Spring 2000


For Alumni


On the Cover

Bridging Disciplines to Squelch Cholera. 

Cover illustration by Calef Brown.

Stanford Medicine, published quarterly by Stanford University Medical Center, aims to keep readers informed about the education, research, clinical care and other goings on at the Medical Center.




By Kristin Weidenbach




Inga Goodnight's kidneys were working just fine on the day she checked into Stanford University Medical Center to have one of them removed. A team of surgeons retrieved the organ, carried it carefully into the next room and stitched it into her 27-year-old son, hoping that it would save his life. Thirty-five years later, Gary Goodnight and his 84-year-old mother rarely reflect on their place in medical history as one of Stanford's pioneering transplant cases or even think about the kidneys that they share.

"I haven't thought about those things for years. It's weird to recap them," Gary said during a recent Christmas visit from his London home to his mother's house in Saratoga, Calif.

Back in 1965, Gary was dying of end-stage renal failure and his doctor considered a kidney transplant the only chance to save his life. "I was turning green because I was so toxic. The doctor said, 'Go check yourself into Stanford, we've got to do a transplant,'" Gary said.

But organ transplantation in the 1960s was not the relatively routine procedure that it is today. In 1965, organ transplantation was risky and experimental. Stanford, the first hospital on the West Coast to carry out the operation, had at that time performed the procedure only twice.

The Goodnights joined the ranks of early transplant cases that helped launch Stanford's transplant program. Surgery professor Roy Cohn, MD, in 1960 led the Stanford surgical team through its first human transplant operation, following the world's first successful human kidney transplant, performed at Peter Bent Brigham Hospital in Boston in 1954. Like the patients in Boston, Cohn's first kidney donor and recipient were identical twins. At the time, researchers had limited understanding of how the immune system was involved in rejection of transplanted organs. Identical twins, who have the same genes and identical immune systems, seemed to offer the best chance for success.

In both operations the physicians first swapped a small piece of skin between the pair and watched how it adjusted to its new home. The skin graft acted as a sentinel for how one twin's immune system would react to tissue from the other. When the skin grew happily with no sign of rejection, the doctors concluded that tissues or organs transplanted from one twin to the other would not be regarded as foreign and provoke an immune response in the recipient.

Flushed with the success of their first human kidney transplant, Cohn and his partner, surgery resident Samuel Kountz, MD, (both now deceased) looked forward to perfecting their technique. But transplants between family members who were not identical twins proved more difficult. "Some aspects of our first human case suggested that part of the immunological problem showed itself in the circulatory system," Cohn wrote in a 1967 review of transplantation for Stanford Today magazine.

It was clear to the Stanford team and other transplant pioneers that certain molecules in the bloodstream were causing rejection and ultimately destruction of the graft when the donor of the new organ was not genetically identical to the recipient. In later years researchers learned that the human leukocyte antigens defined self and non-self tissues. If these antigens were not matched, then the recipient's immune system would attack the foreign molecules and rejection would occur.

At the time, all the transplant doctors knew was that they had to suppress the recipient's immune system to prevent this response and preserve the graft. For a while, doctors else where tried irradiating the patient in an effort to destroy the cells that could manufacture antibodies against the incoming foreign antigens. But it was difficult to destroy sufficient cells to permit survival of the graft and yet not so many that the patient's immune system was completely devastated and he or she was left fatally vulnerable to bacterial infections. The development of immunosuppressive drugs provided a great leap forward but finding a dose that would strike the right balance still proved tricky.

Cohn and Kountz, joined by Donald Laub, MD, who also was a surgery resident at the time, began experimenting on dogs to try to tease out the details of the "immunological problem." Transplanting kidneys from one dog to another, they compared responses in the native kidney with those in the grafted kidney. They soon noticed that the rate of blood flow through the transplant gradually but steadily declined. When Kountz took a tissue sample from the graft and examined it under the microscope, he saw that immature blood cells had begun to attack the cells lining the small blood vessels of the grafted kidney: the first sign of rejection. He learned that soon the blood vessels of the kidney would become blocked by a mass of infiltrating cells and, starved of blood and oxygen, the kidney cells would die.

The canine experiments taught Kountz and his colleagues that a drop in blood flow through the graft was the first sign of trouble. By monitoring the blood flow they could predict when rejection was about to occur and administer immunosuppressive drugs to stave off the crisis. Discovering this early-warning system was a significant achievement because it enabled the transplant physicians to keep the dosage of drugs to a minimum the remainder of the time. Prior to this discovery, almost half the dogs died from an overdose of immunosuppression.

Buoyed with their newfound knowledge, Cohn and his team scheduled a kidney transplant between a mother and daughter in July 1964. The patient, 22-year-old Ruth Bell, received her mother's kidney in the historic operation, which was the team's first transplant since the identical twins four years before. Gary Goodnight was the second Stanford patient to receive a new kidney from a non-identical-twin donor. He remembers that the dogs were still an active part of the research program at the time of his treatment.

"At the same time that they did us upstairs, they were doing an experimental dog. So I'd go down and visit 'my' dog," says Gary. "Based on body weight they were medicating him as a control on me. But one day I went down there and asked, 'How's my dog?' and found out he was dead," he exclaims. "At the time, there was a lot of guesswork involved -- a lot of grasping at straws at how to track these things," he adds with a chuckle.

Thirty-five years ago, Gary was no stranger to roaming hospital corridors. As a child, his kidneys had become so damaged by glomerulonephritis that they stopped filtering waste from his blood and failed to excrete fluid from his body in the form of urine. At eight years old, he was admitted to an Indianapolis hospital where he stayed for a year. "Essentially they put me in there to die. I was like a big water balloon -- all flat on one side from lying in bed," he recalls. On his doctor's advice, the family moved to Arizona believing that the hot, dry climate might ease Gary's condition.

When they got there, after towing a tiny house trailer more than a thousand miles, the first thing Gary's new doctor said was "What are you doing here?" Gary recounts. "He said, 'He's not gonna live. Just put him out in the sun,' " Gary says with a laugh. In fact the weather did its work and Gary's edema disappeared, r elieving the load on his kidneys to such an extent that they functioned without interruption for another 15 years. But despite the respite, it was clear that eventually they would permanently fail. It was their ultimate demise that brought Gary to Stanford.

At the time, kidney transplantation was approved only for patients believed to have no other means for survival. "Since renal transplantation is regarded as an experimental procedure, only those patients in terminal stages of chronic renal failure are taken," Cohn wrote in 1967. "The entire problem is discussed, usually in its grimmest light so that no one can fail to understand the difficulties for the patient, family and donor, as well as for the medical staff."

"It was a last-resort operation," says Gary. "[The doctors] didn't tell me, but they did tell my family that it might buy me an extra year," he says. Unbeknownst to him, members of his family had already been tested to see if any would be a compatible kidney donor. His mother, Inga, was found to be a good match and preparations for the transplant proceeded. Gary's kidneys were removed under general anesthesia and he had dialysis for two weeks to cleanse his body of the accumulated toxins. Robert Swenson, MD, a fellow in the endocrinology and metabolism division, was the nephrologist who cared for Gary, administering his dialysis.

"The initial recipients were a remarkable group of individuals," says Swenson. "There was no precedent for the program but they were highly intelligent and highly motivated. They didn't have to be coaxed into anything in terms of their care. They knew the alternative really was unthinkable. It was death," he says.

The day of the transplant, both Gary and his mother were prepared for surgery. Inga's operation began first. According to Cohn's notes, the donor operation is "by far the longer and more tedious procedure owing to the necessity of proper preparation of the renal artery and vein." Next came Gary's surgery. General anesthetic was still considered quite dangerous at the time and Gary's doctors did not want to risk a second dose in a two-week interval so he was given a spinal block and remained awake throughout the operation. When the kidney was removed from his mother in the adjoining operating room, Gary asked to see it before it was inserted. "Cohn said, 'For God's sake knock him out. He's driving me crazy!' " Gary says with a laugh. "I was asking too many questions."


In the same way that renal transplantation continues to be done today, Gary's new kidney was placed low in the pelvic cavity and was connected to the renal artery and vein and the ureter. The kidney began producing urine right away and everyone was thrilled when the operation was declared a success. Gary was taken in a wheelchair to visit his mother and there were congratulations all around. "Sam Kountz was just the sweetest man," says Inga. "He kept patting me on the back and saying, 'He's gonna be all right.' He was absolutely confident."

Gary agrees. "I'd wake up at two or three in the morning and Sam Kountz would be there looking at me. And we had a huge amount of respect for Cohn. We just thought he walked on water," he says while Inga nods in agreement.

Gary says that after the operation he felt fine for the first time in years. There were no episodes of rejection and with a daily dose of Imuran, his mother's kidney has served him well for the past 35 years. Likewise, Inga has had no deleterious effects from the transplant operation. "I just had a physical and they said the [remaining] kidney was fine," she says.

Compared with the seven days that today's kidney transplant recipients typically spend in hospital, Gary's two-month-long inpatient recovery time was lengthy but he believes that he was probably kept in the hospital longer than really needed because it was a learning experience for the doctors and nurses.

"I was up and around and fine but it was a big deal for them and I became kind of the pet of the hospital," he recalled. "I didn't like hospital gowns, didn't want to wear pajamas and they wouldn't give me street clothes, so the interns would sneak in surgical gowns and I'd put a stethoscope around my neck and go on clinical rounds with them," Gary laughs. "I'm sure every one of them would deny it to this day," he quickly adds.

"It was a remarkably integrated team," says Swenson, who retired in 1993 from his position as associate professor in medicine (nephrology) and chief of staff at the Veterans Affairs hospital in Livermore, Calif. "Sam and Roy were really superb surgeons and Sam absolutely inspired the patients. They were devoted to him." According to Swenson, John (Jack) Palmer, MD, provided excellent urological service and psychiatrist David Dorosin, MD, was also a key member of the team. "He was involved with counseling patients and donors and served as a real good man to have around the shop. Another big factor was Rose Payne. She did the tissue typing and she worked beautifully with the whole team. It was a very big outpouring of effort."

Kidney transplants for Ruth Bell and Gary Goodnight signaled the beginning of a stream of successful transplant operations over the ensuing years. By 1969, an average of two transplants per month were being performed and in December 1970 Stanford doctors celebrated their 100th kidney recipient. But the program ground to a halt in 1971 when costs became prohibitive. "We had a problem here with financing," Cohn later said of the program's closure. "The [federal] government wouldn't finance the operations and they were very expensive." In 1967, according to Cohn, hospitalization fees alone ranged from $6,000 to $30,000 for each successful kidney transplant operation, excluding medical fees and outpatient medications. With the shutdown, Kountz left for an associate professor of surgery position at the University of California, San Francisco (UCSF), where the expensive operations could continue because UCSF received financial aid from the state. On the Peninsula, the institution that once had been a leader in the surgical specialty had only intermittent renal transplant services to offer over the next 20 years.


In 1991 the program was back on track. That year, surgeons Donald Dafoe, MD, and Edward Alfrey, MD, joined the Stanford faculty and helped reestablish the kidney transplant program. In 1998, 155 people were transplanted and last year 127 people, 107 adults and 20 children, received a new kidney at the medical center. The program now welcomes all kinds of kidney donors provided that there is a good match with the recipient. Today, 30 percent of renal transplants utilize living donors including family members from parents to siblings and cousins, as well as unrelated donors such as spouses. The remainder use cadaveric donors. Stanford surgeons are using advanced surgical techniques on living donors to remove the kidney through a small incision measuring two to three inches wide, and they are refining methods to successfully transplant adult kidneys into babies and young children. "We're transplanting one of every 10 infants transplanted in the U.S.," says Oscar Salvatierra Jr., MD, professor of transplant surgery and of pediatrics and director of adult and pediatric renal transplantation. He became director of the adult program following Dafoe's departure in December. "But the one who really made it go was Kountz," Salvatierra says, paying homage to the man who trained him as a transplantation fellow at UCSF in 1972. "He was my mentor."

With the future of kidney transplantation at Stanford now more assured, the program's major obstacles are those plaguing organ transplantation programs around the world. "The big problem now is the drastic absence of available cadaver donors," says Swenson. According to Salvatierra, there is a shortage of all kinds of organs. "In the U.S., there are 65,000 people awaiting organs. This is a national problem," he says.

The two doctors, who span a generational divide in the transplantation era, also agree on the biggest future challenge facing the field. "When you look at the future of transplantation, the Holy Grail is tolerance -- permanent acceptance of the organ without drugs. Hopefully, in 10 years we will have achieved that," says Salvatierra. And when that time comes, the years of experimentation will extend back all the way to lessons learned from patients like Ruth Bell and Gary Goodnight. In 1970 in a letter to Spyros Andreopoulos, then director of the Stanford University Medical Center News Bureau, Kountz wrote: "It was the transplantation of Ruth Bell that convinced me that transplantation had a real future. Among the many things that we have learned from this patient I think the most important is the fact that certain kidney transplants may be expected to survive indefinitely."

Salvatierra could not agree more, "We've come a long way and we're still moving." SM