For more than three decades, Gerald M. Rubin has thrived as an experimental geneticist, research director, teacher, mentor, and biotech-company cofounder. A vice president of Howard Hughes Medical Institute (HHMI) since 2000, Rubin was named in 2003 the first director of HHMI’s Janelia Research Campus.
At Janelia, Rubin directs scientific programs that are speeding the development and application of new tools for transforming the study of biology and medicine.
A native Bostonian, Rubin gravitated to math and science in high school at Boston Latin, and obtained his first paying job at the age of 14 washing glassware in a cancer research laboratory at Massachusetts General Hospital. Planning to major in chemistry, he entered the Massachusetts Institute of Technology (MIT), where he took his first formal biology courses. Rubin was deeply impressed by the humility of one professor, biologist Salvador E. Luria, who came to work the morning he learned he won the Nobel Prize and immediately erased a big “congratulations” message the students had written on the board. “He told us that just because he had won the Nobel Prize, it didn’t mean his work was superior to that of his peers,” says Rubin.
It had been 15 years since the discovery of the DNA double helix, and Rubin recognized that biology had entered a new era and that he wanted to be a part of it. He also discovered, at MIT and in the two summers he spent at the Cold Spring Harbor Laboratory, that he had a strong affinity for experimental science.
After receiving his B.S. in 1971, Rubin won scholarships to study at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge, England, where scientists such as Francis Crick, Sydney Brenner (now a senior fellow at Janelia), Fred Sanger, and Max Perutz, were making great discoveries in biology. “All these heroes I had read about in my courses were there, walking around and doing experiments in the lab,” says Rubin.
For his Ph.D., which he received in 1974, Rubin sequenced a yeast RNA made up of 158 bases. Nowadays, he points out, automated machines can read out 1,000 such sequences a second. “What took two years of my life now can be done in a millisecond!”
From England, Rubin went to Stanford University for postdoctoral studies in the biochemistry laboratory of David S. Hogness, who has been called the founder of modern genomic analysis. Hogness was using the common fruit fly, Drosophila melanogaster, a longtime workhorse of genetics research, in expanding the techniques of gene cloning. Hogness had begun cloning Drosophila sequences in bacterial plasmids, and Rubin’s initial postdoctoral project was to compile the first library large enough to represent the entire fly’s genome.
After his postdoctoral fellowship, Rubin returned to Boston and a position at Harvard-affiliated Dana-Farber Cancer Institute, continuing work on Drosophila genetics. But his scientific style was at odds with Harvard’s highly political and competitive academic culture, and in 1980 he accepted a position in Baltimore at the Carnegie Institution of Washington, in the embryology department headed by Donald D. Brown.
Rubin fluorished at Carnegie. He and developmental biologist Allan C. Spradling, now an HHMI investigator, achieved a breakthrough by inserting, for the first time, foreign genes into the embryos of multicellular organisms—Drosophila—and showed that the genes were expressed in the cells of the adult. The key was harnessing a certain type of naturally occurring transposable DNA sequence, called the “P element,” that can insert itself into a cell’s DNA. In their much-cited 1982 paper published in Science, Spradling and Rubin reported that they had used P elements carrying a wild-type gene for red eye color to correct a white-eye mutation in fruit flies.
Rubin’s growing scientific stature soon caught the interest of Daniel E. Koshland, a biochemist at the University of California, Berkeley, who had taken on a controversial revamping of that institution’s biological sciences program. Rubin came aboard in 1983 as the John D. MacArthur Professor of Genetics and later became head of the genetics division. In 1987, a banner year, he was chosen to be an HHMI investigator and elected to the National Academy of Sciences—at the unusually young age of 37.
While in California, Rubin and two colleagues founded a biotech company, Exelixis, located in South San Francisco, for the purpose of translating discoveries about genetic pathways in the fruit fly to problems of human medicine.
Rubin’s highest public profile emerged from his partnership with the maverick scientist-entrepreneur J. Craig Venter to sequence the Drosophila genome as a warm-up to the contentious race to sequence the human genome. While the National Institutes of Health (NIH)-funded effort took a more cautious path to the enormous task, Venter and his company, Celera Genomics, gambled on a faster and less expensive—but potentially riskier—“whole-genome shotgun” method.
In 1998, Venter approached Rubin, then head of the Berkeley Drosophila Genome Project, and proposed that they collaborate to perform the fruit fly genome sequencing at no cost to the public. In March of 2000, Venter and Rubin announced the nearly complete sequence of the 120 million units of DNA contained in the fruit fly’s five chromosome arms.
With the raw sequence in hand, Rubin and about 60 Drosophila researchers, computer scientists, and staff gathered at Celera headquarters for a frenzied, two-week-long “annotation jamboree.” Using algorithms being refined in all-night sessions, the scientists analyzed the sequence and discovered a total of 13,600 genes on the chromosomes. Rubin calls it “the most intellectually stimulating time of my career.”
In 2000, Rubin was named vice president for biomedical research at HHMI, a job that would bring him back to the East Coast and, three years later, make him director of planning for Janelia. His fantasy for success at Janelia, Rubin says, is that people will say, “‘Nothing extraordinary came out of Janelia for a while, but then, truly unanticipated discoveries started coming out after five or ten years. (Those discoveries) clearly only happened because they patiently supported very bright people to work on difficult problems. They had the right people and a synergy developed between those people—those discoveries might never have been made in another setting.’”