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Second Chance: Duke Marks Transplant Anniversary

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Duke Health News 919-660-1306

James Souther is fortunate that he came from a large
family.

Thirty-five years ago, on Feb. 26 to be exact, he received a
kidney from one of his six brothers to replace his failing
organ. In those early days before the advent of the
anti-rejection drug cyclosporine, researchers screened family
members as potential donors, so kidney patients with many
siblings were at an advantage.

That procedure marked the first organ transplant for Duke,
and the first south of Virginia. Now aged 70, Souther is a
living testament to a program that began in the heady early
days of transplantation at Duke and whose initial successes can
largely be attributed to Dr. D. Bernard Amos, a young British
immunologist who was lured to Duke as much by North Carolina's
clime as Duke's reputation.

"My first day here was a day much like today ‚ one of those
wonderful warm winter days under a shiny sky ‚ and the first
thing I saw was a large stand of pine trees," Amos recalls of
that February day in 1962. "Coming from Buffalo and all that
snow, I didn't have to be asked twice to stay."

Amos, now professor emeritus of immunology, had spent the
previous seven years at the Roswell Park Memorial Institute in
Buffalo investigating the possibility of using the immune
system to fight tumors in mice. At Duke, he was to use
knowledge gained identifying genetic markers in cancer cells of
mice for a completely new enterprise ‚ improving outcomes for
kidney transplant patients.

Souther's transplant also marked the first for young surgeon
Dr. Del Stickel, who had recently completed his surgical
residency at Duke and had decided that his future lay in
transplant surgery. A new drug called Immuran had shown promise
in maintaining the function of transplanted kidneys and Stickel
was learning the techniques from the experts at the time.
Things were beginning to fall into place.

"I was delighted to know Amos was coming to Duke to work on
tissue typing," said Stickel, now professor emeritus of
surgery. "We had the new drug, but graft rejection was still a
major barrier to successful transplantation. Theoretically,
using tissue typing to get even a partial match was one of the
ways to prolong survival. In Bernard Amos, we had someone on
the leading edge of that aspect of transplant biology."

The key to a successful organ transplant is keeping the
recipient's immune system from recognizing the new organ as
foreign and attacking it. Amos had already investigated the
mechanisms of tumor rejection in mice ‚ now it was time to
study the flip side of that immunologic coin.

"The basic idea is to use immune mechanisms in both cases ‚
against tumors we want to augment or stir up the immune system;
in transplantation we want to find ways to avoid the immune
response," Amos said.

Amos's contribution to transplantation biology was the
identification of a group of genes that came to be known as the
major histocompability complex (MHC). These genes code for
proteins called antigens found on the surface of cells that
determine how the immune system will respond. Since the MHC
contains more than 50 genes, the more matches between a donor
and recipient, the better. A simple analogy is to that of blood
types, where every human has a specific blood type ‚ A, B, AB,
O ‚ and transfusions across blood types provoke immune
responses and are very risky.

"But for organs, it's much more complex," Stickel explained.
"Instead of just an A or B, for example, there are a host of
antigens inherited from our parents. For donors, we were
looking for compatible siblings, since they were more likely to
have a closer match. Early in the program, we focused on large
families that would have many siblings who could be tested in
Amos's lab."

In Souther's case, all six brothers, his sister, and his
parents agreed to be tested as potential kidney donors.

"My sister was the best match, but since she was still
considered to be in her child-bearing years, the doctors
decided to use one of my brothers who was the next-best match,"
Souther said. As it turned out, his sister got another chance
to donate ‚ in 1988, the first kidney gave out, and he received
his sister's organ in a second operation.

Though Amos was an MD, he spent much of his time in the
laboratory, and this collaboration with the clinical team of
surgeons, nephrologists and urologists marked one of the first
such comprehensive transplant programs in the country.

"At that time, the idea of transplanting organs and
prolonging life for our patients was exciting in itself, but
for the program to be coupled to a basic biological research
program focused on the main barrier to success made it doubly
exciting," Stickel said.

The kidney transplant program started slowly and
deliberately, with one more transplant performed that year ‚ a
Raleigh man who is also still alive. By 1969, Duke surgeons had
performed 50 kidney transplants, and the program now performs
about 80 such procedures each year.

Stickel credits Amos's work as the reason why so many of the
early transplant patients did so well, more than a decade
before the advent of cyclosporine, the anti-rejection drug that
has led to the boom in the transplantation of all organs.

"It was because of his early pioneering work that we were
able to pick out compatible family members," Stickel said.

"Duke has been a such a wonderful place for me to work,"
Amos said. "There were few places for basic scientists to work
side-by-side with clinicians. There was a tremendous openness
of information, the standard of clinical care was wonderful,
the nursing support and the availability of Rankin Ward was
superb."

As for Souther, he didn't hesitate in being the first person
to undergo such a new medical procedure. Kidney dialysis was
still relatively new, and the doctors gave him little chance of
regaining kidney function. "I had to take the chance," he
recalls. "It sure has been great to have 35 years that I wasn't
expected to have."

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