Second Chances

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."

Highlights of the Duke transplant program

Organ

First Transplant

Number to Date

Kidneys 1965 1,665 Livers 1984 395 Heart `985 231 Pancreas 1989 10 Kidney/Pancreas 1990 147 Lungs 1992 254 Heart/Lung 1992 15