Michael Rosbash, Ph.D.
For a decade, Michael Rosbash's research was as basic as fundamental research gets: the metabolism and processing of RNA, which forms the molecular link between gene and protein. But in the early 1980s, he found himself increasingly interested in a more sweepingeven philosophicalquestion: the genetics of human intelligence and personality. That's why today Rosbash is one of the world's leading experts on circadian rhythmsthe internal body clockin the fruit fly Drosophila melanogaster.
Flies? Aren't the waking and sleeping patterns of insects far removed from the genetics of human personality?
"I've asked myself the same question," Rosbash says. But noting that personality involves an unknown (but presumably vast) number of unidentified genes, he explains: "Once you have multiple factors, with variable genetic expression, which then also interact with the environment, it becomes a very complex problem."
"My taste in doing science," Rosbash says, "is heavily skewed toward asking questions where I think there will be substantial answersand where you can solve the problem to some degree of satisfaction within your lifetime."
Rosbash, 56, a Howard Hughes Medical Institute investigator at Brandeis University in Waltham, Massachusetts, already has plumbed the mystery of the circadian clock to a considerable degree of satisfaction, although he says lots of questions still remain. He and his major collaborator, Jeffrey Hall, also of Brandeis, cloned the first Drosophila circadian clock gene, period, in 1984, and in 1990 they proposed the mechanisma transcriptional negative feedback loopby which the clock works. A decade later, after many additional gene discoveries, their model and mechanism still hold up. Moreover, the mechanism appears to apply not just to flies but also to mammalsincluding peoplemaking clear that the workings of Drosophila's clock are indeed relevant to human neuroscience.
When Rosbash entered the field, several behavioral mutations had been identified in Drosophila through phenotypic studies that identified mutations by their effects on fly behaviors. "Seymour Benzer and his students were pioneers in these important early studies," says Rosbash. But scientists were unable to determine how those genes actually functioned until the advent of modern recombinant DNA techniquesthe ability to clone the genes themselves, identify and analyze their proteins, and transfer a mutated or a normal gene into an organism. "That broke open the field," Rosbash says. "It allowed one to understand what the genes might do and then to make links to the same processes in other organisms."
Rosbash was well positioned to apply cutting-edge molecular genetics techniques to the problem of circadian clocks. Since his days as a graduate student at the Massachusetts Institute of Technology in 19661970, his research had centered on the role of RNA in the many steps between the transcription of the DNA sequence that forms a gene to the assembly of a finished proteinone of the most fundamental processes in biology.
He continues his RNA research today. The graduate students, postdoctoral students, and technicians in his lab are divided into two groups, one studying circadian clocks and the other RNA synthesis, processing, transport, and function. Most scientists, although they may have multiple projects running, engage in only one specialized field; Rosbash balances two.
Unlike some researchers, Rosbash doesn't trace his interest in science back to early childhood. In fact, he recalls attending a symposium several years ago during which "one guy would say, 'When I was six years old, I was fascinated with the problem of consciousness.' The next guy would get up and say, 'When I was eight, I built an artificial intelligence computer in the basement.'" Somewhat skeptically, Rosbash says, "When I was that age, I was playing with toy trains and watching the Red Sox." (He remains a long-suffering "pathological and pathetic" Boston Red Sox fan.)
His childhood wasn't as idyllic as that may sound, however. Rosbash's parents fled Nazi Germany in 1938, "and my mother went from a wealthy family to cleaning toilets in New York City before my father found a job." His father was a cantor, a Jewish clergyman who sings or chants prayers; his mother had earlier been forced out of medical school when the Nazi government expelled Jews from German universities.
Rosbash was born in Kansas City, Missouri, but the family moved to the Boston area when he was about 2 years old. When he was 10 and his younger brother was 6, his father died of a heart attack at the age of 42. His mother, who had just registered at Boston University Medical School to resume her training, had to abandon medicine again and go to workfirst as a technician in a cytology laboratory and ultimately as the chief technician thereto support her family.
In high school, Rosbash was "reasonably interested" in science, mostly math, "but I didn't work very hard. I wasn't inspired by anything." At the California Institute of Technology, he originally planned to major in math, but "I found myself not very interested in math or, I might add, very outstanding at that level of competition with abstract math."
During his sophomore year, he found his first biology course electrifying. The genetic code was just being cracked, and there were weekly updates. In the summer after his sophomore year, he worked in the laboratory of Norman Davidson, a renowned chemist who was transitioning into the nascent science of molecular biology. Davidson was "a personal inspiration."
"This guy was not only a brilliant scientist, but he also absolutely loved his work," Rosbash says. "He was happy as a clam in the lab. Now and then, Davidson wore a tee shirt bearing the motto 'I'd rather be in the lab (or maybe playing tennis).' And I thought, 'Gosh, if anybody can enjoy work so much, there must be something to this stuffnot just as a student researcher but as a life's pursuit,'" Rosbash says.
Caltech was good for Rosbash in other ways, too. For the first time in his life, he made a mark in sports. He played on the freshman baseball team and throughout college as a tackle on the varsity football team. "I was sort of a semi-jock in college, albeit the definition at Caltech was a very low standard," he says. "It was very strange to go to Caltech and fulfill your desire to be a reasonably competent athlete."
Rosbash is married to a fellow scientist, Nadja Abovich, who came to Brandeis in 1979 and worked in his laboratory for almost 20 years. He has a 25-yearold stepdaughter, Paula, who is studying to become a graphic artist, and a 14-yearold daughter, Tanya, who is in ninth grade and "a good athlete as well as a good student."
"We spend a lot of time with our 14 year old and her athletic exploits," Rosbash says. He helps out with her basketball team, and his wife resigned from the lab late last year, in part to spend even more time with Tanya.
Combining a research career with a family is difficult, Rosbash agrees, but he doesn't think this situation is unique to research. "Being a researcher is no different from doing anything with unbridled enthusiasm," Rosbash says. "People who are obsessed by what they do, or very ambitious, or both, work very hard. But I think people who are healthy and well balanced, and have a spouse who helps them maintain a little more balance, are well served to take that time and build a family and enjoy it," he adds. "Someone once said to me, 'No scientist ever looks back on his career and says I wish I'd spent more time in the lab.' They all say, 'I wish I'd spent more time with my kids.'"
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