Jack Strominger (left) and Don Wiley. Photos by Jon Chase.

Jack Strominger, Higgins Professor of Biochemistry, and Don Wiley, Loeb Professor of Biochemistry and Biophysics, have won the prestigious Japan Prize. They were honored for their discoveries of how the immune system protects humans from infections.

Awarded by the Science and Technology Foundation of Japan, the Prize recognizes original and outstanding achievements that advance knowledge and serve the cause of peace and prosperity for humankind."

Wiley, 54, and Strominger, 73, share the honor with W. Wesley Peterson from the University of Hawaii, who invented methods for error correction of computer codes used for communication, broadcasting, and data storage. The three will be feted at a ceremony in Tokyo on April 28 attended by the Emperor and Prime Minister of Japan. They will receive a commemorative medal, certificate of merit, and 50 million yen (about $440,000). Peterson will receive 50 million yen with his prize in information technology. Strominger and Wiley will get 25 million yen each with their prize for molecular biology.

"It's really a thrill to get the [Japan] Prize, but not as big a thrill as having done the work," Strominger said.

"I am terrifically excited about this award because it recognizes the accomplishments of a diversely talented group of students and postdoctoral fellows in my research laboratory," Wiley commented.

Strominger and Wiley won Albert Lasker Medical Research Awards in 1995 for their work on the immune system, which has revealed both how the body fights infections and rejects organ transplants. More than 50 scientists who won Lasker awards have gone on to receive Nobel Prizes. Previous winners of the Japan Prize include David Turnbull, Gordon McKay Professor of Applied Physics Emeritus, in 1986, and Elias J. Corey, Emery Professor of Organic Chemistry, in 1989. Corey then won a Nobel Prize in Chemistry in 1990.

Telling Self from Non-Self

Strominger (AB '47) started thinking about how the immune system works in 1968, when he came to Harvard from the University of Wisconsin Medical School. "I wanted to know how molecules recognize the difference between foreign substances that invade the body and molecules that are part of the 'self,'" he recalls.

"Everyone knew that if you could solve this mystery, it would lead to a better understanding of how the body reacts to infection and tumor growth, and how transplants are rejected," adds Wiley (PhD '71).

The surfaces of virtually all cells in our bodies hold proteins known as major histocompatibility (MHC) molecules. These molecules grab or bind fragments from foreign proteins and present them to so-called T-cells. These cells can recognize as foreign, or "not self," any protein fragment made by a virus or bacteria, and then attack and destroy it.

By 1983, Strominger accomplished the extremely difficult task of isolating the paired MHC molecule and invader fragment. He and members of his laboratory then collaborated with Wiley and his laboratory team to form the complex into a solid crystal. Finally, the two groups used an x-ray technique known as x-ray crystallography to map the paired structure atom by atom.

The collaborators found that MHC molecules could hold a variety of foreign protein pieces much like a baseball glove holds a ball. This complex then presents itself to T-cells, which attack it or leave it alone.

"The process was mind-blowing and told us how the immune system works," Strominger comments.

"Many of us believe this new understanding will lead to new therapies against viruses, bacteria and other microbes, transplant rejection, and tumor growth," Wiley notes.

It is already helping researchers find ways to treat auto-immune diseases, in which the immune system attacks the body's own tissue as though they are foreign pathogens. Such disorders include rheumatoid arthritis, insulin-dependent diabetes, and multiple sclerosis.

"The seminal contributions of Drs. Strominger and Wiley are fundamental in understanding the molecular and chemical bases for functioning of the immune system," according to the Science and Technology Foundation of Japan. "Their innovative work is one of the highlights of modern biology."