George Melville Williams (Mell) was born in Soochow (now Suzhow) China in 1930 and lived on the Soochow University campus, where his father led the Department of Sociology. Mell was bilingual and even had the lead in a Chinese kindergarten play. After the Japanese invasion in 1937, the Williamses and portions of the University moved to the French-controlled portions of Shanghai, which included the well-known Shanghai American School. In 1940, the family returned to the U.S. because of Mell’s father’s illness.
After his recovery, Mell’s father was chosen by the Church to plan how to best serve the war-torn world. He subsequently became Secretary of the Methodist Board of Missions.
Mell played varsity baseball and football at Leonia High School and Oberlin College. He entered Harvard Medical School and was fascinated by medical science, particularly auto-immune diseases. He spent one summer searching for antibodies to explain rheumatic fever. He was elated to be chosen as an intern in surgery at the MGH. His interest in immunity prompted his selection of transplantation as a surgical calling. Following completion of his residency and service in the Army in Tehran, he received an NIH fellowship to work with Burnet and Nossal in Australia to be “immunologically competent” enough to be part of Dr. David Hume’s transplant team at the Medical College of Virginia. Dr. Hume was brilliant and taught surgery from a deep knowledge base, citing chapter and verse to win debates. He was especially critical of professors purporting new knowledge. You had to know your stuff to win any debate.
Imagine Mell’s plight when he did MCV’s 100th transplant, which became the “bellwether” of hyperacute rejection. Only after Milgrom’s group in Buffalo agreed that this was antibody-mediated rejection, and only after Hume experienced his own hyperacute rejection, did Hume believe antibodies were the culprit. Hume graciously acknowledged Mell’s contribution.
In 1969, Mell’s fellow MGH resident, George Zuidema, recruited him to join Johns Hopkins to initiate a transplantation program. However, despite a new group of potential recipients, the number of immunized patients on dialysis grew and cadaver donor transplant numbers were stagnant. To increase the donor pool, surgeons agreed to share cadaver kidneys. Initially, Hopkins, MCV, and Duke collaborated, and they were quickly joined by other centers creating the South-Eastern Organ Procurement Foundation (SEOPF). When 28% of good kidneys were still wasted, Mell brought this to the attention of ASTS in his presidential address, and UNOS was formed. The failure of sharing serum to perform distant crossmatches accurately - and other logistical issues - resulted in the failure to eliminate organ wastage. However, living donor transplants made more donors tolerable using laparoscopic techniques, and more success with better immunosuppression and anti-viral treatment filled the void, offering 90% success at one year. While UNOS failed to stop organ wastage, it was successful in prompting collaboration with federal agencies. Transplantation remains the sole discipline to exert the right to establish its own training programs, rules for membership, and priorities of service.
Mell retired from clinical transplant duties at age 70 and vascular surgery five years later, claiming liver recovery and thoracoabdominal aneurysm repairs were young men’s jobs. He was amazed by the richness of the internet allowing him to catch up with molecular biology. More importantly, he developed a relationship with a brilliant Chinese fellow, Zhaoli Sun. Zhaoli could transplant livers and kidneys in rats and found that acceptance of Lewis livers by weakly rejecting BM rats was associated with the massive influx of host BM cells into the Lewis liver, creating a hybrid liver which was accepted without immunosuppression. To study a more clinically alike model, Zhaoli and Mell chose to use strongly rejecting Lewis rats as hosts and low dose tacrolimus to “dampen” the expected aggressive acute rejection.
Zhoali found that the natural acceptance of Lewis livers by BM rats was associated with massive influx of BN host cells. Working with a strong and rapidly rejecting Lewis host to reflect clinical conditions more closely, low dose tacrolimus (to prevent acute rejection), and AMD310, a strong CXCR4 agonist to mobilize stem cells, long term acceptance resulted. Further, all medication could be stopped after ten days. The non-immunosuppressive tacrolimus B protein was responsible for mobilizing needed BMSCs in synergy with the CXCR4 agonist. This serendipitous combination of drugs has been found to speed wound healing, allow drug-free survival of kidney transplants (rats and pigs), the healing of burns, the healing of venous stasis ulcers (human), and the healing of diabetic wounds (rats).
Mell developed renal failure in 2013. After a year of home dialysis administered by his wife, Linda, she said she would rather donate a kidney. Using the Ratner technique, the kidney was removed with the renal artery divided distal to a stent placed to treat hypertension 8 years previously. At age 89, Mell’s creatinine is as good as Linda’s at 1.3. Mell is grateful for the contribution of many who made this outcome possible. The current awards are exceedingly meaningful to him, and more than make up for the natural early skepticism about the power of drug-induced autochthonous stem cells.