Innovative Russian Molecular Biologist To Head Argonne's Genome Project; Husband-And-Wife Research Team Share Nobel 'Predictor' Prize From Columbia

Two immunologists, John W. Kappler and Philippa Marrack, have been awarded Columbia University's 1994 Louisa Gross Horwitz Prize for their ground-breaking work in identifying the mechanisms by which T cells, one of the immune system's central components, are able to differentiate between foreign antigens and proteins of the self. Kappler and Marrack both are Howard Hughes Medical Institute investigators at the National Jewish Center for Immunology and Respiratory Medicine in Denver and members

Feb 6, 1995
Karen Young Kreeger
Two immunologists, John W. Kappler and Philippa Marrack, have been awarded Columbia University's 1994 Louisa Gross Horwitz Prize for their ground-breaking work in identifying the mechanisms by which T cells, one of the immune system's central components, are able to differentiate between foreign antigens and proteins of the self. Kappler and Marrack both are Howard Hughes Medical Institute investigators at the National Jewish Center for Immunology and Respiratory Medicine in Denver and members of the National Academy of Sciences. Kappler, 51, and Marrack, 49, are partners in marriage as well as colleagues in the laboratory.

The prize, which included a $22,000 award shared by the two scientists, was presented by Columbia's president, George Rupp, on January 19 in New York. Established in 1967 to honor research in biology or biochemistry, the Horwitz Prize is seen as a strong predictor for the Nobel Prize--29 of 53 recipients later received the Nobel.

In the early 1980s, Kappler and Marrack were one of three research teams to first describe the T-cell receptor and how it recognizes antigen in the body. Then, in 1987, they discovered how T cells that target the body's own tissues are identified and destroyed (J.W. Kappler, et al., Cell, 49:273-80, 1987). Without such a mechanism--or when this process malfunctions-- destructive autoimmune diseases of various kinds can result. Through November 1994, the Cell paper had been cited 1,210 times by fellow scientists in other publications.

"The cells of the immune system randomly generate receptors that can recognize almost anything," says Marrack. "Inevitably, some of the receptors will be able to react with chunks of the host. And if that happens, the host will get pretty sick. So, the question was, if you have a random generating system, how do you get rid of the T cells that can react with the host itself?"

The answer is that, in the thymus, where T cells develop and rearrange their receptor genes to generate the capability to recognize almost any substance, a screening process takes place.

"Before the T cells are allowed out to go on patrol in the rest of the body, they're checked for whether or not they can react with anything in the thymus," Marrack reports. "If they can, they self-destruct. In that early stage of their development, if their receptors react with some bit of self, that causes the cell bearing that receptor to die."

The "repertoire of self" is well represented in the thymus, according to Marrack, and so the majority of T cells with the potential to damage the host are destroyed in this way.

Kappler received his B.A. in chemistry from Lehigh University in 1965 and his Ph.D. in biochemistry from Brandeis University in 1970. After postdoctoral and research associate posts at the University of San Diego, he moved to the University of Rochester School of Medicine and Dentistry as an assistant professor of oncology and, in 1978, an associate professor.

In 1979, he moved to the National Jewish Center, where he is now a member of the department of medicine. Additionally, he joined the University of Colorado Health Sciences Center as an associate professor of medicine and immunology in 1980 and professor in 1984.

Marrack received her B.A. in biochemistry in 1967 and Ph.D. in biological sciences in 1970 from New Hall College at Cambridge University. Postdoctoral positions at Girton College, Cambridge, the MRC Laboratory for Molecular Biology, Cambridge, UC-San Diego, and the University of Rochester were followed by assistant professorships in microbiology, at Rochester in 1975 and in oncology at the university's School of Medicine and Dentistry in 1976, and promotion to associate professor in 1979. In 1980, she joined the Colorado Health Sciences Center as an associate professor; she is now a professor in the departments of biophysics, biochemistry and genetics, medicine, and immunology. She joined the National Jewish Center in 1979, where she is a member of the department of medicine.

Referring to their somewhat unusual combination of domestic and professional roles, Marrack calls the separation of family and work responsibilities that characterizes most people's lives an "artifact of modern life." She says that, in the past, when more people lived in tribal or similar settings, a couple often integrated their lives into a single set of tasks.

"That didn't mean you both went out to shoot the deer together," Marrack says. "And, likewise, we don't do the same experiments, John and I, but we have a single goal."

--Franklin Hoke