Alumni Profile • Melvin Bosma '60
Staying ready for nature's surprises

In the summer of 1980 four mice revolutionized the direction of Melvin Bosma’s (’60) research. An immunologist at the Fox Chase Cancer Center in Philadelphia, he was studying, in genetically defined strains of mice, the development of lymphocytes — white blood cells — especially the antibody-forming ones, called B cells. Blood tests of these particular four mice showed they lacked an antibody marker specific to the strain under study.

“I thought we may have made a mistake in the typing of these mice,” Bosma recalled. He soon realized, however, that he and his co-researcher and wife, Gayle, had been given “a gift of nature.”

They discovered that the four mice, littermates, were sired by a male with a spontaneous mutation in an unknown gene that was apparently essential for the development of a normal immune system. Named scid mice (for “severe combined immunodeficiency”), the mutant mice lacked both B and T lymphocytes, cells that provide protection against harmful microbes and that are able to cause the rejection of foreign transplanted tissues. The Bosmas selectively bred the mice to establish them as an independent strain. Now used in laboratories around the world, the scid mouse has become an invaluable tool for studies of the immune system.

The scid mouse presented a new big question for the Bosmas: Just how did the scid mutation impair lymphocyte development?

"That got us into some pretty heavy molecular biology,” Bosma said, “a lot of which I had to learn as we went along. What we found is that the scid mutation crippled a gene that lymphocytes use to make receptors that recognize anything foreign to the body.”

More recently, the Bosmas have become interested in autoimmune lymphocytes — cells that express receptors directed against an individual’s own tissues. Normally, the body eliminates such anti-self lymphocytes by specific control mechanisms, but when these mechanisms fail, autoimmune disease is a likely consequence. To study the regulation of anti-self B lymphocytes, the Bosmas have engineered scid mice to produce B — but not T — lymphocytes that react to the body’s own DNA. “In this way,” Bosma said, “we can study the regulation of autoimmune B cells in the absence of T cells.”

One thing the Bosmas have learned in 40 years of research is that at any moment an unexpected result may lead to a change one’s thinking, and perhaps also to a change in the thinking of those in the field. “Because the systems we’re working with are so open- ended,” Bosma explained, “there are surprises around every corner. So one must be like a child, in a sense, always ready to learn new things.”

The increasing pressure on researchers in health-related fields to justify their work by explaining its practical application troubles Bosma. “Basic research is a curiosity-driven endeavor,” he said, “and may not have immediate application. But it’s the time-honored way by which we come to new understanding.”

In reflecting on his career, Bosma said, “I still enjoy the challenge of this kind of research and the mentoring of graduate students and post-doctoral fellows who come to my lab for training.”