John C. McDonald's Search for the Holy Grail

John C. McDonald, M.D. is recognized as a pioneer in the field of organ transplantation. His ground-breaking work on the local, state, regional and national level has brought recognition to both McDonald and his institutional affiliations. From 1964 to 2000, McDonald performed more than 1000 kidney, liver and pancreas transplants. Through his work with the Louisiana Organ Procurement Agency, the South-Eastern Organ Procurement Foundation and the United Network of Organ Sharing, he was instrumental in the establishment of national policies and procedures for organ procurement and transplantation.  

In his Presidential Address to the Southern Surgical Association in 1994, McDonald said, “The production of acquired immunologic tolerance in the human being remains the Holy Grail of the transplant surgeon…When the Holy Grail is found, human transplantation will become safe, predictable, durable, and much less expensive. It will certainly be worth the odyssey no matter how long. It has been a great privilege for me to be a soldier in this army of scholars for some 32 of the 41 years of study.”

The story of John McDonald’s search for the Holy Grail unfolds here.

State University of  New York at Buffalo

McDonald credits his mentor, Dr. John D. Stewart, with starting him on this path of study that began with the Buswell Research Fellowship in Immunology at the State University of New York at Buffalo from 1963 to 1965. It was during this fellowship period that he performed his first kidney transplant in August 1964. From 1965 through 1968 McDonald held a number of appointments, often concurrently, at several Buffalo medical institutions. He served the State University of New York at Buffalo as head of the section of transplantation and as an assistant professor of surgery. At the Deaconess Hospital he was also head of the transplantation section as well as an attending surgeon. At the Meyer Memorial Hospital he was associate director of the Surgical Research Lab, attending surgeon, and head of their transplantation section. And finally, he served as the consultant in transplant immunology at the Roswell Park Memorial Institute.  

During his immunology fellowship in 1964, McDonald, in collaboration with Felix Milgrom, worked out the distribution of histocompatibility antigens in the rabbit, developed a serodiagnostic test for allograft rejection, and performed some seminal studies on characterizing antibodies accompanying graft rejection. This research and laboratory work resulted in the publication of ten scientific articles in a few short years:

“Antiglobin Consumption Test in Rabbit Homotransplantations” 1964
“Mixed Agglutination with Cell Cultures in Rabbit Homotransplantation” 1965
“Studies on Antibodies Accompanying Homograft Rejection” 1965
“Rabbit Renal Homografts 1. Techniques for Grafts to the Neck” 1966
“Serum Antibodies in Transplantation” (see also)
1966
“The Distribution of Histocompatibility Antigens in the Rabbit” 1966
“Serodiagnosis of Allograft Rejection in Rabbits Treated with Cortisone” 1966
“Humoral Antibodies in Transplantation” (see also) 1966
“Serum Antibody Response of Cortisone Treated Rabbits to Skin Allografts:  Serodiagnosis of Allograft Rejection?”
1967
“Two Groups of Transplantation Antigens and Antibodies in the Rabbit” (see also) 1968


Attica Skin Graft Study
 
In 1966, McDonald conducted experiments to study the leukoagglutinin response of the healthy adult male to repeated skin allografts. His subjects were inmates of the Attica State Prison in Attica, New York. Fifty healthy adult male volunteers were divided into 25 pairs. Each member of each pair was expected to donate to and receive from his partner 3 successively applied full-thickness allografts of skin, 6.25 cm. in size.

Second-set allografts were applied 6 weeks after the first set, and the third-set allografts were applied 4 weeks after the second-set allografts. Serum samples were obtained from each subject prior to the first allograft and at weekly intervals throughout the experiment until 14 days after the third-set allograft. Ultimately, serum was obtained from 46 volunteers who had received 3 successive allografts, from 2 subjects who received only 2 allografts, and from 2 individuals who received only one allograft.

The volunteers elected to call this study the Skingraft, Attica Group, Experiment. Therefore the sera was referred to as the SAGE sera. Data resulting from this study was presented at the 29th Annual Meeting of the Society of University Surgeons in February 1968 and a scientific article, “Agglutination of Established Cell Lines of Human Leukocytes by Human Transplantation Sera”(see also) was published in the July 1968 issue of Surgery.

Data from this study was also used in “Rejection of Skin Allografts by Healthy Humans: Relationship of Type of Rejection to Degree of Immunity” a paper presented at the 25th Annual Meeting of the Central Surgical Association in February 1968 and published in the August 1968 issue of Archives of Surgery. A shorter article based on the same data, “A Comparison of the Cytotoxins and Leuko-agglutinins in Human Transplantation Sera: Implications Regarding Human Tissue Typing” was published in the Surgical Forum in 1968.

This study resulted in the production of nearly 1000 slides that show the twenty-five pairs of volunteers and document the changes that took place during the three allografts. These slides have been digitized and are part of the McDonald Archive.
A sampling of the slides can be seen here.

Tulane University
 
In late 1968, McDonald began his duties as Associate Professor of Microbiology and Immunology at Tulane University, where he also was the Director of their Transplantation Laboratory. At the same time, he served as Director of Transplantation at Charity Hospital of Louisiana in New Orleans and as the Director of the Tulane University Medical Center Histocompatibility Testing Laboratory.

The transplantation program at Tulane gained national recognition under his direction. Along with Dr. Theodore Drapanas, McDonald performed the first liver transplant in Louisiana in 1972. His immunologic research continued, focusing on the importance of cellular and humoral inmmunity, transplant rejection, and the development of methods to detect early rejection episodes. McDonald and his team of kidney transplant specialists discovered a new system that was found to be responsible for acute transplantation rejection. They called this discovery the Heterophile Transplantation Antigen or HTA System. McDonald reported on this major advance at the 4th International Congress of the Transplantation Society in September 1972.  (see also: 1 | 2)

Further investigation into the HTA system was funded by three research grants awarded by the National Institutes of Health from 1973 through 1981. Data generated by this research was published in a ten-part series, “A Heterophile System in Human Renal Transplantation” that appeared in Transplantation, Transplantation Proceedings, and Surgery from 1973 through 1982. For documentation of each article, click on the specific following link:

Heterophile System part 1 (see more)
Heterophile System part 2 (see more)
Heterophile System part 3 (see more)
Heterophile System part 4 (see also: 1 | 2)
Heterophile System part 5 (see also)
Heterophile System part 6 (see also)
Heterophile System part 7 (see also)
Heterophile System part 8
Heterophile System part 9
Heterophile System part 10 (see also)


Louisiana State University Medical Center

Dr. McDonald served as a consultant to the LSU Medical Center in Shreveport during the development of their kidney transplant program, which led to their first kidney transplant in April 1976. McDonald’s formal affiliation with the LSU Medical Center began on June 1, 1977 when he assumed the position of Chairman of the Surgery Department, Surgeon in Chief at the LSU Hospital, and Director of the Histocompatibility Testing Laboratory and director of the Medical Center’s Louisiana Organ Sharing Program.

Over the next five years, McDonald and his colleagues continued their research into the HTA system and its role in organ rejection. Thirteen kidney transplants were successfully performed by early 1978, which led to the LSU Medical Center’s designation as a kidney transplant center by the Department of Health, Education, and Welfare. One of only 100 such centers in the United States, the LSU Medical Center in Shreveport was the only Louisiana institution capable of performing all end stage renal disease activities in-house. By late 1979, 65 kidney transplants had taken place with an 80% success rate.

The first dual transplant was performed in February 1982 when a cadaver kidney and a pancreas were grafted in a young woman. Interestingly, the pancreas was implanted in the woman’s right thigh. The reasoning was that if it were superficially placed it could be removed at less risk in case of complications. Complications did occur and the pancreas was removed. Two other kidney-pancreas transplants were subsequently performed with similar results.
 
But prior success with kidney transplants encouraged the local transplant team to consider yet another challenge. On July 29, 1983, Dr. John C. McDonald, Dr. Michael S. Rohr and the transplant team performed the first liver transplant in Shreveport. The patient was 34-month-old Veronica Rice and the 10-hour surgery generated, not unexpectedly, a great deal of media coverage. Four months after the transplant, Veronica slipped into a coma as the result of internal bleeding. It was determined that a new liver was needed and her name was re-entered into the computerized organ-sharing network. A suitable liver was located on January 5, 1984, but the child died during the second transplant due to uncontrollable bleeding. It was later determined that rejection was a major factor in the failure of the first liver. By the middle of 1985, two additional liver transplants were performed that were ultimately unsuccessful.

The outcomes of LSUMC’s liver transplant program were not unique. The procedure was still quite experimental and life-saving anti-rejection drugs were yet to be discovered. National survival rates for liver transplants stood at 50% and were dependent on the severity and progression of the patient’s disease. McDonald believed the deaths of his patients were not in vain. In local newspaper coverage he was quoted as saying, “We feel that, in spite of the outcome of this instance, a great deal of good has come from it. It encourages us to continue, in a careful way, the clinical trial of liver transplantation.”

Willis-Knighton /Louisiana State University Regional Transplant Center

The end of the 1980s brought reduced state funding that threatened to halt LSUMC’s cutting-edge efforts in organ transplantation. As a remedy, John C. McDonald and James Elrod, President of the Willis-Knighton Health System, forged the institutional partnership that created the Willis-Knighton/LSU Regional Transplant Center. Established in July 1989, the Regional Transplant Center combined the expertise of LSU Medical Center’s transplant surgeons with Willis-Knighton’s clinical facilities, experience and support.

The Medical Center’s successful renal transplant program became the foundation for the multi-organ transplantation program planned for this joint venture. Heart transplant surgeon, Dr. Mohsin Hakim of the Mayo Clinic, joined the staff in August 1989. The Regional Transplant Center opened with the capacity to perform heart and renal transplants. The first heart transplant in Shreveport was performed on June 4, 1990 and in the span of three years, another 58 heart transplants had been completed. In 1991, the liver transplant program was added, and in 1995, the Center gained approval for pancreatic transplantation.

The first simultaneous heart-kidney transplantation in Louisiana was successfully performed here in 1993 and in 1995, the first kidney-pancreas transplant was done. Also in 1995, the Willis-Knighton/LSUHSC Regional Transplant Center received the "Center of Excellence" designation from the Department of Health and Human Services for its liver transplantation program. This placed the Center among only 42 liver transplant programs nationwide with this recognition.

Patients from Louisiana, Texas, Arkansas and Mississippi can thank Dr. John C. McDonald and James K. Elrod for their foresight in the creation of this partnership that continues to provide local treatment for those patients needing kidney, liver and pancreas transplants.

 

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