About

Dr. Rolf Zinkernagel

Dr. Rolf Zinkernagel is an accomplished immunologist whose work with Dr. Starzl produced a paradigm-shifting work on the nature of immunological tolerance. Zinkernagel grew up in Switzerland, graduating from the University of Basel in 1970 with his MD. He accepted a fellowship in Canberra and began working at the Australian National University, where he received his PhD in 1975. During his fellowship, Zinkernagel worked closely with Dr. Peter Doherty. Together, the two discovered the way in which the immune system recognizes viral infections; this work earned the pair the 1996 Nobel Prize in Physiology or Medicine. After then spending some time in the United States, Zinkernagel eventually returned to Switzerland as a professor at the University of Zurich in 1979.

In the United States, though retired from his active surgical role, Dr. Starzl continued to immerse himself in the intricacies of transplant immunology. A paper published in 1992, “Cell migration, chimerism, and graft acceptance,” became one of Starzl’s most oft-cited articles, based on its revolutionary discoveries. Here, Starzl advanced the idea of microchimerism, an immunological process by which specialized white blood cells (leukocytes) from a donor organ migrate into the recipient body. In ideal situations, leukocytes from the recipients’ body would then move into the transplanted organ, eventually reaching a balancing point at which the grafted organ is no longer attacked by the recipient’s immune system. Though this revelation was revolutionary in and of itself within the transplantation field, Starzl was intrigued by Zinkernagel’s work on viral immunology. Starzl struck up a correspondence with Zinkernagel, who soon responded by elaborating on his theories concerning antigen migration. (Doc. 1) Starzl’s swift response resulted in a volley of ideas lobbed back and forth across the Atlantic. (Doc. 2) This exchange of ideas resulted in what was among Starzl’s most iconoclastic papers, “Antigen localization and migration in immunity and tolerance,” published in the New England Journal of Medicine in 1998. [ref 1]  In this publication, Starzl and Zinkernagel posited that Starzl’s discoveries concerning chimerism could be expanded to a more general immunological paradigm. Starzl summarized this new theory in an early presentation to the Transplantation Society in 1998: “Immunity, or alternatively tolerance, to any antigen is governed by the migration and localization of that antigen.” (Doc. 3) Together, the two argued that the movement of leukocytes was not only responsible for tolerance in organ transplantation, but for all immunological processes in general.

The immense discovery of Starzl and Zinkernagel is even more impressive when one considers that the two wrote “Antigen localization and migration in immunity and tolerance” without having ever met in person. This is reflected in the mass of correspondence between the two that is held in the archives; everything from the first emergence of ideas, to revisions, to background reading material, is included in the Zinkernagel file. The two later wrote a second paper,” Transplantation tolerance from a historical perspective,” which would be published in Nature Reviews: Immunology in 2001. [ref 2] (Doc. 4) As this new paradigm gains traction in the scientific world, it is clear that the collaboration of these two men is truly revolutionary in its significance.

References 

1. Starzl, TE and Zinkernagel, R: Antigen localization and migration in immunity and tolerance. The New England Journal of Medicine 339: 1905-1913, 1998.
   http://d-scholarship.pitt.edu/5390/
2. Starzl, TE and Zinkernagel, R: Transplantation tolerance from a historical perspective. Nature Reviews: Immunology 1: 233-239, 2001.
   http://d-scholarship.pitt.edu/5553/