Fascinated by living things as a small child, Richard Flavell admits he wasn't much of a student until an inspiring teacher turned him on to chemistry as a teenager. "Then, it seemed natural to want to understand living things from a chemical viewpoint," he remembers. "That was an early decision I made."
After obtaining degrees in biochemistry, he completed postdoctoral stints at the University of Amsterdam and the University of Zurich. In Zurich, working with Charles Weissmann, Flavell modified genes in a virus and looked at the effects of those changes. The results, published in 1974, represented the first example of what scientists now call "reverse genetics"—changing a gene and analyzing the results.
"Before that, all genetics was forward genetics," Flavell says. "You had a mouse, for example, with a funny phenotype—maybe it runs in circles. So you try to get at the genes causing that behavior. If you worked hard enough, you discovered them. The new way was different—we changed the gene and then saw the consequences."
The research left a lasting impression on the field of genetics, as well as on Flavell.
"It was great fun, and it had broad implications," he says. "That work taught me that if you think it through, you can do something big, and doing something big takes just as much effort as doing something small."
A few years later, Flavell did something else big. As a faculty member at the University of Amsterdam, he showed that mammalian DNA contains introns: sections of genetic code that split up a gene into pieces.
In 1982 Flavell felt the time was right to dip a toe in the biotech pool, so he left the academic world to spend six years as chief scientific officer of Biogen, a biotechnology company headquartered in Cambridge, Massachusetts.
"I thought it would be an exciting thing to do," he remembers. "It was the dawn of biotech, when the technologies of molecular biology were first being applied to medicine."
Though Flavell enjoyed the experience, the balance between research and management eventually tipped too far toward the managerial end, and he accepted a position at Yale School of Medicine.
Flavell has spent the past two decades at Yale, where he uses reverse genetics in the mouse to study the immune system.
Recently, he made a startling discovery in T cells, the workhorses of the immune system. "We've found that genes interact across chromosomes," he says. In the nucleus of a T cell, a master control gene on chromosome 11 may physically touch a gene on chromosome 10, inducing it to produce a protein that primes the cell to fight infection in a specific way.
"The genes use the same machinery they use to regulate one another within a chromosome," he says. "But they apparently can regulate genes on other chromosomes." The finding has wide-ranging implications for diseases that include autoimmune conditions and cancer.
While his scientific discoveries have advanced the field of genetics in multiple ways, Flavell also is known as a musician. He plays lead guitar and sings for the Cellmates, a band with a sound he describes as "classic rock, with an eclectic mix."
Formed in 1992, the band—all scientists save for Flavell's wife, Madlyn, on the keyboard—plays covers and original works. A Cellmates live set can include tunes from Chuck Berry, the Who, Tori Amos, and Phish, as well as songs about prions and grant writing.
The Cellmates isn't Flavell's first band, but he never seriously considered a career in music. "We do it because it's fun," he says, an echo of his thoughts about scientific research. "It's incredible fun."