Two Immunologists Win the Horwitz Prize

Photograph: Horwitz Prize Winners John W. Kappler and Philippa Marrack in their laboratory.

Two scientists who unraveled the mystery of why the body's immune system does not attack its host have won Columbia's 1994 Louisa Gross Horwitz Prize, it was announced Monday. Since the Horwitz Prize was first presented in 1967, more than half its recipients--29 of 53--have gone on to win the Nobel Prize. The most recent is Alfred G. Gilman, one of two winners of last year's Nobel Prize in Physiology or Medicine, who received the Horwitz Prize in 1989.

President Rupp will present the prize in formal ceremonies this Thursday evening in Low Rotunda.

The Horwitz Prize, which includes a $22,000 award shared by the two recipients, is given annually for outstanding research in biology or biochemistry.

Kappler and Marrack will deliver the 1994 Louisa Gross Horwitz Prize Lectures.

Marrack is to speak on "T-Cell Tolerance" Jan. 19 at Noon in the C.P. Davis Alumni Auditorium of the Schapiro Center for Engineering and Physical Science Research.

Kappler speaks on "The T-Cell Receptor and its Ligands" Jan. 20 at 12:30 P.M. in the Physicians & Surgeons Alumni Auditorium. The human body produces thousands of proteins--as do foreign invaders. Yet the cells that protect the body must distinguish between the former, which perform valid functions, and the latter, which can result in disease.

Marrack and Kappler showed how T-cells, the foot soldiers of cell-mediated immune response, recognize foreign invaders and activate the body's defenses.

T-cell Discovery

More recently, they also discovered that most of the T-cells that can bind to the body's own proteins--the T-cells that cause the first step in an autoimmune response--are destroyed early in their development.

This phenomenon is one of the major reasons why most people do not develop autoimmune diseases.

"This body of work is extremely important," said Leonard Chess, an immunologist and professor of medicine at the College of Physicians and Surgeons. "It was known that T-cells become educated to respond to foreign material, but not to the self. Yet the precise mechanism in that process was not understood."

Malfunctions of the immune system can result in several autoimmune diseases, among them rheumatoid arthritis, multiple sclerosis, insulin-dependent diabetes, hemolytic anemia and systemic lupus.

And organ implants and skin grafts are now commonly performed using pharmaceuticals that impair the immune system to prevent an immune response to the new organ.

Such substances leave the body with few defenses against pathogens, however.

The work of Marrack and Kappler in identifying T-cell receptors has allowed researchers to develop substances that bind only to the T-cells attacking human tissue, thus rendering them inactive without impairing the entire immune system.

Pharmaceuticals based on their research are under development. The immune system has two distinct means for dealing with pathogens such as viruses and bacteria.

In the humoral immune system, B-lymphocytes (also called B-cells) each carry a different antibody that binds to target molecules, known as antigens, circulating in the blood.

The second means for combatting invaders is the cell-mediated immune response, which relies on T-lymphocytes, or T-cells, to recognize and destroy viruses and bacteria independently of antibody molecules.

More Receptors

Marrack and Kappler, working in the early 1980s, identified the structure of one of two T-cell systems that recognize antigens. The receptors on the surface of lymphocytes, they found, are made by combinations of specialized gene segments.

Those segments combine at random to create about a trillion different T-cells in each human being, meaning a huge variety of receptors, each recognizing a different antigen, is possible. Kappler and Marrack subsequently cloned the specialized genes encoding the receptors, allowing for further wide-ranging studies. Kappler, 51, is an investigator for the Howard Hughes Medical Institute and is a member of the department of medicine at the National Jewish Center for Immunology and Respiratory Medicine, both in Denver.

He is also a professor in the departments of medicine and immunology at the University of Colorado Health Sciences Center. He received the B.A. in chemistry from Lehigh in 1965 and the Ph.D. in biochemistry from Brandeis in 1970.

He was a postdoctoral fellow and research associate at the University of San Diego and was named assistant professor of oncology at the University of Rochester School of Medicine and Dentistry in 1973. He became associate professor at Rochester in 1978 and joined the National Jewish Center in 1979.

He was named associate professor at the University of Colorado Health Sciences Center in 1980 and professor in 1984. He has been an investigator with the Howard Hughes Medical Institute since 1986.

NAS Members

He is a member of the National Academy of Sciences and is on the editorial board of the Journal of Immunology. He has published more than 250 research articles in refereed journals.

Marrack, 49, is also an investigator for the Howard Hughes Medical Institute, and is a member of the department of medicine at the National Jewish Center.

She is a professor in the departments of biophysics, biochemistry and genetics; medicine, and immunology at the University of Colorado Health Sciences Center.

She received the B.A. in biochemistry in 1967 and the Ph.D. in biological sciences, both from New Hall College at Cambridge. She was a postdoctoral fellow at Girton College, Cambridge; the MRC Laboratory for Molecular Biology, Cambridge; UC-San Diego, and the University of Rochester, where she was also assistant professor of microbiology in 1975-1976.

She became an established investigator for the American Heart Association and an assistant professor of oncology at the University of Rochester School of Medicine and Dentistry in 1976.

In 1979, she was promoted to associate professor, a post she held until 1982, and also became affiliated with the National Jewish Center, where she served as head of the Division of Basic Immunology from 1988 to 1990.

Her affiliation with the University of Colorado Health Sciences Center dates from 1980, when she was named associate professor. She has been a Howard Hughes Medical Institute investigator since 1986. She is a member of the National Academy of Sciences and is a fellow of the American Academy of Arts and Sciences.

Marrack is on the editorial boards of four refereed journals and has published more than 250 research articles.

Nobel Laureates

Besides Gilman, Horwitz Prize winners who subsequently won the Nobel Prize are Luis F. Leloir, Har Gobind Khorana, Marshall W. Nirenberg, Max Delbruck, Salvador Edward Luria, Albert Claude, George Emil Palade, Renato Dulbecco, Sune Bergstrom, Bengt Samuelsson, David H. Hubel, Torsten N. Wiesel, Walter Gilbert, Frederick Sanger, Cesar Milstein, Aaron Klug, Barbara McClintock. Also, Susumu Tonegawa, Stanley Cohen, Rita Levi-Montalcini, Michael S. Brown, Joseph L. Goldstein, Erwin Neher, Bert Sakmann, Thomas R. Cech, Philip A. Sharp, Edwin G. Krebs and Richard Ernst.

The Louisa Gross Horwitz Prize was established under the will of the late S. Gross Horwitz, in memory of his mother, to honor outstanding contributions to knowledge in biology or biochemistry.

Columbia University Record -- January 20, 1995 -- Vol. 20, No. 13