In a bold scientific step that helps open the door
to organ transplants from animals, researchers at Harvard and a private company
have created gene-edited piglets cleansed of viruses that might cause disease in
humans.
The advance, reported on Thursday in the journal Science, may make it possible
one day to transplant livers, hearts and other organs from pigs into humans, a
hope that experts had all but given up.
There were 33,600 organ transplants last year, and 116,800 patients on waiting
lists, according Dr. David Klassen, chief medical officer at the United Network
for Organ Sharing, a private, nonprofit organization that manages the nation’s
transplant system.
If pig organs were shown to be safe and effective, “they could be a real game
changer,” said Dr. Klassen, who was not involved in the new study. Dr. George
Church of the Harvard group now says the first pig-to-human transplants could
occur within two years.
The new research combines two great achievements in recent years — gene editing
and cloning — and is unfolding quickly. But the work is novel and its course
unpredictable, Dr. Klassen noted. It may be years before enough is known about
the safety of pig organ transplants to allow them to be used widely.
Major religious groups have already weighed in on the ethical questions,
however, generally concluding that pig organs are acceptable for lifesaving
transplants, noted Dr. Jay Fishman, co-director of the transplant program at
Massachusetts General Hospital. Pig heart valves already are routinely
transplanted into patients.
(Leaders in the Jewish and Muslim communities, though, would not accept pig
kidneys, reasoning that patients with kidney failure can survive with dialysis.)
The idea of using pigs as organ factories has tantalized investigators for
decades. Porcine organs can be the right size for human transplantation, and in
theory, similar enough to function in patients.
In the 1990s, scientists began pursuing the idea in earnest. But in 1998, Dr.
Fishman and his colleagues discovered that hidden in pig DNA were genes for
viruses that resembled those causing leukemia in monkeys.
When researchers grew pig cells next to human embryonic kidney cells in the
laboratory, these viruses — known as retroviruses — spread to the human cells.
Once infected, the human cells were able to infect other human cells.
Fears that pig organs would infect humans with bizarre retroviruses brought the
research to a halt. But it was never clear how great this threat really was, and
as years have gone by, many experts, including Dr. Fishman, have become less
concerned.
Some patients with diabetes have received pig pancreas cells, hidden in a sort
of sheath so the immune system will not reject them. And burn patients sometimes
get grafts made of pig skin. The pig skin is eventually rejected by the body,
but it was never meant to be permanent anyway.
There is no evidence that any of these patients were infected with porcine
retroviruses. In any event, said Dr. A. Joseph Tector, a transplant surgeon at
the University of Alabama in Birmingham, pig retroviruses are very sensitive to
the drugs used to treat H.I.V.
“We don’t know that if we transplant pig organs with the viruses that they will
transmit infections, and we don’t know that the infections are dangerous,” Dr.
Fishman said. “I think the risk to society is very low.”
Dr. Church and his colleagues thought the retrovirus question could be resolved
with Crispr, the new gene-editing technology. They took cells from pigs and
snipped the viral DNA from their genomes. Then the scientists cloned the edited
cells.
Each pig cell was brought back to its earliest developmental stage and then
slipped into an egg, giving it the genetic material to allow the egg to develop
into an embryo. The embryos were implanted in sows and grew into piglets that
were genetically identical to the pig that supplied the initial cell.
Cloning often fails; most of the embryos and fetuses died before birth, and some
piglets died soon after they were born. But Dr. Church and his colleagues ended
up with 15 living piglets, the oldest now 4 months old. None have the
retroviruses.
Dr. Church founded a company, eGenesis, in hopes of selling the genetically
altered pig organs. Eventually, Dr. Church says, the company wants to engineer
pigs with organs so compatible with humans that patients will not need to take
anti-rejection drugs.
Dr. David Sachs, a professor of surgery at Columbia University, was skeptical
that it would be straightforward to make pigs with such compatible organs.
“I am afraid that he may find these goals more difficult to achieve than he
expects, but I would be happy to be mistaken,” said Dr. Sachs, who is also
studying ways to create pigs suitable for organ donation.
Part of the organ rejection problem is already being solved with gene editing
and cloning. It is an issue that emerged in the early 1980s when surgeons put a
pig heart into a baboon. To their shock, the baboon died in minutes.
Researchers soon discovered that pig organs are covered with carbohydrate
molecules that mark the organs for immediate destruction by human antibodies.
Dr. David Cooper, at the University of Alabama at Birmingham, and his
colleagues, including Dr. Tector, have used gene editing and cloning to make
pigs without the carbohydrates on the surfaces of their organs.
They successfully transplanted hearts and kidneys from those pigs into monkeys
and baboons. So far, the animals have lived more than a year with no problems,
Dr. Tector said.
They also gave insulin-producing islet cells from a pig to diabetic monkeys, and
the monkeys lived for a year without requiring insulin. In partnership with
United Therapeutics, the group has already built a farm for gene-edited pigs.
Dr. Church says he, too, is making pigs whose organs lack the carbohydrates, and
he wants to combine the two advances so the organs also do not have
retroviruses. The Alabama group, though, does not think pig retroviruses are a
major concern.
Surgeons are used to evaluating the risks of infection from transplanted organs,
Dr. Tector said. The advantage of the transplant to the desperately ill
recipient often outweighs that risk.
To some, the idea of growing pigs to be organ factories is distasteful, if not
unethical.
But, Dr. Cooper noted, the few thousand pigs grown for their organs would be a
small fraction of the 100 million pigs a year that are killed for food in the
United States. And, he said, the pigs would be anesthetized and killed humanely.
Many patients may prefer a human organ, Dr. Cooper acknowledged, but that is not
always possible. “About 22 people a day die waiting for a transplant,” he said.
“If you could help them with a pig organ, wouldn’t that be wonderful?”
Ronald Lee Herrick donated kidney
to his dying twin brother
in pioneering 1954
operation
Thursday 30 December 2010
The Guardian
David Batty
This article appeared on p22
of the Main section section of the Guardian
on
Thursday 30 December 2010.
It was published on guardian.co.uk
at 01.10 GMT on Thursday 30 December 2010.
It was last modified at 08.01 GMT
on Thursday 30 December 2010.
A man who donated a kidney to his dying twin brother 56 years
ago in the world's first successful organ transplant has died in the United
States.
Ronald Lee Herrick died, aged 79, on Monday in the Augusta Rehabilitation
Centre, a hospital in Maine, New England, following complications from heart
surgery in October, his widow, Cynthia, said.
Herrick donated a kidney to his identical twin, Richard, in a pioneering
operation on 23 December 1954.
The successful surgery kept Herrick's brother alive for eight years and was the
first successful organ transplant, according to the United Network for Organ
Sharing. Lead surgeon Dr Joseph Murray went on to win the Nobel prize.
The operation proved that transplants were possible and led to thousands of
other successful kidney transplants, and later the transplant of other organs.
Doctors around the world had tried a few transplants before the breakthrough
operation, without success, said Murray, who went on to perform another 18
transplants between identical twins.
"This operation rejuvenated the whole field of transplantation," said Murray,
91, who lives in Wellesley, Massachusetts.
"There were other people studying transplants in four or five different
countries, but the fact that it worked so well with the identical twins was a
tremendous stimulus."
Herrick grew up on a farm in Rutland, Massachusetts, and later served in the US
army.
He was 23 when he donated a kidney to his brother, who was dying from chronic
nephritis, an inflammation of the kidneys. Murray thought the odds of a
transplanted organ being accepted would be enhanced since they were identical
twins.
Before the operation, many opposed the idea of transplanting an organ, equating
it with desecration of a body. Others argued it was unethical to operate on
healthy humans, and editors of medical journals wrote that it was contrary to
the Hippocratic oath to never do harm to anyone, Murray said.
But Herrick was not dissuaded from the operation. "He was the only one in the
world who could save his brother's life, so he was going to do it," said Cynthia
Herrick. "There was no question about it."
Background
When were the first organ transplants?
The first successful kidney transplant, in 1954,
was Ronald
Lee Herrick.
The first heart transplant was 1967.
Which organs can be transplanted?
Organs that can be transplanted include the heart, kidneys, liver, lungs,
pancreas, thymus, ovaries, penis and uterus. Tissues that can be transplanted
include bones, tendons, cornea, skin, heart valves, and veins. Recent
developments include hand and full face transplants.
How many are on UK waiting list for a transplant?
As of 17 December 2010, 7,927;
most of them, 6,779, were waiting for a kidney.
How many transplants were made this year?
Between 4 January and 12 December,
there were 2,583 organ transplants;
698 were
from living donors.
How many people have registered as organ donors?
As of September, there were 17.4 million people
on the NHS organ donor register.
JACKSON, Miss. (AP) — For 16 years, sisters Jamie and Gladys
Scott have shared a life behind bars for their part in an $11 armed robbery. To
share freedom, they must also share a kidney.
Mississippi Gov. Haley Barbour suspended the sisters' life sentences on
Wednesday, but 36-year-old Gladys Scott's release is contingent on her giving a
kidney to Jamie, her 38-year-old sister, who requires daily dialysis.
The sisters were convicted in 1994 of leading two men into an ambush in central
Mississippi the year before. Three teenagers hit each man in the head with a
shotgun and took their wallets — making off with only $11, court records said.
Jamie and Gladys Scott were each convicted of two counts of armed robbery and
sentenced to two life sentences.
"I think it's a victory," said the sisters' attorney, Chokwe Lumumba. "I talked
to Gladys and she's elated about the news. I'm sure Jamie is, too."
Civil rights advocates have for years called for their release, saying the
sentences were excessive. Those demands gained traction when Barbour asked the
Mississippi Parole Board to take another look at the case.
The Scott sisters are eligible for parole in 2014, but Barbour said prison
officials no longer think they are a threat to society and Jamie's medical
condition is costing the state a lot of money.
Lumumba said he has no problem with the governor requiring Gladys to offer up
her organ because "Gladys actually volunteered that as part of her petition."
Lumumba said it's not clear what caused the kidney failure, but it's likely a
combination of different illnesses over the years.
Barbour spokesman Dan Turner told The Associated Press that Jamie Scott was
released because she needs the transplant. He said Gladys Scott will be released
if she agrees to donate her kidney because of the significant risk and recovery
time.
"She wanted to do it," Turner said. "That wasn't something we introduced."
Barbour is a Republican in his second term who has been mentioned as a possible
presidential contender in 2012. He said the parole board agreed with the
indefinite suspension of their sentences, which is different from a pardon or
commutation because it comes with conditions.
An "indefinite suspension of sentence" can be reversed if the conditions are not
followed, but those requirements are usually things like meeting with a parole
officer.
The Scott sisters have received significant public support from advocacy groups,
including the NAACP, which called for their release. Hundreds of people marched
through downtown Jackson from the state capital to the governor's mansion in
September, chanting in unison that the women should be freed.
Still, their release won't be immediate.
Mississippi Department of Corrections Commissioner Chris Epps said late
Wednesday that he had not received the order. He also said the women want to
live with relatives in Florida, which requires approval from officials in that
state.
In general, that process takes 45 days.
Mississippi NAACP President Derrick Johnson said the Scott sisters' release will
be "a great victory for the state of Mississippi for two individuals who
received an excessive sentence" and he has no problem with the kidney donation
requirement because Gladys Scott volunteered.
"I think it's encouraging that she's willing to share a kidney so her sister can
have a better quality life," Johnson said.
National NAACP President and CEO Benjamin Todd Jealous said the suspension of
the sentences represents the good that can come with the power of governors.
"It's again proof that when people get engaged, keep the faith, we can win,"
Jealous said.
THE body parts market is lucrative and lightly
regulated in the US. Estimates of its value range from $500 million to $1
billion (£530 million) a year.
The use of tissue goes far beyond the familiar world of organ transplants, and
involves a host of different materials including bone, skin, muscle, tendons and
ligaments.
Bones can be used in fracture repair, skin can aid wound healing, and heart
valves can be used as replacements in ailing patients.
Tendons and ligaments may be used to treat sports injuries, long bones to
replace those damaged by cancer, shaped-bone products in spinal surgery, and
ground bone in dental surgery. Collagen can be used to plump up lips, while
bodies or body parts can be used in crash tests or in demonstrations of new
techniques for surgeons.
In Britain the number of body parts that are taken in is unknown, because there
is no requirement to keep a tally. Premises that store tissues, however, have to
have a licence from the Human Tissue Authority (HTA), and of these 41 are either
importing or exporting tissues.
The quantity of such imports and exports is not known, because the HTA does not
gather figures.
There are moves to change the law so that such data would in future be
collected. Up to 77 patients in Britain may have had grafts from bones imported
from the New Jersey company involved in the Alistair Cooke case, the Medicines
and Healthcare products Regulatory Agency said last month.
Patients were offered screening and counselling to detect any problems.
Every year it is estimated that 25,000 US bodies are used as source material for
as many as 750,000 operations and procedures.
Heart valves can fetch up to $7,000 each, and skin $1,000 per square foot. A
body could be worth about $150,000 if broken down into its component parts,
according to Art Caplan, Professor of Bioethics at the University of
Pennsylvania.
There are two legitimate sources of body parts in the US. The vast majority of
bodies donated to science go to medical schools, where they are used to teach
anatomy.
Surplus parts can be sent to not-for-proft biomedical corporations, and it is
illegal to charge for them. But medical schools can charge fees to cover
administrative costs, and these can be high.
A second source is the tissue and organ banks, non-profit organisations to whom
individuals can leave their bodies. They are often linked to trading companies
to whom they pass on the parts.
There is no real ethical reason why the trade should not continue, so long as
proper consents are obtained.
But some orthopaedic surgeons, such as Professor Angus Wallace, of Nottingham
University, believe that officials are discouraging the harvesting of parts
because of fears of an Alder Hey-style public backlash.
He believes that it is unethical to treat British patients with imported body
parts and could be dangerous because of uncertainties over quality.
