Sketchbook

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D. Bernard Amos
(1923 - 2003)

Field

Immunology

Contributions

As described by his Duke University colleagues - Thomas F. Tedder and Jeffrey R. Dawson in the Journal of Immunology in 2003 - "Dr. Bernard Amos' leadership, mentoring, and scientific discoveries have had a worldwide impact. He was a leader and innovator in all of his efforts. Scientifically, Dr. Amos made seminal and enduring contributions to the areas of immunogenetics, tumor immunity, and transplantation immunology. He accomplished what few investigators dream: to discover basic mechanisms of immune function and to translate those findings into the treatment of human disease. From the very beginning, Dr. Amos was one of the major players in the field of HLA genetics and biology."

Pesonal Recollections

I was fortunate. I got to know Dr. Amos very well, but it was after I completed my graduate studies at Duke University (1976-79), and had moved to Seattle. Dr. Amos was recruited to Duke University in 1962. Our paths did not cross while I was a graduate student at Duke. Between 1982 and 1986, transplantation was in the media spotlight. The precipitating event was a liver transplant performed on Jamie Fiske at the University of Minnesota by Dr. John S. Najarian on November 5, 1982. The Fiskes were among the first families to appeal publicly for an organ donor. This set into motion a series of Congressional hearings to address organ donation and allocation policy, and eventually led to the passage of the National Organ Transplant Act, which became law on October 19, 1984, thus creating the National Organ Procurement and Transplantation Network (OPTN). Years earlier, Dr. Amos and Dr. David Hume had co-founded the South-Eastern Regional Organ Procurement Program (later known as SEOPF). SEOPF was the model for what later became the United Network for Organ Sharing (UNOS). Bernard was amongst the many people I worked with in helping to lay the groundwork for equitable organ allocation in the U.S. We participated in what seemed like an endless number of meetings. Bernard was fun to be around. I truly enjoyed our time together.



Christiaan N. Barnard
(1922 - 2001)

Field

Cardiothoracic Transplantation

Contributions

Dr. Christiaan N. Barnard was a South African cardiothoracic transplant surgeon who performed the world's first human heart transplant on December 3, 1967. The patient was Louis Washkansky and the donor was Denise Darvall. Washkansky survived for 18 days. Soon thereafter Barnard transplanted Dr. Philip Blaiberg, who lived for more than 18 months. Based on this initial experience, cardiac surgeons worldwide performed heart transplants with very little success. A media circus ensued, and a moratorium on heart transplantation was eventually declared.

Barnard did his internship and residency at the Groote Schuur Hospital in Cape Town, South Africa. According to the New York Times, in 1955 Barnard went to Minneapolis to study general surgery with Dr. Owen H. Wagensteen at the University of Minnesota. During the first few weeks in Minneapolis, Barnard was so hard up for cash that he had to mow lawns, wash cars, and do other odd jobs in order to make ends meet.

When Barnard arrived in Minneapolis, open heart surgery was in the early stages of development. In 1956 Barnard received a two-year scholarship for postgraduate training in cardiothoracic surgery at the University of Minnesota. His teachers and mentors were Drs. Walter Lillehei and Richard L. Varco. It was during this time that Barnard met Dr. Norman E. Shumway who, later, in collaboration with Dr. Richard R. Lower at Stanford University, completed the research necessary to make heart transplantation a clinical reality. In 1958 Barnard received a Master of Science in Surgery at the University of Minnesota. His thesis was entitled "The Etiology of Congenital Intestinal Atresia."

Shumway earned his Ph.D. in cardiovascular surgery at the University of Minnesota in 1956. He became an Instructor in Surgery at Stanford University in 1958. In 1966, when Barnard visited Lower's laboratory at Stanford University, Lower had no idea that Barnard and Shumway had previously worked together at the University of Minnesota.

Barnard returned to South Africa in 1958 and established the first heart unit at Groote Schuur Hospital. Gradually, Barnard became recognized as an outstanding surgeon, and was promoted to Head of the Cardio-Thoracic Surgery Department at Groote Schuur Hospital in 1961. He became Professor Emeritus at the University of Cape Town in 1983. From 1985 through 1987 Barnard was Scientist in Residence at Baptist Medical Center in Oklahoma City, Oklahoma.

Pesonal Recollections

I never met Dr. Barnard but, by all accounts, he was an interesting character who, based on my experience, was either appreciated or ridiculed. There are many people who considered him an opportunist. Those who disliked Barnard did so because they felt Shumway and Lower at Stanford University should have been the first in the world to perform a human heart transplant. After all, Shumway and Lower first described the modern surgical technique of orthotopic heart transplantation in 1960, and they spent years studying ways to combat the rejection of the transplanted heart. Instead, according to McRae, Barnard, "who had been given the idea of attempting a heart transplant after watching Lower at work in his laboratory in September 1966," engaged in what most people consider to be a form of one-upmanship. After a mere 13 months in the field, and with very little relevant experience, he performed the world's first heart transplant.

For years, Shumway avoided Barnard, and the two didn't speak, although, later in life, their relationship became more congenial. The New York Times published Barnard's obituary, which included comments by Shumway. According to Shumway, Dr. Barnard's surgical feat was outweighed by his decision to choose as the first heart donor a brain-dead accident victim. "It made use of brain-dead victims acceptable for organ transplantation" because at the time "there was a terrible furor about the brain death issue in the United States." Shumway went on to say "Without Dr. Barnard's initial use of the brain-dead patient, we could not have gone ahead" to make heart transplants standard therapy. "It was a monumental advance, more societal perhaps than medical, because it applied to all organ transplants."

Nonetheless, according to McRae, Shumway was "most moving when he spoke about his lone professional setback." "It seemed cruel, he said of Barnard's transplant. "What is it they always say about the first? We all know the first guy to get to the North Pole or to step across the moon. It's just the second or third guy's name which is a little more elusive. I understand the whole drama of being the first. I've lived with it for a few years now." Shortly before his death, Shumway seemed resigned, and had this to say: "Maybe it was a blessing we weren't the first. We had enough trouble with the press and all that hoo-hah. Maybe it all worked out for the best."

Barnard's personal life was at times controversial. He often ignored racial barriers in South Africa. He was an opponent of apartheid. He became an international savant, with people seeking his views on topics about which he knew little, if anything. Barnard was married three times, had six children, and was known to have had extramarital affairs and, as a result, was referred to as the "Doctor of Hearts." He aspired to be a novelist, and failed. Late in life he became interested in anti-aging research. In 1986 he promoted Glycel, an expensive anti-aging skin cream. His reputation suffered when the Food and Drug Administration withdrew its approval. However, to his credit, he established the Christiaan Barnard Foundation which helps underprivileged children.

Barnard died of an asthmatic attack on September 2, 2001 while vacationing in Cyprus. While giving an interview to Time Magazine a little before his death he said, "The heart transplant wasn't such a big thing surgically. The point is I was prepared to take the risk. My philosophy is that the biggest risk in life is not to take the risk."



Margaret E. Billingham
(1930 - 2009)

Field

Pathology

Contributions

Margaret Billingham, M.D. was a founder of the field of cardiac transplantation pathology who developed the “Billingham’s criteria” that physicians still use to grade heart transplant rejection.

Billingham was director of cardiac pathology emeritus and professor of pathology emeritus at the Stanford University Medical Center. She was best known for her work in the field of pathology of cardiac transplant rejection, she also made major contributions to research into the toxicity of the chemotherapy drug adriamycin and the development of heart biopsy techniques. She was a reflective and generous mentor, whose support was especially beneficial to younger female faculty members during a time when few women had achieved such a senior position.

Billingham was born on September 20, 1930 in Tanga, Tanzania, where her father worked for the British government. She graduated with her medical degree from the Royal Free Hospital School of Medicine in London in 1954.

In 1966, she went to Stanford as a postdoctoral fellow in cardiology, staying on as a pathology resident and postdoctoral fellow in surgical pathology. There, she impressed colleagues with her efficiency and interest in cardiac pathology. It was an era of excitement in that field—Norman Shumway, M.D., Ph.D., would perform the first successful heart transplant in the United States at Stanford in 1968—and Billingham became interested in the pathology of cardiac transplant rejection. Along with visiting scientist Philip Caves, MD, she developed methods of diagnosing transplant rejection from tiny snippets of heart tissue. She would carry on that work through her appointment as an assistant professor of cardiac pathology in 1975, associate professor of pathology in 1981 and professor of pathology in 1988.

She developed the grading system for the diagnosis and reporting of acute rejection; she also described the pathology of chronic rejection in heart transplants, and she taught legions of pathologists how to diagnose rejection. She basically developed the whole area of pathology of cardiac transplantation.

One of Billingham’s contributions, a standardized scale for interpreting the biopsy results from transplanted heart tissue, still bears her name: The Billingham Scheme, or Billingham’s criteria. Not only did Billingham create the grading system, she also successfully worked to get a similar method accepted as standard by the international community.

In addition to her academic contributions, Billingham mentored her Stanford colleagues as well as pathologists from around the world who came to study with her.

As a woman who started her career at a time when it was rare to find female medical faculty at academic medical centers, Billingham was particularly dedicated to advocating for female faculty in her department. In 1991, she was appointed director of women in medicine and medical sciences at the School of Medicine. Beyond her formal role, she provided a role model for the balance of career and family, and her calm demeanor made her a sought-after advisor.

Billingham was a Fellow of the Royal College of Pathology. She became the first female president of the International Society for Heart and Lung Transplantation in 1990, and was elected president of the Society for Cardiovascular Pathology in 1993. Among her many honors was the Award of Distinguished Pathologist of the Year for 2001 from the U.S. and Canadian Academy of Pathology.

In 1994, Billingham became an emeritus professor, and she and her husband retired to Penn Valley in the foothills of the Sierra Mountains in Northern California. There, she enjoyed gardening, fishing, traveling and exploring California with her family.

Source: Written by Stephanie Pappas, edited by Dr. Roger W. Evans. Link to the original source: http://news.stanford.edu/news/2009/july22/obit-billingham-0721.html.

Pesonal Recollections

I had the privilege to know Dr. Margaret Billingham very well, although we never had occasion to work together. I have limited knowledge of pathology, and there would have been virtually little reason for us to participate in a project of mutual interest.

Dr. Billingham was a longstanding member of the International Society for Heart and Lung Transplantation (ISHLT), having served as a past president. Likewise, I have been a member of and very active in the ISHLT, having served on the Board of Directors. In this regard, professional societies sometimes form task forces, work groups, or consensus panels to address various issues. Some of the work Dr. Billingham completed involved ISHLT consensus panels.

Dr. Billingham had a remarkable influence on the careers of many people. She was an exceptional mentor and role model. It goes without saying that many women in transplantation found her to be an inspiration, and looked up to her. She found her professional niche at a time when medicine and surgery were primarily dominated by men. This would not have been easy, but she surely benefitted from having understanding colleagues, including Dr. Norman E. Shumway. A supportive environment is critical under such circumstances. To this day there are many women involved in transplantation who aren’t hesitant to point out the important role Dr. Billingham played in the development of their careers. Likewise, many men point to the strong influence she has on the entire field of heart transplantation. Regardless of gender, respect is mutual.

Dr. Billingham quietly went about life, and it would not be surprising to me if she had been equally subdued upon receiving the unfortunate diagnosis that took her life. Her passing came as a total surprise to me. I will forever miss Dr. Billingham – one of the kindest transplant professionals I have ever met.



Rupert E. Billingham
(1921 - 2002)

Field

Immunology/Biology

Contributions

Dr. Leslie B. Brent, in a tribute published in The Lancet (2003) following Dr. Rupert E. Billingham's death, described his contributions as follows: "Rupert Everett Billingham (generally known as Bill) was a distinguished pioneer of transplantation immunology who contributed notably to the development of the field of organ transplantation. He will be remembered for a number of major advances. With T. Boswell he was the first to show that rabbit corneal allografts are not exempt from the strict rules of graft rejection when transplanted to a vascularised area on the chest and, with A. Smith, that the cornea can be successfully preserved in the frozen state. With P. L. Krohn and P. B. Medawar he demonstrated that steroid hormones can significantly prolong the life of rabbit skin allografts. He was co-discoverer, with P. B. Medawar and L. Brent, of acquired immunological tolerance, the discoverer (with Brent) of graft-versus-host disease, the ingenious investigator of immunologically 'privileged' sites, and the leader of the team that did much to elucidate the reasons for the survival of nature's 'natural allograft'-the mammalian fetus-in the womb. Bill was also a devoted university teacher who took much trouble over preparing his lectures- a fact that twice earned him the Award for Excellence in Teaching by the University of Texas."

Pesonal Recollections

Dr. Billingham retired in 1986. I can recall meeting Dr. Billingham, but I don't remember where, or at what meeting, but the possibilities are few. Most likely it was at and International Congress convened by The Transplantation Society, perhaps Minneapolis in 1984. At the time, my knowledge of his contributions was likely to have been minimal. Early in my career, my interest in immunology was very limited. I was more intrigued with the surgical aspects of transplantation. I had no problem identifying the vast majority of surgeons who had some involvement in transplantation. In fact, if I didn't know them, I often made it a point to introduce myself at meetings. This was no small feat for someone with a Ph.D. in sociology. As I became increasingly interested in immunosuppression, I took the time to learn a bit more about immunology. In this regard, perhaps the greatest stimulant was the introduction of cyclosporine, which initially appeared to be a "wonder" drug when used in solid organ transplantation, and a whole host of autoimmune disorders. Unfortunately, the hype was inconsistent with reality in the treatment of autoimmune disorders, including diabetes.



Jean-Francois Borel
(1933 - )

Field

Microbiology/Immunogenetics

Contributions

As a microbiologist working for Sandoz Laboratories in Switzerland, Jean-Francois Borel discovered cyclosporine in 1969 when he was vacationing in Norway. Sandoz employees were encouraged to gather samples of naturally occurring organisms for analysis in the laboratory. When Borel visited Hardanger Vidda, a desolate highland plateau in southern Norway, he collected some soil samples and brought them back to Sandoz for testing.

Sandoz Laboratories was involved primarily in antibiotics research, and the purpose of their first series of tests on cyclosporine was to determine the substance's potential as an antibiotic. The tests yielded little of interest as far as antibiotics were concerned, but did show that cyclosporine had distinct immunosuppressive capabilities. Since his doctoral studies involved immunogenetics (the study of how the immune system works), Borel decided that he wanted to learn more about cyclosporine.

Borel ran a second series of tests and found that cyclosporine inhibits the activity of lymphocytes (white blood cells), the part of the immune system that starts the process of detecting and attacking foreign invaders. Lymphocytes aid in the formation of cytotoxic (toxic to cells) T cells. These cells, along with blood cells called monocytes and macrophages, are thought to be responsible for the rejection of transplanted organs. Cyclosporine does not actually destroy the T cells, but fends them off. It acts at an early stage in the life cycle of the T cell, inhibiting its action by blocking the intercellular message carried by a cellular compound called interleukin-2.

It looked as if Borel had discovered a superior drug for transplantation, but his employer was not sufficiently impressed by the findings he reported in 1972. The estimated costs for production and testing of the drug were too high, and organ transplantation was just getting started. The potential demand for cyclosporine was questionable. Sandoz was unwilling to put the necessary money and energy behind the drug for further exploration.

An immunologist and a surgeon recognized the importance of Borel's discovery, however, when the researcher presented his results to the British Society of Immunologists in 1976. Dr. David J.G. White and Sir Roy Calne asked Borel for samples of cyclosporine and began their own clinical studies using organ transplantation in rats. The results were remarkable: rejection was almost nonexistent, and the survival rate was far better than for other immunosuppressants. In mid-1977, White and Calne informed Borel of their findings and requested more samples of cyclosporine to continue their clinical trials, this time on dogs. Borel, hoping to revive Sandoz's interest in cyclosporine, asked White and Calne to present their findings to Sandoz. The pharmaceutical company agreed that the drug looked much more promising now that there was evidence of its effectiveness.

The success of cyclosporine suffered a setback in 1979 when further studies showed it to be nephrotoxic (poisonous to the kidneys) and to cause lymphomas (tumors). These side effects proved to be the result of high doses of the drug. The practice at the time was to administer as much cyclosporine as the body could handle, short of a toxic level. Research later showed it should be given in small amounts, just enough cyclosporine to prevent rejection of a transplanted organ. With the decreased dosage, the lymphoma was eliminated and nephrotoxicity was reduced.

Later research by Dr. Thomas E. Starzl, who was then at the University of Colorado in Denver, indicated that cyclosporine worked most effectively when administered with steroids. In 1983 the Food and Drug Administration approved cyclosporine for use in all transplant patients, but said it must be given only in conjunction with steroids. Cyclosporine must be taken indefinitely by organ transplant recipients, however, and the possibility of irreversible kidney failure remains a serious concern.

Cyclosporine is not a perfect drug. It is effective in treating infections after the surgery, and it is associated with a lower mortality rate among transplant patients. It is commonly used in kidney, heart and lung, liver and pancreas, and bone marrow transplants. Cyclosporine is also used to treat viral and fungal infections and immune disorders, to promote healing of wounds, and in certain kinds of tissue grafts. The drug is also used in treating certain autoimmune diseases such as myasthenia gravis and is being tested for use in treating inflammatory bowel disease.

Source: http://www.discoveriesinmedicine.com/Com-En/Cyclosporine.html.

Pesonal Recollections

I met Dr. Jean-Francois Borel many years ago, but I never got to know him very well. He is a quiet person, who keeps a low profile. If you didn’t know him when you entered a room, you wouldn’t notice him. Most likely, he would be standing somewhere talking to a small group of people who are familiar with what he has accomplished.

The impact of cyclosporine on transplantation was tremendous, as chronicled by Dr. Lawrence K. Altman in the New York Times in 1982. In my opinion, its role cannot be overstated. In many respects, cyclosporine transformed transplantation, and opened an entirely new era. Dr. Clyde Barker, in his historical overview of transplantation, refers to cyclosporine as a “wonder drug” and, indeed it was just that, as demonstrated by Sir Roy Calne, Dr. David J. G. White, and Dr. Thomas E. Starzl. As shown by Starzl, cyclosporine combined with prednisone was far superior to azathioprine (Imuran) and prednisone. As noted by Barker, in addition to advancing kidney transplantation, cyclosporine transformed the transplantation of extrarenal organs into a practical clinical service.

In 2012, Sir Roy Calne, upon looking back, described his feelings about cyclosporine as follows: “… cyclosporine was the real watershed. We tested it in my laboratory at the University of Cambridge during the mid-1970s. By 1977, it had moved the success rate from 50 percent to 80 percent. That really changed attitudes. Before cyclosporine, you had only 10 centers around the world doing organ transplants. Afterwards, it was 1,000. And now we had a whole new problem: not enough donor organs to meet demand.”

Worldwide, numerous clinical trials were conducted in an effort to document the benefits of cyclosporine in transplantation. Many of these were single center studies, which were often faulted for their lack of generalizability. In this regard, perhaps the most influential study of cyclosporine was conducted by what was then called The Canadian Multicentre Transplant Study Group, which was chaired by Dr. Calvin R. Stiller at University Hospital, The University of Western Ontario in London, Ontario. The primary report of the study results, entitled “A Randomized Clinical Trial of Cyclosporine in Cadaveric Renal Transplantation,” was published in the New England Journal of Medicine on October 6, 1983. It goes without saying, this report had dramatic implications for the future of cyclosporine from both a clinical and a health policy perspective.

In the ensuing years (1983-92), numerous immunosuppressive drug protocols were developed and used by various transplant teams around the world. These included what were often called “double-drug,” “triple-drug,” and “quadruple-drug” protocols. In addition, there was a distinction between “induction therapy” and “maintenance therapy.” In some cases, an antilymphocyte globulin (ALG), such as Minnesota ALG, was used for induction. Later other monoclonal antibodies were added to what was sometimes referred to as the immunosuppressive drug “cocktail.”

At this time (1979-92), I was at the Battelle Seattle Research Center in Seattle, Washington, where my colleagues and I had been conducting numerous studies on a variety of aspects of transplantation, many of which addressed costs, outcomes, and insurance coverage and reimbursement policy. Our first major study was the National Kidney Dialysis and Kidney Transplantation Study (1981-84), followed by the National Heart Transplantation Study (1981-85), then a study entitled A Comparative Analysis of the Cost and Outcomes of Kidney Transplantation (1984-88) and, later, the National Cooperative Transplantation Study (1989-91).

The study entitled “A Comparative Analysis of the Cost and Outcomes of Kidney Transplantation” specifically focused on how costs and outcomes in kidney transplantation varied according to immunosuppressive protocol. Five transplant centers participated in the study. They were: the University of California at San Francisco, the Ohio State University, the University of Pittsburgh, the University of Texas at Houston, and the University of Wisconsin. The study included 396 patients. Patients were placed in two groups based on their immunosuppressive drug induction protocol. Some patients in the study received double-drug therapy for induction, consisting of cyclosporine and prednisone, while others received triple-drug therapy for induction, consisting of azathioprine, prednisone, and antilymphocyte globulin (ALG). We then followed patients based on their maintenance immunosuppressive drug protocol. At nine months posttransplant, the majority of patients were on one of two protocols – prednisone and cyclosporine or prednisone, azathioprine, and cyclosporine.

Since the introduction of cyclosporine (Neoral, Gengraf, Sandimmune), a whole host of immunosuppressive drugs have been developed and, as a result, multi-drug protocols have evolved accordingly. Amongst these drugs, in no particular order, are the following: alemtuzumab (Campath), lymphocyte immune globulin, rabbit (Thymoglobulin), lymphocyte immune globulin, equine (Atgam), mycophenolate mofetil (Cellcept), muromonab (Orthoclone or OKT3), mycophenolate sodium (Myfortic), sirolimus (Rapamune), tacrolimus (Prograf), daclizumab (Zenapax), basiliximab (Simulect), and belatacept (Nulojix).

Given the availability of the foregoing immunosuppressive drugs, the use of cyclosporine has sharply fallen, as is apparent from the 2012 Annual Report for the Scientific Registry of Transplant Recipients. In 1998, 64.4% of kidney transplant recipients received cyclosporine, compared with 3.2% in 2012. In 1998, 30.3% of liver transplant recipients received cyclosporine, compared with 5.0% in 2012. In 1998, 83.8% of heart transplant recipients received cyclosporine, compared with 6.0% in 2012. Finally, in 1998, 73.0% of lung transplant recipients received cyclosporine, compared with 3.4% in 2012.

Thus, based on the foregoing data, it is apparent that the so-called “golden age” of cyclosporine is over. Many immunosuppressive medications are available, and are being used accordingly. In many respects this reflects a new era consistent with the development of “personalized medicine” and tailored, or individualized therapy. In other words, as new immunosuppressive medications have become available, immunosuppression can be tailored to the needs of individual patients. Unfortunately, in the future, the development of new immunosuppressive medications may be hampered to some extent, given the relatively small size of the marketplace associated with transplantation.



Leslie B. Brent
(1925 - )

Field

Immunology

Contributions

On his Web site, Dr. Thomas E. Starzl describes the significance of Dr. Leslie B. Brent's contributions as follows: "In the early 1950s, Brent began studying with Peter Medawar, a biologist who had first started exploring the possibility of transplantation while seeking to improve skin grafts during World War II. The two, along with biologist Rupert Billingham, began carrying out the research that would be the basis of the entire transplantation field: the concept of immunosuppression and immunological tolerance. Their successful experiments on mice demonstrated that dampening the body's immune system delayed tissue rejection. Later, their research would reveal something even more interesting: baby mice, injected with leukocytes from an adult donor mouse, were able to receive successful transplants from the donor mouse later in life. This demonstrated the concept of acquired immunological tolerance, a concept that was absolutely critical in the development of organ transplantation, and which also helped Medawar garner the Nobel Prize in 1960. Dr. Starzl developed much of his own research off of what he calls the "holy trinity" of Brent, Medawar, and Billingham. After these historic discoveries, Brent continued to research and publish over the course of a long and distinguished career."

Pesonal Recollections

On April 1, 2014, I wrote the following personal recollection of Dr. Brent: "I don't recall meeting Dr. Brent, although we most certainly crossed paths at various International Congresses convened by The Transplantation Society (TTS). The first such meeting I attended was the 10th International Congress, which was held in Minneapolis in 1984. Subsequently, I attended the 11th through the 17th TTS International Congresses which were respectfully held in Helsinki (1986), Sydney (1988), San Francisco (1990), Paris (1992), Kyoto (1994), Barcelona (1996), and Montreal (1998). TTS meetings are held every two years. Dr. Brent, who retired in 1990, undoubtedly participated in several of the foregoing TTS International Congresses." On April 10, 2014 I was extremely fortunate. I met Dr. Brent at the International Society for Heart and Lung Transplantation Annual Meeting and Scientific Sessions, which was held in San Diego. At a session entitled "Crossing Clinical Barriers on the Wings of Science: Evolution of ABO Incompatible Heart Transplantation," Dr. Brent gave a presentation entitled "Neonatal Tolerance: The Biological and Historical Background of Exploiting the Immature Immune System for Transplantation." Dr. Brent and I had a very pleasant conversation thereafter, and I had my picture taken with him.



Alexis Carrel
(1873 - 1944)

Field

Transplantation

Contributions

Dr. Carrel's research focused on experimental surgery, including the transplantation of tissues and whole organs. In 1902 he published a paper describing a technique for the end-to-end anastomosis of blood vessels. He was truly a pioneer in vascular suturing techniques. In 1910 he demonstrated that blood-vessels could be preserved for long periods in cold storage before being used in surgical transplantation. Earlier, in 1908, he had devised methods for the transplantation of whole organs and later, in 1935, in collaboration with Charles Lindbergh (the aviator), he helped develop an extracorporeal perfusion machine for organs excised from the body, thus, making transplantation a more practical clinical reality.

Dr. Carrel received the Nobel Prize in Physiology or Medicine in 1912 "in recognition of his work on vascular suture and the transplantation of blood vessels and organs." He was the first scientist working in an American laboratory to do so.

Pesonal Recollections

Obviously, Dr. Carrel died before I was born. My connection with Dr. Carrel is straightforward. In 1979 I completed my graduate studies at Duke University. Shortly thereafter, I accepted a position at the Battelle Human Affairs Research Centers (Seattle, WA). In 1980, Medicare coverage and reimbursement for heart transplantation became an issue. The Health Care Financing Administration, the federal agency which then administered the Medicare program, decided to explore the issue through a contracted research effort. I led an outstanding multidisciplinary team that wrote a proposal to conduct the study. Battelle was awarded the contract in 1981, and I, as the principal investigator, directed the study. As a result, I intensely studied the history of heart transplantation, reading virtually anything that I could get my hands on about the very early experimental era (1958-64), which was almost entirely the work of Dr. Norman E. Shumway, and his many Stanford University colleagues - Richard R. Lower, Edward B. Stinson, Eugene Dong, Jr., Raymond B. Stofer, Randall B. Griepp, and Edward J. Hurley. In doing so, I became aware of Dr. Carrel's landmark contributions. It's noteworthy that, over the years, abdominal transplant surgeons have been less forthcoming about the work of Dr. Carrel. At most, they mention the "Carrel patch." In short, for reasons I don't understand, Dr. Carrel's contributions have been overlooked by the abdominal transplant community.



Jean Dausset
(1916 - 2009)

Field

Immunology

Contributions

Dr. Jean Dausset demonstrated the existence of H antigens in man and elucidated the genetic factors regulating their formation. At the time he received the Nobel Prize, Dr. Jean Dausett's contributions were described in a press release as follows: "Between 1930 and 1950 when knowledge about transplantation immunology was increasing in the mouse, nothing was known about a corresponding system in man. Experimental tissue transplants comparable to those practiced on laboratory animals were not possible. Nevertheless, Jean Dausset's research was to dramatically blaze the trail to studies of rules for transplantation in man. Originally, Dausset studied auto-immuno diseases, and one of his methods was through immunological investigations of patients who had undergone repeated blood transfusions. The antibodies found in these patients proved to have no significance at all when it came to auto-immune diseases, but were instead an important indicator of differences in the cell-membrane structure of white blood cells between blood donors and recipients. When he went on to study the antibodies of women who had given birth to several children, Dausset was able to show that one single genetic system, localized on one single chromosome, determined these antigens. They came to be called human leukocyte antigens (HLA), and the genes that determined their formation, HLA genes. Thereby Dausset had identified the human equivalent to the H-genes in mice. The similarities between the two systems were soon shown to be much greater than originally suspected."

The Nobel Prize in Physiology or Medicine 1980 was awarded jointly to Baruj Benacerraf, Jean Dausset and George D. Snell "for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions".

Pesonal Recollections

I don't recall meeting Dr. Dausett, although our paths would have surely crossed. I began attending international transplantation society meetings in 1983. In 1984, I presented a paper on the quality of life of kidney and heart transplant recipients at the 10th International Congress of The Transplantation Society (TTS) in Minneapolis. This was my first TTS meeting. I am sure Dr. Dausett would have been there. Subsequently, between 1986 and 1998, I attended the 11th through the 17th TTS International Congresses which were held in Helsinki, Sydney, San Francisco, Paris, Kyoto, Barcelona, and Montreal. TTS meetings are held every two years. Dr. Dausett probably attended and participated in many of aforementioned meetings. (Note: Also, for further explanation, please see my personal recollections of Dr. George D. Snell.)



Gertrude B. Elion
(1918 - 1999)

Field

Pharmacology

Contributions

Gertrude B. Elion was a pioneer in drug research who shared the Nobel Prize in Physiology or Medicine in 1988.

Ms. Elion developed drugs for use in a vast array of conditions. They included drugs for herpes, leukemia, malaria, gout, immune disorders, and AIDS, and immune suppressants to overcome rejection of donated organs in transplant surgery. In perfecting one compound after another, Ms. Elion worked for four decades with Dr. George H. Hitchings.

Ms. Elion broke down gender barriers in the male-dominated world of scientific research, becoming one of the rare women to win a Nobel Prize and, even rarer, a scientist who did not have a doctorate.

Ms. Elion shared the Prize with Dr. Hitchings, who hired her as a $50-a-week assistant in 1944. Also sharing the Prize was Sir James Black of Britain, who discovered two classes of drugs, beta blockers, for high blood pressure and heart disease, and H-2 antagonists, for ulcers.

Seldom does the Nobel committee in Stockholm honor employees of pharmaceutical companies, but all three that year worked or had worked for such a company. Ms. Elion and Dr. Hitchings collaborated throughout their careers at the company known today as GlaxoSmithKline or GSK. In awarding the Prize to the three scientists, the Nobel committee said their work ''had a more fundamental significance than their discovery of individual drugs.''

Ms. Elion was noted for her precise work, intellectual brilliance and ability to work with others.

Few scientists matched the wide array of drugs that Ms. Elion and Dr. Hitchings developed. The drugs include acyclovir (Zovirax) for herpes; azathioprine (Imuran) to help prevent rejection of transplanted organs and in treatment of severe rheumatoid arthritis; allopurinol (Zyloprim) for gout; pyrimethamine (Daraprim) for malaria and trimethoprim (a component of Septra) for bacterial infections.

The two worked in lock step for much of their careers, but Dr. Hitchings was always one step ahead of Ms. Elion; as he moved into a new job, she filled the old one.

The two scientists wrote many papers together, sometimes with her name first, sometimes his. As Ms. Elion said, ''He had two arms of research and I was one of them.''

In 1991, President George Bush awarded Ms. Elion a National Medal of Science, saying her work had ''transformed the world.''

Gertrude Belle Elion was born in New York City on Jan. 23, 1918, and graduated with highest honors in chemistry from Hunter College in 1937. Ms. Elion decided to go into medical research as a teen-ager after her grandfather died of cancer and her father, a dentist and Lithuanian immigrant, encouraged her to develop a career. Her mother was from Russia.

But unable to find a laboratory position because she was a woman, Ms. Elion took a succession of jobs. First, she worked as a laboratory assistant in biochemistry. Then she worked as a food analyst, checking the acidity of pickles and making sure the berries slated for jam were not moldy. Next, she taught chemistry and physics in the New York City school system before earning a master's degree in chemistry at New York University in 1941.

After working for Johnson & Johnson for two years, Ms. Elion, helped by labor shortages in World War II, joined what was then Wellcome Research Laboratories, in Tuckahoe, N.Y., as a biochemist. Ms. Elion later became head of the company's experimental therapy department.

She retired in 1983, but continued working, helping to oversee work on the development of AZT as the first drug against H.I.V., the AIDS virus. Ms. Elion also served on the faculty of Duke University and the University of North Carolina.

While working for the drug company, Ms. Elion felt that her lack of a doctorate was a disadvantage, so she began a Ph.D. program at Brooklyn Polytechnic Institute. She took courses at night, commuting an hour and a half each way. But she eventually had to quit because she was told she would have to attend school full time to get a Ph.D., and she could not afford to give up her job.

When she gave her first scientific paper at a major meeting, she said she got into an argument with a distinguished scientist and stood her ground because ''I knew I was right.''

Ms. Elion never married. She was once engaged, but her fiancé died of a heart infection. Ms. Elion said she would not have advanced in her career if she had chosen to marry and have children because women were not encouraged then to work while their children were young.

Source: Written by Lawrence K. Altman, and lightly edited by Dr. Roger W. Evans: http://www.nytimes.com/1999/02/23/us/gertrude-elion-drug-developer-dies-at-81.html.

Pesonal Recollections

I never met Ms. Elion, but I was a graduate student in sociology at Duke University in Durham, North Carolina from September 1976 through June 1979. At the time I was admitted, I did not receive any form of financial assistance from Duke University. As a result, I took out a student loan, and began to look for a job, even before I arrived in Durham. I was told Dr. Jay R. Williams at the Research Triangle Institute (RTI, now RTI International) in Research Triangle Park, North Carolina may be in need of a research assistant, or that he might be able to help me find a position.

At the time, I was interested in kidney dialysis as a treatment modality for end-stage renal disease. I knew RTI had a contract to maintain what was then called the National Dialysis Registry, which was directed by Dr. Fred Bryan, whom I contacted concerning employment. Dr. Bryan informed me that RTI had submitted a contract proposal to what was then called the Health Care Financing Administration (HCFA, now known as the Center for Medicare and Medicaid Services, or CMS) to conduct a study to determine if a dialysis paid aide program would encourage dialysis patients to dialyze at home as opposed to a center. Center dialysis was generally considered to be more expensive than home dialysis. It was felt that by paying for an aide more in-center patients would opt for home dialysis and that, even with a paid aide, the cost of home dialysis would still be lower than in-center dialysis.

When I arrived in Durham I met with Dr. Fred Bryan and Dr. Lynn Guess, who would be working on the study if RTI were awarded the contract. Dr. Williams also participated in the meeting. Fortunately, RTI was awarded the contract by HCFA, and Dr. Bryan offered me employment as a Health Systems Analyst. I then worked at RTI for the three years I was at Duke. I actually used the data collected during the paid aide experiment for my doctoral dissertation, which was funded by what was then known as the National Center for Health Services Research.

My personal link to Ms. Gertrude Elion is nothing more than physical location. The RTI campus was/is directly across from what was then called the Burroughs-Welcome Co. headquarters building, an iconic building, which is where Ms. Elion and Dr. George Hitchings conducted their research. In 1988, the headquarters building was renamed the Elion-Hitchings Building. It has since been sold to United Therapeutics. Strangely, this means I spent my graduate school years at Duke working in close proximity to Ms. Elion and Dr. Hitchings.



Robert A. Good
(1922 - 2003)

Field

Immunology/Microbiology/Pathology

Contributions

Dr. Robert Alan Good was a pediatrician, microbiologist and pathologist. He gained international recognition in nearly 30 years of research at the University of Minnesota Medical School. He documented the importance of the thymus gland, gave the misunderstood tonsil its due and, in 1968, performed the first successful human bone marrow transplant.

He was a winner of the Albert Lasker Medical Research Award in 1970, recognizing his pioneering work in solving the mysteries of immunity and applying the findings to fatal diseases.

In the 1970's, Dr. Good became the chief scientist, president and director of the Sloan-Kettering Institute for Cancer Research in New York, as well as a professor of medicine, pediatrics and pathology at Cornell University Medical College. At his death he was the physician in chief and director of research at All Children's Hospital in St. Petersburg, and a distinguished research professor at the University of South Florida.

He was a founding member of the National Institutes of Medicine. He was author, co-author or editor of more than 2,000 papers and book chapters, received more than a dozen honorary degrees, and trained hundreds of students in immunology.

Dr. Good began his work in immune research in the 1940's, and helped identify types of cells that work together to fight off infections.

He first drew notice nationally when he reported his findings on the thymus gland to the annual meeting of the Federation of American Societies of Experimental Biology in 1962. He identified the gland, near the base of the throat, as a primary source for the body's defense mechanisms. (At that meeting he was cited for outstanding research by a scientist under 40.)

Next, in 1965, he reported evidence that the tonsils, widely regarded as useless, actually performed important functions in the very young. They had a role, he found, in developing the immune defense systems of mammals, including humans, and he advised even then that they should be removed only if involved in some serious health problem.

Dr. Good was one of a number of researchers whose work laid the foundations for transplanting healthy bone marrow, the part of the body in which many of the cells that make up the body's defenses are produced, into people with diseased or damaged immune systems. He referred to it as cellular engineering.

The 1968 transplant involved a 5-month-old boy with a profound immunal deficiency that had killed 11 male members of his extended family. Dr. Good led a team that corrected his fatal condition with bone marrow transplanted from his 8-year-old sister. The infant grew up to healthy adulthood.

Robert Good was born in Crosby, Minnesota. He graduated in 1944 from the University of Minnesota, where he received both a Ph.D. and an M.D. in 1947. He started teaching at the University of Minnesota in 1944 and was made an instructor in pediatrics at its medical school in 1950 after a stint as an investigator at Rockefeller Institute in New York. His career advanced in Minneapolis at the university hospitals and medical school, where he was named a professor of microbiology in 1962 and Regents' Professor in Pediatrics and Microbiology in 1969.

He was a member of President Richard M. Nixon's cancer panel in 1972 when he was recruited as president of the Sloan-Kettering Institute for Cancer Research. The position allowed him, aided by his trainees from Minnesota, to continue his research into the body's defenses against the invasion of foreign organisms, particularly cancer.

His tenure at Sloan-Kettering was marred by the discovery in 1974 of an academic fraud perpetrated by a former associate at his Minnesota laboratory, Dr. William T. Summerlin. Dr. Summerlin drew wide attention when he announced a breakthrough in skin transplantation. Actually, Dr. Summerlin's efforts to graft skin from a black mouse onto a white mouse had failed, but he used a dark pen to make the experiment appear to be a success.

Dr. Good ordered an immediate investigation of the matter, which gained notoriety as the case of the painted mice. But he was criticized as having failed to supervise Dr. Summerlin closely and, thus, having lent credence to his claims.

At Children's Hospital in Florida, Dr. Good developed a bone transplantation program for treating ailments including leukemia, aplastic anemias, and inborn errors of the metabolism. At the time of his death, his research involved the influence of nutrition on longevity and diseases of old age, as well as the practical aspects of bone-marrow and stem-cell transplantation and related forms of cellular engineering.

Source: Written by Wolfgang Saxon, but lightly edited by Dr. Roger W. Evans: http://www.nytimes.com/2003/06/18/us/robert-a-good-81-founder-of-modern-immunology-dies.html.

Pesonal Recollections

From 1988 through 2000 I was a member of the Board of Directors for the National Marrow Donor Program (NMDP). While serving in this capacity, I met Dr. Good, as I recall at a meeting in Washington, D.C. At the time, the Board of Directors meetings were often jointly scheduled with an NMDP social function intended to enhance the visibility of the organization. While I was well aware of Dr. Good’s seminal contributions, and had heard a lot about him, I really didn’t get to know him very well. I would call him more of an acquaintance than a friend. It’s unfortunate I did not have the time to get to know him better



Phillip S. Hench
(1896 - 1965)

Field

Rheumatology

Contributions

Dr. Phillip S. Hench specialized in arthritic disease. At the time he received the Nobel Prize, Dr. Hench's contributions were described as follows: "In the course of his work he observed the favorable effects of jaundice on arthritic patients, causing a remission of pain. Other bodily changes, for example pregnancy, produced the same effect. These and other observations led him gradually to the conclusion that the pain-alleviating substance was a steroid. In the period 1930-1938, Dr. Edward C. Kendall had isolated several steroids from the adrenal gland cortex. After several years of collaboration with Dr. Kendall, it was decided to try the effect of one of these substances, Compound E (later named cortisone), on arthritic patients. Delay in implementing this decision was caused by Dr. Hench's military service in World War II and by the costly and complicated isolation of the substance. In 1948-1949, cortisone was successfully tested on arthritic patients. Hench also treated patients with ACTH, a hormone produced by the pituitary gland which stimulates the adrenal gland."

In 1950, the Nobel Prize in Physiology or Medicine was awarded jointly to Edward C. Kendall, Tadeus Reichstein, and Philip S. Hench "for their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects."

Pesonal Recollections

I was a freshman in high school when Dr. Hench died. I initially learned about Drs. Hench and Kendall in relationship to transplant immunosuppression. From the early 1960s, azathioprine and steroids served as the basis for immunosuppressive therapy in clinical renal transplantation. Subsequently, antilymphocyte globulin, cyclosporine, and numerous other agents were introduced into the clinical immunosuppressive armamentarium.

I learned more about Drs. Hench and Kendall when I joined the Mayo Clinic staff in 1992 as Head of what was then called the Section of Health Services Evaluation. As an organization, Mayo Clinic took great pride in their Nobel Prize laureates. They were often referred to, and served as a source of motivation. Usually they were used to underscore the importance of an informal Mayo Clinic covenant implying that no individual is greater than the organization of which they're a part. Upon receiving the Nobel Prize, Dr. Hench affirmed this covenant when he commented as follows: "In our opinion, the awards we received belong truly to all the men and women of the Mayo Clinic because it was the spirit of cooperative endeavor, the fundamental credo of the institution, which made possible the work which resulted in our trip to Stockholm." In 1998 I was interviewed by Forbes magazine regarding the work of my section at the Mayo Clinic. The reporter was enamored with what I was attempting to accomplish, given the considerable adversity I faced. The article was published on June 14, 1999. Below a photograph of me he wrote: "For the first time in its 85-year history, the Mayo Clinic is being forced to think about the bottom line. The heretic behind it all is Roger Evans." He then closed the article with the following sentence: "The doctors who run Mayo would do well to let Evans get busy." As expected, through a convoluted assessment, it was decided that I violated the informal covenant and, as a result, I had no choice but to resign on December 3, 1999.



George H. Hitchings, Jr.
(1905 - 1998)

Field

Pharmacology

Contributions

Dr. George H. Hitchings won the Nobel Prize in Medicine in 1988 for pharmaceutical research that led to the creation of drugs to treat leukemia, gout, malaria and disorders of the human immunity system and that eventually made organ transplants possible.

For more than 33 years, Dr. Hitchings was the chief researcher and biochemist with the Burroughs Wellcome Company in Research Triangle Park, N.C. (now GlaxoSmithKline or GSK). For most of his career he worked closely with Ms. Gertrude Elion, and their work led to the development of important drugs such as AZT, used to treat AIDS.

The two joined forces in 1944. At the time, drug research was done on a trial-and-error basis. But Dr. Hitchings and Ms. Elion developed compounds for specific diseases, testing them in vitro and in animals, then watching for unexpected results. They perfected one new compound after another, shedding light on a variety of diseases afflicting humanity.

Their work was monumental, but because they were industry scientists, they were often overlooked by the Nobel Committee. Considered by many scientists to be the founders of the field of chemotherapeutics, they were eventually awarded the Nobel Prize in Medicine, nearly 30 years after most of their discoveries.

''He revolutionized the world of drug exploration and design,'' said Robert A. Ingram, chief executive of Glaxo Wellcome.

Dr. Hitchings pioneered the biochemical approach to chemotherapy. He theorized that it was possible to alter the way that deadly cells develop by introducing compounds into the cells slightly different from those that occur naturally. Those false building blocks would inhibit the growth of unwanted cells, like cancerous ones, by fooling them into thinking that they were replacing themselves.

The first false building block he used, in 1945, was closely related to thymine, one of four chemical roots that make up DNA. ''This was the key discovery from which everything else stems,'' he said.

In 1956, he helped synthesize trimethorpim, one of the active ingredients in Septra, an antibacterial medication that is effective against meningitis, the blood disorder septicemia and other bacterial infections.

Scientists have estimated that Dr. Hitchings' work, including the development of drugs like Imuran -- which blocks the immune response that triggers rejection of foreign tissues, making organ transplants possible -- has saved more than a million lives.

''His greatest joy was meeting people whose lives were saved by his medicine,'' said his son, Thomas. ''Across the planet, he met people who had been saved by his work. People married with children. The idea of this made him weep.''

The son of a ship builder, George Herbert Hitchings was born on April 18, 1905, in Hoquiam, Wash. He received bachelor's and master's degrees in chemistry at the University of Washington, and a doctorate in biochemistry at Harvard in 1933.

He authored or co-authored more than 300 published papers and was responsible for 89 United States patents. He was also involved in charitable organizations, serving as president of the Burroughs Wellcome Fund, which supports academic research, and the Red Cross.

Source: Written by Charlie LeDuff, lightly edited by Dr. Roger W. Evans: http://www.nytimes.com/1998/03/01/nyregion/dr-george-h-hitchings-92-won-nobel-prize-in-medicine.html.

Pesonal Recollections

I never met Dr. Hitchings, but I was a graduate student in sociology at Duke University in Durham, North Carolina from September 1976 through June 1979. At the time I was admitted, I did not receive any form of financial assistance from Duke University. As a result, I took out a student loan, and began to look for a job, even before I arrived in Durham. I was told Dr. Jay R. Williams at the Research Triangle Institute (RTI, now RTI International) in Research Triangle Park, North Carolina may be in need of a research assistant, or that he might be able to help me find a position.

At the time, I was interested in kidney dialysis as a treatment modality for end-stage renal disease. I knew RTI had a contract to maintain what was then called the National Dialysis Registry, which was directed by Dr. Fred Bryan, whom I contacted concerning employment. Dr. Bryan informed me that RTI had submitted a contract proposal to what was then called the Health Care Financing Administration (HCFA, now known as the Center for Medicare and Medicaid Services, or CMS) to conduct a study to determine if a dialysis paid aide program would encourage dialysis patients to dialyze at home as opposed to a center. Center dialysis was generally considered to be more expensive than home dialysis. It was felt that by paying for an aide more in-center patients would opt for home dialysis and that, even with a paid aide, the cost of home dialysis would still be lower than in-center dialysis.

When I arrived in Durham, I met with Dr. Fred Bryan and Dr. Lynn Guess, who would be working on the study if RTI were awarded the contract. Dr. Williams also participated in the meeting. Fortunately, RTI was awarded the contract by HCFA, and Dr. Bryan offered me employment as a Health Systems Analyst. I then worked at RTI for the three years I was at Duke. I actually used the data collected during the paid aide experiment for my doctoral dissertation, which was funded by what was then known as the National Center for Health Services Research.

My personal link to Dr. George H. Hitchings is nothing more than physical location. The RTI campus was/is directly across from what was then called the Burroughs-Welcome Co. headquarters building, an iconic building, which is where Dr. Hitchings and Ms. Gertrude B. Elion conducted their research. In 1988, the headquarters building was renamed the Elion-Hitchings Building. It has since been sold to United Therapeutics. Strangely, this means I spent my graduate years at Duke working in close physical proximity to Dr. Hitchings and Ms. Elion..



Olga Jonasson
(1934 - 2006)

Field

Transplant Surgery

Contributions

Dr. Olga Jonasson was a pioneer in transplant medicine and surgery, but also as a leader, mentor, teacher and the first woman transplant surgeon.

The collection of representations and images of Olga Jonasson can be viewed most coherently in the context of a revolution—a liberation movement in which she was at the forefront. Dr. Jonasson, was a pioneer in transplant surgery; her contributions to the practice of medicine spanned more than 40 years. As a very humble person who disliked being lauded, she would not have acknowledged the comments offered by her many friends, colleagues, former students, neighbors, fellow parishioners and peers in response to her death—comments such as ‘smart, intimidating, kind, tough, a luminary, respectful, larger than life, compassionate, principled, supportive, direct, loyal, generous, unforgettable’. Diminutive would not befit Olga, or OJ, as those who had the great fortune to be among her colleagues affectionately called her. In both stature and personality, she was indeed a grand woman.

Born in Peoria, Dr. Jonasson moved with her family to Chicago, where her father was a Lutheran minister and her mother was a nurse. When her family moved on later to Connecticut, Olga stayed in Chicago to begin her studies at Northwestern University; she was 16. She attended medical school and did her surgical residency at the University of Illinois. After her residency, she became a postdoctoral Fellow under the guidance of Dr. Elmer Becker at the Walter Reed Army Institute of Research in Washington, D.C., and followed with a clinical and research Fellowship at Massachusetts General Hospital under the direction of Dr. Henry J. Winn and Dr. Paul S. Russell. She also completed a Fellowship in cardiovascular and thoracic surgery in Chicago.

She became one in the tiny community of women surgeons, at a time when few had known or heard of any, and male patients and colleagues often dismissed them. By taking the inevitable hits, and doing so unflinchingly, Olga made it easier for all those women who followed as well as for others who had been arbitrarily excluded from a surgical career because of equally irrelevant ethnic reasons.

At the time Dr. Jonasson was certified by the ABS in 1965 she was only the 37th woman certified, while the number of men certified to that date exceeded 14,000. She was well on the way to becoming a leader who would change forever the demography of medicine, and specifically the specialty of surgery.

She became the first woman transplant surgeon, established the division of transplantation at UIC in 1968, performed the first kidney transplant in Illinois in the same year, and was a founding member of the National Tissue Typing and Histocompatibility Organization in 1974. In 1976, she became the first woman member of the Board of Regents at the American College of Surgery. A year later, she was named chief of surgery at Cook County Hospital. In 1987, she left Chicago for Ohio State University, where she became the first woman in the country to lead an academic surgery department at a co-educational medical school.

For her outstanding mentorship of minority surgeons, Dr. Jonasson was named honorary member of the American College of Black Academic Surgeons. In 1988, she was inducted as an honorary Fellow of the Royal College of Surgeons of England. Thereafter she became the Chief of Surgical Education and Research at the American College of Surgeons, where she initiated multi-center clinical trials on the topics of inguinal hernia repair and surgical quality of care, garnering in excess of $13 million of research funds. She continued to work as Education Editor of the Journal of the American College of Surgeons until her death. She was featured at a recent exhibit at the National Institutes of Health's National Library of Medicine, profiling groundbreaking female doctors.

No one would suggest that Olga Jonasson's body of work was ‘remarkable for a woman’. It was simply remarkable, by anyone's standard. That, in fact, is the only praise Olga would want or would accept.

One of her toughest jobs resulted from the passage by Congress in 1983 of the National Organ Transplant Act. Olga subsequently was named Chairperson of a task force that held meetings and hearings to determine how this complex legislation could be enacted and enforced. As a policy instrument, she was the lightning rod to which wildly disparate points of view, ugly protests and bitter criticisms of the law itself were directed. She presided over her task force with dignity and always with intelligence and firmness. Olga could not be swayed by false arguments. She had an uncanny ability to identify people who were lying or were out for personal gain. After it was all over, many people took credit for the resulting American transplant system that quickly became an object of national pride, and a world-wide standard. The one individual who never claimed any kind of personal credit was Olga Jonasson. Yet, we all knew that nothing could have been accomplished without the presence of this magnificent leader.

Dr. Jonasson's life-long quest for knowledge set the bar for all who followed. She rigorously provided several levels of peer review in study sections, editorial boards and surgical societies. Having meticulously researched her opinion, she frequently provided formidable mental sparring. Dr. Jonasson was generous with her knowledge and served as confidant and advisor to many nationwide; she enjoyed helping careers behind the scenes with the beneficiaries frequently unaware of her assistance.

An inspiring teacher, Dr. Jonasson was renowned for her ‘lively’ and rigorous student/resident teaching rounds. This commitment to excellence in teaching was acknowledged numerous times; as the 1971 Outstanding Educator in America Award and with several Golden Apple Awards. The Chief's club, a three-decade-long monthly tradition of dinner for chief residents held in her home, was prized (and feared) for the after dinner Socratic ‘grilling’ by an invited expert. She opened her heart and her home to furnish newly emerging surgeons with the art and critical thinking needed in excellent surgical practice.

There is no way to know the frustration, despair and ultimately the exhilaration and redemption of a unique individual like Olga Jonasson who was willing to give so much for her noble causes. In winning these battles, she taught those around her how to maintain the humanity often lost by people under perpetual siege. When asked why she chose surgery, she responded, ‘the act of actually intervening in someone's suffering was a prime motivation’. Giving to others and responding to their needs were strong family values that influenced all aspects of her life. Known among her friends, colleagues, neighbors and students for her gracious hospitality, she quietly dedicated her personal time to causes and communities that were important to her. When the Church of the Epiphany was in desperate need of repairs to address safety hazards and deterioration, nearly single-handedly, Dr. Jonasson raised almost $3 million and gave hundreds of volunteer hours herself.

With the passing of Olga Jonasson, the world lost not only a pioneer in transplant medicine, but also a dedicated leader, a renowned mentor, a remarkable teacher, a good friend and a most generous soul. In the ways she lived her life, personally and professionally, she set an admirable example, and made a place for those, men and women alike, who followed in surgery. While her accomplishments and honors denote contributions to the practice of medicine, most importantly, they advanced the care of surgical patients. Truly she cared for everyone.

Source: Bartholomew, A., Ascher, N. and Starzl, T. (2007), TRIBUTE: Dr. Olga Jonasson Born in Peoria, Illinois, August 12, 1934 Died in Chicago, Illinois, August 30, 2006. American Journal of Transplantation, 7: 1882–1883. doi: 10.1111/j.1600-6143.2007.01872.x. Link to the original source: http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2007.01872.x/full.

Pesonal Recollections

My personal reflections will be added at a later date.



Samuel L. Kountz, Jr.
(1930 - 1981)

Field

Transplant Surgery

Contributions

Dr. Samuel L. Kountz was an international leader in transplant surgery who tragically died at age 51.

In 1977, following a trip to South Africa as a visiting professor, he became ill. The illness was never diagnosed. However, he remained brain-damaged the remainder of his life and had to be cared for at home.

Occasionally, he was able to sit up in bed, and he apparently recognized certain things, but he was unable to speak. He responded emotionally with tears or laughter, and sometimes he recognized people.

At the time he fell ill, he had been head of surgery at the Downstate Medical Center in Brooklyn for five years and had performed 500 kidney transplants, then believed to be the most in the world. He was also chief of general surgery at Kings County Hospital Center.

Dr. Kountz previously was associated with the University of California School of Medicine in San Francisco, where he helped advance the techniques in transplanting kidneys.

He had a deep social drive beyond his scientific interest in advancing transplant surgery. He told friends that an important reason why he moved to Brooklyn was to improve medical care for the black community.

He once sat in the emergency room of Kings County Hospital to see how patients were treated. Dr. Kountz's interest in medicine stemmed from an incident when he was a young boy in Lexa, Ark., where he was born. He accompanied an injured friend to the local hospital. Moved by the ability of doctors to ease the friend's suffering, he decided to become a physician. His father, a Baptist minister, and his grandmother, who had been born into slavery, encouraged him.

In 1952, he graduated third in his class at the Agricultural, Mechanical and Normal College of Arkansas (now University of Arkansas at Pine Bluff). Dr. Kountz went on to graduate school at the University of Arkansas, where he earned a master's degree in chemistry.

He told friends that when he was a graduate student, he met Senator J. W. Fulbright, who advised him to apply for a scholarship to medical school. He won it on a competitive basis and became the first black to enter the University of Arkansas Medical School at Little Rock.

Dr. Kountz interned at San Francisco General Hospital and then spent seven years in surgical training at the Stanford Medical Center. While there, he did animal experiments on kidney transplantation and immunology.

Dr. Kountz discovered that large doses of a drug called methylprednisolone could help reverse the acute rejection of a transplanted kidney. That steroid drug was used for many years in the standard management of kidney transplant patients. Other researchers took advantage of Dr. Kountz's observations and used similar large doses of methylprednisolone in the treatment of many other conditions.

When he moved to the University of California in 1967, he worked with other researchers to develop the prototype of a machine that now is able to preserve kidneys for up to 50 hours from the time they are removed from a donor's body. The machine is used worldwide and is named the Belzer kidney perfusion machine in honor of Dr. Kuntz's partner, Dr. Folkert O. Belzer.

At the University of California at San Francisco and at Downstate Medical Center, Dr. Kountz and his colleagues advanced tissue typing tests to improve the results of kidney transplantation.

One of his major efforts was to help persuade the public to donate kidneys and other organs to help save the lives of others.

Source: Written by Lawrence K. Altman, lightly edited by Dr. Roger W. Evans. Link to original source: http://www.nytimes.com/1981/12/24/obituaries/dr-samuel-kountz-51-dies-leader-in-transplant-surgery.html

Pesonal Recollections

I completed my graduate studies in sociology at Duke University in 1979. In September 1979 I accepted a Research Scientist position at the Battelle Human Affairs Research Centers in Seattle, Washington, my first position out of graduate school. My wife and I relocated to Seattle in November 1979, just before Thanksgiving.

My primary research interest at that time was the treatment of end-stage renal disease (ESRD). Upon arriving at Battelle, I immediately set to work on a research proposal to conduct a multi-center study comparing the outcomes of ESRD patients who were on one of four treatment modalities – in-center hemodialysis, home hemodialysis, peritoneal dialysis, and kidney transplantation. The proposal was eventually submitted to the Health Care Financing Administration (now the Centers for Medicare and Medicaid Services).

One of my primary considerations in taking the position at Battelle was an opportunity to work with Dr. Christopher R. Blagg, who was Director of the Northwest Kidney Center. I had gotten to know Dr. Blagg while I was working as a Health Systems Analyst at the Research Triangle Institute in Research Triangle Park, North Carolina (1976-79).

At the time we arrived in Seattle, the Northwest Kidney Center was essentially the mecca for home hemodialysis, which was then considered a less expensive treatment option than in-center hemodialysis. In addition, it was felt that home hemodialysis patients had a better quality of life than in-center hemodialysis patients. People from around the world were coming to Seattle to gain firsthand experience with the program at the Northwest Kidney Center.

It was at this time that I also met Dr. Belding H. Scribner and Dr. Thomas L. Marchioro. Dr. Scribner invented the Scribner shunt, which essentially made maintenance hemodialysis a clinical reality. Dr. Marchioro was a transplant surgeon who, before moving to the University of Washington, was a member of the all-star transplant team led by Dr. Thomas E. Starzl at the University of Colorado in Denver. Drs. Blagg and Marchioro were directly involved in the preparation of my research proposal, which wasn’t funded the first time it was submitted. However, Mr. Carl Josephson at the Health Care Financing Administration encouraged us to pare down the proposal, and resubmit. We did so, and what became known as the National Kidney Dialysis and Kidney Transplantation Study was funded.

This was my first direct exposure to kidney transplantation. At the time, kidney transplant surgeons felt that kidney transplantation was more cost-effective than any kidney dialysis modality. Kidney transplant recipients, provided the transplant was successful, had a superior quality of life, thought to be even better than that of home hemodialysis patients. However, people were still concerned about costs and outcomes when a kidney transplant failed.

During my graduate school training I had visited many dialysis centers, and spent time with home hemodialysis patients while they were dialyzing. I had never seen a kidney transplant performed. I asked Dr. Marchioro if this was possible. He said it was, and I eventually joined him in the operating room to actually view a living donor kidney transplant.

Undoubtedly, it was during one of my many meetings with Dr. Marchioro that I learned about the tragedy that had befallen Dr. Samuel L. Kountz. The kidney transplant community was, and still is, fairly close-knit, and I recall people were greatly saddened about Dr. Kountz’s dismal prognosis for an unidentifiable condition. I first learned about Dr. Kountz approximately three years after he became ill, and was confined to his home. On a positive note, people have kept him in mind during the ensuing years. Even today, his name occasionally comes up at meetings. Most people remain baffled as to the underlying cause of his eventual death.

Unfortunately, I never had an opportunity to meet Dr. Kountz, but I have taken the time to better understand his contributions, both as a transplant professional, and as a person. He was a remarkable man whose life was tragically cut short.



H.M. Lee
(1926 - 2013)

Field

Transplant Surgery

Contributions

H. M. Lee, M.D. was an internationally renowned pioneer in organ transplantation and former professor and chairman in the Division of Vascular and Transplant Surgery at the Medical College of Virginia (MCV), which became the Virginia Commonwealth University (VCU) School of Medicine.

In the 1950s at MCV, Lee was an integral member of one of only four transplant programs in the world. He was a charter member and the 11th president of the American Society of Transplant Surgeons (ASTS), where he pushed for the passing of the National Organ Transplant Act, and he helped found, along with his mentor, David Hume, M.D., the organization that gave rise to the United Network for Organ Sharing, or UNOS.

Lee was born on Oct. 17, 1926, in Korea. He received his bachelor’s degree at Keijo Imperial University in 1945 and his M.D. at Seoul National University Medical School in 1949. In 1959, Lee made his way to MCV and met Hume, under whom Lee would study and work for more than a decade – first as a resident, then instructor, assistant professor, associate professor and finally professor.

In the late 1960s, Lee helped Hume and Bernard Amos, M.D., found the first regional organ sharing program in the United States, SEROPP, which later became the South-Eastern Organ Procurement Foundation (SEOPF). SEOPF gave rise to UNOS, a non-profit organization that today manages the nation's organ transplant system under contract with the federal government.

In 1973, following Hume’s death, Lee became director of the Clinical Transplant Program, professor and chairman of the Division of Vascular and Transplant Surgery and director of the Clinical Transplant Fellowship Program at VCU.

From 1984-1985, Lee was president of ASTS where he pushed for the signing into federal law of the National Organ Transplant Act, which outlawed the sale of human organs and established the Organ Procurement and Transplantation Network (OPTN) to maintain a national registry for organ matching, allocation and distribution.

His term as ASTS president established rigorous ethical standards for transplant candidate listing and prioritization, transplantation of “foreign nationals” and transplant surgeons’ minimum qualifications.

Under Lee’s 20-year leadership, the VCU Medical Center added liver, pancreas and liver cell transplantation to its capabilities, sustaining its reputation as an internationally renowned center for transplantation.

Until his retirement in 1997, Lee had the opportunity to mentor countless medical students, residents and fellows just as Hume had mentored him.

While patient, Lee had no desire to sit idly.  

After his retirement, he earned a law degree and practiced part-time as a consultant. Lee graduated at the age of 74 as the oldest graduate ever from the T.C. Williams School of Law at the University of Richmond.

On March 12, 2002, the transplant center Lee directed for two decades, which opened in 1964 and is now the oldest transplant unit in the United States, was re-designated and officially named The Hume-Lee Transplant Center by the VCU Health System Board of Visitors.

Source: Virginia Commonwealth University, edited by Dr. Roger W. Evans. Link to original source: http://news.vcu.edu/article/HM_Lee_Organ_Transplant_Pioneer_Dies.

Pesonal Recollections

I knew Dr. H.M. Lee very well. We were good friends, and colleagues. I always enjoyed talking to H.M. There was never a time when we didn’t have something to discuss. He understood what I did, and always complimented me on the research I had done, or was doing. We worked closely together on the National Organ Transplant Act of 1984.

I still recall where I got to know H.M. well. We were Helsinki, Finland in 1986. It was the Eleventh Congress of The Transplantation Society (TTS). We all had a great time. The gala event at the conclusion of the meeting was held in a wonderful facility, the name of which I don’t recall. It was all wood, and on several levels, having the “feel” of a log structure, and a rustic retreat.

It was also at this TTS meeting that I spent time with my good friends, including Dr. Nancy L. Ascher, Dr. Peter Stock, Barbara Elick, and Dr. Goran Klintmalm. One evening Nancy, Peter, Barb, and I, accompanied by a few other friends, all went out to a discotheque in Helsinki. Unannounced Goran Klintmalm showed up in red trousers and a green shirt, or vice versa. He looked as if he was dressed for a holiday event. We all shared a laugh behind his back. He had no idea we were making fun of him. Dr. John S. Najarian eventually walked in and, by the next morning, when we were on our way back stateside, we were all worst for the wear. Eventually, most of us who were on the same flight came around, and a few of us even picked up where we left off the night before! Needless, to say, Dr. H.M. Lee wasn’t in our company for any of the foregoing. H.M. was usually quiet and subdued, and certainly didn’t have much to drink!



Georges Mathé
(1922 - 2010)

Field

Oncology

Contributions

In the morning of the atomic age, there was optimism that the nuclear genie could heal as well as kill. By the mid-1950s, researchers had cured mice of leukemia by destroying diseased bone marrow with near-lethal doses of radiation, then rescuing them by transplanting healthy marrow.

But experiments on humans were stymied by fears that radiation exposure sufficient to kill the cancer might also kill the patient. Then came the news that six physicists had become ill from radiation exposure during a 1958 nuclear reactor accident in Yugoslavia.

One physicist died from especially heavy exposure, and one was relatively unaffected. Dr. Georges Mathé used the remaining four as guinea pigs in a radical experiment.

He injected bone marrow collected from donors to replace the damaged marrow. Bone marrow is spongy tissue found inside bones that contains stem cells that produce the body’s blood cells. For the first time, a human marrow transplant seemed to take, and the physicists survived. It was called the first successful bone marrow transplant not performed on identical twins.

In 1963, four years after treating the physicists, Dr. Mathé shook the medical world by announcing that he had cured a patient of leukemia by means of a bone-marrow transplant. In this case, there was no doubt that he had performed the feat of obliterating the patient’s stem cells and replacing them with a donor’s: the patient’s blood type had changed to that of the donor, the first time this had happened.

Most important, he demonstrated that stem cells injected in a patient not only heal radiation damage but also fight cancer. The reason is that the donor’s cells rule the body of the patient — whose own cells have been devastated — and attack the cancer as a foreign invader. The donor cells, however, can also attack the patient’s healthy ones, and vice versa. Preventing these attacks has been a principal concern of transplant science.

The leukemia patient died after 20 months, apparently of encephalitis. Judgments vary on whether the patient’s survival was long enough for Dr. Mathé to declare success.

But Dr. Brian Bolwell, chief of hematology at the Cleveland Clinic, said in an interview that Dr. Mathé had proved an important principle: “You can cure an incurable leukemia patient.”

In the process, Dr. Bolwell said, Dr. Mathé developed both a technique and an important term, “adoptive immunotherapy,” to describe how a person’s own immune system can be used to combat cancer and other diseases.

“It was quite a leap of scientific genius,” Dr. Joseph H. Antin, chief of stem cell transplantation at the Dana-Farber Cancer Institute in Boston, said in an interview. “He’s one of the original innovators. Much of what we have accomplished can be linked back in a fairly direct way to the work that he did in the 1950s and ’60s.”

Dr. Mathé worked at a time when original research on bone marrow transplants was percolating. A leader was Dr. E. Donnall Thomas, an American who in 1956 performed the first bone marrow transplant on a leukemia patient using marrow from an identical twin. (For years, such twin transplants were the only ones that worked.) In 1969, Dr. Thomas led the team that performed the first transplant between people matched by molecular analysis.

Dr. A. John Barrett, while president of the American Society for Blood and Marrow Transplantation, believed, like Dr. Antin, that Dr. Mathé should have shared the Nobel Prize in Physiology or Medicine with Dr. Thomas, who received the award in 1990.

“It’s always dangerous to say who was first,” Dr. Barrett said of Dr. Mathé in an interview, “but he was a leader, he was an inspiration, he was certainly ahead of his time.”

Dr. Barrett said Dr. Mathé’s insights helped lay the foundation for today’s sophisticated versions of immunotherapy that direct specific molecules to specific molecular targets. Transplants of stem cells have given way in many cases to removing stem cells from the patient or a donor, modifying them in a test tube, then putting them in the patient to fight cancer.

Georges Mathé was born on July 9, 1922, in Nièvre, France, earned his medical degree from the University of Paris and fought with the Resistance against the Nazis in World War II. He was arrested and sent to a concentration camp in Poland in a cattle car, but the war ended shortly after he arrived.

In 1951 he worked for a year at the Sloan-Kettering Institute in Manhattan, where, he said, he became skeptical of overreliance on chemotherapy. He became chief of hematology at Institut Gustave Roussy in Villejuif in 1961 and in 1964 founded the Institute of Cancer and Immunogenetics in Paris, where he was director.

He was also founder and president of the European Organization for Research and Treatment of Cancer, president of the European Society for Medical Oncology and a fellow of the Royal Society of Medicine and the New York Academy of Sciences.

Early in his career, Dr. Mathé contracted hepatitis B and spent two years in a hospital bed. The memory motivated him to visit his patients at the end of each day in the lab. In a 1974 interview with New Scientist, he explained, “Experiencing suffering is necessary to be a complete doctor.”

Source: Written by Douglas Martin, and lightly edited by Dr. Roger W. Evans: http://www.nytimes.com/2010/10/21/health/research/21mathe.html?_r=0.

Pesonal Recollections

Unfortunately, I never met Dr. Georges Mathé and, therefore, I have no personal recollections to offer. However, as noted above, some people feel Dr. Mathé should have shared the 1990 Nobel Prize with my good friend and former colleague, Dr. E. Donnall Thomas. However, as is often the case, frequently there is controversy surrounding the selection of Nobel Prize laureates. For example, there are many people who believe Dr. Thomas E. Starzl is worthy of the Nobel Prize, yet he has never received the award. In fact, there are many people who are convinced that Dr. Starzl, instead of Dr. Joseph E. Murray should have shared the 1990 Nobel Prize with Dr. Thomas. Unfortunately, like Dr. Mathé, Dr. Starzl may never be awarded the Nobel Prize.

As a footnote, the Georges Mathé Award was launched in March, 2010 by the Institut du Cancer et d'Immunogénétique (ICIG), to promote the therapeutic innovations and translational research initiated by Professor Georges Mathé. This annual distinction rewards a young researcher who has demonstrated audacity and originality in his / her work on the development of experimental and therapeutic research in the fields of cancer and immunology.

In addition, the European Society for Medical Oncology (ESMO) inaugurated the Georges Mathé Translational Research Fellowship in 2012. This Fellowship provides intuitive medical oncology researchers the opportunity to receive training in translational research in an European centre of excellence in medicine and therapeutic innovation in the field of oncology and cancer immunology. 



Sir Peter B. Medawar
(1915 - 1987)

Field

Immunology/Biology

Contributions

In 1960, when he received the Nobel Prize, Dr. Peter B. Medawar's contributions were described as follows: "Medawar's earlier research, done at Oxford, was on tissue culture, the regeneration of peripheral nerves and the mathematical analysis of the changes of shape of organisms that occur during this development. During the early stages of the Second World War he was asked by the Medical Research Council to investigate why it is that skin taken from one human being will not form a permanent graft on the skin of another person, and this work enabled him to establish theorems of transplantation immunity which formed the basis of his further work on this subject. When he moved to Birmingham in 1947 he continued to work on it, in collaboration with R. Billingham, and together they studied there problems of pigmentation and skin grafting in cattle, and the use of skin grafting to distinguish between monozygotic and dizygotic twins in cattle. In this work they took into consideration the work of R. D. Owen and concluded that the phenomenon that they called 'actively acquired tolerance' of homografts could be artificially reproduced. For this earlier work on transplantation and growth, Medawar was elected a Fellow of the Royal Society, London. When he moved to London in 1951, Medawar continued to work with R. Billingham and L. Brent, on this phenomenon of tolerance, and his detailed analysis of it occupied him for several years. He also carried out other researches into transplantation immunity."

Sir Peter B. Medawar received the Nobel Prize in Physiology or Medicine in 1960, which he shared with Sir Frank Macfarlane Burnet. They were awarded the Nobel Prize "for discovery of acquired immunological tolerance." Dr. Medawar was knighted in 1965 and, in 1981 he received the Order of Merit, the most prestigious of all royal honors.

Pesonal Recollections

I never met Sir Peter Medawar. The reasons are clear. As described in his obituary published by The London Times, in 1969, Sir Peter Medawar suffered a "grievous blow." He was then President of the British Science Association, which was meeting in Exeter, and while reading the lesson during the Sunday service in the cathedral he suffered a brain hemorrhage that left him seriously handicapped for the remainder of his life. He relinquished his post as director of the National Institute of Medical Research in 1971, and died in 1987 at age 72.



Joseph E. Murray
(1919 - 2012)

Field

Transplantation Immunology/Kidney Transplantation

Contributions

On December 23, 1954, Dr. Joseph Murray performed the world's first successful renal transplant between identical twins at the Peter Bent Brigham Hospital (now Brigham and Women's Hospital). In 1959 he performed the first successful transplant to a non-identical recipient and, in 1962, the first using a deceased donor (cadaver) kidney.

Dr. Murray received the Nobel Prize in Physiology or Medicine in 1990, which he shared with Dr. E. Donnall Thomas. They were awarded the Nobel Prize "for their discoveries concerning organ and cell transplantation in the treatment of human disease."

Pesonal Recollections

I met Dr. Murray many years ago. It was shortly after he received the Nobel Prize. I believe it was in Boston at the American Transplant Congress. I did not know Dr. Murray well enough to call him a friend. He was essentially an acquaintance. However, at a very early point in my career (1974), I became intimately familiar with his work, and the impact it had on transplantation. I was a graduate student at Eastern Michigan University (1974-76). At the time, I was interested in quality of life and suicide amongst hemodialysis patients. My intent was to write my master's degree thesis on this topic. When reading Renée C. Fox and Judith P. Swazey's book entitled The Courage to Fail: A Social View of Organ Transplants and Dialysis (Chicago, IL: The University of Chicago Press, 1974), I first learned of Dr. Murray's noteworthy contributions.



Hamilton Naki
(1926 - 2005)

Field

Surgery

Contributions

Hamilton Naki was a laborer who became a self-taught surgeon who worked with Dr. Christiaan N. Barnard. There have been numerous reports that Barnard chose him to assist in the world's first human heart transplant in 1967. However, this claim has been widely disputed.

The transplant took place on Dec. 3, 1967 at Groote Schuur Hospital in Cape Town.

Dr. Barnard allegedly began to acknowledge Mr. Naki's work only after the end of apartheid in 1991. In an interview shortly before his death in 2001, he called Mr. Naki "one of the great researchers of all time in the field of heart transplants."

Mr. Naki, who left school at 14 and had no formal medical training, spent five decades working at the University of Cape Town. Originally hired as a gardener there in about 1940, he acquired his formidable surgical skills through years of silent observation and covert practice at the university's medical school. He retired in 1991.

In 2003, the university awarded Mr. Naki an honorary master of science degree in medicine.

South Africa's apartheid laws forbade blacks from performing surgery on whites. Nonetheless, Mr. Naki worked alongside Dr. Barnard for decades as a lab technician, perfecting his craft, allegedly assisting in many operations on people. Operating on animals, Mr. Naki also taught surgical techniques to generations of medical students.

Hamilton Naki was born, most likely in 1926, in a poor, rural village in Transkei, a largely black former British protectorate in what is now South Africa's Eastern Cape Province. At 14, lacking the money to continue his education, he hitchhiked to Cape Town to find work. The university hired him to tend its grounds and tennis courts.

In the late 1950's, Mr. Naki took a job at the medical school, where he cleaned lab animals' cages. He was quickly recognized for his intelligence, keen powers of observation and steady hands, and was gradually allowed to become involved in more serious work.

Mr. Naki learned to anesthetize animals, and eventually to do surgery on them, operating on rabbits, pigs, dogs and even a giraffe. Many of the animal surgeries he performed, including coronary bypasses and heart and liver transplants, helped to perfect techniques that were later used on humans.

"Hamilton Naki had better technical skills than I did," Dr. Barnard said in an interview quoted in The Daily Telegraph of London. "He was a better craftsman than me, especially when it came to stitching, and had very good hands."

On Dec. 2, 1967, Denise Darvall, a young white South African woman, was hit by a car as she was crossing a Cape Town street. Taken to Groote Schuur Hospital, she was declared brain-dead. Her family gave permission for her heart to be transplanted into the chest of Louis Washkansky, a 55-year-old grocer whose own heart was failing.

As a black man, Mr. Naki could not operate on Ms. Darvall even after she was dead. But, allegedly, Dr. Barnard so prized his ability that he drafted him as a member of the team that would lift out her heart. Again, as mentioned above, this claim has been widely disputed.

In a painstaking operation, allegedly lasting many hours, Mr. Naki's team removed Ms. Darvall's heart, washing it repeatedly to cleanse it of her blood before introducing some of Mr. Washkansky's. On Dec. 3, Dr. Barnard transplanted the heart into Mr. Washkansky, who lived for 18 days before dying of pneumonia.

During his years at the university, Mr. Naki lived on the outskirts of Cape Town in a one-room shack without electricity or running water. When he retired, he was paid a gardener's pension, far less than a lab technician's.

In 2002, Mr. Naki was awarded the Order of Mapungubwe, one of South Africa's highest honors, for outstanding contribution to medical science.

In an interview with The Guardian of London in 2003, Mr. Naki expressed little bitterness about a lifetime spent working in the shadows. "I was called one of the backroom boys," he said. "They put the white people out front. If people published pictures of me, they would have gone to jail."

Source: Written by Margalit Fox, but substantially edited by Dr. Roger W. Evans. The link to the original source, which can be read in its entirety as published, is as follows: http://www.nytimes.com/2005/06/11/obituaries/11naki.html.

Pesonal Recollections

I first learned about Mr. Hamilton Naki in February of 2014. A friend, who was originally from Kenya, told my wife that a black man had assisted Dr. Christiaan Barnard with the first heart transplant. My wife asked me if this was so. I told her it was unlikely, but I would check. In short order, based on an Internet search, I identified Mr. Naki. Initially, everything I read seemed to be consistent, and Mr. Naki appeared to be a remarkable man, and a gifted “surgeon,” although not formally trained as such. However, as I delved deeper into Mr. Naki’s biography, it became clear that much of what had been written was inaccurate. In fact, what I read was deeply disconcerting. It seemed as if everyone who had written about Mr. Naki had relied on the same source documents, which later proved to be in error. In several instances, retractions have been made, or footnotes citing inconsistencies have been added to previous publications.

I must say I’m unsure what to make of what I have read. Clearly, Mr. Naki worked with Dr. Barnard in some capacity, but I think it’s reasonable to assume that he did not assist with the first human heart transplant. He may have had role, but it remains unclear, and subject to considerable controversy. Given the number of people involved in the first heart transplant, as well as the number of people who knew Mr. Naki, it seems someone should have been able to provide indisputable evidence if Mr. Naki was present for the first heart transplant. Instead, all we have are conflicting reports. However, perhaps the most credible account comes from Dr. John Terblanche, who reached the following conclusion in a letter published in The South African Medical Journal: "Thus, the claims that he (Naki) was an integral part of the first human heart transplant team and performed the operation on the donor are fictitious, mischievous and false. Like me, Hamilton’s first knowledge of this great event would have been after the event, in the newspapers or from the wireless."



Hans Popper
(1903 - 1988)

Field

Hepatology

Contributions

Dr. Hans Popper was an authority on liver diseases and a principal figure in the founding of the Mount Sinai School of Medicine of the City University of New York.

Dr. Popper played a major role in the understanding of hepatitis viruses. He was known internationally as the founder of hepatology, the study of the liver and its diseases.

Among his contributions to medicine was his research demonstrating that the liver is the only organ in the body that does not deteriorate with age. The research had major ramifications in the field of liver transplantation. The author of 800 papers and 28 books, he established diagnostic guidelines for several major liver diseases.

Dr. Popper, the Gustave L. Levy Distinquished Service Professor at the Mount Sinai School of Medicine, was the medical school's first dean of academic affairs when it was created in 1963. He also served as president and dean of the Mount Sinai Medical Center in 1972 and 1973.

Born in Vienna in 1903, Dr. Popper attended medical school at the University of Vienna. As a young physician in Austria, he conducted research in biochemistry, then a new field of medical inquiry.

With Austria under Nazi occupation, Dr. Popper came to the United States in 1938, settling in Chicago. Between 1938 and 1957, he received a research fellowship at the Cook County Hospital, earned a doctorate in pathology at the University of Illinois and held a succession of senior positions at the Cook County Hospital, including director of pathology.

He moved to New York City in 1957, accepting a position as chief pathologist at Mount Sinai. As its first dean, he played a central role in shaping the academic philosophy of the Mount Sinai Medical School, which was incorporated in 1963 and admitted its first students in 1968.

He was chairman of the medical school's department of pathology until 1973, when he gave up his administrative duties. He remained active in research and teaching until his death.

Source: Written by Thomas J. Luek, lightly edited by Dr. Roger W. Evans. Link to original source: http://www.nytimes.com/1988/05/08/obituaries/dr-hans-popper-an-authority-on-liver-diseases-is-dead-at-84.html.

Pesonal Recollections

I never met Dr. Hans Popper, but I became very familiar with his work. The circumstances were as follows.

By 1982, liver transplantation was becoming a reasonably successful treatment modality for end-stage liver disease. As is often the case, there was considerable debate as to whether or not liver transplantation was “experimental or therapeutic.” This, in turn, had implications for insurance coverage and reimbursement policy. At the time, I was a Research Scientist at the Battelle Seattle Research Center in Seattle, Washington, where I was directing the National Heart Transplantation Study (NHTS). The NHTS was a multi-center study which was intended to provide the Health Care Financing Administration (HCFA, now the Centers for Medicare and Medicaid Services) with guidance on the current status of heart transplantation relative to coverage and reimbursement policy. In 1980, HCFA suspended Medicare coverage of heart transplantation, which had been limited to heart transplants performed only at Stanford University.

The issues surrounding liver transplantation were identical to those surrounding heart transplantation, with one exception – Medicare did not cover liver transplantation under any circumstances. To address the issues, the National Center for Health Services Research and Health Care Technology Assessment conducted an analysis. The resulting report was entitled “Transplantation of the Liver. Health Technology Report, 1983, No. 16.” As expected, the report was negative, concluding that liver transplantation was essentially experimental and, in effect, should not be covered by third party payers. The transplant community was unhappy with this result, and considerable debate ensued.

Based on the research my colleagues and I were doing on heart transplantation, I proactively directed my attention to liver transplantation. Two key issues were relevant to both heart transplantation and liver transplantation – how many people might benefit from each procedure (i.e., need), and how many donor organs could conceivably be available (i.e., supply).

In estimating need, it is important to establish all relevant indications for transplantation. It is this regard that I became familiar with the work of Dr. Popper, as well as many other hepatologists (Popper’s book entitled “Progress in Liver Diseases,” of which there have been numerous editions and co-authors, was particularly helpful). I established a list of conditions for which liver transplantation was indicated, and then estimated the number of persons who died each year from each of these conditions. From an epidemiological perspective, the work of Dr. Popper and his hepatologist colleagues throughout the world was essential.

Given my research, I prepared a short report entitled “The Need for and Cost of Liver Transplantation in the U.S.” (dated February 20, 1984). This report provided an objective review of the current status of liver transplantation in the U.S. I concluded that approximately 9,500 people might benefit from liver transplantation each year and, of these, about 300 would be children under age 15.

Earlier, another noteworthy event had occurred. On June 20 through 23, 1983, the National Institutes of Health had convened a Consensus Development Conference on Liver Transplantation, in which I participated. The consensus panel report included the following statement: “after extensive review and consideration of all available data, this panel concludes that liver transplantation is a therapeutic modality for end-stage liver disease that deserves broader application.”

Subsequently, in March 1990, the Agency for Health Care Policy and Research (AHCPR) updated the aforementioned 1983 National Center for Health Services Research and Health Care Technology Assessment report (“Assessment of Liver Transplantation: Number 1”). The 1990 report concluded that “transplantation of the liver is an established treatment for certain conditions that cause irreversible damage to the liver resulting in end-organ failure.”

Despite the available evidence, the evolution of insurance coverage and reimbursement policy proved uneven. Medicare began to cover pediatric liver transplantation in 1983, although there were few beneficiaries due to Medicare qualifications. Nonetheless, with much broader implications, private insurers followed suit. However, it was not until April, 1991 that Medicare extended coverage to adult liver transplantation, by which time, many private insurers had already done so.



Felix T. Rapaport
(1929 - 2001)

Field

Transplant Surgery/Immunology

Contributions

Dr. Felix T. Rapaport was an accomplished surgeon and scientist whose early contributions in the field of transplantation made him well-known throughout the community. Born in Munich in 1929, the Jewish Rapaport family fled to France in 1936, and later was forced to leave the continent altogether to avoid the atrocities of World War II. After initially settling in the Dominican Republic, Rapaport came to the United States in 1945, where he received both his undergraduate and his medical degree from New York University. His mentor, Dr. John Converse, was an early researcher in the field of transplantation; Rapaport quickly inherited this interest.

After battling a near-fatal case of hepatitis, and a stint in the United States Navy as an officer, Rapaport’s influence on the medical community began to take off rapidly. Beginning in 1958, his studies of skin allograft rejection in human subjects supported the belief in tissue typing. His research, along with the studies being done in dogs by Dr. Jean Dausset in France, defined the human (and dog) leukocyte antigen systems, a key piece of the transplantation puzzle. Dausset received the Nobel Prize for his discoveries in 1980, crediting Rapaport for his equal contribution to the revolutionary findings. Rapaport made many other contributions to the field, as well, including describing the tolerogenic role of stem cells, factors that negatively influenced cellular immunity, and further studies into antigens. In addition to his scientific contributions, Rapaport also served as a “professional father” to the foundling study of transplantation. He was heavily involved in the Transplantation Society from its very beginning, and was its very first Secretary, a later President, and a 35-year council member. He served as the editor of the journal Transplantation Proceedings for over three decades, and was an outspoken advocate for issues relating to transplantation, especially on an international scale.

Rapaport and Starzl were acquainted through their early work, and the two were close friends and colleagues, even when they did not always necessarily agree. Though they did not work together physically in the lab or operating room, their correspondence reveals a relationship of intellectual exchanges of ideas, concerns, and new findings. Starzl’s respect for his colleague is apparent when reading through the documents, particularly in his introductory speech for Rapaport’s 1998 receipt of the Medawar Prize. Dr. Rapaport passed away on April 12, 2001.

Source: Written by Dr. Thomas E. Starzl, but lightly edited by Dr. Roger W. Evans: http://www.starzl.pitt.edu/people/rapaport.html.

Pesonal Recollections

I met Dr. Felix T. Rapaport in Minneapolis, Minnesota in March of 1982. I had been asked by the National Institutes of Health (NIH) to serve on a review committee for what was then called a Program Project Grant. The grant had been submitted by Dr. John S. Najarian and his colleagues at the University of Minnesota. Dr. Najarian was Chair of the Department of Surgery. The proposal was a continuation of an existing Program Project Grant.

At the time, Program Project Grants consisted of a large number of small projects (grants), all of which were organized around a general theme, and bundled together. As I recall, Dr. Najarian’s Program Project Grant consisted of approximately 30 individual projects dealing with various aspects of transplantation. Each grant had a Principal Investigator, or multiple Co-Investigators.

Every member of the review committee was assigned multiple projects to evaluate. I was asked to review 2 or 3 projects for which Dr. Roberta G. Simmons was the Principal Investigator. Dr. Simmons, now deceased, was a University of Minnesota sociologist with an interest in the quality of life of kidney transplant recipients and living kidney donors. Dr. Simmons was the first author of a book entitled Gift of Life: The Social and Psychological Impact of Organ Transplantation, which was published in 1977. Her co-authors were Dr. Susan D. Klein and Dr. Richard L. Simmons, who was her transplant-surgeon husband.

As I recall, Dr. Rapaport was asked to review several projects focused on various aspects of transplant immunology. He was very thorough in his reviews, and voiced well-reasoned opinions concerning the quality of the proposed research. He was fair in his assessments, and kind in presenting his remarks. I don’t recall anyone taking issue with his reviews.

I remained friends with Dr. Rapaport right up until he died. I would always see him at various transplantation society meetings, and we often stopped to talk. Although he wasn’t entirely conversant with my work, he always expressed an interest in what I was doing. I suspect he thought of me as an economist or a quality of life researcher. I count it a privilege to have known Dr. Rapaport.



Keith Reemtsma
(1925 - 2000)

Field

Transplant Surgery/Cardiac Surgery/Xenotransplantation

Contributions

In 1964, Dr. Keith Reemtsma transplanted a kidney from a chimpanzee into a woman who then lived with it for nine months.

In addition to performing cross-species transplants, known as xenotransplantation, Dr. Reemtsma was an expert in all kinds of human transplants. For 23 years, he was Chairman of the Department of Surgery at Columbia Presbyterian Medical Center, where he helped create a leading heart transplant center.

''Keith was a giant in the field of transplantation,'' said another surgical pioneer, Dr. Thomas E. Starzl of the University of Pittsburgh, who developed liver transplants.

''If xenotransplantation eventually works, no doubt the starting point will be traced to Keith Reemtsma,'' Dr. Starzl said.

Dr. Reemtsma is credited with being the first to show that nonhuman organs could be transplanted into humans and function for a significant period. He achieved that by giving six humans chimpanzee kidneys in the first chimpanzee-to-human organ transplants in 1963 and 1964.

A 23-year-old teacher survived with a chimpanzee kidney for nine months; she died of overwhelming infection. The other five recipients also died from infections, from 8 to 63 days after receiving chimpanzee kidneys.

Still, the length of the teacher's survival, as well as the nine-week survival of a 44-year-old dock worker, surprised many experts. ''That was his signature contribution,'' Dr. Starzl said, and ''it has been the one real beacon of hope'' for researchers who have tried to break the cross-species transplantation barrier.

Dr. Reemtsma undertook the controversial transplants in desperation, because of an impasse in obtaining donor organs and a reluctance to use live human donors ''for ethical, scientific and legal reasons,'' he wrote later in a scientific journal.

In the 1960's, doctors knew that certain blood cells recognized transplanted organs as foreign and attacked them, but they did not know which cells were involved or how the process worked. Now, as the field of immunology has flowered, scientists have identified several cells that act in concert to reject foreign cells. Also, scientists have developed several drugs to suppress the immune system to prevent such rejection. Dr. Reemtsma lived to see his students achieve one-year survival rates of up to 90 percent for human kidney transplants and 85 percent for heart transplants.

But as the results improved, the waiting list for organs grew. Dr. Reemtsma continued to promote research into xenotransplantation in the belief that there would never be a sufficient supply of human organs. But protests from advocates for animal rights and concerns that giving humans animal organs could unleash another AIDS virus have heightened the controversy over cross-species transplants.

Dr. Reemtsma spent his career seeking to transplant islet cells from the pancreas as a cure for diabetes. A month before his death, he learned that scientists in Canada had apparently succeeded with this procedure in eight patients.

''He always thought it was going to work,'' said his wife, Judy Reemtsma.

Dr. Reemtsma, who stood 6 feet 3 inches, was born in Madera, Calif., on Dec. 5, 1925. He grew up on a Navajo Indian reservation in the Southwest, where his father, Henry, was a Presbyterian minister and missionary.

Dr. Reemtsma attended schools in Oklahoma and Utah and graduated from Idaho State College in Pocatello in 1945. After earning a medical degree at the University of Pennsylvania in 1949, Dr. Reemtsma began training at Columbia to become a surgeon. But in 1951 his career was interrupted by the Korean War; he served in the Navy and Marine Corps.

According to Mrs. Reemtsma, Dr. Reemtsma was a model for the character Dr. Hawkeye Pierce in the movie and television series ''M*A*S*H.''

After the war, Dr. Reemtsma became the chief resident at Columbia. He received a doctorate in medical science from Columbia in 1958 as he was leaving for Tulane.

In 1966, he became chairman of the Department of Surgery at the University of Utah. Organ transplantation remained his main interest. But when he learned that Dr. Willem Kolff, who had developed the artificial kidney, was unhappy at the Cleveland Clinic, Dr. Reemtsma recruited him to Salt Lake City to establish one of the world's first programs to develop a variety of artificial organs for implantation in humans.

''Reemtsma was a man who immediately inspired confidence,'' Dr. Kolff said. He went on: ''I bought a house in Salt Lake City before I had a contract because there was never any doubt about his word. I came with an extensive program, and he offered me wooden barracks from World War I that no one wanted but that I thought were ideal.''

The work in Utah led to the first implantation of an artificial heart, in Dr. Barney Clark in 1982 at the University of Utah. Mechanical hearts, known as ventricular assist devices, are now used as temporary bridges to transplants at Columbia and other hospitals.

When Columbia recruited Dr. Reemtsma to be its chief surgeon in 1971, ''he had no desire to leave Utah,'' Dr. Kolff said. He made demands that ''he never expected Columbia would accept,'' and Columbia accepted, Dr. Kolff said.

Much later, after stepping down at Columbia, Dr. Reemtsma founded an international center for health outcomes research there. Dr. Reemtsma advocated a system of ''your fault'' insurance in which individuals paid for medical problems that developed from having ignored clear health warnings.

Dr. Starzl recalled coming down with the flu, while he and Dr. Reemtsma were at a meeting in Japan. When Dr. Reemtsma learned of his condition, he advised Dr. Starzl to go home.

''Keith seemed fine then,'' Dr. Starzl said, ''but 10 days later, he called me from home and said he had turned yellow'' from cancer of the liver.

Source: Written by Lawrence K. Altman, although lightly edited by Dr. Roger W. Evans. The link to the original article in its entirety is as follows: http://www.nytimes.com/2000/06/28/nyregion/keith-reemtsma-74-pioneer-in-medical-transplants-dies.html.

Pesonal Recollections

My personal reflections will be added at a later date.



George W. Santos
(1928 - 2001)

Field

Bone Marrow Transplantation

Contributions

George Wesley Santos was a pioneer in the development of bone marrow transplants.

Dr. Santos received his bachelor's degree in quantitative biology from the Massachusetts Institute of Technology (MIT). He also completed his master's degree in physical biology at MIT. After completing his studies at MIT, he received his medical degree and completed both a residency and fellowship at Johns Hopkins University.

At the time of death, Dr. Santos was professor emeritus of oncology and medicine at the Johns Hopkins University School of Medicine. He performed his first human bone marrow transplant in 1968 at what is now known as the Johns Hopkins Bayview Medical Center.

He founded the marrow transplant program at the Johns Hopkins Oncology Center that year and directed it until retiring in 1994. Throughout his career he worked on ways to improve the outcome of transplants in cancer patients.

In the early days of such transplants, the patient was often given nearly fatal doses of radiation to kill all the cancer cells before being given a transplant of cancer-free marrow cells. Dr. Santos worked to develop alternatives that were less dangerous to the patient.

He was also among the first medical scientists to recognize the importance of giving patients drugs to suppress their immune systems, avoiding a life-threatening complication in which the transplanted marrow attacks a patient's own tissues as alien material. He was one of the first to test the drug cyclosporine for the treatment of that complication.

Initially, he and his colleagues at Johns Hopkins successfully treated leukemia and aplastic anemia, an often fatal form of anemia, then explored transplanting marrow to fight other types of cancer.

George Santos was born in Oak Park, Ill., and graduated in 1951 from M.I.T., where he also received a master's degree in physical biology that year. He completed medical school and his residency at Johns Hopkins. He began to focus on bone marrow transplantation while serving in the Naval Reserve at the Naval Radiologic Defense Laboratory in San Francisco in the late 1950's. Returning to Johns Hopkins on a fellowship in 1960, he conducted the institution's first transplant studies on animals.

In 1988, he won the Bristol-Myers Award, which is given annually to a ''scientist who has made a unique contribution to fundamental or clinical cancer research.''

On that occasion he said he had recently attended the wedding of a woman he had treated for aplastic anemia as a teenager 15 years earlier. A wall of his office at Johns Hopkins was covered with photographs of such former patients.

Source: Written by Wolfgang Saxon, lightly edited by Dr. Roger W. Evans. Link to original source: http://www.nytimes.com/2001/01/29/us/george-w-santos-72-pioneer-in-bone-marrow-transplants.html.

Pesonal Recollections

Unfortunately, I never had occasion to meet Dr. Santos.

From 1988 through 2000 I was a member of the Board of Directors for the National Marrow Donor Program (NMDP). I don’t recall Dr. Santos being directly involved with the NMDP, although it is possible he served on one or more committees, which met separately from the Board. He may have attended some NMDP functions, but I don’t recall seeing him. What I do remember are occasional references to him and his work. Everyone held him in very high regard.



Rudi Schmid
(1922 - 2007)

Field

Hepatology/Liver Transplantation

Contributions

Dr. Rudi Schmid was a hepatologist whose work began in the 1950s with studies on porphyrias - disorders that can cause neurological symptoms and mental health problems. Subsequently he focused his attention on bilirubin, its impact on child jaundice, and its relationship to brain damage. He later became an advocate for liver transplantation, insisting that the procedure should be more widely available at a time when third party payers were unwilling to pay. Dr. Schmid did not agree, and was firm in his beliefs. In the ensuing years, Dr. Schmid served as dean of the medical school at the University of California at San Francisco (1983-89). He was both a medical educator, and an academic innovator.

Pesonal Recollections

In 1982, public and private insurers did not cover liver transplantation, which they considered to be an experimental procedure. This outraged the transplant community. There were numerous high profile cases involving children with biliary atresia in need of liver transplants who had health insurance coverage, but their insurers refused to pay for the procedure. In hopes of sorting out the issues, on June 20-23, 1983, the National Institutes of Health (NIH), at the insistence of Surgeon General C. Everett Koop, convened a Consensus Development Conference on liver transplantation. Many prominent physicians, surgeons, and scientists were asked to speak, or participate, amongst them, Dr. Schmid, who chaired the NIH panel. I was asked to address the economic issues associated with liver transplantation - a bit part in a much larger drama. I met Dr. Schmid at this conference. I was very impressed. He was steadfast in his thoughts. The consensus conference report included the following statement: "After extensive review and consideration of all available data, this panel concludes that liver transplantation is a therapeutic modality for end-stage liver disease that deserves broader application." Dr. Schmid was forceful in this regard and advocated accordingly. In 1983, Medicare began to cover pediatric liver transplantation, although there were few beneficiaries due to Medicare qualifications. Nonetheless, with much broader implications, private insurers followed suit. However, it was not until April, 1991 that Medicare extended coverage to adult liver transplantation, by which time, many private insurers had already done so. A new era in transplantation was ushered in, thanks to Dr. Schmid.



Dame Sheila Sherlock
(1918 - 2001)

Field

Hepatology

Contributions

For decades Sheila Sherlock was the world's foremost hepatologist, an audacious thing for a woman to be, especially in the 1950s. She was a small, plump bundle of energy and her clinical, research, teaching, editorial, and written output was phenomenal. She was the first woman to be appointed professor of medicine in the United Kingdom and she was the Royal College of Physicians' first woman vice president. She wrote the first textbook on the subject, Diseases of the Liver and Biliary System, in 1954; it has been translated into at least six other languages, and the 11th edition, co-authored with James Dooley, came out a fortnight before her death.

Little was known about liver disease when she began her career. Her clinical research, innovation, and teaching led to improved diagnosis and treatment and helped establish and develop hepatology. She introduced needle biopsies, replacing laparoscopy and aiding diagnosis in patients too ill to undergo general anesthetics. Jaundice was common in allied troops, and the biopsy material shed light on its causes. In 1966 she helped create what is now a standard test in diagnosing primary biliary cirrhosis, later showing that it was an autoimmune condition.

From Folkestone Grammar School she went to Edinburgh University, graduating top of the class in 1941. She was appointed lecturer and honorary consultant physician at the Hammersmith Hospital and Postgraduate Medical School when she was still only 30. By the time she was 35 she and her liver unit were famous.

She became an FRCP in 1951, aged 33, by far the youngest woman to be elected. In 1982 she was narrowly defeated for the college presidency, when, it is said, a gang of fellows in Birmingham chartered a charabanc to vote in person for her rival, Bill (later Sir Raymond) Hoffenberg.

In 1959 she moved—like a tornado, according to Sir Roy Calne—to the Royal Free Hospital and medical school. Doctors came from all over the world to learn from her, and at one time all of the world's liver doctors had been through her unit. She did a weekly ward round for them, treating them like small children, and they took it like lambs.

She was a mother hen to those working under her and in her department, and did all she could to teach them and advance their careers, pushing them out of the nest when she felt they were ready. One of her protégés was Ellis Samols, who brought radioimmunoassay to Britain. Once, on a US trip, she met someone who hadn't heard of her but knew Ellis, and asked her if she worked in his lab. Instantly, Ellis was deemed ready to spread his wings and fly.

She has reduced male junior doctors to tears, and she could tear up a third and fourth draft of a research paper while enumerating her criticisms. Dr Alex Paton, who worked under her, recalls the interview: “Are you prepared to push patients in a bed to the laboratory? You are? The job is yours.” Many years later when he was working for the BMJ, she received a copy of his critique of a paper she had submitted. As expected, she gave him a rocket. Criticism was a one way process. Despite all this he and numerous others held her in terrific affection.

If she was maternal to her staff, she was paternalistic to her patients. She knew what was best for them and would tell them what she thought and what she was going to do. There was little place for good taste or patients' feelings.

In the 1950s and 1960s consent to research on patients was rarely questioned or discussed. Doctors on Sheila's team might go, quaking, to a patient with pneumonia, and perform a procedure; but most patients adored her and would submit to almost anything. Then, Dr Maurice Papworth questioned the way patients were being experimented on in a magazine called Twentieth Century, following this up in his 1969 book Human Guinea Pigs. Sheila was a prime target, the storm raged for some time, and she never forgave Maurice.

In 1990, when the Scientist magazine published a list of the world's 10 most cited women scientists of the previous decade, she was among them. She received awards and honors too numerous to list.

Sheila let her hair down at parties. She loved sport. She played tennis competitively, could name the Kent County Cricket Club's team, understood Rugby football, and was an Arsenal supporter.

Source: Written by Caroline Richmond, lightly edited by Dr. Roger W. Evans. The link to the original source is as follows: http://www.bmj.com/content/324/7330/174.1

Pesonal Recollections

Fortunately, I had the opportunity to meet Dame Sheila Sherlock, and to spend a little time with her. The occasion was as follows.

In 1982, liver transplantation was shrouded in considerable controversy. A lively debate was taking place as to the status of liver transplantation. Some people claimed liver transplantation was established therapy, and should be covered by public and private health insurers. Others, mostly payer representatives, insisted that liver transplantation was “experimental,” and should not be covered.

At the time, Dr. Thomas E. Starzl was almost singlehandedly spearheading the effort to have liver transplantation declared “therapeutic.” He was quietly creating a coalition of supporters. As it turned out, this wasn’t too difficult to accomplish. Amongst children, biliary atresia was a leading indication for liver transplantation. Dr. C. Everett Koop, a pediatric surgeon, was the Surgeon General, and a friend of Dr. Starzl’s. Dr. Starzl engaged Dr. Koop who became involved, underscoring the plight children faced in getting access to liver transplantation.

In 1982, Jamie Fisk, the infant daughter of Mr. and Mrs. Charles Fiske of Massachusetts, was dying of congenital liver disease. A liver transplant was necessary if she was to survive. The Fiske case highlighted two issues – an inadequate supply of organ donors, and an insurance community convinced liver transplantation was experimental and, thus, they shouldn’t pay for it. Mr. Fiske made a public plea on behalf of his daughter for donors. This was unusual, highly emotional, and very controversial.

Through some backroom negotiations, about which only the participants know, the National Institutes of Health (NIH) was convinced to convene a Consensus Development Conference on Liver Transplantation, which was held on June 20 through 23, 1983. The conference was to address five questions. They were as follows: (1) Are there groups of patients for whom transplantation of the liver should be considered appropriate therapy? (2) What is the outcome (current survival rates and complications) in different groups? (3) In a potential candidate for transplantation, what are the principles guiding selection of the appropriate time for surgery? (4) What are the skills, resources, and institutional support needed for liver transplantation? (5) What are the directions for future research?

I participated in the conference as a “forum member,” as did Dame Sheila Sherlock. As a speaker the title of my presentation was “Perspective Gained from Kidney and Heart Transplantation." The title of Dame Sherlock’s presentation was "Chronic Hepatitis/Cirrhosis."

Ultimately, the consensus panel report proved instrumental in resolving the experiment/therapy debate, thus facilitating the evolution of favorable insurance coverage and reimbursement policy. The panel did so by reaching the following conclusion: “After extensive review and consideration of all available data, this panel concludes that liver transplantation is a therapeutic modality for end-stage liver disease that deserves broader application.”

Despite the available evidence, the insurance coverage and reimbursement policy proved inconsistent and uneven. Medicare began to cover pediatric liver transplantation in 1983, although there were few beneficiaries due to Medicare qualifications. Nonetheless, with much broader implications, private insurers followed suit. However, it was not until April, 1991 that Medicare extended coverage to adult liver transplantation, by which time, many private insurers had already done so.

The following is a footnote. Ultimately, Jamie Fiske received a liver transplant on November 5, 1982 at the University of Minnesota. Because the Fiskes had initially been guaranteed coverage for the transplant by a Massachusetts Blue Cross and Blue Shield employee, the Blues eventually agreed to pay for Jamie’s treatment even though the procedure was technically excluded from plan coverage.



Norman E. Shumway
(1923 - 2006)

Field

Cardiac Transplantation/Cardiothoracic Surgery

Contributions

Norman Edward Shumway, M.D., was born on 9 February 1923, in Kalamazoo, Michigan, and died on 10 February 2006, from metastatic squamous cell carcinoma—one day after his 83rd birthday. He was educated in the public schools in Kalamazoo and entered the University of Michigan intending to pursue law. In 1943, he was drafted into the Army, where an aptitude test revealed that he would be suited to a medical or dental career. He chose the former and subsequently enrolled at Baylor University for premedical studies. After 3 years, he transferred to Vanderbilt University, graduating in 1949 with a Doctor of Medicine degree. He then continued surgical training at the University of Minnesota, where he pursued his interest in cardiovascular research under Dr. C. Walton Lillehei, who gained early fame in open heart surgery by using the technique for cardiopulmonary bypass known as cross-circulation. While at Minnesota, Shumway showed an early interest in applying induced hypothermia to protect myocardial and other vital body tissue during temporary ischemia. He also performed experiments in the animal laboratory using the pulmonary valve as an autograft for treatment of aortic regurgitation—a technique later developed and known as the Ross procedure.

Together with his colleague Richard Lower, Shumway did extensive and pioneering work in cardiac transplantation. He developed a simplified transplant technique in dogs, in which the atria of the donor’s heart are opened and then sutured to the atria of the recipient’s heart. Among those witnessing these experiments was Christiaan Barnard, also a research fellow at Minnesota. Interestingly, the first successful clinical cardiac transplantation was performed by Barnard in Capetown, South Africa, in December 1967.

A month later, Shumway performed the first cardiac transplant in the United States. He had planned to do as many as 10 cases before making a formal report, but the news media intervened, and Shumway became somewhat reluctantly a celebrity, as had Barnard. Others, including ourselves, also started performing transplants, initially with success; however, limited long-term survival, due to tissue rejection and problems with the immunosuppressive methodology, caused most surgeons to declare a moratorium on heart transplantation. Shumway persisted as the only investigator in the field until the early 1980s, when the remarkably effective immunosuppressive drug cyclosporine became available. Cardiac transplantation is now performed throughout the world.

At Stanford University, Shumway initiated clinical and research programs in which he trained many aspiring cardiovascular surgeons, including Richard Lower, Edward Stinson, Vaughn Starnes, William Frist (former U.S. senator), and Bruce Reitz, who performed the earliest experiments with total heart-lung transplants in primates. Later, in 1981, Reitz and Shumway’s colleagues at Stanford reported the first clinical application of heart-lung transplantation.

Shumway was known as an innovator and teacher who inspired young associates to think of possible advances and to pursue their ideas in the laboratory. He stimulated and encouraged his pupils to improve their technical skills and prided himself on being the best “first assistant” in surgery. He was admired and well-liked by his students.

Throughout his career, Shumway deserved and received many honors. Among them was the René Leriche Prize of the International Surgical Society, which he received in 1971 for the most important contribution in cardiovascular surgery that year. He received many honorary degrees from universities and medals from foreign countries. Honorary fellowships followed from the Royal Colleges of Surgeons in Glasgow, England, Edinburgh, and Ireland. He was elected president of the American Association of Thoracic Surgeons in 1986 and received the prestigious Medallion for Scientific Achievement from the American Surgical Association in 1993. In 1972, Shumway became the first recipient of our Texas Heart Institute Medal for outstanding contribution to science related to cardiovascular disease. One of Shumway’s more recent honors was Lister Medalist, received from the Royal College of Surgeons of England in 1994. Other awards are too numerous to mention. He retired from clinical surgery in 1993 but continued to attend hospital functions.

In his later years, one of Shumway’s favorite societies was the Senior Cardiovascular Surgical Society, which consisted of 12 mostly illustrious members who enjoyed golf and good fellowship. I have many fond memories of being with Norman on these and many other occasions. I enjoyed especially his sometimes acerbic wit and critical opinions of personalities and events. We maintained a close and personal friendship throughout his medical career.

Source: Written by Denton A. Cooley, M.D., but lightly edited by Dr. Roger W. Evans. The link to the original article in its entirety is as follows: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413616/.

Pesonal Recollections

My personal reflections will be added at a later date.



George D. Snell
(1903 - 1996)

Field

Genetics/Immunology

Contributions

Dr. George D. Snell discovered the genetic factors that determine the possibilities of transplanting tissue from one individual to another. It was Snell who introduced the concept of H antigens. At the time he received the Nobel Prize, Dr. George D. Snell's contributions were described in a press release as follows: Dr. George D. Snell "laid the foundation for our knowledge of the laws that govern the body's ability to distinguish 'self' from 'non-self'. He did this by studies on mouse strains that, through repeated sibling mating, were made as genetically identical as monozygous twins. Originally, he studied the possibility of transferring tumor cells from one strain to another. The rules of transplantability that he established proved to apply also to normal tissue, such as skin. Snell showed that transplantability was determined by the presence of special structures (antigens) on the surface of the cell. He called these antigens histocompatibility antigens. He showed, further, that the formation of these antigens was controlled by genes (designated H) found within a limited area on a specific chromosome. This area was called the major histocompatibility complex (MHC). So far it has been possible to establish the existence of about 80 different genes within the MHC in mice. With Snell's fundamental discoveries came the birth of transplantation immunology."

The Nobel Prize in Physiology or Medicine 1980 was awarded jointly to Baruj Benacerraf, Jean Dausset and George D. Snell "for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions".

Pesonal Recollections

Unfortunately, I never had an opportunity to meet Dr. Snell. Early in my career I was more fascinated with transplant surgery, and not particularly interested in histocompatibility and immunology. It was later in my career when I became more intrigued with histocompatibility, largely through the work of Dr. Paul Terasaki and his colleagues, and later through the work of Drs. Jon J. van Rood, Gerhard Opelz, and their respective colleagues. The timeline here is critical. By his own account, Dr. Snell retired from active research in 1973; this was the year in which I began graduate studies in sociology at the University of South Carolina. I later withdrew from the University of South Carolina, became interested in hemodialysis and transplantation, and went on to complete my master's degree in sociology under the direction of Dr. Ira Wasserman at Eastern Michigan University (1974-76). My thesis - "The Suicide Potential of an Urban Population: An Exploratory Investigation" - was concerned with suicide in Detroit.



E. Donnall Thomas
(1920 - 2012)

Field

Transplantation Immunology/Bone Marrow Transplantation

Contributions

Dr. Thomas and his colleagues demonstrated that some patients with advanced leukemia, aplastic anemia or genetic diseases could be cured by bone marrow transplantation. Don is recognized as "the father of bone marrow transplantation."

Don received the Nobel Prize in Physiology or Medicine in 1990, which he shared with Dr. Joseph E. Murray. They were awarded the Nobel Prize "for their discoveries concerning organ and cell transplantation in the treatment of human disease."

Pesonal Recollections

Don Thomas was a friend, and colleague. He didn't always agree with my economic perspective, but that did not preclude us from working together. We both served on the Board of Directors for the National Marrow Donor Program when the program was in its infancy. The most memorable evening I spent with Don and Dottie, his wife, was the celebration in Seattle at the Columbia Center that was organized to honor him as a Nobel Prize recipient. It truly was an unforgettable event.



Jon J. van Rood
(1926 - )

Field

Immunology/Immunohematology

Contributions

Dr. Jon van Rood's contributions have been described as follows: "In the field of immunohematology, the discovery and description of the HLA system has been especially significant in the development of transplant medicine. After the discovery of the first, genetically-determined HLA antigen, van Rood discovered that antibodies against white blood cell antigens could be induced not only by blood transfusions but also during pregnancy. Because of the close relationship between mother and child, the number of different antibodies induced is much smaller and hence more accessible for research purposes than in the case of blood transfusions. This made it possible to carry out a systematic computerized analysis of the specificity of antibodies in relation to tissue antigens determined by the HLA system. This enabled Professor van Rood and his co-researchers to discover nine different HLA antigens. In addition to its value for kidney, heart and bone-marrow transplants and blood transfusions, his work has provided new insights into the relation between HLA genotypes and predisposition towards disease. The molecular and immunological basis of this is still being studied, but significant links between susceptibility to disease and HLA types have been identified."

In 1978, Dr. van Rood was awarded the Wolf Prize in Medicine, jointly with George D. Snell and Jean Dausset, "for his contribution to the understanding of the complexity of the HLA system in man and its implications in transplantation and in disease." Dr. van Rood was also awarded the Dr A.H. Heineken Prize for Medicine 1990.

Pesonal Recollections

Dr. van Rood and I first met very early in my career at a congress convened by The Transplantation Society (TTS). The first such meeting I attended was the 10th International Congress, which was held in Minneapolis. Subsequently, I attended the 11th through the 17th TTS International Congresses which were respectfully held in Helsinki, Sydney, San Francisco, Paris, Kyoto, Barcelona, and Montreal. TTS meetings are held every two years. Dr. van Rood probably participated in all of the foregoing TTS congresses. (Note: Also, for further explanation, please see my personal recollections of Drs. George D. Snell and Jean Dausett.)



Sir Michael Woodruff
(1911 - 2001)

Field

Transplantation Surgery/Immunology

Contributions

In an obituary published in The Telegraph on March 15, 2001, the contributions of Sir Michael Woodruff were described as follows: "Professor Sir Michael Woodruff performed the first organ transplant operation in Britain and later developed a drug that helped prevent the rejection of transplanted organs by the body's immune system. Before he performed the operation in October 1960, Woodruff had carried out extensive research into the immunological aspects of transplant surgery and in particular the problem of organ rejection. When he discovered that one of his patients, a miner by the name of Lewis Abbot, had an identical twin brother, he realized that a transplant between twin brothers would minimize the risk of rejection. The transplant was carried out at the Edinburgh Royal Infirmary and proved a complex and hazardous operation. Post-operative care proved problematic as immunosuppressive drugs were in their infancy and the patient remained in danger for some time. The operation eventually proved successful and established Woodruff as pre-eminent in transplant surgery. In 1968 the Nuffield Transplantation Surgery Unit was built to his specifications at Edinburgh's Western General Hospital and he was appointed its director. There Woodruff carried out further research into post-operative care and immunosuppressive drugs. By extracting different vitamins from a variety of grasses he discovered that an effective drug could be created that prevented transplanted kidneys being rejected.

Woodruff was greatly respected in his profession, and in 1968 was elected a Fellow of the Royal Society, a rare accolade for a practicing surgeon. The following year he won the Lister Medal and in 1974 the Gold Medal of the Apothecaries. He was knighted in 1969.

Pesonal Recollections

Sir Michael Woodruff retired from surgical work in 1976. At that time, I was just beginning my graduate studies in sociology at Duke University. Consequently, I never met Sir Michael Woodruff, although I eventually became familiar with his work, particularly in relationship to the development of antilymphocyte globulin or ALG - an immunosuppressive drug. However, my good friend Sir Peter Morris has offered his own recollections of Sir Michael Woodruff, which I consider to be noteworthy. According to Sir Peter, despite his profound influence on transplantation and "a commanding presence in any gathering", Woodruff was not known for his ability as a lecturer as he had a rather uncertain style of presentation and had a tendency to mumble. Nevertheless Morris said that Woodruff has "a great turn of phrase and a rather wicked sense of humor." Morris concluded that "What is surprising is that he was not successful in producing many surgeons in his own mold, despite the intellectual talent that was entering surgery and especially transplantation in the 1960s. However, his influence in transplantation at all levels was enormous."