Now the NIH is funding the Drosophila genome project as a complement to the human genome project, and the fruit fly genome is expected to be completely sequenced within a year, as part of a collaborative effort with Celera Genomics. The publicly funded efforts are led by Gerald M. Rubin, a University of California, Berkeley-based investigator with the Howard Hughes Medical lnstitute (HHMI) and a Drosophilist whose impact on the field has been undeniable. Rubin has done pioneering work on the use of transposable elements—in particular, "P elements"—as vectors for doing gene transfer in Drosophila. He has published over 50 papers that have garnered 100 or more citations each, and his 1982 article on "Genetic transformation of Drosophila with transposable element vectors" (Science, 218(4570):348-53, 1982) has been cited nearly 1,300 times. (Five of Rubin's papers published during the 1980s have now been cited more than 500 times;a listing of his highest-impact papers from the 1990s appears on the next page.)

   Rubin, 49, did his undergraduate research in biology at the Massachusetts Institute of Technology and then received his doctorate at the University of Cambridge, England, in 1974. He did a two-year postdoc in David Hogness’s lab at Stanford before moving on to Harvard Medical School and then the Carnegie Institution of Washington, before eventually settling in 1983 at Berkeley. In addition to his activities as an HHMI investigator, he is also director of the Drosophila Genome Center and a professor of genetics.

You’ve spent the past 15 years or so studying pattern formation in the retinas of fruit flies? What possible relevance does that have to humans?

   Rubin: The relevance, actually, has been one of the big take-home messages from all of molecular biology over the last five years: a demonstration of just how similar different organisms are, and how, when evolution invented something that worked, it maintained it over very long evolutionary periods. So, for instance, all signal transduction pathways that we’ve discovered in flies exist in humans. None of the things we’ve discovered in flies are unique to flies. A lot are also found in other systems, such as the roundworm Caenorhabditis elegans. Some go all the way back to yeast. So in fact we’ve discovered genes in Drosophila—because the experimental techniques are better in Drosophila—that are important for the same signaling events in humans, and these genes weren’t previously known in humans. These days, we isolate the gene in Drosophila, clone it, and then isolate the corresponding gene in humans. That’s a very well proven method of gene discovery. There are now literally hundreds of examples where researchers have been able to identify new important genes in humans by first finding the homologous genes in flies.

When did the idea come about to do a Drosophila genome project, and why?

Why not?

   Rubin: They were spoiled. They had a lot of tools, since Drosophila had been studied for so many years, and they didn’t appreciate the impact a genome project would make. Fly researchers could do most of the experiments they wanted to without the genome project. Drosophila, for instance, has something called polytene chromosomes in some of its tissues. Those are chromosomes within giant cells, and the DNA keeps replicating. You have 1,024 DNA strands for each chromosome and they’re all lined up in unison. You can actually see the chromosomes and map sequences on the chromosome without having a map derived from cloned DNA. So, because the techniques were already there, researchers could take an interesting mutation and clone the gene in Drosophila without having a formal genome project. And it was the heyday of developmental genetics—everybody was cloning important regulatory genes that control pattern formation. Researchers were all heavily invested in doing interesting science. It’s hard to take people like that and convince them to spend five years building an infrastructure that the whole field can use.

So how did you get involved?

   Rubin: Allan Spradling, another HHMI researcher and long-time collaborator, visited me at Berkeley in 1991 and we were sitting around saying, "Isn’t it too bad nobody's really jumped in with a full scale effort to do a Drosophila genome project? Someone ought to." And then we realized that we were the ones in the best position to do it. We were established, we could slow down our other work and make some effort along this line, and we realized that we shouldn’t be sitting here complaining and whining about why no one else was doing it if we weren't doing it ourselves. After that, it all came together very quickly.

Now everyone in the field seems very excited. What changed?