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Wilson Greatbatch, a professed “humble tinkerer” who, working in his barn in 1958, designed the first practical implantable pacemaker, a device that has preserved millions of lives, died on Tuesday at his home in Williamsville, N.Y. He was 92.

His death was confirmed by his daughter, Anne Maciariello.

Mr. Greatbatch patented more than 325 inventions, notably a long-life lithium battery used in a wide range of medical implants. He created tools used in AIDS research and a solar-powered canoe, which he took on a 160-mile voyage on the Finger Lakes in New York to celebrate his 72nd birthday.

In later years, he invested time and money in developing fuels from plants and supporting work at the University of Wisconsin in Madison on helium-based fusion reaction for power generation.

He also visited with thousands of schoolchildren to talk about invention, and when his eyesight became too poor for him to read in 2006, he continued to review papers by graduate engineering students on topics that interested him by having his secretary read them aloud.

“I’m beginning to think I may not change the world, but I’m still trying,” Mr. Greatbatch said in a telephone interview in 2007.

He was best known for his pacemaker breakthrough, an example of Pasteur’s observation that “chance favors the prepared mind.”

Mr. Greatbatch’s crucial insight came in 1956, when he was an assistant professor in electrical engineering at the University of Buffalo. While building a heart rhythm recording device for the Chronic Disease Research Institute there, he reached into a box of parts for a resistor to complete the circuitry. The one he pulled out was the wrong size, and when he installed it, the circuit it produced emitted intermittent electrical pulses.

Mr. Greatbatch immediately associated the timing and rhythm of the pulses with a human heartbeat, he wrote in a memoir, “The Making of the Pacemaker,” published in 2000. That brought to mind lunchtime chats he had had with researchers about the electrical activity of the heart while he was working at an animal behavior laboratory as an undergraduate at Cornell in 1951.

Back then, he had surmised that electrical stimulation could compensate for breakdowns in the heart’s natural circuitry. But he did not believe the electronic gear of that era could be bundled into a stimulator for continuous use, much less into a device small and reliable enough to implant.

After the unintended circuit rekindled his interest, Mr. Greatbatch began experiments to shrink the equipment and shield it from body fluids. On May 7, 1958, doctors at the Veterans Administration hospital in Buffalo demonstrated that a version he had created, of just two cubic inches, could take control of a dog’s heartbeat.

Mr. Greatbatch soon learned he was in a race with other researchers in the United States and Sweden to perfect a practical implant for humans. Relying on $2,000 in savings and a large vegetable garden to help feed his growing family, he went to work full time on the device in the barn behind his home in Clarence, N.Y. He was assisted by his wife, Eleanor, who administered shock tests for the pacemaker’s transistors by first taping them to a bedroom wall.

His major collaborator was Dr. William C. Chardack, chief of surgery at the hospital where he had first tested the device on dogs. Mr. Greatbatch’s device was implanted in 10 human patients in 1960, including two children. The device was licensed in 1961 to Medtronic, a Minneapolis company that had developed an external pacemaker. Buoyed by the new implanted devices, Medtronic went on to become the world leader in cardiac stimulation and defibrillation.

The American Heart Association says that more half a million pacemakers are now implanted every year.

Mr. Greatbatch profited handsomely from his invention and invested in other projects. In one, he adapted for human use equipment he had designed to monitor the health of test monkeys launched into space by the government. But he soon returned to address a crucial limitation in his pacemaker: its zinc-mercury batteries, which could drain in as little as two years.

Mr. Greatbatch acquired rights to a lithium iodine design invented in 1968 by researchers in Baltimore, and by 1972 he had re-engineered the device — it had been potentially explosive — into a compact sealed package that could be implanted in the body for a decade or more.

A company he founded in 1970 to make the batteries, today called Greatbatch Inc., became a leading power-component supplier for the entire medical device industry and later expanded into related businesses.

Mr. Greatbatch often told students that 9 out of 10 of his ideas failed, either technically or commercially. His last major interest, helium fusion experiments, may be the longest shot of all.

The reaction is theoretically attractive; unlike nuclear fusion, it produces no radioactive materials. But the raw material for it is an isotope of helium that exists only in trace amounts on earth. For the fusion to generate significant amounts of power, the isotope would have to be mined on the moon.

Wilson Greatbatch was born on Sept. 6, 1919, in Buffalo, the only child of Warren Greatbatch, a construction contractor who had immigrated from England, and the former Charlotte Recktenwalt, who worked as a secretary and named him in honor of Woodrow Wilson.

As a teenager, Mr. Greatbatch became fascinated with radio technology. He put his skills to use in the Navy during World War II working on shipboard communications and guidance systems before being assigned to fly combat missions. Mr. Greatbatch, a Presbyterian, cited the seeming randomness of death in wartime as the inspiration for his religious faith.

Returning from the war, Mr. Greatbatch married Eleanor Wright, his childhood sweetheart, and worked for a year as a telephone repairman before entering Cornell.

Nothing in Mr. Greatbatch’s grades foretold success, but that was partly because he was also working at outside jobs to support his family. The jobs kept him abreast of developments in the electronics industry. After earning a master of science degree in electrical engineering at the University of Buffalo, he became manager of the electronics division of the Taber Instrument Corporation in Buffalo.

When Taber was unwilling to take on the risk of his pacemaker implant experiments, he began his life as an independent inventor and entrepreneur.

Eleanor Greatbatch died in January. Besides his daughter, Anne, of Sarasota, Fla., Mr. Greatbatch is survived by three sons, Warren, of Buffalo, Kenneth, of Swanzey, N.H., and John, of Paris, Ky.; 12 grandchildren, and eight great-grandchildren. Another son, Peter, died in 1998.

Mr. Greatbatch saw a divine hand in much of what he did. When experiments bore no fruit, he wrote, it was impossible to know whether what looked like failure had not been intended by God as a contribution to success in the future. And he saw invention as an end in itself.

“To ask for a successful experiment, for professional stature, for financial reward or for peer approval,” he wrote in his memoir, “is asking to be paid for what should be an act of love.”

Daniel E. Slotnik contributed reporting.

Wilson Greatbatch, Pacemaker Inventor, Dies at 92,
NYT,
28.9.2011,
https://www.nytimes.com/2011/09/28/
business/wilson-greatbatch-pacemaker-inventor-dies-at-92.html

Dr. Adrian Kantrowitz,

Cardiac Pioneer,

Dies at 90

November 19, 2008

The New York Times

By JASCHA HOFFMAN

Dr. Adrian Kantrowitz, who performed the first human heart transplant in the United States in 1967 and pioneered the development of mechanical devices to prolong the life of patients with heart failure, died Friday in Ann Arbor, Mich. He was 90.

The cause was complications of heart failure, said Jean Kantrowitz, his wife of nearly 60 years and a longtime colleague in developing the devices.

On Dec. 6, 1967, when he removed the heart of a brain-dead baby and implanted it into the chest of a baby with a fatal heart defect, Dr. Kantrowitz became the first doctor to perform a human heart transplant in the United States. The patient lived for only six and a half hours, but the operation was a milestone on the way to the routine transplants of today.

Along with Dr. Michael E. DeBakey of Texas and a few others, Dr. Kantrowitz helped open the new era in care for seemingly terminally ill heart patients, using both surgery and artificial devices. His work at Maimonides Medical Center in Brooklyn and Sinai Hospital in Detroit had a lasting impact, starting with his first headlines in 1959, when he gave a healthy dog a booster heart muscle.

Over six decades of surgical practice, he designed and used more than 20 medical devices that aided circulation and other vital functions.

Although his 1967 transplant was the first in the United States, it was not the first in the world, following by three days Dr. Christiaan Barnard’s in Cape Town. But Dr. Kantrowitz had been methodical in laying the groundwork for the procedure. He practiced hundreds of heart transplants in puppies over the previous four years, and had planned a human operation the previous year, but was prevented at the last minute because the donor infant had not been declared brain-dead.

“Although Dr. Kantrowitz had the dedication and perseverance to accomplish this remarkable surgical tour de force, it was the notion that, for the first time, science could view the heart as yet another organ that could be fixed that was a revolutionary concept,” Dr. Stephen J. Lahey, director of cardiothoracic surgery at Maimonides Medical Center, said in a statement on the 40th anniversary of Dr. Kantrowitz’s transplant.

While many doctors have worked to replace failing hearts altogether with artificial ones, Dr. Kantrowitz concentrated on finding ways to supplement the work of the natural heart with an impressive array of circulatory devices of his own invention. The most influential was the “left ventricular assist device,” or LVAD, which, for the first time in 1972, allowed a patient with severe chronic heart failure to leave the hospital with a permanent implant.

Another of his inventions was the intra-aortic balloon pump, described in The New York Times in 1967 as “a long, narrow gas line” inserted through the patient’s thigh that inflated “a six-inch-long sausage-shaped balloon” in the aorta. The device deflated when the heart pumped blood and inflated when it relaxed, thereby reducing strain on the heart, according to Dr. Kantrowitz’s theory of “counterpulsation.” The device has been used to treat about three million patients since it went into general use in the 1980s.

He also invented an early implantable pacemaker, designed with General Electric in 1962, and captured the first film of the mitral valve opening and closing inside a beating heart in 1951.

His inventiveness extended beyond cardiology. In 1961, inspired by the way the muscles in the heart were stimulated, he was the first doctor to enable paraplegic patients to move their limbs by electronically triggering their muscles.

Adrian Kantrowitz was born on Oct. 4, 1918, in New York City, to a mother who designed costumes for the Ziegfeld Follies and a father who ran a clinic in the Bronx that charged its patients 10 cents a week.

“My mother told me from the age of 3 that I wanted to be a doctor,” he told The New York Post in 1966.

As a boy he worked with his older brother Arthur to construct an electrocardiograph from old radio parts. The brothers later collaborated on the left ventricular assist device.

After graduating from New York University with a degree in mathematics in 1940, Dr. Kantrowitz enrolled in the Long Island College of Medicine (now a part of SUNY Downstate Medical Center) and completed an internship at Brooklyn Jewish Hospital. He earned his medical degree early, in 1943, as part of an accelerated program to supply doctors for the war effort. After serving two years as a battalion surgeon in the Army Medical Corps, Dr. Kantrowitz began a career in cardiac research and became a major figure in the first generation of cardiac surgeons.

From 1948 to 1955, he practiced surgery at Montefiore Hospital in the Bronx. From 1955 to 1970, he held surgical posts at Maimonides Medical Center in Brooklyn, where he led a team that devised many influential devices with support from the National Institutes of Health, including an electronic heart-lung machine and a radio transmitter that allowed paralyzed patients to empty their bladders.

In 1970 Dr. Kantrowitz left Maimonides when “it became apparent that a small community hospital in Brooklyn was not the proper environment for the development of innovative cardiac surgical techniques,” according to a recent profile in the journal Clinical Cardiology. Remarkably, he was able to move his entire team of 25 surgeons, engineers and nurses — and with them a nearly $3 million research grant — to Detroit, where he taught at Wayne State University School of Medicine and held surgical posts at Sinai Hospital for the rest of his career.

Besides his wife, Jean, who helped him start a medical device company, LVAD Technology, in 1983, his survivors include three children, Dr. Niki Kantrowitz, a cardiologist in Brooklyn; Dr. Lisa Kantrowitz, a radiologist in Newport Beach, Calif.; and Dr. Allen Kantrowitz, a neurosurgeon in Williamstown, Mass.; and nine grandchildren.

Dr. Kantrowitz received a lifetime achievement award from the American Society for Artificial Internal Organs in 2001. He did not rest on his laurels. This year the Food and Drug Administration approved a clinical trial of his latest cardiac assistance device, which promises to allow seriously ill patients to move around and even exercise.

Dr. Adrian Kantrowitz, Cardiac Pioneer, Dies at 90,
NYT, 19.11.2008,
http://www.nytimes.com/2008/11/19/us/19kantrowiztz.html

Team Creates Rat Heart

Using Cells of Baby Rats

January 14, 2008

The New York Times

By LAWRENCE K. ALTMAN

Medicine’s dream of growing new human hearts and other organs to repair or replace damaged ones received a significant boost Sunday when University of Minnesota researchers reported success in creating a beating rat heart in a laboratory.

Experts not involved in the Minnesota work called it “a landmark achievement” and “a stunning” advance. But they and the Minnesota researchers cautioned that the dream, if it is ever realized, was still at least 10 years away.

Dr. Doris A. Taylor, the head of the team that created the rat heart, said she followed a guiding principle of her laboratory: “give nature the tools, and get out of the way.”

“We just took nature’s own building blocks to build a new organ,” Dr. Taylor said of her team’s report in the journal Nature Medicine.

The researchers removed all the cells from a dead rat heart, leaving the valves and outer structure as scaffolding for new heart cells injected from newborn rats. Within two weeks, the cells formed a new beating heart that conducted electrical impulses and pumped a small amount of blood.

With modifications, scientists should be able to grow a human heart by taking stem cells from a patient’s bone marrow and placing them in a cadaver heart that has been prepared as a scaffold, Dr. Taylor said in a telephone interview from her laboratory in Minneapolis. The early success “opens the door to this notion that you can make any organ: kidney, liver, lung, pancreas — you name it and we hope we can make it,” she said.

Todd N. McAllister of Cytograft Tissue Engineering in Novato, Calif., said, “Doris Taylor’s work is one of those maddeningly simple ideas that you knock yourself on the head, saying, ‘Why didn’t I think of that?’ ” Dr. McAllister’s team has used a snippet of a patient’s skin to grow blood vessels in a laboratory, and then implanted them to restore blood flow around a patient’s damaged arteries and veins.

The field of tissue engineering has been growing rapidly. For many years, doctors have used engineered skin for burn patients. Engineered cartilage is used for joint repairs. Researchers are investigating the use of stem cells to repair cardiac muscle damaged by heart attacks. Also, new bladders grown from a patient’s own cells are being tested in the same patients.

Dr. Taylor is a newcomer to tissue regeneration. She began her professional career at the Albert Einstein College of Medicine in the Bronx investigating gene therapy and then cell therapy. She said she switched to tissue regeneration when she realized the limiting step in trying to generate an organ was not the number of cells needed, but the complexity of creating a three-dimensional structure.

“The heart is a beautiful organ,” Dr. Taylor said, “and it’s not one that I thought I’d ever be able to build in a dish.”

Her view changed about three years ago when she recalled that cells were removed from human and pig heart valves before they were used to replace damaged human ones. As she contemplated replacing the old rat cells with new ones, Dr. Taylor followed another of her mantras: “Trust your crazy ideas.”

Progress came in fits and starts. “We made every mistake known, did every experiment wrong and had to go back and do them right,” Dr. Taylor said.

She poured detergents like those in shampoos in the rat’s arteries to wash out the heart cells and then injected neonatal cardiac cells. The first two detergents she tested failed. But a third concoction led to a clear, translucent scaffold that retained the heart’s architecture.

After injecting the young rat heart cells into a scaffold, she stimulated them electrically and created an artificial circulation as the equivalent of blood pressure to make the heart pump and produce a pulse. The steps also helped the cells mature. Tests like examining slices of the heart under a microscope showed they were living cells.

To test the biological compatibility of the new hearts, the team transplanted them into the abdomen of unrelated live rats. The hearts were not immediately rejected. A blood supply developed. The hearts beat regularly. And cells from the host rats moved in and began to reline the blood vessels, even growing in the wall of the hearts.

Dr. Taylor is now conducting similar experiments on pigs as a step toward human work. “Working out the details in a pig heart made a lot more sense” because the anatomy of the porcine heart is the closest to humans and pigs are plentiful, she said.

“The next goal will be to see if we can get the heart to pump strongly enough and become mature enough that we can use it to keep an animal alive” in a replacement transplant, Dr. Taylor said.

As for human hearts, the best-case situation would be to obtain them from cadavers, remove their cells to make a scaffold and then inject bone marrow, muscle or young cardiac cells from a patient. The process of repopulating the scaffold with new cells would take a few months, she said.

The body replaces its proteins every few months, so the hope is that the body will create a matrix that it recognizes as its own.

One potential problem is that antirejection drugs might be required to prevent adverse immune reactions from the scaffold. In that case, Dr. Taylor hopes such therapy would be needed only temporarily.

Many things that work in experiments on animals fail in humans because of the species barrier. Dr. McAllister said that in Dr. Taylor’s case “the principal problem in escalating it to humans is one of scale, not of cell biology, and that is an easier problem to solve potentially.”

Dr. Taylor said, “If it works, it means that there will be many more organs available for transplants.”

Because the components of the biologic matrix differ for every organ, Dr. Taylor expects that scientists will be able to do tests to answer two fundamental questions: Can a stem cell be placed anywhere in the body and still produce a heart, kidney or other organ? Or must a stem cell be placed in its anatomic position to do so?

Such tests might include taking stem cells from one organ, for example a kidney, and putting them in a kidney, liver or heart to begin to understand if the stem cells are innately committed to produce kidneys or whether they will convert to produce livers or hearts.