By Melanie Parker From UAB Magazine, Spring 2000 (Volume 20, Number 1)

There is no music in the operating room of Arnold Diethelm, M.D. He tolerates no distractions.

“I consider the performance of an operation to be a great privilege and a great responsibility—not only to the patient, but also to the patient’s family. An operating room must be totally organized. It is a serious place.”

During his 30 years as a surgeon at UAB, Diethelm has operated countless times, often in the middle of the night, and on every holiday. He has trudged through the snow from home to reach the hospital. He has often performed multiple, back-to-back transplants in a single day. He has personally tracked down deathly ill patients’ family members to find compatible kidney donors. He works from sunup to sundown, six and a half days a week.

In spite of the demands on him as UAB’s chief surgeon, Diethelm appears younger than his 68 years. His hands are strong, rugged. They gesture just as he speaks—with economy, precision, and grace. His eyes are kind, yet intense. They have seen so much.

Prelude to Progress

Medicine is in Diethelm’s blood. His father was a professor of psychiatry at Cornell; his mother, a nurse. He knew when he was in college that he wanted to become a doctor. He studied with the best at Cornell Medical College, New York Hospital, and Peter Bent Brigham (now Brigham and Women’s) Hospital, where the first kidney transplant was performed in 1954.

In September 1966, he began a research fellowship in surgery at Harvard Medical School with Joseph E. Murray, M.D., who would later win the Nobel Prize for his work in transplantation. For Diethelm, it was the beginning of a lifelong fascination. In 1967, he was invited to Birmingham to meet renowned cardiac surgeon John Kirklin, M.D., who was building a department of surgery and was anxious to develop organ transplantation.

“Kirklin was persuasive,” he says. “I realized that he was going to develop a new, somewhat different department of surgery. No one had ever performed transplantation in Alabama. There wasn’t a lot here, but there was enough to get started.”

In the presence of this pioneer of medicine and surgery, one is acutely aware of the roots of UAB and the visionary leaders who energized its evolution—mavericks on multiple frontiers, making and bending the rules ... innovators with dreams of creating something new, extraordinary, and enduring ... talented trailblazers who came together at a critical time to make things happen—and to help people.

Diethelm came to UAB when the opportunity to start from scratch attracted physicians and researchers who could have written their own tickets to any of the best medical centers in the country. He came because he wanted the opportunity to help build an exceptional surgical program from the ground up. He stayed because he was able to find and seize opportunities to build new programs, particularly in transplantation.

In 1982, Diethelm succeeded Kirklin, his mentor, as chair of the Department of Surgery. Eighteen years, dozens of breakthroughs, and thousands of transplant operations later, he is retiring from that post.

Starting from Scratch

Looking back on his career, Diethelm reflects on his early years in Birmingham, when both the field of transplantation and UAB itself were in their infancy. He remembers, most of all, that the road to successful transplantation seemed long, open, untraveled—and yet full of promise.

He also remembers the many obstacles. The greatest hurdle of all, he says, was the human immune system’s tendency to see transplanted organs as foreign and reject them.

In those days, there were few commercial preparations of immunosuppressants to combat rejection. So Diethelm made his own. In the early 1970s, he and a technician traveled in his brown VW station wagon to Trussville, Alabama, where he injected horses with human lymphocytes. Two weeks after the last injection, when the horses had developed antibodies to the lymphocytes, the animals’ blood was drawn and processed in a UAB laboratory into anti-lymphocyte serum.

When at last the first organ—a kidney—was transplanted in Alabama on May 8, 1968, Diethelm performed the operation in borrowed facilities. For many years after that, he was the transplant program at UAB. Until a transplant floor was built in 1980 at UAB Hospital, he performed transplants at the Veterans Affairs (VA) Hospital under a sharing agreement with UAB.

Restricting Rejection

Diethelm witnessed the first two big breakthroughs in transplantation—the development of the first immunosuppressant drug, azathioprine, in 1962 and the introduction of the powerful anti-rejection drug cyclosporine in 1983.

“In the late sixties and early seventies,” he reflects, “there were only two medications used for immunosuppression. One was azathioprine and the other prednisone. Acute rejection was almost the rule. Irreversible acute rejection in patients receiving cadaver kidneys occurred in 30 to 35 percent of patients in the first year; in patients receiving living related donor kidneys, the rejection rate was 25 percent. Infectious complications were common. Mortality was high.”

With the advent of cyclosporine and the discovery of other anti rejection drugs in the 1980s and early 1990s, heart, lung, liver, and pancreas transplants were made possible. And the chance of surviving a kidney transplant nearly doubled. Today, the recipient of a kidney from a living donor has a 95- to 97-percent likelihood of surviving in the first year after transplantation.

Because he believes that most advances in patient care come from research, Diethelm has focused on building a strong research enterprise, as well as clinical programs in transplantation. Early on, he set up a lab to study kidney rejection, develop an anti-lymphocyte serum, and study organ preservation. In the late 1980s, UAB was the first center in the United States to study bone marrow transplantation from donor into recipient.

“We’ve been able to develop a complete transplant program, including solid organs—heart, lung, liver, pancreas, kidney—as well as develop a bone marrow transplant program in the Department of Medicine.”

Diethelm’s efforts also created an environment that helped convince the United Network for Organ Sharing (UNOS) to approve an organ procurement program for the state of Alabama in 1978. In the same year, the Health Care Financing Administration (HCFA) approved UAB to administer the Alabama Organ Bank. Soon after came approval for the Alabama Tissue Bank.

Rewards of Research

Today, UAB transplants more kidneys than any other medical center in the world. Surgeons here recently performed their 5,000th transplant, a milestone about which Diethelm says he is “unemotional.” The important accomplishment, for him, is that individual patients are living longer, with better quality of life—patients such as Margaret Tresler, for whom three of four kidneys were transplanted by Diethelm.

“He is concerned that his patients get back to a full life—not just that a kidney is functioning,” says Tresler, an education coordinator at the Alabama Organ Center.

Diethelm emphasizes that many factors have contributed to UAB’s success in transplantation. The university’s geographic location, for example, has been important to its research programs, which have brought about many advances in the field. “Because of the prevalence of hypertension and diabetes in Alabama and the high rate of renal failure in the Southeast,” he says, “we’ve been able to carefully study diabetes and hypertension and develop treatments for transplant patients with those diseases.

“We’ve also been able to show, through our research, that older patients, as well as very young patients, can be treated satisfactorily with kidney transplants. UAB’s first kidney transplant recipient was in his twenties, and for years, we rarely transplanted anyone older than 35 to 40. But for the last 20 years, we’ve been transplanting patients of all ages, from neonates to 70-year-olds.”

Transplantation Tomorrow

Diethelm predicts “spectacular advances” in transplantation in the next 10 to 15 years (which is the length of time, he says, that’s typically required for new forms of treatment to get into the clinical field).

While the greatest contributions to transplantation have come through pharmacological research, Diethelm predicts that breakthroughs in the future will be in the immunologic field, in the form of greater understanding of rejection and how to prevent it.

“We’re at the beginning of that chapter now,” he says. However, many of the problems that dogged transplant success in 1965 are still with us—preservation of organs, acute rejection of those organs, and chronic rejection. The ultimate goal of all transplant surgeons is to prevent rejection through the mechanisms of tolerance—that is, to get the body to accept a transplanted organ by making its own immunologic adjustments, rather than using immunosuppressive drugs.

Three world leaders in the field of immunologic tolerance are already at UAB. Professors of Surgery Judith (Judy) Thomas, Ph.D., Frank Thomas, Ph.D., and John Thompson, Ph.D., have “made important contributions in chronic rejection and molecular biology,” Diethelm says. “The work of those three scientists will form the basis of future advances.”

A Dearth of Donors

Another exciting advance, Diethelm says, will be the use of stem cells—precursor cells that contain complete genetic instructions for forming all of the different tissues in the body—to potentially generate new livers, hearts, pancreases, even neural cells to transplant into degenerated areas of the brain.

“Stem cells represent great opportunity, with enormous medical implications. We shouldn’t let this get tied up in politics,” he says of societal resistance to the use of human fetal brain stem cells to generate new organs. “Cell transplantation will be a great field of the future. If you could use cells as a means of endocrine function—to produce insulin, for example—then the field of transplantation would reach a whole new level of interest, and of clinical value.”

Despite these exciting possibilities, there’s one limitation on transplantation that isn’t likely to change, says Diethelm. “There probably never will be enough organs to go around. Realistically, human disease will exceed the supply of human organs. Organs can neither be made nor bought. They can only be received as gifts.”

Although organ donation in Alabama is higher than the national average, the need far outpaces the supply. There are currently more than 1,200 people on the waiting list in Alabama for a kidney.

The most practical solution to the shortage might be xenografts—the transplantation of organs from animals to humans. The surgeon-scientist analyzes the possible applications: “The question is, how would you start with xenografts—in what organ? One choice would be the heart or liver—potentially lifesaving, but also highly risky. A different approach might be to use islet cells from a pig pancreas to treat a patient with insulin-dependent diabetes. That would not be such an all-or-nothing, life-or-death form of treatment, and failure would be tolerated better by the patient and, therefore, by the field of medicine.”

The Scope of Surgery

When asked to reflect on the changes he’s seen in surgery during the past 30 years, Diethelm says there have been striking advances, with tremendous improvements in technology. Radiological imaging allows for more accurate diagnosis, creating “maps” that guide surgeons quickly to diseased tissues. Operating rooms (ORs) are much improved, with better lighting, instruments, and equipment, including video and on-site imaging.

And the future?

“The place for the whole field of minimally invasive surgery is still to be determined,” he says, “but it surely will have an important impact and will change the way we care for patients. Incisions will be smaller, recovery quicker, pain and discomfort less, and some operations will be done better using minimally invasive techniques.”

Technique and Intellect

Diethelm will be missed in his OR, where he has trained a generation of the best and brightest.

“You can’t tell people what to do. You have to lead them, gently. Then you must be able to produce. If you don’t go to the OR, surgeons won’t think much of you. In fact, they won’t think anything of you.”

Diethelm is considered very fast and technically efficient, but UAB’s chief surgeon says it takes a lot more than hands.

“A surgeon needs good technical skills but must also be interested in the physiology and pathology of surgical diseases. Many people think it’s all technique. I would say that a great part of surgery is technique, and a great part is intellectual. You have to know who should be transplanted. What are the risks? What are the chances of success and failure? Is a 65 year-old with diabetes and heart disease too great a risk? In order to do well, you need to understand all the steps—and then be able to take care of the patient afterward.”

Diethelm always returns to his priority: patient care. It is the reason for quiet operating rooms, new technology, research programs, and training. The best patient care, he says, occurs when programs are combined across disciplinary lines. And “all the right people” are now in place at UAB—in nephrology, cardiology, pulmonary medicine, and hepatology—for the highest-quality interdisciplinary transplantation effort.

“You need those teams in place or it won’t happen. And it doesn’t just happen. It takes years to find the right people, keep them, and develop them.”

Others point out that it takes extraordinary individuals such as Arnold Diethelm.

“He inspires our best effort through his leadership,” says Alabama Organ Center Director Chuck Patrick. “He raises the bar for us all, and he leads by example. Our respect for him keeps us going.”

Gifts of Freedom

Diethelm, who will remain at UAB as professor in the Division of Transplantation until age 70, says the timing of his retirement as chair feels right.

“There comes a time when you need different, younger people. I didn’t always think so, but I do now. It’s the proper time for change in the Department of Surgery. There’s greater stability in the medical center; other departments are functioning very well. It’s as good a time as any.”

He says he’ll redirect his energies into other things, including four children, six grandchildren, and a cattle farm in the Ozark Mountains of Arkansas that has been an interest for 25 years.

Diethelm says he’s never thought about a personal legacy. But surely his greatest legacy will be the lives he has touched—and saved—through his years of service to medicine and science.

“Progress in medicine, which continues every day, is translated into length and quality of life for patients. Whatever personal satisfaction I receive comes from patients living longer, better lives. It’s an indirect return.”

Margaret Tresler personifies his gift, and his return. “I am grateful to participate in life as a healthy person, without end-stage organ failure,” she says. She is especially grateful to Diethelm for the freedom she’s gained from her transplanted kidney—a gift from her brother.