PAGE 4 OF 7
Working among “heroes” like Nobelist Sydney Brenner, now a senior adviser at Janelia Farm, has had a lasting effect on Gerry Rubin.
The unconventional style of the place suited him perfectly. “I liked that they didn't have required courses,” he says. “Because I didn't learn well in the classroom, the MRC-LMB was wonderful for me. I liked reading and bringing in things informally, in small groups. You'd sit down with these scientists at afternoon tea in the cafeteria.”
“Oh, he loved the very easy regulation of the place,” recalls Brenner. “I remember he came to me and said, `Isn't it time I put in my thesis?' And I said, `What thesis?' I'd forgotten he was a grad student—he acted more like a postdoc, he was so completely independent.”
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 10 such sequences a second. “What took 2 years of my life now can be done in one-tenth of a second!”
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 that had just been discovered by Stanley Cohen (Stanford University) and Herbert Boyer (University of California, San Francisco). 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. “It was an exciting time to be there,” recalls Rubin. “Anything you did was brand new.”
A newly minted drosophilist, 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 lab headed by Donald Brown.
Rubin's stint at Dana-Farber nevertheless brought a lasting benefit. He began spending time with the manager of another Harvard laboratory, Lynn Mastalir. “He worked all the time,” she says, “so the only way he was going to meet anybody was in a lab.” She soon learned that romance with Gerry Rubin also meant that dates could be punctuated by visits to the lab—or the lab might visit them. One evening, on arriving for a date, he pulled vials of fruit flies out of his pockets and asked if he could leave them in her house while they went out. “If I leave them in the car, they'll freeze,” he explained. The couple married while still in Boston and had a son, Alan, 4 days after Rubin's 30th birthday. Alan is now entering graduate school in genome sciences at the University of Washington in Seattle.
Rubin thrived 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. The paper “jump-started our careers,” Rubin says, and paved the way for bioengineering higher animals for research and biotechnology purposes.
Photo: Tom Kochel