Thomas E. Starzl, M.D., transplant pioneer
Doctors nationwide are mourning the loss of Thomas E. Starzl, the surgeon and researcher who pioneered the liver transplant and the medications that made the procedure successful in the long term. Starzl died on March 4 at his home in Pittsburg at age 90.
The immunosuppressive drug that he championed became the standard for liver transplant patients and is now the primary drug used in bone marrow transplants for patients with leukemia and lymphoma as well.
That drug, tacrolimus, “still forms a mainstay of our immunosuppressive therapy in caring for patients” undergoing bone marrow or blood stem cell transplants, said Joseph Alvarnas, M.D., a hematologist, oncologist and associate clinical professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.
“His discoveries had legs,” Alvarnas said.
performed the first successful liver transplant on a human patient in 1967, according to his obituary in the New York Times
. He led a team at the University of Colorado that successfully transplanted a liver in a toddler with liver cancer. Four earlier attempts had failed after patients experienced complications from blood-clotting agents.
Starzl greatly increased the survival rate of early liver transplant patients once he realized that their survival depended on their body’s immunological response to the implanted foreign tissue.
He first identified the drug cyclosporine in the late 1970s as a medication to inhibit the body’s immune response. This drug, paired with steroids, was subsequently used to prevent organ rejection. It was approved by the Food and Drug Administration in 1983.
“A lot of his research wasn’t just in the surgical mechanics, it was directed at trying to better understand ways in which you could successfully suppress the immune system without overdoing it,” Alvarnas said.
One of the challenges, whether with a solid organ transplant or a bone marrow transplant, is that “you’re trying to navigate the issue of having either someone’s body part or someone else’s immune system in your body,” Alvarnas said.
Our immune system tries to reject tissue that it perceives as being of foreign origin, “So in order for a transplant to be successful, we have to suppress the immune system. But if we over suppress it, then we render patients deeply vulnerable to life-threatening and potentially life-ending infections.”
“A large part of Starzl’s legacy was working to develop more effective immune-suppressing regimens,” Alvarnas said.
In the 1980s, Starzl began investigating an experimental anti-rejection drug called FK-506 (also known as tacrolimus), using it on a multiple-organ transplant patient in 1984. FK-506 went on to become widely used in transplant surgeries.
The benefit of FK-506 is that it neither over- nor under-suppresses the immune system. “It’s a drug that allows us to really interpolate those two poles and have more effective immune suppression while avoiding overly immunosuppressing the patient,” Avarnas said.
Starzl lobbied hard for the use of FK-506, studying it and publishing his findings in the British medical journal, The Lancet in 1989. FK-506 was approved by the FDA in 1994. The use of FK-506 led to a medical breakthrough for patients and to Starzl being appointed director of the University of Pittsburgh’s transplant unit in 1990. Six years later the unit was officially renamed the Thomas E. Starzl Transplantation Institute.
“That drug plays an important role these days not only in the care of patients with liver transplant, but it’s one of our standard drugs for immunosuppressant therapy for blood and marrow stem cell transplants,” Alvarnas said. “There’s nothing that’s come down the pike since that replaces it.”
“There was this transition from when we were using mainly cyclosporine-based immunosuppression toward tacrolimus, and a lot of the foundation for that work was based upon his experience using the drug before it was approved and before it was available,” Alvarnas said. “He was an extraordinary pioneer. That quest to advance the state of the art, not to serve an individual patient but to serve many patients — even when you’re at the pinnacle of success in one avenue, the recognition that there is room for improvement and rededicating your life to doing that, is quite extraordinary.”