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THE
STORY OF A 1965 KIDNEY TRANSPLANT CONVEYS THE
ESSENCE OF THE STANFORD TRANSPLANT PROGRAM'S PIONEERING
SPIRIT
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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
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