had already been published in journal articles. Bringing it all together creates a persuasive case for smoking bans, Dr. Healton said.

The report is online at surgeongeneral.gov/library/secondhandsmoke/.

    A Warning on Hazards of Secondhand Smoke, NYT, 28.6.2006, http://www.nytimes.com/2006/06/28/health/28smoke.html

    Related > http://surgeongeneral.gov/library/secondhandsmoke/

Charities Tied to Doctors

Get Drug Industry Gifts

June 28, 2006
The New York Times
By REED ABELSON

As she presented research results indicating that a new medical device was "an important breakthrough," the doctor's enthusiasm was clear. Less evident were some of the financial links between the researchers and the device's maker.

Dr. Maria Rosa Costanzo, making her presentation at a March conference of cardiologists, said the study found that a $14,000 blood filtering device was better than intravenous diuretic drugs at removing excess fluid from patients with heart failure.

Although outside researchers raised questions about the study's conclusions, the doctor betrayed little doubt. "We believe these results challenge current medical practice and recommendations," said Dr. Costanzo, who predicted many patients might benefit.

Dr. Costanzo did disclose to the audience that she was a paid consultant with stock in the device's maker, a Minnesota company called CHF Solutions. But she omitted another potentially important detail: CHF Solutions was also one of the largest donors to the nonprofit research foundation that had overseen the study. The company contributed about $180,000 in 2004, according to the foundation's federal filings.

Nor did she note that the nonprofit entity, the Midwest Heart Foundation, was in turn an arm of the thriving for-profit medical group outside of Chicago where Dr. Costanzo and more than 50 of her fellow doctors treat heart patients — in many cases using products and drugs made by CHF Solutions and other big donors to their charity. Although the CHF Solutions device has generally been slow to catch on, physicians at Dr. Costanzo's medical group have treated many patients with the company's filtration system.

The Midwest Heart Foundation, and the way it has become quietly interwoven into its doctors' professional lives, is far from unique. Around the country, doctors in private practice have set up tax-exempt charities into which drug companies and medical device makers are, with little fanfare, pouring donations — money that adds up to millions of dollars a year. And some medical experts see that as a big problem.

The charities are typically set up to engage in medical research or education, and the doctors involved defend those efforts as legitimate charitable activities that benefit the public. But because they operate mainly under the radar, the tax-exempt organizations represent what some other doctors, as well as regulators and industry consultants, say is a growing conduit for industry money. The payments, they say, can bias the treatment decisions of physicians, may lead to suspect research findings and at times may even risk running afoul of anti-kickback laws.

Federal officials are starting to take notice of such tax-exempt charities, which critics say are becoming increasingly popular as other forms of industry support to physicians — like lucrative consulting agreements that involve little actual work — have come under scrutiny from regulators and others worried about the potential conflicts.

The potential for abuse by these charities is clear, critics say. "It obviously sets a fertile ground for conflict of interest and misuse of funds," said Dr. Robert M. Califf, vice chancellor for clinical research at Duke University Medical Center.

The charities at issue are not philanthropies like the Bill and Melinda Gates Foundation that dispense grants for medical research but remain independent of any one group of doctors or medical practice. Instead, the charities drawing scrutiny are set up by doctors in private practice and are closely linked to those doctors' for-profit medical groups.

The Midwest Heart Foundation, which has received millions of dollars from medical industry donors, including the drug makers Amgen and AstraZeneca, and the Cordis and Scios units of Johnson & Johnson, says it stands behind its charitable work, which currently involves about 30 studies and dozens of doctor-education lectures each year.

Dr. Mark Goodwin, a managing partner for the Midwest Heart for-profit practice, said the foundation was created to help prevent potential conflicts by keeping the industry money separate from the doctors' private practice. Companies contribute to the foundation, he said, because they can rely on its research and the doctors involved can enroll large numbers of patients in studies. "We are able to deliver excellent research to our community in a timely fashion," Dr. Goodwin said, "and we are proud of it."

But some of its research has drawn criticism from federal regulators. Earlier this year, moreover, the foundation received a Justice Department subpoena as part of an investigation into the marketing activities of one of its big contributors, Scios.

Experts aware of the various doctor-run charities say that even if much of the donated money is spent on legitimate medical research or education, the funds can also go toward studies that while lending prestige to the doctors and luster to the companies, may do little to advance scientific understanding. The tax-exempt money also sometimes flows to the for-profit medical groups affiliated with the charities, sometimes covering business expenses or even paying parts of the salaries of doctors.

Too often, the critics contend, the industry donations amount to a form of "relationship funding" — to use one skeptical doctor's term — in which companies hope to sell more drugs and devices by currying favor with the doctors. That skeptic, Dr. John Cherf, is a knee surgeon at the Neurologic and Orthopedic Institute of Chicago who also consults for a market research firm specializing in health care topics. He says the donor arrangements are fraught with potential conflicts of interest and are likely to come under greater scrutiny as the costs of devices and drugs rise.

"There's undoubtedly corruption in the system," Dr. Cherf said. "We need healthy relationships between physicians and industry. Both parties have been too aggressive."

Number of Charities Is Unknown

No one knows precisely how many of these doctor-run charities exist. Although each one files with the federal government as a tax-exempt entity, they are hard to discern among other health-related charities. And because in many cases each has no more than a few hundred thousand dollars in annual revenue, they tend to escape the attention of the federal and state regulators who oversee charities.

"The reality of it is that these are small organizations that are off the radar screen," said Douglas M. Mancino, a lawyer at McDermott Will & Emery in Los Angeles who specializes in health care law and nonprofit groups.

As long as the activities being financed benefit the public rather than the doctors or companies involved, they are legitimate charities, according to lawyers who specialize in nonprofits.

But concerns can arise when a corporate donation appears to be helping pay the salary of an additional doctor at a for-profit medical practice — through a fellowship, for example — that brings in additional revenue to the practice. Another problem area, they say, would be when donations go toward expenditures that would normally be part of the practice's business cost.

Lawyers say that determining whether a charity's activities are legitimate tax-exempt activities would typically require a close look at the facts in each case.

"If they're really underwriting normal business expenses to the group, then I think you have a problem," Mr. Mancino said.

As a group, these relatively obscure charities are attracting sizable amounts of corporate money. And many of their activities focus on the companies that have made the donations or the doctors' medical groups.

Consider the Arizona Orthopedic Education Foundation, which was created by a surgeon in Phoenix and which in 2003 received a $200,000 donation from a unit of the orthopedic device company Stryker. Most of the charity's efforts are devoted to public education, according to the founder, Dr. Anthony K. Hedley. But its activities also include teaching other doctors how to use Stryker products.

Stryker said this training was "critical" for surgeons.

Dr. Hedley says the fact that he mainly uses Stryker devices with his own patients may account for Stryker's contributions. "That was probably why I was able to leverage support," Dr. Hedley said.

Another charity is the Blue Ridge Bone and Joint Research Foundation, run by Dr. Joseph T. Moskal, an orthopedic surgeon in Roanoke, Va. It received a $75,000 contribution from the DePuy Orthopaedics unit of Johnson & Johnson in the year ended July 31, 2004, according to federal filings. The Blue Ridge foundation appears to have paid $30,000 of that money to the for-profit Roanoke Orthopaedic Center, where Dr. Moskal practices, to defray the costs of a fellowship program there.

Dr. Moskal did not return repeated phone calls seeking comment. DePuy, in a brief response to questions, said in part, "Fellowships are vital to advance the education and training of orthopaedic surgeons."

Corporate donors are also major contributors to the Vascular Specialists Education Foundation, which is led by a vascular surgeon in Norfolk, Va., Dr. Marc H. Glickman. The foundation spent $30,000 in 2003 to pay for the further medical education of doctors in his for-profit practice.

Although the public filings offer few details about the charity's activities, Dr. Glickman said such expenditures are part of the foundation's mandate, which includes offering fellowships to doctors being trained and paying for continuing medical education for those doctors. One of Vascular Specialists' two big donors, the device maker Guidant, now part of Boston Scientific, said it contributed $25,000 in 2003 and $40,000 the next year, through its own foundation. The company says the money was given with the understanding that it would go to finance the group's fellowship program.

The other big donor, the device maker Medtronic, says it gave Dr. Glickman's charity $80,000 last year to help pay for the group's fellowship program. "Dr. Glickman and his colleagues have trained hundreds of physicians and fellows on life-saving procedures associated with vascular disease — a notable accomplishment," Medtronic said in a written statement.

Donors have been so generous to Dr. Glickman's foundation that he says it is currently sitting on $100,000 he has not yet decided how to spend. "I'm very cautious with what I do," he said.

Whatever the issues of tax-exempt status among the various charities, federal regulators say the groups could find themselves in trouble in another way — in violation of federal anti-kickback laws — if donations appear to be little more than a way for companies to funnel money to doctors.

If the contributions amount to payments or gifts to doctors who then use or recommend a certain drug or device, companies could be breaking the law, said Vicki Robinson, a top lawyer in the Office of Inspector General at the federal Health and Human Services Department.

"From a legal perspective, it's really no different," Ms. Robinson said.

Patrick L. Meehan, the United States attorney in Philadelphia, whose office has a long history of prosecuting health care fraud, said the doctors' charities could warrant scrutiny. "What we would be concerned about are end runs around the system," Mr. Meehan said. "We want to be sure there is independent and fully informed medical judgment at the heart of the physician-patient relationship."

For their part, Midwest Heart officials defend the activities of their foundation. Contributions to the charity, which was created in 1988, have more than doubled in the last few years — to $1.7 million in 2004, the most recent period for which federal filings are available.

In a written statement, the foundation said it had "strict internal controls and systems in place to ensure the independence and integrity of all research and education activities."

Questions About Research

Outside researchers have questioned some of the foundation's work. Some doctors say the study of the CHF Solutions filtration device that Dr. Costanzo presented in March may have been flawed, for example, because heart failure patients who were given conventional diuretic drugs may not have received enough medicine to provide meaningful comparisons.

One heart doctor critical of those findings was Dr. JoAnn Lindenfeld, who was quoted in a cardiology publication, Heartwire, in March as saying, "I wouldn't view these data as persuasive enough to use it full-scale in a million patients a year with acute decompensated heart failure." Dr. Lindenfeld did not dispute the accuracy of that quote but declined to comment further.

Through the Midwest Heart Foundation, Dr. Costanzo declined to comment. Both CHF Solutions and the foundation say she no longer has stock or stock options in the company.

CHF Solutions said that most of its contributions to the Midwest Heart Foundation covered the cost of conducting the research project that Dr. Costanzo led and the company helped design.

John L. Erb, CHF's chief executive, said "we were very careful" in designing the research, but he conceded that it was "not the perfect study where we could answer all the questions."

Dr. Goodwin, at the foundation, said the research was only a starting point. "We fully agree that further investigation is needed to validate the findings and carry them forward to a larger number of patients," he said.

Some of Midwest Heart's research has also fallen short of federal rules governing clinical studies. In August 2004, the Food and Drug Administration sent the foundation a warning letter about a study of a new carotid stent — a device designed to open up a major artery in the head and neck.

The F.D.A. said Midwest Heart had failed to get necessary approval before beginning its research, which involved different types of stents and 168 patient procedures. The regulators also found that some patients were not properly informed and that the foundation was too slow in reporting serious complications. The results of the study were never published, although the foundation says they were submitted to the F.D.A.

The shortcomings were simply "record keeping" issues, said Wendy Landow, the chief executive of the Midwest Heart Foundation, who said her organization had in fact received the necessary approval to do the study but had poorly documented it. The issue has been resolved, she said, adding that the foundation had adopted tighter procedures to avoid future lapses.

A separate controversy surrounds the heart failure drug Natrecor made by Scios, which gave the Midwest Heart Foundation a total of more than $300,000 for the years 2003 and 2004, according to federal filings. The Justice Department, which is investigating whether Scios improperly marketed Natrecor, has issued a subpoena to the foundation.

Scios said that most of its Midwest Heart contributions went toward educational programs that Scios had no influence over. It said it could not comment on the Justice Department investigation. Midwest Heart said it was cooperating with federal officials and had been told it was not a target of the investigation.

Natrecor was approved by the F.D.A. in 2001 for use in hospitals for patients only in an extreme, or decompensated, stage of heart failure. But it also became heavily used by doctors who administered it intravenously in outpatient clinics for periodic patient "tune-ups," as they were sometimes known. Natrecor's enthusiasts included some Midwest Heart doctors, who participated in studies of the drug and also used it in outpatient settings.

While doctors can use federally approved drugs for any purpose they see fit, a pharmaceutical company is prohibited from actively encouraging such off-label uses.

A Debate Over Drug's Merits

In mid-2005, after researchers elsewhere published an article in a scholarly medical journal raising concerns that Natrecor could seriously impair kidney function, one of Midwest Heart's cardiologists, Dr. Mitchell T. Saltzberg, continued to staunchly defend the drug. Dr. Saltzberg, who has also been a paid Scios consultant, wrote to Medicare officials in July 2005 to argue that the drug was being "unfairly targeted."

Dr. Saltzberg's letter cited a study of Natrecor's outpatient use — a study for which the foundation had provided some work — saying that this research and "the body of anecdotal experience" indicated the drug posed no kidney risks.

His comments to Medicare, though, came a few days after Scios itself sent a safety alert to doctors warning against the outpatient use of Natrecor. The Scios alert, issued in consultation with the F.D.A., relied on the findings of an expert panel that the company had asked to look into issues involving the drug's safety.

The Scios alert referred to the very study Dr. Saltzberg had cited and found it lacking. That study "was not powered to adequately assess the effectiveness or safety of serial infusions of Natrecor," the alert said. "The size of the study, its design and its findings provide an inadequate basis to recommend the use of intermittent, serial or scheduled repetitive infusions of Natrecor." Through the foundation, Dr. Saltzberg declined to comment. Foundation officials, though, said they agreed with the Scios panel's findings.

Outpatient use of Natrecor around the country has fallen precipitously. Scios has said it plans to conduct further research into the drug's safety.

The Midwest Heart Foundation said that only one of its patients, who is part of a study, is still being given the drug as an outpatient. But while the foundation says it believes more research is needed, Dr. Goodwin also said that he believes that many doctors had positive results with the drug and that he had seen it keep patients out of the hospital.

"It worked great," he said.

    Charities Tied to Doctors Get Drug Industry Gifts, NYT, 28.6.2006,
http://www.nytimes.com/2006/06/28/business/28foundation.html

Buffett's Billions Will Aid Fight Against Disease

June 27, 2006
The New York Times
By DONALD G. McNEIL Jr. and RICK LYMAN

Warren E. Buffett's $31 billion gift to the Bill & Melinda Gates Foundation will help the foundation pursue its longstanding goal of curing the globe's most fatal diseases, Mr. Gates said yesterday, along with improving American education.

The foundation hopes to use the enormous gift, among other things, to find a vaccine for AIDS, Mrs. Gates said. And Mr. Gates went further, saying that while he might be "overly optimistic," he believed there was a real shot at finding cures for the 20 leading fatal diseases, as well as ensuring that every American has a chance at a decent education.

"Can that happen in our lifetime?" Mr. Gates said, sitting next to Mr. Buffett at the New York Public Library, where the gift was formally announced after news of it broke on Sunday. "I'll be optimistic and say, Absolutely."

But Mr. Gates acknowledged that spending the money effectively would be difficult. The scientific tasks the foundation has set for itself in fields like malaria and tuberculosis take time as well as money, because they require years of laboratory work followed by years of clinical trials, sometimes ending fruitlessly. Improving American education — once better ideas have been found — can take just as long.

"It's incredibly difficult to give this much money away well," said Jean Strouse, a biographer who has compiled an oral history project on the Gates Foundation. "And giving it away to people who can use it well, especially in places where poverty is so overwhelming, where there's not much real infrastructure."

Both Mr. Buffett, who will join the foundation's leadership, and the Gateses acknowledged as much.

"In the last few months we have begun to really talk about and try to come up with a plan for that," Mrs. Gates said.

They must, for instance, improve their dialogue with the governments of poor nations to make sure that vaccines get down to the people who need them.

Mr. Buffett, for his part, said he saw no need to tinker with the foundation's essential goal: improving the lot of poor people elsewhere in the world without regard to their color, religion or other differences.

Describing his own way of choosing companies to invest in, Mr. Buffett, one of history's most successful investors, said, "I've learned to adapt to other managers" and then jokingly compared the process to picking a spouse. "It's not a good idea to marry one expecting them to change," he said.

Mrs. Gates was a Microsoft executive when she married Mr. Gates when he was 38 and she was 29. Upon hearing Mr. Buffett's remark, Mr. Gates leaned back on his stool with a big sheepish grin as his wife glanced knowingly at him.

Then Mr. Buffett said, "I'm happy with the ones I'm marrying here."

Later in the exchange, which was in front of 200 philanthropy executives, scientists, students and a few reporters, Mr. Gates got in his own reflection on the partnership. "It's scary," he said. "If I make a mistake with my own money, it isn't as big as making a mistake with Warren's money."

To which Mr. Buffett replied: "I won't grade you more often than daily."

Mr. Buffett is giving away about 85 percent of his fortune, most of it to the Gates foundation. The gift, representing the current value of 10 million Class B shares of Berkshire Hathaway, the insurance conglomerate he formed nearly 50 years ago, will nearly double the wealth of the Gates Foundation, which was already the world's biggest, at almost $30 billion. The stock will be transferred to the foundation in increments over many years; the first transfer will be half a million shares this year, worth about $1.5 billion.

Although the money will not change the foundation's larger goals, Mrs. Gates mentioned yesterday that it had been moving quietly for the last 18 months into microlending, which is the granting of small loans to poor people so they can start small businesses. A microloan of less than $50 might finance, for example, the purchase of a loom or a set of bicycle repair tools.

Though he is also leaving billions to separate foundations for his children, Mr. Buffett said he felt he was "not cut out" to be a philanthropist like the Gateses and preferred to remain at the helm of his company.

"They'll spend more time and energy on it," he said. "I'm having so much fun doing what I do, and I think they'll be more able to accept any mistakes they made than I would if I made them."

Bill Gates was a quicker study on new topics, like medicine, that he would have to master, Mr. Buffett said, and added: "I wouldn't want to listen to as many people with as many different opinions as they do."

Rather than spend every cent on fruitlessly trying to rebuild broken health care systems, the Gates Foundation follows a pattern of spending generously to chase solutions like a malaria vaccine. It also buys supplies, like vaccines or mosquito nets, but then tries to get rich countries to match its donations and poor countries to get organized well enough to distribute the goods.

Similarly, in education, it creates model schools that public school systems can use as examples, rather than spending endlessly to pay the expenses of every impoverished American school district.

Her "fondest dream," Mrs. Gates said, is an AIDS vaccine, something scientists have been pursuing since the 1980's and which she admitted could take an additional 20 years. A stopgap measure, she said, could be a microbicide: an undetectable protective gel that women could insert before sex.

Mr. Gates said he wanted to use improved global health as a base upon which to build what he called "the virtuous cycle" of longer lifetimes, jobs, markets, infrastructure, tax bases and all the other steps that lift poor countries out of poverty.

Dr. Richard Klausner, a former director of the National Cancer Institute and the Gates Foundation's former head of global health, said that besides microlending he also would not be surprised if the foundation followed the Rockefeller Foundation's example in seeking higher-yield, drought-resistant seeds for poor farmers.

Dr. Harold E. Varmus, president of the Memorial-Sloan Kettering Cancer Center, said the foundation could fight some of the major preventable causes of death in poor countries: cigarettes, alcohol abuse and automobile injuries.

Dr. Varmus was the chief scientific adviser for the Grand Challenges in Global Health, a sort of contest in which Mr. Gates gave out $437 million to teams pursuing exotic goals like vaccines that can be inhaled or chemicals that can knock out mosquitoes' sense of smell. He said his advisory committee particularly wished it could make grants for water purification and for chronic diseases like diabetes and cancer that have loomed larger in the poor world as people live longer.

Asked if a richer Gates Foundation could divert scientists from other fields, Dr. Varmus said he was "more concerned with using the scientific horsepower we've already developed."

Noting that the National Institutes of Health give out $28 billion a year — ten times as much as even the enriched Gates Foundation will — he said its inflation-adjusted budget has been shrinking.

Some aid recipients also worry that the Gates-Buffett fortune will let other donors, including the American government, feel that they can back away from public health. That would be disastrous for the world's poor, they said, since the foundation is only one stream in a vast river. If anyone does back away, Dr. Klausner said "it's because they were looking for an excuse, not because there's no need."

Diana Aviv, president of Independent Sector, a nonpartisan coalition that represents charities and foundations, said she expected the Buffett money to give the Gates Foundation more power.

"They haven't served multiple programs," Ms. Aviv said. "They've been much more generous in a few. This gives them leveraging opportunities."

Mr. Buffett said yesterday that he was a student of the same philanthropists that Mr. Gates modeled himself on: the oilman John D. Rockefeller; the steel magnate Andrew Carnegie; Irene Diamond, the widow of the real estate developer Aaron Diamond; and Joan Kroc, the widow of Ray Kroc, who founded McDonald's.

Mr. Buffett is also famous for loving efficiency. He runs a company with 200,000 employees from an Omaha headquarters with fewer than 20 employees. The Gates Foundation, in Seattle, has about 300.

Mr. Buffett was scathing yesterday in describing his feelings about estate taxes, which the Bush administration is trying to kill. The ability of rich men to pass on "dynastic wealth" to their grandchildren is offensive to the American tradition of meritocracy, he said.

He gets particularly upset at his country club, he said, hearing members complain about welfare mothers getting food stamps "while they are trying to leave their children a more-than-lifetime-supply of food stamps and are substituting a trust officer for a welfare officer."

To widespread applause, he smiled and asked: "Is there anyone I forgot to insult?"

    Buffett's Billions Will Aid Fight Against Disease, NYT, 27.6.2006, http://www.nytimes.com/2006/06/27/us/27gates.html

The DNA Age

That Wild Streak?

Maybe It Runs in the Family

June 15, 2006
The New York Times
By AMY HARMON

Jason Dallas used to think of his daredevil streak — a love of backcountry skiing, mountain bikes and fast vehicles — as "a personality thing."

Then he heard that scientists at the Fred Hutchinson Cancer Research Center in Seattle had linked risk-taking behavior in mice to a gene. Those without it pranced unprotected along a steel beam instead of huddling in safety like the other mice.

Now Mr. Dallas, a chef in Seattle, is convinced he has a genetic predisposition for risk-taking, a conclusion the researchers say is not unwarranted, since they believe similar variations in human genes can explain why people perceive danger differently.

"It's in your blood," Mr. Dallas said. "You hear people say that kind of thing, but now you know it really is."

A growing understanding of human genetics is prompting fresh consideration of how much control people have over who they are and how they act. The recent discoveries include genes that seem to influence whether an individual is fat, has a gift for dance or will be addicted to cigarettes. Pronouncements about the power of genes seem to be in the news almost daily, and are changing the way some Americans feel about themselves, their flaws and their talents, as well as the decisions they make.

For some people, the idea that they may not be entirely at fault for some of their less desirable qualities is liberating, conferring a scientifically backed reprieve from guilt and self-doubt. Others feel doomed by their own DNA, which seems less changeable than the more traditional culprits for personal failings, like a lack of discipline or bad childhoods. And many find it simply depressing to think that their accomplishments might not be the result of their own efforts.

Parents, too, are rethinking their contributions. Perhaps they have not scarred their wayward children so much as given them bad genes. Maybe it was not their superior parenting skills that produced that Nobel laureate.

Whether a new emphasis on genes will breed tolerance or bigotry for inborn differences remains an open question. If a trait like being overweight comes to be seen as largely the result of genetic influence rather than lack of discipline, the social stigma connected to it could dissipate, for instance. Or fat people could start being viewed as genetically inferior.

Because tests for the genes that influence personality and behavioral traits are not yet commercially available, there is no way for most people to know which ones they have. And even if they could, the newly uncovered genes are thought merely to influence, not determine, their personalities. Biologists are also quick to emphasize the role environment plays in activating genetic dispositions that might otherwise never be expressed, or mitigating those that are.

But that has not stopped people from acting on their assumptions.

Mr. Dallas's wife, Mari, for instance, convinced that her husband is in some sense hostage to his daredevil genes, has insisted he draw the line at certain activities.

"If he had his choice, he would be getting a motorcycle," said Ms. Dallas, a pediatric oncologist. "I don't think that's such a good idea."

The public embrace of genetics may be driven as much by wishful thinking as scientific truth. In an age of uncertainty, biology can appear to provide a concrete answer for behavior that is difficult to explain. And the faith that genetics can illuminate the metaphysical aspects of being human is for some a logical extension of the growing hope that it can cure disease.

"More and more stories about who we are and how we live are becoming molecular," said Paul Rabinow, an anthropologist at the University of California, Berkeley, who studies the interrelation of science and culture. "The older liberal worldview that it's all a question of willpower is still very present in America, but genetics has become a strong countercurrent."

That may be partly because the science has become more credible. Armed with the human genome sequence, along with a catalog of genetic variation in the human population, and tools that can inexpensively gauge any individual's genetic makeup, scientists can now pinpoint the genes associated with inherited traits.

Developed to dissect the genetic basis for complex ailments like heart disease and cancer, the methods are now being applied to less pressing areas like the way genes may influence sexual desire or attention deficit disorder. While scientists have yet to demonstrate any genetic cause that directly affects such behavior, they have found plausible associations. And for many people, that is all that matters.

"The scientific facts have changed," said Steven Pinker, a psychologist at Harvard who documented cultural resistance to the influence of genetics on behavior in his 2002 book "The Blank Slate."

"We now have real evidence that some of the variation in personality is inherited," Dr. Pinker said, "and I think it may be affecting people's everyday choices."

Some people persist in believing in the power of the human spirit, but a growing number prefer to submit it to a DNA test. In the wake of the recent discovery that millions of people who carry a specific genetic variation are more likely to gain weight, Mike DeWolfe, a computer programmer who considers himself overweight, cannot help wondering if he is one of them.

"I really would like to have a test, because it would help reduce my guilt over it," said Mr. DeWolfe, 38, of Victoria, British Columbia, noting he would also welcome a genetic treatment as an alternative to his constant dieting. "That would make a big difference."

There is nothing new about the idea that temperament and behavior are shaped by genetic endowment. Families have long clucked over a trademark stubborn streak showing up in a new generation, or crowed about inherited creative abilities. But as science begins to corroborate intuition, the public is reassessing where credit and responsibility lie for character traits that may be in part genetically preordained.

"To summarize, want to live until a ripe old age? Have parents that live long," Joe Pickrell, a 23-year-old graduate genetics student wrote in a recent blog entry. "Think you're a friendly, peaceful guy 'cause your mom raised you right? Think again. Able to try drugs just a couple times and never get hooked because of your strong will? Nope." (Mr. Pickrell, of Chicago, punctuated each clause with a link to a recent scientific journal article describing the genetic component of life expectancy, aggression and susceptibility to drug addiction.)

Jacki Thorpe wondered for years why her older sister could quit smoking so easily, while her own numerous attempts have failed. After all, their upbringing had been virtually identical, and they had started smoking together when they were 12 and 14. Then she heard about a genetic variation that predisposes some people to nicotine addiction.

"I have it," guessed Ms. Thorpe, 42, an administrative assistant in Whidbey Island, Wash. "My sister doesn't." Determined to fight her presumed genetic destiny, Ms. Thorpe has sworn to try quitting one more time this summer.

A Stanford University student in a focus group on smoking and genetics was more accepting: "Let's say I'm still addicted to cigarettes 10 years from now," the student said in a telephone interview, asking that his name not be used because he has concealed his smoking habit from his family. "It might feel like it's not a total personal failure, just that certain things made it harder for me than other people. It kind of takes the weight off."

Friends and family members who worry about behavior that seems unhealthy or self-destructive sometimes suspect that blaming genes is an easy out. When Representative Patrick J. Kennedy, Democrat of Rhode Island, cited his family's history of addiction in admitting to a prescription drug addiction after he crashed his car near the Capitol last month, for instance, some scoffed. "Kennedy blames crash on 'car accident gene,' " read the headline on Antimatternews.com, a satirical blog, an allusion to the 1969 crash in which his father, Senator Edward M. Kennedy, was driving and a passenger was killed. Some bioethicists warn that the embrace of genetics as an explanation for troubling behavior threatens to let society off the hook, too. Taxing cigarettes, banning smoking in bars and not glamorizing it in movies is far more likely to lower smoking rates than drugs tailored to certain genotypes, these critics say.

Still, at Hazelden, an addiction-treatment center in Minnesota, teaching about genetics has become standard. Learning that roughly half the risk of alcohol addiction is associated with genes can remove a burden of guilt that otherwise serves as an obstacle to recovery, said Dr. Marvin D. Seppala, the center's chief medical officer.

"They've driven drunk, and they have children, and they're saying, 'I can't believe I did this,' " Dr. Seppala said. "To learn they have a disease with a genetic component like other diseases really helps them understand these crazy sort of behaviors."

As genetics comes to rival childhood experience as the favored lens through which to interpret behavior seen as deviant, parents who blamed themselves for their children's disorders are also finding some relief. Recent research has found that conditions like anorexia or autism, once thought to be largely psychological, are at least partly genetic.

"You would wonder, 'What's wrong, what aren't we providing?' " said Kathy Ramsay, 55, a legal secretary in Sacramento who has had three daughters who suffered from anorexia. The new DNA paradigm, however, can come with a new guilt trip.

"I passed it on to them," added Ms. Ramsay, whose daughter Heather volunteered for a genetic study of anorexia at the University of North Carolina after reading about the research in her local newspaper this year. "It was in me."

Some adults are more forgiving of parents' sins they now consider DNA-enabled. Others get angry, however irrationally, for being saddled with inferior genes. Tim McGrath, 45, said learning about the genetics of alcoholism had made him more determined not to follow the path of his father. Still, he is haunted that he has seen his own fate.

"It's like this demon out there, lurking," said Mr. McGrath, a teacher in Chicago. "And without the proper vigilance, or whatever, it could strike."

By suggesting a genetic basis for behavior previously believed by some to be the result of character flaws, scientists and others say the discoveries could make for more understanding of human differences. Some overweight people, for instance, hope it will reduce the stigma associated with being fat.

"Maybe it will help the rest of the world realize it's not lack of willpower, it's not stubbornness, it's not laziness," said Jane Perrotta, 52, a medical writer and contributor to the weight-loss blog The Skinny Daily Post.

"It's the hand you're dealt," Ms. Perrotta said.

Others fear that when certain behaviors once ascribed to personal choice are seen as genetic, the next step will be not tolerance for difference, but support for intervention. On a "fat-acceptance" e-mail list, several members suggested recent research will lead only to new ways for them to lose weight through genetic alteration, rather than be accepted as they are. And when scientists caused fruit flies to pursue flies of the same sex by altering a gene last year, some gay-rights advocates worried it would lend credence to the notion that homosexuality could be "cured."

People could also find their genes being held against them. Already, some scientists suspect a specific gene plays a role in violent behavior, for instance, and a discussion has already begun over how people bearing such genes should be treated.

"If we find a murder mutation, are we going to be more accepting of murderers, or are we going to lock them up even more tightly?" asked Jeffrey M. Friedman, director of the Starr Center for Human Genetics at Rockefeller University. "The more we find genes that play a role in determining all sorts of attributes, the more we're going to face these kinds of ethical issues."

Of course, for traits that are socially desirable, people may not be as eager to accept genetic explanations that seem to trivialize their skills or accomplishments. When scientists this year found two gene variations that appear at higher rates in professional dancers than in the general population, many dancers bristled at the news. In online message boards for the ballet magazine Pointe, several writers said success in dance was the result of hard work, passion and good mentors. "Being a dancer requires so much more than what's there in your body, an emotional strength," said Virginia Johnson, editor of Pointe and a former principal dancer with the Dance Theater of Harlem.

She paused.

"That genes can't really — well, I guess that's genetic, too, isn't it?"

    That Wild Streak? Maybe It Runs in the Family, NYT, 15.6.2006, http://www.nytimes.com/2006/06/15/health/15gene.html

Surgeons Work to Separate Twins in L.A.

June 14, 2006
The New York Times
By MARIA NEWMAN

A huge team of doctors at a Los Angeles hospital began a procedure early this morning to separate a pair of conjoined twins attached from the chest to the pelvic areas. The operation is expected to last at least 24 hours.

The complex surgery on Regina and Renata Salinas Fierros began at about 6 a.m. at the Childrens Hospital Los Angeles. About 80 doctors and staff members will try to separate many of the girls' vital organs.

The girls, whose parents are from Mexico, are considered ischiopagus tetrapus twins, which doctors at the hospital said are among the rarest and most complex to separate because they share many organ systems. The twins are fused on their front, and today doctors will attempt to separate their liver, intestine, urinary, reproductive, vascular and musculo-skeletal systems.

"They're attached in a way that even walking across the street would likely be impossible for them the rest of their lives," the lead surgeon, Dr. James E. Stein, said at a news briefing on Tuesday. "What we are hoping to do is give them not just that opportunity but really an opportunity to do everything else in life that would be considered normal."

A video report from The Associated Press shows the twins a few days ago, two gurgling dark-haired babies, smiling as they face each other, their little arms happily flailing about.

The hospital said the girls were born on Aug. 2, 2005, at Los Angeles County-USC Medical Center. Their parents, Sonia Fierros, 23, and Federico Salinas, 36, are from Juarez, Mexico. Last spring, when Ms. Fierros was pregnant, she was hospitalized with a urinary tract infection during a visit to Los Angeles to visit relatives and learned then that she was carrying conjoined twins.

The couple decided to stay in Los Angeles on an extended tourist visa because they thought their babies would receive better medical care here, The Associated Press reported.

Dr. Stein, an attending pediatric surgeon at Childrens Hospital Los Angeles and an assistant professor of surgery at the Keck School of Medicine of the University of Southern California, also led the team that successfully separated conjoined twins in 2003, the hospital said. The hospital said those twins, wards of the state known publicly as 'Baby A' and 'Baby B', were adopted, along with their triplet sister, by a "wonderful family and continue to thrive together in another state."

Today's procedure will likely involve a dozen surgical procedures, Dr. Stein said.

"The first phase includes dividing the breastbone, liver, intestine, urinary bladders, genital organs and the bony pelvis," he said. "During the second phase, the chests, intestines, vaginas, ureters, pelvises and body walls all will be reconstructed."

    Surgeons Work to Separate Twins in L.A., NYT, 14.6.2006, http://www.nytimes.com/2006/06/14/us/14cnd-twins.html

In Diabetes,

One More Burden for the Mentally Ill

June 12, 2006
The New York Times
By N. R. KLEINFIELD

Dr. John Newcomer is a psychiatrist who generally treats people with severe ailments of the mind and spirit. But before his patients sit down, before he hears about their clammy paranoia or renegade voices, Dr. Newcomer wants to know about their waist size.

He steers them to a scale to learn their weight. He orders a blood sugar test. If big numbers come up, he begins a conversation about Type 2 diabetes, a disease associated with obesity that is appearing with alarming frequency among the mentally ill.

"Uncontrolled diabetes can ruin a person's life as much as uncontrolled schizophrenia," said Dr. Newcomer, a professor of psychiatry at Washington University School of Medicine in St. Louis.

In fact, among the mentally ill, roughly one in every five appear to develop diabetes — about double the rate of the general population. This is a little-recognized surge, but one that is jolting mental health professionals into rethinking how they care for an often neglected population.

For decades, psychiatrists have worried primarily about patients' mental states, making sure they did no harm to themselves or others because of unrelenting voices or a smothering depression.

Far more of the mentally ill, however, die today from diabetes and complications like heart disease than from suicide. Given that mental health specialists are often the only doctors a mentally ill diabetic ever sees, some have begun to debate the customary limits of psychiatric practice, deciding to pay much more attention to physical ailments.

In particular, psychiatrists must confront the fact that diabetes, marked by dangerously high blood sugar, is often aggravated, if not precipitated, by some of the very medicines they prescribe: antipsychotic pills that have been linked to swift weight gain and the illness itself.

"It's bad enough that these people have mental illness, and then they take treatments and they bring on diabetes," said Dr. Jeffrey Lieberman, chairman of the psychiatry department at the Columbia University College of Physicians and Surgeons.

Treating the diabetic mentally ill can be formidable. The regimen of blood testing, dieting and exercise that controls Type 2 diabetes is often beyond the attentions of the mentally ill. For patients, the task of taming two debilitating illnesses can haunt their lives. Michael Schiraldi, 44, a Manhattan man who has both schizoaffective disease and diabetes, said his mental illness, now stabilized, was the lesser of his concerns.

"I can't really control the diabetes," he said. "I might die from it."

The doctors who regard diabetes as a galloping threat to the mentally ill acknowledge that many in their profession still dispute, or ignore, its consequences. Dr. Newcomer said colleagues often whine about how hard it is to weigh patients. " 'Oh', they'll say, 'there's no scale' or 'It's in a closet someplace,' " he said.

Yet he says he hopes other doctors will eventually share his perspective as diabetes expands among the mentally ill and deepens into an even graver problem.

Betrayals of Body and Mind

Carole Ernst doesn't know how she got diabetes.

Genes? Her mother had it.

Lifestyle? She eats more than she should, exercises less than advisable.

Or was it the pills that shushed the TV?

The TV no longer speaks to her. She stared levelly at the set in her messy room. It was blessedly quiet.

She is 53 and has battled mental illness since childhood. The pills for her illness, diagnosed as schizoaffective disorder, have helped. But she feels they have also made her fat around her abdomen, the kind of fat that can lead to diabetes.

So even though Ms. Ernst feels better mentally — she no longer imagines everyone despises her — diabetes has been a crippling insult to her troubled psyche. In the late hours, alone in her room on the Lower East Side of Manhattan, trapped in the undertow of two potent diseases, she runs on empty.

"Some nights, the only thing I can do is read my Bible," she said. "I look in there to find answers. They're hard to find."

Diabetes on top of mental illness asks a lot of a person, and of society. Mental illness is itself a money sponge, an expense borne largely by tax dollars. But that cost may be dwarfed by the bill to manage the heart attacks and amputations that diabetes bestows.

With numerous mental institutions emptied, patients often live in lightly supervised settings. Many occupy adult homes that struggle, for good reasons and bad, at providing basic services and are poorly equipped to treat diabetes. Others live on their own, sometimes in boxes beneath bridges or crumpled in doorways.

Imagine taking on diabetes if you live alone and find living itself to be a handful.

"I try not to drink sugared sodas, but sometimes I forget," Ms. Ernst said. "I'll buy candy — Mary Janes or banana cookies. I know I'm not fooling anybody — it's my arms and legs they're going to cut off — but sometimes I get the craving for something sweet."

She sat at a round table in her room, a cool evening of early spring, cradling a stuffed bunny. She flicked a small smile. "I'm sorry it's not neater," she said, looking around. "I'm trying."

Ms. Ernst embodies the difficulty of confronting the two diseases with all their complexities. She takes clozapine for her mind because she can't manage without it. She has diabetes and can't defeat her weight.

"Disgusting, that clozapine," she said. "Makes you eat everything under the sun." She takes a lineup of other drugs, too, not all positive for her weight. She had hit 250, fought her way to 198, and is now at 221.

She lives at Gouverneur Court, a residence run by a nonprofit organization, where about 15 of the 66 mentally ill residents have diabetes. "Some say they don't have it, but they do," said Abby Stuthers, the nurse who works there. "Or they say they have a little diabetes."

Ms. Ernst freely recounts her callused life. Her marriage exploded. Once she was smacked in the face with a glass ashtray. She opened her mouth — every tooth was missing.

Now diabetes. Her blood sugar has been O.K., but her vision has worsened. And she is inconsistent, prey to the fury of her demons.

Susanne Rendeiro, a family nurse practitioner who serves as her primary care physician, said Ms. Ernst misses half her appointments. Recently, in reviewing her drugs, Ms. Rendeiro asked about her blood pressure pills. Puzzled, Ms. Ernst said she was not on blood pressure pills.

Mrs. Rendeiro said she had supposedly been taking them for two years.

"I want to be the best I can be," Ms. Ernst said. "Nobody changes overnight."

Treatment and Cruel Ironies

There was always a lot else wrong with the mentally ill — heart problems and cancer and H.I.V., as well as diabetes. But for psychiatrists and clinicians it was enough to worry about mental needs that beggared the imagination.

The spread of diabetes, however, is making the physical conditions impossible to ignore. "Psychiatrists are literally watching patients balloon up before their eyes," said Dr. Gail Daumit, an assistant professor of medicine at Johns Hopkins Medical Institutions.

This has been especially true since the advent of so-called atypical antipsychotic drugs in the early 1990's. Studies indicate that these drugs can alter glucose metabolism and stimulate weight gain, particularly in people predisposed to diabetes.

"Sort of a cruel irony in this," said Dr. Lieberman of Columbia, "is that all of the drugs do it to some degree, but the ones that have the most effect cause the most weight gain and metabolic side effects. There's increasing discomfort that these are driving up deaths and lowering quality of life."

Some cases have been striking: a patient packing on 50 pounds in mere months, for example. Diabetes arrived as quickly, and sometimes subsided if the drugs were halted. In certain instances, there was no weight gain, but still diabetes came, often in patients who were already heavy. Studies have indicated that dozens of these patients died from diabetes-related complications.

The Food and Drug Administration requires atypical antipsychotics to bear warning labels about diabetes risk, though drug makers say patients taking them who develop diabetes were destined to get it anyway.

Robin Stigliano's psychiatrist has her taking Haldol by injection as well as one of the drugs most closely associated with weight gain, Zyprexa. They have helped her schizophrenia, but Ms. Stigliano, 37, who lives in a Brooklyn adult home, has seen her weight soar to 241 pounds from 150. And when she gets her Haldol infusion every three weeks, all she wants to do is sleep. "It's my favorite activity," she said.

Without the drugs, psychiatrists believe, many high-functioning patients would find themselves in institutions or jail. "These drugs are enormously beneficial," said Dr. P. Murali Doraiswamy, head of biological psychiatry at Duke University. "But they have an Achilles heel."

A few years ago, Dr. Doraiswamy reported a case of a mentally ill person who got diabetes and was prescribed insulin. The impact of having two serious conditions overwhelmed him. He wound up trying to kill himself by insulin overdose.

Some researchers think it is possible the rash of diabetes stems in part from mental illness itself. Studies associate the onset of diabetes with depression. The mentally ill are also at high risk because they tend to eat poorly, get little exercise and have limited access to health care.

In a 2003 survey, the city's health department found that about 17 percent of adults who reported symptoms of a mental illness, or 52,000, have diagnosed diabetes. Elsewhere, rates are as great or greater. Even these estimates may be low, experts said, because the mentally ill see doctors sporadically and their illnesses may be underdiagnosed.

The rates of diabetes and obesity are nudging Dr. Doraiswamy and others in his field — in modest ways thus far — toward prevention, toward screening people for diabetes before choosing drugs and connecting better with primary care doctors.

"This wouldn't be a big problem if most mentally ill patients had a primary care provider, but they don't," said Dr. Newcomer at Washington University. "And it's never been part of the game plan for the psychiatrist to write the prescription for your blood pressure medicine or your diabetes medicine."

He feels change is imperative. "The days when I don't do windows can't go on," he said.

Dr. Kenneth Duckworth, medical director for the National Alliance on Mental Illness, agreed. "I think the field has been passive," he said. "We viewed it that we do symptoms and you run your life."

Stimulating change is not easy. Psychiatrists have a problem simply getting patients to stay on their drugs. Resources are inadequate.

"Psychiatry is historically a couch and the chair," Dr. Duckworth said. "How do you get movement into the equation?"

He said that he weighed his patients, checked sugars. But few psychiatrists are set up to do this. Treating diabetes, they say, was not what they were trained to do. And where, they ask, do they find time in 15-minute appointments?

"Most psychiatrists barely look at their patients," said Dr. Donna Ames Wirshing, a staff psychiatrist at the West Los Angeles Veterans Administration Medical Center. She recently asked 30 how many weighed their patients; 3 hands went up.

Dr. Wirshing and her husband, Dr. William Wirshing, are experimenting with the use of nutrition and exercise coaches for mentally ill patients.

Couches could be replaced with exercise bikes. Or, as Dr. David Hellerstein, associate professor of clinical psychiatry at Columbia's College of Physicians and Surgeons, noted, "Instead of having the patient lie down and you say, 'So tell me why you fight with your brother,' you could say to the patient, 'Let's take a walk around the block while you tell me about why you fight with your brother.' "

For the most part, however, psychiatrists confront the knotty questions without ready answers.

If some 10 percent of schizophrenics kill themselves, and clozapine is the only antipsychotic medication demonstrated to significantly reduce suicide, but it has grave side effects, like its association with diabetes, is it miracle or monster? Or both?

"When I chat with patients, about clozapine, I say, 'This may give you your mind back, but it may hurt your body,' " Dr. Duckworth said. "I think of it as psychiatric chemotherapy. Your hair won't fall out, but you may get diabetes."

How do patients respond? "Some say, 'If this will give me my mind, I'll take anything,' " he said. "Some say, 'There's nothing wrong with me, why are we even having this conversation?' About 60 percent of schizophrenics don't recognize that they have it. There are very few easy answers in my line of work."

Housing the Ill and Diabetic

Surf Manor squats on the tip of Coney Island, one of the dozens of profit-making adult homes in the city where thousands of the mentally ill live. Residents complain about the food. Activities are light on exertion. The week's offerings are taped to the wall: dominoes, blackjack, manicures, jewelry class.

So the men and women eat, sleep, smoke, watch TV, sleep — then do it all over again. Unsurprisingly, those who live there say, dozens of the 200 residents struggle with diabetes.

These often-troubled homes where so many of the mentally ill are housed, frequently grumbling about inadequate attention to their needs and their dignity, can be hideously difficult places for someone at high risk for diabetes. And that is basically everyone who lives there.

Leslie Hinden, a chatty man of 51, sat listlessly in the lounge, near the junk food dispensers. He'd be buying sweets but was broke from binging.

He has had schizoaffective disease — characterized by symptoms of schizophrenia and depression — for most of his life. Sometimes he hears Indian war whoops in his head. About 17 years ago, he picked up diabetes, too.

His blood sugar was 289 that morning, he said. A normal fasting blood sugar reading is below 126 milligrams per deciliter.

"I cheated," he said. "Last night I ate two eclairs. Had a Coke. A lot of times I don't cheat and it goes up to 300. I don't know what to do."

Why the binge last night?

"I don't know," he said. "I felt scared."

A recent State Department of Health sampling of 19 homes found that nearly a quarter of residents had diabetes. The homes say they do what they can. Some have diabetes sections in the dining halls, where occupants get a sugar-free dessert.

"I'm not a doctor, but we're very helpful," said Mordechai Deutscher, the case manager at Surf Manor, who said he did not think the home had many diabetics. "The people here are doing very well."

Even mental health advocates have not given diabetes much attention. The Commission on Quality of Care and Advocacy for Persons with Disabilities, a state watchdog agency, said it has never examined diabetes prevalence or care.

At Surf Manor, Mr. Hinden, like the other diabetic residents, cannot have a blood sugar meter or give himself insulin. Needles are considered perilous. He depends on the staff. But no one prescribes motivation or understanding. And where diabetes requires vigilant self-management, illnesses like schizophrenia often mean memory problems and lack of drive.

"I'll be honest with you, I don't understand diabetes," Mr. Hinden said. "I don't understand it at all."

Joseph Franklin, 47, sat down, all 300-plus pounds of him. He said he has been taking diabetes drugs for seven years. "It's just in case," he said.

He said he was bipolar: "I couldn't see people with shoes on. If I saw someone with shoes on, it could do something to my forehead."

He spread out some greeting cards he had made. He leaned close. "Listen, I don't want everyone to hear this," he said, "but it's very possible that, unless the doctor made a mistake, I do have diabetes."

A stoic man of great girth named Lee Symons, 57, nodded. He had it, too. He hears guitars and banjos thrumming in his head.

Was he trying to diet?

"No one told me to," he murmured.

What about the diabetes?

"As long as it doesn't hurt, I don't mind it," he said. "It's just diabetes."

    In Diabetes, One More Burden for the Mentally Ill, NYT, 12.6.2006,
http://www.nytimes.com/2006/06/12/health/12diabetes.html

U.S. Approves Use of Vaccine for Cervical Cancer

June 9, 2006
The New York Times
By GARDINER HARRIS

WASHINGTON, June 8 — Federal drug officials on Thursday announced the approval of a vaccine against cervical cancer that could eventually save thousands of lives each year in the United States and hundreds of thousands in the rest of the world.

The vaccine, called Gardasil, guards against cancer and genital warts caused by the human papillomavirus, the most common sexually transmitted disease. It is the culmination of a 15-year effort that began at the National Cancer Institute and a research center in Australia, and health officials described the vaccine as a landmark.

Federal vaccine experts are widely expected to recommend that all 11- to 12-year-old girls get the vaccine, but its reach could be limited by its high price and religious objections to its use.

Merck, Gardasil's maker, said a full, three-shot course would cost $360, making Gardasil among the most expensive vaccines ever made.

"This is a huge advance," said Dr. Jesse Goodman, director of the Food and Drug Administration's biologics center. "It demonstrates that vaccines can work beyond childhood diseases to protect the health of adults."

The vaccine prevents lasting infections with two human papillomavirus strains that cause 70 percent of cancers and another two strains that cause 90 percent of genital warts. But if girls have already been exposed to those strains, the vaccine has no effect, so health experts want the vaccine given before girls have sex. The median age at which girls have sex is 15.

A Merck spokeswoman said Gardasil, which was approved for girls and women ages 9 to 26, would be available in doctors' offices by the end of June.

The vaccine is not approved for use in boys, although Merck hopes one day to change that. If the company is successful, analysts expect that sales could surpass $4 billion by 2010.

Cervical cancer is the second-leading cause of death in women across the globe, affecting an estimated 470,000 women and killing 233,000 each year. Widespread use of Pap smears has reduced its toll in richer nations. In the United States, about 9,710 women contract cervical cancer each year, and some 3,700 die.

Private health insurers are likely to cover the vaccine for 11- and 12-year-old girls, although older women may have to pay for it themselves.

Vaccines are one of the most cost-effective medical interventions available. But Gardasil's price could put it out of reach for most women in poor countries and some in the United States who lack private insurance.

A federal program is expected to provide the vaccine to 45 percent of the children in the United States for whom it is recommended. But state programs that cover other children are having trouble buying other expensive vaccines.

North Carolina, for instance, spends $11 million annually to provide every child with seven vaccines. Gardasil alone would probably cost at least another $10 million.

"Increasingly, states are asked to make a Sophie's choice about which diseases they will allow children to be hospitalized or killed by," said Dr. Paul Offit, director of infectious diseases at Children's Hospital of Philadelphia.

Liberals in Congress and elsewhere have warned that the Bush administration and religious groups should not interfere with Gardasil's approval or required use.In response, many conservative groups have made statements supporting the vaccine.

"Despite rumors to the contrary, our organization doesn't oppose the vaccine and we have taken no position regarding mandatory laws," said Wendy Wright, president of Concerned Women of America, a conservative group based in Washington.

Some groups support the vaccine but oppose mandatory vaccinations because cervical cancer is caused by a sexually transmitted virus.

"We can prevent it by the best public health method, and that's not having sex before marriage," said Linda Klepacki of Focus on the Family, a Christian advocacy organization based in Colorado Springs.

But scientific and budgetary issues are much more likely to determine Gardasil's uptake. Three shots must be given over six months. Such a schedule is routine among infants, but preteens are tougher to corral into doctors' offices.

An independent panel formed by the Centers for Disease Control and Prevention is scheduled to decide June 29 who should get the vaccine.

The panel is expected to recommend vaccinations for all 11- to 12-year-old girls, while agreeing that girls as young as 9 or women as old as 26 can get the vaccine if they wish. It is also expected to suggest that states make vaccinations mandatory.

Many states will not have the money to do much more, said Dr. Leah Devlin, state health director for North Carolina and president of the Association of State and Territorial Health Officials.

Already, North Carolina has been unable to provide six federally recommended vaccines to all children because of cost, Dr. Devlin said. The state cannot mandate any vaccine that it does not agree to provide.

In the United States, about 20 million people are infected by the human papillomavirus each year. By the time women reach the age of 50, 80 percent have been infected.

Most infections are quickly dealt with by the immune system. But some strains cause changes in cells that line the cervix in some women. The changes years later can turn into cancer. Most patients contract the disease in their 40's and 50's.

GlaxoSmithKline, based in London, is also developing a vaccine against cervical cancer that it expects to submit for F.D.A. approval at the end of the year.

Pap smears can detect precancerous changes to the uterus, but the tests are sometimes wrong, missing some cases and leading to unnecessary procedures in others. Because Gardasil protects against only four viral strains and its effects in those four will take decades to have widespread effect, health officials are recommending that women continue to undergo routine Pap tests.

Silvia Ford, a 35-year-old stay-at-home mother from Maryland, learned in November 2004, just three months after bearing her second child, that she had cervical cancer. Surgeons removed her uterus, for which she has no regrets. "I wanted to be around to take care of the two children I've already got," she said.

Ms. Ford is checked every three months for signs of cancer. She plans to have her daughter, now 6, vaccinated at some point.

"This vaccine should not lead to an argument about when girls have sex," Ms. Ford said. "It's about saving the lives of women in their child-bearing years, letting them have children or take care of the children they already have."

Merck had originally hoped to get the vaccine approved for use in boys. But although women have routinely allowed swabs to be taken of their vaginal cells, the company found that men rebelled against the use of emery boards to collect cells from their penises. Researchers eventually discovered that jeweler's-grade emery paper effectively removed cells without alarming men and were able to complete their studies.

    U.S. Approves Use of Vaccine for Cervical Cancer, NYT, 9.6.2006,
http://www.nytimes.com/2006/06/09/health/09vaccine.html

Dr. Sara Gibson, right, with a patient who asked to be identified only as C.

They say they sometimes forget they are not in the same room.

Jeff Topping for The New York Times        June 8, 2006

 TV Screen, Not Couch, Is Required for This Session        NYT        8.6.2006

http://www.nytimes.com/2006/06/08/us/08teleshrink.html

TV Screen, Not Couch,

Is Required for This Session

June 8, 2006
The New York Times
By KIRK JOHNSON

FLAGSTAFF, Ariz. — Dr. Sara Gibson looked into the television screen and got right down to it.

"What's keeping you alive at this point?" she asked her patient, a middle-aged woman who asked to be identified only as D. D grimaced, looked down, then to the side and finally into Dr. Gibson's face, which filled the screen before her in a tiny clinic three hours east of here in the Arizona desert.

"Nothing," said D, who Dr. Gibson says suffers from bipolar disorder and post-traumatic stress from the sexual abuse she suffered as a child.

It is Wednesday in the hinterlands of rural Arizona, and the psychiatrist is in. Sort of.

Actually, Dr. Gibson was here in Flagstaff in a closet-size office of a nonprofit medical group, with a pale blue sheet behind her as a backdrop and a cup of tea at her side. She is one of a growing number of psychiatrists practicing through the airwaves and wires of telemedicine, as remote doctoring is known.

Psychiatry, especially in rural swaths of the nation that also often have deep social problems like poverty and drug abuse, is emerging as one of the most promising expressions of telemedicine. At least 18 states, up from only a handful a few years ago, now pay for some telemedicine care under their Medicaid programs, and at least eight specifically include psychiatry, according to the National Association of State Medicaid Directors. Six states, including California, require private insurers to reimburse patients for telepsychiatry, according to the National Conference of State Legislatures.

Growing prison populations have a lot to do with the trend. Since reimbursement for prison care is easy and safety issues for doctors are significant, many telemedicine programs, notably an ambitious one in Texas, started there. Now, the falling price of technology is making care available to far-flung rural residents like D.

Dr. Gibson rides a disembodied circuit through this terrain. On Wednesdays, she sees patients in the tiny community of Springerville near the New Mexico border through a firewalled T1 data line, and on Thursdays in St. Johns. Each side of the exchange has its own television-mounted camera, angled so that doctor and patient can maintain the illusion of looking into each other's eyes in real time.

And so, through illusion and delusion, depression, anxiety, paranoia — and here and there a laugh or two — a day in the life of a rural telepsychiatrist and her patients unfolded.

"Is there self-harm going on, too?" Dr. Gibson pressed D, typing notes into the computer and glancing back at the screen. D paused, then quietly said, "Yeah."

Dr. Gibson, 44, was a pioneer in the field. She has been seeing patients only this way for 10 years and is still one of a handful of doctors in the country who practice telepsychiatry exclusively. Her territory is Apache County, which is about the size of Massachusetts and Connecticut combined, but which lacks even a single psychiatrist on the ground for its 69,000 residents despite widespread problems of poverty, drug use, child abuse and a suicide rate that is twice the national average.

The American Psychiatric Association says on its Web site that it supports telemedicine, "to the extent that its use is in the best interest of the patient," and practitioners meet the rules about ethics and confidentiality. But in places like Apache County, where the alternative is no treatment at all, most mental health workers say that every new wire and screen is to be deeply cheered.

"Basically, doctors can do, surprisingly, almost everything," said Don McBeath, the director of telemedicine and rural health at the Texas Tech University Health Sciences Center in Lubbock. "The difference is they can't touch you or smell you."

Dr. Gibson said the lack of smelling and touching, at least when it comes to psychiatry, has proved to be a good thing. Being physically in the presence of another human being, she said, can be overwhelming, with an avalanche of sensory data that can distract patient and doctor alike without either being aware of it.

"Initially we all said, 'Well, of course it would be better to be there in person,' " she said. "But some people with trauma, or who have been abused, are actually more comfortable. I'm less intimidating at a distance."

Some of the doctor's patients, who agreed to allow a reporter and photographer to observe their therapy sessions over two recent days — one day in Flagstaff with Dr. Gibson, the second day in a field clinic in St. Johns, population 3,000 — said they were in fact perfectly happy with the doctor's being hundreds of miles away, though some were quick to add that no offense was intended.

"Some people don't want to have to deal with a real person," said one patient, a 63-year-old woman who has dementia and bipolar disorder.

One thing Dr. Gibson has learned over the years is that she should not wear stripes or zigzag patterns, which can look strange on television, especially to already disturbed people. For patients with paranoia, she regularly pans the camera around her little room to prove that no one else is lurking and listening. (A white-noise machine purrs outside Dr. Gibson's office door, muting the exchanges within, and no session is ever recorded.)

She worries, sometimes, about the children she sees, almost all of whom immediately and enthusiastically embrace the idea of a talking to the nice, chatty woman on the television. "Do they understand that the TV doesn't always talk to them?" Dr. Gibson said.

Another patient, Mike Kueneman, who allowed his full name to be used, has seen Dr. Gibson for about five years, through the periods with the voices in his head and what he calls the "psychotic episode" that landed him in jail this year on burglary charges. Mr. Kueneman said he felt more comfortable with Dr. Gibson, even though they have never met in person, than he does with most of the people he knows.

Like most of Dr. Gibson's patients, he pays little or nothing to see her. State programs for low-income and mentally ill people pay for the $120 psychiatric evaluations and $40 follow-up visits — and for the medicines she prescribes, which can cost thousands of dollars.

"It's hard for me to trust any other doctor," said Mr. Kueneman, who attended a telesession in the St. Johns clinic in leg shackles and handcuffs, accompanied by an Apache County sheriff's deputy.

Some things did not happen as expected. Dr. Gibson predicted, for example, that at least one patient would incorporate the teleconferencing technology into his or her delusions and come to believe that telemedicine could be used to read people's thoughts or get inside their heads.

To the contrary, in matters of the psyche — two people in two rooms looking at each other across a cool electronic medium — it is still all about human connection.

"I just feel like she's here," said a 24-year-old mother of three who asked to be referred to as C. C was struggling with depression, anxiety and fantasies of suicide. "I sometimes forget we're not in the same room."

Dr. Gibson spoke up from her room in Flagstaff: "That's funny, I would say that I feel the same way."

Dr. Gibson and C have known each other across the telewaves since C became a single mother on her own at age 17.

The emotions ran deep as they spoke and C described the dark thoughts that sometimes come at night. Gripped by insomnia, convinced that someone else is in the trailer she lives in, her mind races, she said, and the fantasy rolls out of how she might take her youngest child with her and disappear, driving off into the night.

"I don't want you killing yourself," Dr. Gibson said with a matter-of-fact tone. "So that means talking."

Apache County had a genuine, in-the-flesh psychiatrist once, Dr. Julia Martin, who practiced there for about 10 years until her retirement in 1996.

Dr. Martin was trained as a pediatrician and went back to school for psychiatry in her 50's. For more than a decade, she was it, the county's solo psychiatrist and also the only one serving the nearby Fort Apache Indian Reservation.

"You did get to know your patients pretty well — sometimes better than you'd like," Dr. Martin, 74, said in a telephone interview from her home in a remote corner of the county. Sometimes people would show up in the middle of the night, she said, desperate to see her. Other times, they delivered brownies.

What Dr. Gibson's patients imagine of her life and what she is like when she is not on camera is unknown. She sometimes mentions her children to them, and her passions for music and singing. She speculated that telemedicine has probably in some ways amplified and enlarged her image in the minds of some patients — that if she is on television she must be really important, larger than life.

She has been to Apache County once, for a "meet the psychiatrist" event in St. Johns years ago. Many of the patients who showed up remarked, she said, about how much shorter she was than they had expected.

    TV Screen, Not Couch, Is Required for This Session, NYT, 8.6.2006,
http://www.nytimes.com/2006/06/08/us/08teleshrink.html

Use of Antipsychotics by the Young

Rose Fivefold

June 6, 2006
The New York Times
By BENEDICT CAREY

The use of potent antipsychotic drugs to treat children and adolescents for problems like aggression and mood swings increased more than fivefold from 1993 to 2002, researchers reported yesterday.

The researchers, who analyzed data from a national survey of doctors' office visits, found that antipsychotic medications were prescribed to 1,438 per 100,000 children and adolescents in 2002, up from 275 per 100,000 in the two-year period from 1993 to 1995.

The findings augment earlier studies that have documented a sharp rise over the last decade in the prescription of psychiatric drugs for children, including antipsychotics, stimulants like Ritalin and antidepressants, whose sales have slipped only recently. But the new study is the most comprehensive to examine the increase in prescriptions for antipsychotics.

The explosion in the use of drugs, some experts said, can be traced in part to the growing number of children and adolescents whose problems are given psychiatric labels once reserved for adults and to doctors' increasing comfort with a newer generation of drugs for psychosis.

Shrinking access to long-term psychotherapy and hospital care may also play a role, the experts said.

The findings, published yesterday in Archives of General Psychiatry, are likely to inflame a continuing debate about the risks of using psychiatric medication in children. In recent years, antidepressants have been linked to an increase in suicidal thinking or behavior in some minors, and reports have suggested that stimulant drugs like Ritalin may exacerbate underlying heart problems.

Antipsychotic drugs also carry risks: Researchers have found that many of the drugs can cause rapid weight gain and blood lipid changes that increase the risk of diabetes. None of the most commonly prescribed antipsychotics is approved for use in children, although doctors can prescribe any medication that has been approved for use.

Experts said that little was known about the use of antipsychotics in minors: only a handful of small studies have been done in children and adolescents.

"We are using these medications and don't know how they work, if they work, or at what cost," said Dr. John March, a professor of child and adolescent psychiatry at Duke University. "It amounts to a huge experiment with the lives of American kids, and what it tells us is that we've got to do something other than we're doing now" to assess the drugs' overall impact.

But many child psychiatrists say that antipsychotic medication is the best therapy available for children in urgent need of help who do not respond well to other treatments. Without them, they say, many unpredictable, emotionally unstable children would end up institutionalized.

Dr. Mark Olfson, a professor of clinical psychiatry at Columbia University and the lead author of the study, financed in part by the National Institute of Mental Health, said the popularity of antipsychotic drugs might result in part from "the fact that psychiatrists have few other pharmacological options in certain patients."

The study, which looked at visits to pediatricians and other doctors, found that psychiatrists were the most likely to prescribe antipsychotic drugs.

In light of how little these drugs have been studied in children, Dr. Olfson said, "to me the most striking thing was that nearly one in five psychiatric visits for young people included a prescription for antipsychotics."

The Columbia investigators analyzed data from the National Center for Health Statistics survey of office visits, which focuses on doctors in private or group practices. They calculated the number of visits in which an antipsychotic drug was prescribed to people under the age of 21 and collected information on patients' medical histories. The total number of visits that resulted in prescriptions for the drugs increased to 1,224,000 in 2002 from 201,000 1993 to 1995.

The researchers attributed some of the increase to the availability of a new class of drugs for psychosis, called atypical antipsychotics, that were introduced in the early and mid-1990's.

The newer drugs, heavily marketed by their makers, were attractive in part because they appeared less likely than older types of antipsychotics to cause side effects like tardive dyskinesia, a neurological movement disorder similar to Parkinson's disease.

From 2000 to 2002, the new study found, more than 90 percent of the prescriptions analyzed were for the newer medications, and most of the patients were boys, predominantly Caucasian children, who were significantly more likely to see psychiatrists than other ethnic groups.

Some experts also pointed to an increase in the diagnosis of bipolar disorder in children as a contributing factor. In recent years, psychiatrists have begun to diagnose the disorder in extremely agitated, often aggressive children with mood swings — short surges of grandiosity or irritation that alternate with periods of despair. These symptoms in children are thought to be related to the classic euphoria and depressions of adult bipolar disorder.

At the same time, several of the atypical antipsychotics, including Risperdal from Janssen and Zyprexa from Eli Lilly, won approval for the treatment of mania in adults.

Some psychiatrists now routinely prescribe atypical antipsychotics "off label" for young people thought to have bipolar disorder, and researchers have begun to study the drugs in children as young as preschool age.

In the new study, about a third of the children who received antipsychotics had behavior disorders, which included attention deficit problems; a third had psychotic symptoms or developmental problems; and another third were suffering from mood disorders. Over all, more than 40 percent of the children were also taking at least one other psychiatric medication.

"We feel the medications are effective in children with bipolar and have some data to show that," said Dr. Melissa DelBello, an associate professor of psychiatry at the University of Cincinnati, who has done several studies of the drugs.

Dr. DelBello said that the field "desperately needs more research" to clarify the effects of the antipsychotic drugs but that many children struggling with bipolar disorder got more symptom relief on these drugs than on others, allowing psychiatrists to cut down on the overall number of medications a child is taking.

Lisa Pedersen of Dallas, the mother of a 17-year-old boy being treated for bipolar disorder, said he was unpredictable, hostile and suicidal before psychiatrists found an effective cocktail of drugs, which includes a daily dose of antipsychotic medication.

"Believe me, I would never choose having him on these meds," Ms. Pedersen said in a telephone interview. "It's not fun watching a child deal with the side effects. But finding the right combination of medicine has made his life worth living."

Yet this process is one of trial and error for many children. Ms. Pedersen said her son had responded badly to the first two antipsychotic drugs he received. And some experts think the way that psychiatric drugs are prescribed is obscuring any understanding of underlying disorders and the optimal treatments.

"If you're going to put children on three or four different drugs, now you've got a potpourri of target symptoms and side effects," said Dr. Julie Magno Zito, an associate professor of pharmacy and medicine at the University of Maryland.

Dr. Zito added, "How do you even know who the kid is anymore?"

    Use of Antipsychotics by the Young Rose Fivefold, NYT, 6.6.2006,
http://www.nytimes.com/2006/06/06/health/06psych.html

2 New Efforts to Develop Stem Cell Line for Study

June 7, 2006
The New York Times
By NICHOLAS WADE

Scientists at two universities — Harvard and the University of California, San Francisco — will try to develop embryonic stem cells from the adult cells of patients suffering from certain diseases.

Their purposes in creating the cell lines, which require making an early human embryo, are to study how the diseases develop and also to see if replacement cells can be generated to repair the patient's own degenerating tissues. But the field, despite its much emphasized promise, faces many serious uncertainties.

"Clinical applications may be a decade or more away," said George Q. Daley, a Harvard expert on blood diseases.

Harvard announced its plans yesterday at a news conference; the University of California, San Francisco, did so less conspicuously a month ago, resuming a program abandoned in 2001. Both universities, having received required approvals, will at first obtain the human eggs needed for cloning from fertility clinics, starting with eggs deemed too low quality to produce a successful pregnancy. Both programs are privately financed because federal support for human stem cell research is available only for cell lines made before August 9, 2001.

Advanced Cell Technology in Worcester, Mass., also has a human nuclear transfer program "well under way," said Robert Lanza, the company's vice president, but has run into problems in recruiting egg donors. Under guidelines issued by the National Academy of Sciences, which are voluntary but widely observed, donors may not be paid anything beyond expenses.

The new efforts, if successful, would accomplish what the disgraced South Korean scientist Woo-Suk Hwang claimed he had achieved in articles published in Science in 2004 and 2005. Both papers turned out to be based on forged data. But the flaws remained undetected by scientists involved in the cloning field, raising doubts about the rigor and expertise with which the new field was being conducted. The problems came to light not through criticism by scientific peers, but only after a whistle-blower in Dr. Hwang's lab contacted a Seoul television station.

The University of California, San Francisco, said last month that one of its researchers, Renee Reijo Pera, would start the cloning procedure, which involves transferring the nucleus of an adult cell into an unfertilized egg whose own nucleus has been removed.

A composite egg of this kind should develop in glassware into an early embryo, or blastocyst, from which embryonic stem cells could be isolated. There is no evident reason why this should not work in people as it has already done in several animal species, yet so far no one has succeeded. Dr. Hwang used no less than 2,000 fresh eggs donated by a healthy women but failed to accomplish anything useful.

Dr. Reijo Pera will switch to using donated eggs if those rejected by fertility clinics do not work, a university spokeswoman said. Harvard researchers said yesterday that they too would seek to derive eggs from healthy donors in the future.

Dr. Lanza, of Advanced Cell Technology, said that freshly harvested human eggs were "much better" for nuclear transfer experiments but that a six-month campaign by his company to recruit donors "appears to be a losing effort."

Many women had come forward, saying they would donate their eggs for research without compensation but, after seeing the battery of tests required, "most of the donors change their mind once they realize what's involved," Dr. Lanza said.

If research should establish that replacement tissues can be developed for a patient through the nuclear transfer technique, probably tens or hundreds of donated human eggs would be needed for each operation. Some scientists regard such a requirement as impractical, arguing that researchers should learn how to reprogram an adult cell's nucleus back to embryonic state without the use of human eggs. But this requires a far deeper understanding of human cells than is yet at hand.

Three Harvard scientists described their proposed research yesterday, promising not to discuss it further in public until they had firm results ready to be published. Dr. Daley hopes to develop, via nuclear transfer, embryonic stem cells from patients with blood diseases. He will try to correct the genetic defect behind the disease, then develop blood stem cells that could be engrafted in the patient's marrow.

The two other scientists, Douglas Melton and Kevin Eggan, said they would develop embryonic stem cell lines from diabetic patients, hoping to understand the development of the disease from its earliest moments at the cellular level.

    2 New Efforts to Develop Stem Cell Line for Study, NYT, 7.6.2006,
http://www.nytimes.com/2006/06/07/science/07stem.html

Racial Component Is Found in Lethal Breast Cancer

June 7, 2006
The New York Times
By DENISE GRADY

Young black women with breast cancer are more prone than whites or older blacks to develop a type of tumor with genetic traits that make it especially deadly and hard to treat, a study has found.

Among premenopausal black women with breast cancer, 39 percent had the more dangerous kind, called a "basal like" subtype, compared with only 14 percent of older black women and 16 percent of nonblack women of any age. Researchers are not sure why.

The study, being published today in The Journal of the American Medical Association, is the first to measure how common the different genetic subtypes of breast tumors are in American women, and to sort the subtypes by race. The authors said more research was needed to test their conclusions.

The finding has no immediate effect on treatment, because there is no treatment that specifically concentrates on basal-like cancer. But scientists are trying to create drugs that will zero in on it.

The study helps explain something that was already known: although breast cancer is less common in blacks than whites, when black women do develop the disease, they are more likely to die from it, especially if they are under 50. Among those younger women, the breast cancer death rate in blacks is 11 per 100,000, compared with only 6.3 in whites.

The new data about tumor types is not the whole story, researchers say, because some of the disparity may also result from a lack of access to health care among blacks or differences in nutrition, personal habits or environmental exposures.

The genetic discovery is "somewhat alarming," but also a "good thing," because it exposes details about the cancer that should help doctors identify specific drugs to fight it, said the study's main author, Dr. Lisa A. Carey, the medical director of the University of North Carolina-Lineberger breast center.

Several research groups including her own have already begun testing new drugs against this type of breast cancer, Dr. Carey said. The work involves finding drugs to block specific molecules that these tumors need to grow. If the trials succeed, new treatments could be available within a few years, perhaps even as soon as a year from now, she predicted.

These tumors are identified not by looking through a microscope, but by special tests that measure patterns of genetic activity.

"Things that to my eye and a pathologist's eye look similar turn out to be biologically very different," Dr. Carey said, adding that the tests were now strictly a research tool and were not done routinely in women with breast cancer.

Dr. Larry Norton, a breast cancer expert at Memorial Sloan-Kettering Cancer Center in New York who was not part of the study, said the research was extremely well done and important. He said there was preliminary evidence from other studies that basal-like tumors were the most common kind found in Africa, and that understanding what caused them could help point the way toward better treatments and methods of prevention.

Dr. Olufunmilayo Olopade, director of the center for clinical cancer genetics at the University of Chicago, said she had found high rates of basal-like tumors in young women in Nigeria and Senegal, most of whom died. In many, the disease ran in their families.

The work has not yet been published, but Dr. Olopade said the message to black women, and to women of all races, was that if their mothers, sisters or daughters developed breast cancer at an early age, they needed to start screening for it well before age 40, to seek genetic counseling and to consider preventive drugs and perhaps preventive surgery if they proved to be at high risk.

Basal-like tumors tend to grow fast and spread quickly, and they are more likely than other types to be fatal. They are not fed by the hormone estrogen, and so cannot be treated or prevented with estrogen-blocking drugs like tamoxifen or raloxifene. Herceptin, another breast cancer drug, is also useless against these tumors. The tumors are not stimulated by the hormone progesterone, either. For that reason, cancer specialists call them "triple negative."

Standard chemotherapy does help, and women with basal-like tumors benefit more from it than women with other breast cancers. But even with treatment, those with basal-like tumors are less likely to survive.

Women with mutations in a gene called Brca1 tend to develop this kind of aggressive breast tumor. In the past, researchers thought Brca1 mutations did not occur in black women, but Dr. Olopade dismissed that notion as a myth, saying the mutations were found just as often in black women as in other populations. She and Dr. Carey said other mutations, not yet discovered, might also predispose black women to the basal-like tumors.

Dr. Carey's research was based on stored tissue samples from 496 women who had breast cancer diagnoses from 1993 to 1996 and who were included in a project called the Carolina Breast Cancer Study. Their average age was 50, and 40 percent identified their race as African-American.

The researchers used new techniques of molecular biology to find patterns of gene activity in the cancer cells, to classify the tumors accordingly and then to sort the genetic subtypes by race, menopausal status, other tumor traits and survival.

"The same technology that identified the subtypes also tells us about the biology of the subtypes," Dr. Carey said. "Once you know what makes it tick, you can figure out how to stop the ticking. It's opened up a window on it."

The goal is to find particular molecules in a cell that drive proliferation or tumor survival, and to block them.

"If it looks like a particular cancer cell is dependent on a certain pathway to live or grow, and if you can shut it down preferentially in that cancer cell, you can stop it," Dr. Carey said.

Newer cancer drugs like herceptin and Gleevec, which is used for certain types of leukemia and gastrointestinal tumors, work in this so-called targeted fashion, and so does Tykerb, a new breast cancer drug described last weekend at a meeting of the American Society for Clinical Oncology. For certain cancers, targeted treatments are far more effective than standard chemotherapy, more of a buckshot approach.

Breast cancer experts hope to find better treatments than chemotherapy for many types of the cancer, and Dr. Carey said, "That's the challenge, getting away from chemo for this subtype."

The next step in the research is to look for risk factors for the basal-like subtype, in hopes of finding ways to prevent it, she said.

"There's a lot of smart people working very hard on this," Dr. Carey said. "I'm very optimistic."

    Racial Component Is Found in Lethal Breast Cancer, NYT, 7.6.2006,
http://www.nytimes.com/2006/06/07/health/07breast.html

In State Races,

Tough Questions About Abortion

June 5, 2006
The New York Times
By MONICA DAVEY

IOWA CITY, June 2 — Even in a room of sixth graders sitting cross-legged on the floor, usually the safest of venues for political candidates, the question emerged from one sweet face: What is your position on abortion?

Mike Blouin, who is running for governor, has been asked that a lot lately, though abortion bans are more typically the purview of presidents who might pick United States Supreme Court nominees or senators who might confirm them. The Supreme Court declared a constitutional right to abortion 33 years ago in Roe v. Wade.

But with South Dakota this year having passed the country's most restrictive state abortion law in decades and a sense among some advocates on both sides of the abortion debate that a changed Supreme Court could one day leave the abortion question in the hands of the states, tough questions about abortion rights are being raised in local races across the country.

Questions about how to regulate or restrict abortion have long been issues in state races. But in campaigns for governor and the Legislature here in Iowa and in numerous other states, many candidates are being asked not only about limits on abortion, but also a far broader, starker question: to outlaw or not to outlaw?

"The State of South Dakota made it an issue," Mr. Blouin said in an interview in the teachers' lounge at Robert Lucas Elementary School after he had met the sixth graders. He is one of four candidates seeking the Democratic nomination on Tuesday to succeed Gov. Tom Vilsack, a Democrat who has decided not to seek re-election after two terms.

A former congressman who in the 1970's pushed for a federal ban on abortion, Mr. Blouin would have a simpler path if the questions went away. He said that he had "transitioned on this issue" over the years — that although he remained "very strongly anchored as a person who believes in life," he would oppose a ban if one was passed by lawmakers. "I'd veto it in a heartbeat," he said.

One of Mr. Blouin's chief rivals, Chet Culver, the secretary of state, has made his own support for abortion rights a central issue of his campaign, raising doubts about Mr. Blouin's stance.

After shaking hands at the Hamburg Inn restaurant here this week, Mr. Culver trumpeted his endorsement by Planned Parenthood of Greater Iowa's Political Action Committee, the organization's first endorsement in a governor's race.

"A woman's right to choose is under assault, and people in this state are absolutely worried," Mr. Culver said. "This has become a very important issue in this state and in state races around the country — and it should be."

In Florida, the Democratic and Republican hopefuls for governor have staked out sides over a state ban. On the Republican side, Charlie Crist has taken criticism from some for seeming to shift on just how many exceptions he thinks a ban should include — solely to save a woman's life or also when rape or incest is involved.

In Arkansas, candidates in one Republican State Senate primary disagreed only about when a state ban should come: before or after Roe v. Wade might be overturned. In Ohio, both Republican hopefuls for governor — including J. Kenneth Blackwell, the secretary of state and now the party's nominee — told newspapers they would sign an abortion ban like South Dakota's if the State Legislature were to pass such a bill.

In many state races, it remains uncertain who will benefit from the sudden focus on abortion bans — candidates who oppose abortion rights or those who favor them. Sometimes the political calculation gets complicated. While support for bans has grown, especially in some Southern states, even those who oppose abortion rights do not agree that direct challenges to Roe v. Wade are the best approach. Some argue that gradual efforts to limit abortion are more likely to win support.

"I think that, in the short term, this issue can be less helpful to pro-life candidates," said Daniel McConchie, vice president of Americans United for Life, a group that opposes abortion rights. "The questions that are being asked are hypothetical, things governors mostly won't control. My concern is that the average person on the ground will misinterpret the questions to be something more real than they really are right now."

Jill June, president and chief executive of Planned Parenthood of Greater Iowa, said that worry about the possibility of additional state bans was real and that supporters of abortion rights had been stirred to action. "It now becomes much more generally understood that a state really could outlaw it," Ms. June said. "We know this is contagious, and we're fear-struck."

In South Dakota, Gov. Michael Rounds in March signed into law the nation's most sweeping state abortion ban, a move intended to set up a direct court challenge to Roe v. Wade. But opponents of the ban, which outlaws abortion except when the mother's life is in jeopardy, have moved to challenge the law at the ballot box instead. They filed petitions last month, hoping to send the question to voters in November. On all sides of the issue, it is clear that some candidates might have preferred for it not to grab quite so much notice.

Another Democratic hopeful for governor in Iowa, Ed Fallon, state representative from Des Moines who has long supported abortion rights, said he would veto any abortion ban.

But Mr. Fallon, who is viewed by some as the most liberal candidate (a label he rejects), said he would rather spend his campaign talking about less "politically polarizing issues," like campaign finance reform, health care, education and the environment.

Sal Mohamed, a little-known candidate who is an engineer, said that he would most likely veto a broad abortion ban, but he, too, suggested that the issue might not warrant so much concern in the race here.

"I just don't think that we're going to get to that point in Iowa anyway," Mr. Mohamed said.

But the terrain is most complicated for Mr. Blouin, who says he considers himself "pro-life" but has, as he says, recognized that issues he considered black and white in his 20's turned "fairly gray" later in life.

"Now you have a pro-life pro-choicer," said David Yepsen, the political columnist for The Des Moines Register. "I don't think either side is happy with him."

A Register poll, published in Sunday's editions, showed Mr. Culver winning among 36 percent of those surveyed, followed by Mr. Blouin with 28 percent, Mr. Fallon with 21 percent and Mr. Mohamed with 1 percent. The survey of 600 likely voters in the Democratic primary found 14 percent undecided. The poll had an error margin of 4 percentage points.

Mr. Blouin, the state's former economic development director, has worked to hold on to the support of those who may favor abortion rights. He picked as his running mate Andrea McGuire, a physician who favors such rights.

But it is the abortion rights opponents who seem most irked at Mr. Blouin, once a champion for their efforts. "He's a hypocrite," said Kim Lehman, executive director of the Iowa Right to Life Committee. "He says he's pro-life, and yet what he's really saying is that he is personally pro-life but would take no action that's pro-life. He's the worst kind of so-called pro-life. I don't think he has a right to call himself pro-life."

Whatever Democratic candidate emerges from the election on Tuesday (if none garners 35 percent of the vote, the winner will be chosen at a state convention), the questions about abortion are not going away; nor is the awkward political terrain.

Representative Jim Nussle, Republican of Iowa, will face the Democratic nominee in November. Asked repeatedly for an interview with Mr. Nussle about his views on abortion, his spokeswoman, Maria A. Comella, said the candidate was too busy.

Ms. Comella provided Mr. Nussle's comments from a Radio Iowa interview on March 7, when he was asked about the possibility of an abortion ban here. "I'm 100 percent pro-life, and that's my voting record," he said, adding that he had promoted a bill that would require parental consent for minors getting abortions.

In the radio interview, Mr. Nussle said he did not believe the Iowa Legislature would consider restrictions as "far reaching" as South Dakota's. He added, "I will work with the Legislature if I have the opportunity to be governor to try and ensure that parents have more of a direct impact on their kids' choices as far as abortions are concerned."

But Mr. Nussle, his spokeswoman acknowledged, has yet to publicly answer this season's question: to outlaw or not.

Gretchen Ruethling contributed reporting from Chicago for this article.

    In State Races, Tough Questions About Abortion, NYT, 5.6.2006, http://www.nytimes.com/2006/06/05/us/05abortion.html

The State of AIDS,

25 Years After the First, Quiet Mentions

June 5, 2006
By THE NEW YORK TIMES

On June 5, 1981, in the Morbidity and Mortality Weekly Report from the federal Centers for Disease Control and Prevention, brief note was taken of a peculiar cluster of pneumonia cases in five otherwise healthy gay men.

The item was the first official mention of a scourge that had no name, no known means of transmission, no treatment and no cure.

AIDS, as it would eventually be called, was already spreading fear in America's gay enclaves, where before long half the young men who came of age at the dawn of the gay liberation movement would be infected, stigmatized, ravaged by rare infections and cancers, and die. It soon reached into neighborhoods already burdened by poverty and drug abuse.

For years after that federal report, one of the few certainties was that this disease, to quote other reports, was "invariably fatal." The United Nations estimates that today, H.I.V., the virus that causes AIDS, has infected more than 65 million people, 25 million of whom have died.

Eventually, scientists discovered the virus that caused AIDS and a test to screen for it. They learned the primary routes of transmission — unprotected sexual intercourse, intravenous drug use and prenatal infection. They found a cocktail of medications that slowed the disease's progression, at least in America. In Africa and Asia, AIDS continues to cut a deadly swath.

The Nurse

The difference between then and now is stark for Joan Vileno, a nurse at Montefiore Medical Center in New York. "In those days," she said, "all of our patients died."

Ms. Vileno, 57, said she chose to start her career at an urban academic medical center for the "unique experiences" that setting would provide. But she had no idea how unique those experiences would be. "No textbook could prepare us for what we were about to see," she said.

In the early 1980's, Ms. Vileno held the hands of angry, terrified and scorned patients, mostly intravenous drug users. They were admitted with lethal infections, rarely seen today, that left them gasping for breath, covered with cancerous lesions, blind, demented and wasted to skin and bones.

There were no medications to cure them of a disease then called Gay Related Immune Deficiency, or GRID, although at Montefiore, in the Bronx, the patients were rarely gay. In a study of a drug that proved ineffective, the average survival time of 300 Montefiore participants was eight months.

Today, Ms. Vileno runs a program for AIDS patients 50 and over who have lived long enough to also have the medical problems that come with middle age.

But a quarter-century ago, absent any effective treatment, the staff improvised. "The things we were able to do had nothing to do with our job descriptions," she said.

Many patients were unwilling to come to the AIDS clinic lest they be seen by someone they knew. So Ms. Vileno made house calls. Other patients, shunned by family and friends, all but moved in to the ad hoc clinic — then a bit of borrowed office space with a tiny staff; now a vast and humming operation.

Ms. Vileno once took a toddler home for the weekend so a husband could stay in the hospital with his dying wife. She organized a wedding in the clinic, officiated by a minister married to a staff member.

When funeral parlors refused to handle bodies, for fear of contagion, Ms. Vileno found a willing undertaker and invited him to staff meetings so he would feel like part of the team.

And returning from an AIDS conference in Paris, she went directly to the hospital. Four patients had died that week, one of them estranged from his family. He had designated Ms. Vileno his representative, so the morgue could not release the body for burial without her signature.

"Everything we did was out of the box," she said. "People today think, 'What are you talking about?' But it was a unique point in time, hopefully never to be repeated."

JANE GROSS

The Mother

ATLANTA — Lisa Mysnyk describes the man who gave her H.I.V. as "one of those African-American men who can't seem to stay out of jail." Still, she stayed with him for three years. Sometimes they used condoms. Sometimes they did not.

Ms. Mysnyk, who is also black, now knows that "sometimes" can be a very dangerous word.

"I got caught up in the idea that he wouldn't cheat on me," she said.

Just over half of new H.I.V. infections in the United States are in blacks, according to the federal Centers for Disease Control and Prevention in Atlanta.

Three years ago, her boyfriend tested positive for the virus while in prison. The staff made him call all his sexual partners to warn them about their own risk. When he phoned Ms. Mysnyk, he said he had something to tell her, but he could not seem to get it out. She finally heard the news from a prison nurse.

Her boyfriend called two other women that day, both of them younger than Ms. Mysnyk, who was 34.

While she waited for her test results, Ms. Mysnyk, a single mother of two young sons, told the doctor, "If I didn't have the Lord by my side, I'd be a nervous wreck right now."

When the doctor told her she had H.I.V., Ms. Mysnyk started to cry. Her doctor cried with her.

A few days later, she taught her younger son, who was 7 at the time, how to use a condom. She had a no-nonsense conversation with her 14-year-old about sexually transmitted diseases. "I didn't want him to ever have to be afraid," she said.

In the beginning, her own fear centered on how long she would live and what she could do to keep herself alive. "I started taking all these medications," she said, "and I never liked taking pills."

Ms. Mysnyk takes six pills a day, her virus level is undetectable and her immune system continues to be strong. She thinks she could live 30 or 40 more years as long as the drugs keep working.

She imagines that having the virus is a lot like having any other chronic disease. But unlike most other diseases, she knows, H.I.V. can almost always be avoided.

That is why, when she learned that a young woman who lives in her building was coping with a second unplanned pregnancy, Ms. Mysnyk, rather than offering words of sympathy, asked her a blunt personal question: "Do you and your boyfriend use condoms?"

Her neighbor admitted that sometimes they did and sometimes they did not. "Sometimes," Ms. Mysnyk told her, "isn't good enough."

BRENDA GOODMAN

The Prostitute

MUMBAI, India — With the strut of a baby-kissing politician, Mrs. Shah strolled down the byways of the red-light district the other day, pausing every few steps to offer a hug and a stern lecture to the prostitutes.

Mrs. Shah — tall and serene at 35, wearing a turquoise sari — began each conversation gently, with a joke or a compliment. A woman's makeup, she might say, was looking nice. Then she would lean in closer, glance around for onlookers, and pull out a pamphlet from the AIDS organization for which she works part time. Pointing at explicit photographs, she fired out her lessons: This is how to wear a condom; this is what an infection looks like.

When her shift ends, Mrs. Shah, who is being identified only by her common last name to help protect her identify, resumes her night job. By midnight, if luck is kind, she will be in a cheap hotel, earning a few dollars from a strange man for what she calls the only work she knows. And because she must survive, Mrs. Shah will fail to tell him — even as she insists on a condom — that she is a prostitute with H.I.V.

The United Nations reported recently that India had become the H.I.V./AIDS capital of the world, its 5.7 million infections surpassing South Africa's 5.5 million. Some Indian officials have disputed that number, but the government has acknowledged that the spread of the virus shows no signs of easing.

AIDS is often cast as an epidemic of bad choices. But it is also, in the life of Mrs. Shah, an epidemic of the choiceless.

Since childhood, she has walked on a path leading, with ever greater inevitably, to AIDS. At 13, she was forcibly married to a 35-year-old who kicked her out when she complained of his infidelities. Days later, a woman found her on the platform of a Bombay train station and offered to find her a job as a maid. By evening, she had been sold to a brothel for 10,000 rupees, $220 today.

Once, she said, a customer became a lover, married her and took her away. When he needed money, though, she was back on the street. She protested, and he stabbed her in the cheek and back, burned her with kerosene on the belly and legs and shaved her hip-length black hair down to the scalp.

Two years ago, a test found her H.I.V. positive. "I went crazy," she said. She drank and took pills, trying to kill herself. Then social workers approached her, looking for prostitutes to educate about AIDS.

"I had an idea," she said over a cup of tea, "that what happened to me, I would not let happen to other girls."

ANAND GIRIDHARADAS

The Researcher

SAN FRANCISCO — Work on AIDS remains his calling, but the grand emotions of the early years have subsided. Today, both the disease and Dr. Paul A. Volberding, a physician and researcher who is graying and has an arthritic curl to his fingers, have settled in.

Strangers on airplanes no longer accost him with questions about quick cures, and young men no longer die in his arms. Now if a patient dies, he said, "We think we've done something wrong."

Dr. Volberding, 56, who for many years ran the AIDS program at San Francisco General Hospital, now heads medical services at the San Francisco Veterans Affairs Medical Center. These days his AIDS research, like much of the pandemic, is focused on Africa.

"It feels good to do something so clearly needed that improves health so dramatically," he said of his work in Uganda.

Dr. Volberding has been touched by AIDS since July 1, 1981, his first day at San Francisco General, when he treated a 22-year-old gay man with Kaposi's sarcoma, a disease that until then was seen mostly in the elderly. After he came across other cases, Dr. Volberding did what academics often do: He studied them.

Because established physicians lacked the time and often the inclination to take on what was known as the gay disease, the field was wide open. At 31 and with a staff of one (himself), Dr. Volberding opened one of the first clinics anywhere for people with the disease. A year later, with assistance, he began conducting small clinical trials.

"The patients were so much like us," Dr. Volberding said. "We were all young." Many of them, he recalled, listened to the same music. He still keeps an old Grateful Dead poster on his office wall.

In those early years, Dr. Volberding and his colleague, Dr. Marcus Conant, both professors at the University of California at San Francisco School of Medicine, listed every patient in the city on a blackboard. They knew each by name.

Financing was scarce. Dr. Volberding remembered Dr. Conant suggesting that they wait until there were 1,000 cases, and then the government would take notice.

Many researchers thought they, too, were at risk. Both Dr. Volberding and his wife, Dr. Molly Cooke, also a physician, experienced such fears. Once when Dr. Volberding found a blotch on his skin, colleagues had to reassure him it was not Kaposi's sarcoma. All that has changed, too. Today, Dr. Volberding said, he and his patients commiserate mostly about arthritis and aging.

CAROL POGASH

The Artist

Art is forced by crisis to become political, and so it has been with AIDS, says the playwright Tony Kushner. The early works came in partly as a response to a society that was slow, even resistant, to accept the reality of a new pandemic.

"It was so clearly the dominant culture's mandate that AIDS death and AIDS suffering should be silenced," Mr. Kushner said. "The obvious thing to fight it would be to speak of it and articulate it."

What followed were works like Larry Kramer's 1985 play, "The Normal Heart," and Mr. Kushner's own Pulitzer Prize-winning 1993 drama, "Angels in America."

Only recently, he said, did he begin to reflect on the impact that the early years of AIDS had on the creative culture, especially on writers and artists.

"We were a community that was in a certain sense ideal in terms of responding in an organized fashion," Mr. Kushner said. "As soon as it became an issue of poverty, it lost a degree of organizational support, as soon as it became more or less brought under control in certain ways in the U.S.," he said. "You can't sustain rage for decades."

The great hole in the landscape is hard to comprehend even now, years past the time when AIDS was ravaging the American art world unchecked.

"There's a group of gay men about five years older than me who no longer exist, who would still be alive and producing work, who are gone," said Mr. Kushner, 49. "And there are a number of people I know who survived the epidemic but who in a certain sense didn't survive, who entered a permanent state of mourning."

CAMPBELL ROBERTSON

The Pioneer

Twenty-five years ago, Lawrence D. Mass was running an addiction treatment program in Manhattan for Greenwich House, a social services group whose clients included drug abusers and gay men.

Fertile ground, it turned out, for first documenting the disease that would become known as AIDS.

A little-known physician, Dr. Mass wrote what AIDS chroniclers regard as the first article on the emergence of — well, of something unusual and terrible, but exactly what was not clear at the time. The article appeared in The New York Native, a small weekly written for a gay audience, on May 18, 1981, several weeks before the first scholarly journal weighed in.

Dr. Mass, who is gay, went on to become a founder of Gay Men's Health Crisis and to devote much of his life to fighting the disease he had stumbled onto.

In early 1981, Dr. Mass, then 34, had heard fragments of rumors about strange health problems cropping up in Lower Manhattan, especially among gay men. He found Dr. Steve Phillips, an epidemiologist with the Centers for Disease Control and Prevention, who was following the new mystery. Based on his conversation with Dr. Phillips, Dr. Mass wrote a short article about "rumors that an exotic new disease had hit the gay community."

There was so little anyone knew at first, and so much that people got wrong. But looking back, said Dr. Mass, who still practices medicine in Manhattan, there is one essential truth he believes he had right all along.

"From the start, I said you need to acknowledge our civil rights, you need to recognize our relationships, to have any chance of containing and preventing AIDS," he said. "Shame and fear make it worse."

RICHARD PÉREZ-PEÑA

The Friends

PROVINCETOWN, Mass. — Jay Critchley's recollection of what happened when AIDS first hit this gay-friendly town on the tip of Cape Cod is clear and stark.

"People just disappeared and died," he said. "It was that dramatic, and it was frightening."

It was common to see men with lesions walking in and out of the shops, bookstores and restaurants that line the town's main street, struggling to breathe the salt air, said Mr. Critchley, an artist and massage therapist. Asking someone if he had lost weight was taboo; it meant asking if he was sick. Friends made sure to stay in close contact, because those who fell out of touch were usually dying.

The town's gay residents drew together and cared for the sick. Many went house to house, making sure they were comfortable, safe, well fed. Still, no one understood the provenance of the suffering, and when investigators from the federal Centers for Disease Control and Prevention came to town on a fact-finding mission, many gay men simply assumed that they, too, would get sick and die quickly.

"There was a time when I just waited for it to happen to me," said Tom Sterns, an antique shop owner and 30-year resident. "There wasn't any point in getting tested because they couldn't do anything for you, and I didn't want to face having it."

In the mid-1980's, he finally got tested. The results were negative.

AIDS changed Provincetown itself, for good and bad. In the summer of 1983, many tourists stayed away, fearful of contracting the disease. But gay men in the once carefree community grew cautious about unsafe sex, Mr. Critchley said.

As advances in drug treatment have allowed infected men to lead longer, productive lives, the disease is no longer visible, Mr. Sterns said, and is not in the forefront of every gay man's mind.

But that is leading to more problems, said Mr. Critchley, who sees more men slipping back into careless sexual practices.

With the reduction in fear, the town too has changed. Rising real estate prices and an influx of tourists have chipped away its neighborliness and bohemian flair.

"The town is so dramatically different now than it was 10 years ago," Mr. Critchley said.

KATIE ZEZIMA

    The State of AIDS, 25 Years After the First, Quiet Mentions, NYT, 5.6.2006,
http://www.nytimes.com/2006/06/05/health/05aids.html

Profile: Generation AIDS

Updated 6/4/2006 11:03 PM ET
USA Today
By Steve Sternberg

Twanashia Clark grew up in sweltering Houston streets teeming, she says, with "guns, gangs and drugs," where poverty and despair masked a more sinister threat: HIV, the AIDS virus.

Few people, if any, suspected that HIV might someday pose a threat to young people like Clark when federal health officials warned on June 5, 1981, that five homosexual men in Los Angeles had fallen prey to a rare form of pneumonia.

Today, on the 25th anniversary of that report, 65 million people are infected with HIV worldwide and more than 25 million have died, reports the Joint United Nations Programme on HIV/AIDS (UNAIDS). Clark, 24, belongs to the first generation of young adults, ages 18 to 25, who have never known a world without AIDS.

She says her diagnosis, on Oct. 10, 2000, influenced every aspect of her life, even prompting her to give her children, Daelon, 5, and Daejhanie, 10 months, similar names. "I want them to know that they are born of each other," she says, "and when they grow up, they're still going to need each other, in case I'm not around to remind them."

Clark represents how much has changed since the early days of the epidemic. Today, about one-third of new infections are transmitted heterosexually, up from 3% in 1985, reports the Centers for Disease Control and Prevention. More than half of those diagnosed with HIV are black, up from 25% in 1986, though blacks account for about 12% of the population. Black women and black gay men are especially at risk.

Infection rates among black women in the USA are 20 times higher than for white women and five times higher than among Hispanic women. Two-thirds of HIV infections in young women like Clark result from unsafe sex with infected partners, the CDC says. "More than half the women we treat had one sexual partner and no idea he was HIV-positive," says Donna Futterman, director of adolescent AIDS at Montefiore Medical Center in New York.

A CDC study of 1,767 gay men in five U.S. cities found that almost half of all blacks were infected and many didn't know it.

Rudolph Carn, 50, of Atlanta, a founder of the National Black Gay Men's Advocacy Coalition, says the high rates should come as no surprise in a community where homophobia is widely accepted, AIDS carries a weighty stigma and gay children are sometimes treated as outcasts. "The parents actually think they're morally right," Carn says. "They feel compelled to throw them out."

AIDS' stigma is nothing new. When news of the epidemic broke in 1981, tabloids quickly labeled it the "gay plague." Even some doctors began calling it "GRID," for "gay-related immune deficiency."

Doctors would soon learn that AIDS comes in many guises. Within months, researchers would report that the disease had turned up in infants, Haitians, needle-sharing drug abusers, transfusion recipients and hemophiliacs, including a Hollywood, Fla., man in his 70s who gave the disease to his wife of 50 years. The couple, diagnosed in 1983, made it clear that AIDS could spread heterosexually as well.

The lingering impression that AIDS is a gay disease helped promote its spread among blacks, says Pernessa Seele, founder of Balm in Gilead, a New York-based AIDS advocacy organization that works with 15,000 churches nationwide.

"The fundamental problem with the African-American community is that information about HIV came at us wrong," she says. "It came to us that this was a gay white disease, you don't have to worry about it. Then it was homosexuals and drug addicts. We're still suffering from the wrong information."

Many young people harbor misconceptions about HIV, according to a 2006 survey of 18- to 25-year-olds by the Kaiser Family Foundation. Nearly 60% don't realize that having another sexually transmitted disease increases their HIV risk; 30% don't realize you can't get AIDS from kissing. Although the survey's margin of error is plus or minus 7 percentage points, the findings are consistent with an overall survey of 2,517 respondents of all ages, with a margin of error of plus or minus 2 percentage points.

HIV exploits misinformation, relaxed sexual attitudes, poverty, drug abuse, prostitution and denial of personal risk. The virus also benefits from globalization, as millions of people crowd into cities and travel worldwide, multiplying opportunities for sexual encounters that spread the disease.

It's a stealth virus, too

The virus's long incubation period also works in its favor. Because they might not feel sick for years, many people don't realize they're HIV-positive until they've infected others, says James Curren, dean of public health at Emory University, who led the CDC's first AIDS task force. "Problems like SARS and bird flu come fast and leave fast. HIV comes slowly. It's creeping up as a cause of death and won't stop."

When AIDS emerged, Curran says, some doctors believed viruses would never surrender to treatment. A drug discovery effort, driven partly by an explosion of deaths and activism by white gay men, proved them wrong.

Taking the lead was a New York-based group called ACT UP, founded in 1987 with the credo: Silence Equals Death. ACT UP activists chained themselves to drug company headquarters and shouted down speech-making politicians to draw attention to the epidemic.

"The scary thing," says activist Eric Sawyer, 53, "is that when we founded ACT UP during the Reagan administration, the number of reported cases of AIDS were in the tens of thousands. If people had just listened to the (gay) community, we wouldn't have 65 million infections and 20 million deaths."

The first AIDS drug, zidovudine, won federal approval in 1987. A decade later, scientists reported that highly active retroviral drug cocktails, known as HAART, could virtually eliminate the virus from the blood, turning AIDS into a chronic, manageable disease.

But understanding how to treat HIV is one thing; figuring out how to stop the epidemic is another. A two-decade effort to develop an effective vaccine has been fruitless.

Conflicting attitudes about sex education, condom use and morality hinder prevention efforts, says Myisha Patterson, 27, a health specialist for the Baltimore-based National Association for the Advancement of Colored People.

"I don't remember hearing about HIV until middle school, when we had family-life education classes," she says. "At that time, AIDS was still considered a disease of gay white men. It was for me until I went to college and focused on health care."

Family-life classes have become a flashpoint in the debate about HIV prevention. In 2006, the Bush administration requested $206 million, up from $168 million in 2005, to fund educational programs that promote sexual abstinence before marriage and highlight the shortcomings of safer sex practices, including condom use.

"It's all because people don't want to accept that people, especially young people, have sex," Sawyer says. "To not arm young people to have sex responsibly, in a way that will protect their lives, is unconscionable."

The CDC's Ronald Valdeserri says: "CDC's official policy is to say that abstinence is the most effective way of preventing HIV and other STDs, but we recognize that there are some young people who are sexually active. For those young people, we have messages like have a single partner, try to know (whether he or she is infected). If you don't know, consistent and correct use of a condom can lower your risk."

'I didn't know he was infected'

Clark, now an AIDS activist and educator, says she had so much to deal with as a child that her HIV risk never entered her mind. "My mother was a diabetic, and she was sick," she says. At 14, she was giving her mother insulin shots. Her father, a drug dealer, was in and out of prison. Both died while Clark was still in her teens.

Her aunt decided to pull Clark from school and teach her at home after she passed out during classes from insulin shock, an indication that she had inherited her mother's diabetes. She was 16.

No parents and no school meant no sex education, though she had become sexually active. "It was scary; I knew that I was on a road I didn't want to be on," she says. "By 17, I was in a steady relationship with a man who was infected. I didn't know he was infected."

Clark's diagnosis came during a routine prenatal exam while she was pregnant with her son, Daelon, born Dec. 1, 2000. Her biggest worry wasn't her health, but his. Both of her children have been spared AIDS by one of the biggest AIDS breakthroughs, a short course of therapy that has dropped the number of HIV-positive newborns from 1,800 a year in the early '90s to fewer than 100 today.

Spreading the word

Monica Johnson, 22, Sandra Jeter and Janeé Herndon, both 15, are unwilling to leave the AIDS fight to their elders. Members of a group called the Young Women of Color Leadership Council, sponsored by the non-profit Metro TeenAIDS in Washington, D.C., they counsel classmates, hand out condoms and staff tables at public gatherings to get the word out about AIDS.

Few young Americans face a challenge more daunting than trying to turn the tide on AIDS in a city where roughly one of every 20 residents is HIV-positive, and where the AIDS rate of 179 per 100,000 is roughly four times that of any state.

Sprawled on couches recently amid festive homemade HIV prevention posters in Metro TeenAIDS headquarters not far from the U.S. Capitol, they discussed coming of age in the AIDS generation.

"Everybody I associate with, they're having sex," says Janeé, who attends Spingarn Senior High. "Some little girls think it's cool to have sex."

Despite the long odds, these young women aren't giving up. Johnson, a high school graduate who works part time at MetroTeen AIDS, says that when someone tells her "I don't want to talk," she responds, "Two minutes could save your life."

    Profile: Generation AIDS, UT, 4.6.2006,
http://www.usatoday.com/news/health/2006-06-04-aids-anniversary_x.htm

No Compromise in Sight on Plan to Fight H.I.V.

June 4, 2006
The New York Times
By DAVID W. CHEN

TRENTON, May 31 — In every legislative session here but one since 1992, at least one bill has been introduced to allow drug users to exchange used syringes for new ones. And though the details have differed from year to year, one goal has remained constant: to reduce the spread of H.I.V. in a state with one of the nation's highest infection rates.

But 14 years later, New Jersey remains one of only two states — the other is Delaware — that still prohibit both needle exchanges and access to syringes at pharmacies without a prescription.

No one disputes that H.I.V. and AIDS are major public health problems in New Jersey. The state has the country's highest rate of H.I.V. infection among women, who make up 36 percent of the cases among New Jerseyans over 13, and the third highest among children. Over all, almost 33,000 people in New Jersey have AIDS, up from 26,000 at the end of 1998. Forty-one percent of all cases resulted from injection drug use, according to the state health department.

Yet in New Jersey, the effort to make needles freely or more easily available has been blocked repeatedly over the years. Gov. Christie Whitman, a Republican, adamantly opposed the idea, for instance, while Gov. James E. McGreevey, a Democrat, dropped his support in the face of opposition from police chiefs and some legislators.

Now Gov. Jon S. Corzine and the State Assembly are determined to legalize needle exchanges. But once again, the effort is being blocked, this time in the State Senate, where Ronald L. Rice, a Democrat, has struck an alliance with Republican lawmakers, who are in the minority, to keep the legislation bottled up in committee.

To Mr. Rice and other critics, including John P. Walters, the director of the White House Office of National Drug Control Policy, making needles more accessible suggests that government is condoning an illegal — and destructive — activity. They favor educational campaigns and treatment programs to discourage drug use.

"Needle exchange is a form of keeping people junkies the rest of their lives," said Mr. Rice, a former Newark police officer.

"You don't wipe out a whole lot of people by gassing them," he said. "And you don't wipe people out like the Tuskegee Institute, where we had a bad experience.

"That's what you're doing with this needle exchange," Mr. Rice said. "Those aren't offensive statements; those are examples of what people have been doing to people, and it shouldn't be."

Supporters of needle exchanges counter that they are backed by just about every major scientific or medical organization, including the National Institutes of Health, the American Medical Association, the Centers for Disease Control and Prevention and, closer to home, the New Jersey Hospital Association.

In New York City, studies have shown that such programs had reduced the rate of new H.I.V. infections by roughly 75 percent since the 1990's, according to Dr. Don C. Des Jarlais, the director of research for the Baron Edmond de Rothschild Chemical Dependency Institute at Beth Israel Medical Center.

He cautioned that individual studies might have had flaws, but emphasized that "the sum of these less-than-perfect studies is sufficiently conclusive: All of the research syntheses have come to the conclusion that the programs can and do work."

Across the Hudson, meanwhile, Governor Corzine has said that one of his biggest disappointments since his inauguration in January has been the lack of progress toward a needle exchange program.

Other officials have voiced similar complaints.

"It's a disgrace, a disgrace, that we are so far out of step with other states," said Assembly Speaker Joseph J. Roberts Jr., a Democrat from Camden County.

Noting that California recently made it easier to buy syringes without prescriptions, Mr. Roberts added: "That great liberal voice Arnold Schwarzenegger has been able to tackle this issue, but New Jersey hasn't. We've allowed a few people who have had very loud voices to demagogue the issue and to tie it up, and people are dying each and every day."

The late Senator Wynona M. Lipman, a Democrat, introduced the first needle-exchange bill in 1993. Republicans controlled the Legislature for most of the 1990's, though, and Governor Whitman was one of the most vocal opponents.

In 1996, Mrs. Whitman appointed David W. Troast, a wealthy businessman and social acquaintance from Somerset County, as the head of the state's Advisory Commission on AIDS. But much to everyone's surprise, he endorsed needle exchange after interviewing experts in public health, AIDS prevention and epidemiology.

"There is nothing that we can come up with as effective as a clean-needle program and the retail distribution of needles," Mr. Troast said at the time, a stance that prompted a public spat with Mrs. Whitman.

By the time the Democrats regained control of the Legislature in 2002, needle-exchange supporters were more optimistic. But it was not until after Mr. McGreevey announced plans to resign in August 2004 that he got behind the effort and issued an executive order authorizing pilot exchange programs in Camden and Atlantic City.

Mr. Rice and three Republican legislators, including State Senator Thomas H. Kean Jr., who is now running for the United States Senate, quickly went to court and blocked those programs.

"If the governor could go so greatly beyond his executive order to obviate criminal standards, that was a very bad precedent," Mr. Kean said. "It sends the absolute wrong message to the youth of our state."

Mr. Rice has often worked with Republicans on the Senate health committee, like Mr. Kean, to prevent his Democratic colleagues from garnering a majority of votes. There are five Democrats and three Republicans now, so Mr. Rice's opposition virtually guarantees a deadlock.

Senate Democrats tried earlier this year to expand the health committee by adding Senator Loretta Weinberg, a Bergen County Democrat and needle-exchange advocate, but the proposal fizzled out. Some legislators and aides have said that Democrats were uncomfortable expanding a committee just to push through one bill.

One ardent needle-exchange supporter, Senator Nia H. Gill, a Democrat, has vowed to use her privilege of "senatorial courtesy" to block nominees to various governmental entities when they are from her home county, Essex, and are supported by the Senate president, Richard J. Codey, also from Essex.

She wants him to use his power to bring the needle measure directly to the Senate floor for a vote, bypassing Senator Rice and his Republican allies. But Mr. Codey, a supporter of needle exchange, has been loath to do so, in part because it would break Senate protocol.

"It's about invoking your power and using it for people who have little or no voice in the process," Ms. Gill said.

In another maneuver, some legislators and aides say Mr. Roberts, the Assembly speaker, may be holding up passage of one of Mr. Codey's signature causes, a stem cell research bill, until needle-exchange legislation passes. When asked about a possible link, Mr. Roberts demurred and said only that "we're going to get this done, and I need some help in the Senate to get it done."

But he also said that he was "hopeful they'll both be advanced before we leave in June."

In recent weeks, Mr. Corzine has also made more noise, prompting speculation that he, Mr. Codey or Mr. Roberts might try to find a creative compromise soon. "He has signaled a more aggressive stance and a willingness to speak out," said Anthony Coley, Mr. Corzine's press secretary. "We have an opportunity here to save people's lives, and that's not overstating the case."

Mr. Rice says he is frustrated that his $100 million proposal for residential substance abuse treatment centers has gotten no traction, while proposals on mental health and stem cell research totaling more than $400 million have either become, or are close to becoming, a reality. Yet he says he also knows that his longtime efforts may come up short.

"I may lose the battle at the end, but I'm never going to vote — never," said Mr. Rice, who recently lost the Newark mayor's race. "I'll die before I give a vote to give free needles to people."

Richard G. Jones contributed reporting to this article

    No Compromise in Sight on Plan to Fight H.I.V., NYT, 4.6.2006,
http://www.nytimes.com/2006/06/04/nyregion/04needles.html

A Spoonful of Foreign Culture

Helps Western Medicine Go Down

June 4, 2006
The New York Times
By NICHOLAS CONFESSORE

When officials at Brooklyn's Maimonides Medical Center were preparing a new clinic in Sunset Park in April, everything was ready for the big opening day except the big opening day itself.

"One of our staff members told us it was an unlucky date," said Pamela S. Brier, the hospital's chief executive. "We had to change it."

So the ribbon-cutting, originally scheduled for April 24, was moved to the following day. It was a difference of only 24 hours, but all the difference in the world to the Chinese immigrants the clinic was largely built to serve, who believed the 25th to be a more auspicious date.

It was one of the many ways in which the $1 million clinic was carefully designed to cater to Sunset Park's fast-growing Chinese population, one of the largest in the city.

Because the color white is associated with death in China, the walls are mostly painted in yellow and pink tones. And because Chinese immigrants have high rates of tuberculosis infection, every patient is tested for it. The chefs in the main hospital's kosher kitchen have learned to prepare rice porridge, a beloved Chinese comfort food. "Language, culture, food — it's all tremendously important," Ms. Brier said.

The new clinic is Maimonides's most ambitious effort to respond to a growing and increasingly diverse population of immigrant patients. It also reflects a broader national shift in health care as urban hospitals move beyond the translation services that started becoming common in the late 1990's and acknowledge that language is not the only barrier they face in treating people from all over the globe.

Some come from cultures that are broadly skeptical of Western medicine, and prefer the herbs and poultices of traditional healers, "cures" that in some cases can retard the effects of prescribed medicines or produce dangerous interactions. Others come from cultures where they are expected to hide sickness from strangers, or where it might be offensive for male doctors to examine female patients.

"It's been a slow trend to develop because it's not always clear to a hospital how big a certain community might be, and sometimes it takes a couple of years to manifest," said Rick Wade, a senior vice president of the American Hospital Association. But now, he said, programs are appearing everywhere, to strengthen what hospitals call "cultural competency."

At Oakwood Hospital in heavily Arab Dearborn, Mich., nurses are trained to point the beds of Muslim patients toward Mecca. In Glendale, Calif., which had a rapid influx of Armenian immigrants during the 1990's, one hospital sponsors a popular health-related call-in show that is broadcast in Armenian on cable-access television.

But challenges can be more varied and daunting for hospitals in places like Brooklyn, home to insular communities of Orthodox Jews, Muslims from conservative Arab countries, recent immigrants from rural China and Hispanics from Central and South America, among many others.

"In each culture that we're dealing with, there are different ideas, family values and beliefs, whether about medicine or life in general," said Virginia Tong, a vice president at Lutheran Medical Center, one of south Brooklyn's largest health care providers. "Let's say you had an Hispanic godparent who brought a patient in to see a doctor. In this country, we would say, 'That's not a parent;' there might be legal issues. But in their culture, godparents are almost as important as parents."

Lutheran's main hospital has a mosque on site; it also runs clinics aimed at Caribbean and Korean immigrants. In 2001, Lutheran opened its own Chinese clinic, on Eighth Avenue in Sunset Park, after a survey showed that most Chinese immigrants in the area were going to Chinatown in Manhattan for medical care.

Maimonides, long known as "the Jewish hospital," in Ms. Brier's words, has in recent years customized the care at many of its 15 clinics, which are around southwest Brooklyn, based on the cultures and needs of the patients each serves.

The doctors at the hospital's Newkirk Avenue clinic, for example, see many Indian immigrants, who have disproportionately high rates of hypertension. Its pediatricians also see many children born in Bangladesh. Because infants there are often not immunized against measles, as most babies are in the United States, that means more effort devoted to vaccination and extra care in reporting cases to public health officials to contain any outbreaks.

But the hospital's outreach to Chinese immigrants is its biggest, driven by what its officials believe will be continued population growth in south Brooklyn. "We go where the patients are," Ms. Brier said.

Maimonides opened its first Sunset Park clinic in a brownstone building in 1996. Within three years, doctors there were seeing 9,000 patients a year, including a growing number of Chinese. The number of patients has doubled since, prompting the latest move from a storefront space to a 10,000-square-foot building on Seventh Avenue and 64th Street.

The attending doctors there speak Mandarin or Cantonese, two major Chinese dialects. About 70 percent of the patients are Chinese, according to Dr. Bing Lu, the clinic's medical director, and a significant number are recent arrivals to the United States. Many hold the traditional belief, he said, that drawing blood for tests drains a person's life force, and they are reluctant to allow it.

"We teach them that they need it," he added, relying on the staff members' language skills and familiarity with Chinese culture to reduce patients' suspicion. "Generally speaking, Chinese people don't believe in preventative care."

Such an attitude can be deadly. A few years ago, doctors at the clinic found early signs of liver cancer in a man in his 30's who was infected with hepatitis B. The man left the clinic, Dr. Lu said, and did not return the clinic's phone calls. When he finally came back six months later, he was jaundiced and underweight, with a severely enlarged liver. The cancer had advanced beyond the possibility of life-prolonging surgery.

It was "a fatal mistake," said Dr. Lu, who believes the man at first sought out traditional healers instead of returning to the clinic.

Several patients praised the doctors' warmth and staff members' willingness to help them with paperwork. Susan Lin, 31, who emigrated from China's Fujian Province five years ago, said, through an interpreter: "Sometimes we're afraid to ask questions, to ask how to follow up. Here, they always smile, they are always welcoming. You feel very comfortable asking questions."

Recently, an 80-year-old woman arrived at the clinic just before closing time, asking to see a doctor. She said it was urgent, but when examined she would say only that she had been unable to sleep for about a week.

Under careful questioning, Dr. Lu said, she eventually revealed that her husband had died the previous week, and that she had been crying and having anxiety attacks, details that a Chinese woman her age might consider inappropriate to admit.

"When you know the culture, you know it's normal, but if you don't, as a practitioner, you can miss a significant problem," Dr. Lu said. "She could easily have been turned away from the clinic that day."

    A Spoonful of Foreign Culture Helps Western Medicine Go Down, NYT, 4.6.2006,
http://www.nytimes.com/2006/06/04/nyregion/04clinic.html

Louisiana House OK's Ban on Most Abortions

June 1, 2006
By THE ASSOCIATED PRESS
Filed at 12:35 a.m. ET
The New York Times

BATON ROUGE, La. (AP) -- The Louisiana House approved a ban on most abortions, a largely symbolic bill that could go into effect only if the U.S. Supreme Court's landmark 1973 decision is overturned.

The measure would allow abortion in cases when the woman's life is in danger or childbirth would permanently harm her health. The bill passed 85-17 and heads to the Senate.

It could take effect only under two circumstances: if the U.S. Constitution is amended to allow states to ban abortion; or if the U.S. Supreme Court strikes down its own Roe v. Wade ruling, which provided for a woman's right to an abortion.

The bill is similar to a South Dakota law passed this year that is expected to land before the high court.

Passage of the Louisiana bill was not in doubt; the fight centered on whether to allow exceptions for rape and incest victims. The amendment failed after opponents argued that the bill should prevent as many abortions as possible.

Under the bill, doctors found guilty of performing abortions would face up to 10 years in prison and fines of $100,000.

Gov. Kathleen Blanco, who campaigned as an anti-abortion candidate, has not said whether she would support such a strict ban.

    Louisiana House OK's Ban on Most Abortions, NYT, 1.6.2006,

http://www.nytimes.com/aponline/us/AP-Abortion-Ban.html