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50 years of organ transplants

The power of perseverance

Dr. Joesph Murray virtually created new field of medicine. Scientists of today could learn from his example

As his diseased kidneys shut down, Richard Herrick became delusional. He accused doctors and nurses at the Peter Bent Brigham Hospital of assaulting him and tore out his catheter in a vain attempt to escape. Normally, Herrick would have died, but, on Dec. 23, 1954, Dr. Joseph Murray tried something new: He took a kidney from Herrick's identical twin brother and implanted it in Herrick.

The world's first successful organ transplant later earned Murray the Nobel Prize and marked the beginning of a new era in medicine that has saved hundreds of thousands of lives. But, at the time, critics accused Murray of ''playing God" and some colleagues said it was unethical to subject healthy people to surgery to extract their internal organs. At one point, Murray got so discouraged over the lack of money for his research that he considered giving up.

''The concept of spare-parts surgery was sort of like landing a man on the moon," recalled Murray, 85, who credits the hospital, his colleagues and his wife, Bobby, for keeping him on course through what some call ''the dark years" of transplant medicine. ''It just didn't enter into people's thinking."

Today, medical researchers speak of Murray with the reverence that baseball fans reserve for legends like Babe Ruth. For all the technology, instant communication and federal funding that modern scientists have at their disposal, few are likely to better Murray's record of virtually creating a new field of clinical medicine in just eight years, through a series of operations from 1954 to 1962. These days, getting approval to sell a single drug typically takes more than a decade from the moment of discovery.

''We are not much better at capturing new ideas and bringing new technology into health care than we were in the 1950s," said Dr. John Parrish of CIMIT, or the Center for Integration of Medicine and Innovative Technology, set up by Massachusetts General Hospital to foster quicker development of promising treatments. As a result, he said, medicine needs more Murrays, ''people who are passionate and relentless, clinicians who are not going to stop until they achieve a breakthrough."

Of course, Murray's revered status, celebrated in a two-day symposium at Brigham and Women's Hospital last week, says as much about the intractability of medicine today as it does about the gifted surgeon from Wellesley. Parrish contends that today's researchers face formidable obstacles to promoting new ideas -- from winning regulatory approval to finding business partners to turn drugs and devices into realities. All these developments, he believes, help explain why cancer remains the second leading cause of death 33 years after President Richard M. Nixon declared ''war on cancer."

Dr. Judah Folkman, the cancer research pioneer at Children's Hospital Boston, said no one should underestimate the pressure on Murray back in 1954. If his first, much-publicized transplant had failed, Folkman believes it would have set back the entire field for years. Instead, by 1982, 40,000 organs were transplanted in the United States alone.

Yet, Murray said he had no sense of destiny when he arrived at Peter Bent Brigham Hospital in 1947 after four years at an Army hospital in Valley Forge, Pa. A modest, deeply religious man, Murray was a plastic surgeon who had done extensive skin grafts on burned soldiers, and he expected to build a practice repairing faces damaged by fire or disease.

At the time, transplant researchers were starting to understand why their experiments so often failed: The same immune system that protects people from disease also attacks the transplanted organ as though it were an invader, causing organ rejection and, often, an agonizing death for the patient. Intrigued by the possibility of helping people who were otherwise doomed, Murray joined Brigham's transplant research, though he knew that many doctors regarded it as a ''fringe project."

The identical twins, Richard and Ronald Herrick, offered the Brigham transplant team a way around the organ-rejection problem. Ronald wanted to donate a kidney to his dying brother and, since the two were genetically identical, the Brigham researchers reasoned that Richard's immune system might accept Ronald's kidney. The doctors grafted a patch of skin from each twin onto the other as a test, and, to their delight, there were no signs of rejection.

Murray and other key doctors, including the Brigham's kidney research chief John Merrill and chief surgeon Francis Moore, knew that their success would raise profound ethical issues: For the first time, doctors would subject a healthy person to the risks of surgery to help another patient. Though the immediate risk to Ronald Herrick was modest, the loss of a kidney would leave him vulnerable should his remaining kidney fail. Only after conversations with doctors, religious leaders and lawyers did the doctors agree to Ronald's request to donate his kidney.

''With that," Murray wrote in his 2001 autobiography, ''we entered uncharted territory."

Less than 90 minutes after one surgical team removed Ronald's kidney, Murray had connected it to Richard's blood vessels and, as the new kidney turned a healthy pink, ''there were grins all around" in the operating room, Murray recalled. Richard Herrick lived for eight years with his brother's kidney, until a recurrence of kidney disease, thanking his brother for the ''extra drink" before he died. Ronald Herrick, now 72, said he's never felt any ill effects from his donation.

Despite the success, Murray faced enormous problems. First, many people felt it was morally wrong to do organ transplants at all, especially if it exposed healthy people to risks. Murray likens the controversy to today's fight over stem cells where some argue that the destruction of embryos to harvest the coveted cells is a form of abortion. Murray argues with both issues that society should address ethical problems raised by new technologies rather than trying ''to curb mankind's curiosity."

Second, the Herrick surgery didn't really solve the organ rejection problem that would confront any patient without an identical twin. The Brigham surgeons attempted several kidney transplants from unrelated donors in the 1950s, weakening the patients' immune system with whole body X-ray exposure to prevent rejection. But the radiation was so debilitating that two of the first three patients quickly died, raising doubts in the halls of the Brigham. Dr. David G. Nathan, then a senior resident, recalled that he ''regarded the entire effort as unethical," because of the misery to which its patients were subjected.

Folkman suspects that Murray's training as a surgeon made him unusually well prepared for the adversity. ''Surgeons, after they've become really good, they can directly know that by their hand they have saved lots of lives. Little things don't bother them any more," said Folkman, himself a former surgeon.

There was, however, one issue potentially even tougher than criticism -- money. Murray received no salary for the kidney research, which involved hundreds of animal experiments, and he considered giving up lab work to better support his growing family. His wife, Bobby, wouldn't hear of it, saying, ''Joe, you belong there, and that's all there is to it."

Ultimately, Murray pushed the Brigham transplant team to abandon irradiation for transplant patients in favor of a new drug called Imuran that selectively shut down the immune system without leaving patients permanently debilitated. The surgeons didn't know how much of the new drug to use, and the first three transplant patients treated with Imuran died. Mel Doucette, 23, was their fourth patient, and, having gotten the dosage right, the cadaver kidney worked. After results of the surgery were published in the New England Journal of Medicine in 1963, other transplant centers quickly emulated the Brigham's approach.

Nathan, who went on to become president of the Dana-Farber Cancer Institute, said he came to admire Murray's perseverance even though very few Brigham doctors ''had any confidence in their efforts." Nathan wrote in the journal Lancet this year that ''Joe Murray was a calm person who never raised his voice and was at peace with himself." In the end, he added, Murray was also right.

Today, Murray's example inspires a whole new generation of medical researchers, such as Dr. Joseph Vacanti at the Massachusetts General Hospital for Children, part of a team trying to grow human organs that could be used for transplant. When Vacanti presented his first results from tissue engineering back at a meeting in 1987, ''Murray came up and congratulated me and said if he was 30 years younger, he'd sign up for the team," Vacanti said. ''That took me through a lot of tough times."

Scott Allen can be contacted by e-mail at allen@globe.com.

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