Gerald M. Rubin
Gerry Rubin began his research career in the lab of the Nobel Laureate Sydney Brenner, who once said that “Progress in science depends on new techniques, new discoveries and new ideas, probably in that order.” Although Rubin began his career as a geneticist, his drive for building new tools and techniques would eventually leave an indelible mark on the field of neuroscience, which includes his efforts to sequence the Drosophila genome and his leadership in mapping the fly connectome, which was a venture that would come to define the field of Drosophila neuroscience. “I wanted to build new tools that would help get us through the barriers,” Rubin said. “That was my intellectual motivation through my career.”
After receiving his Ph.D. from the University of Cambridge, Rubin did his postdoctoral training at Stanford University, under the guidance of David Hogness, which is where he first started working with the model organism Drosophila melanogaster. At the time, recombinant DNA had just been shown to work. During Rubin’s efforts to clone DNA, he became interested in understanding why there were so many repetitive elements in the fly genome. This eventually led to the realization that there were a number of mutations that were caused by transposable elements, the fact of which could be used to selectively modify genes within the fly genome.
In a series of experiments, using the white locus, Rubin was able to demonstrate that some of the mutations found in the white locus were the result of transposon insertion, a fact that he and his collaborator Allan Spradling realized could be useful for manipulating the fly genome. Rubin and Spradling conducted a series of experiments, which were published in back-to-back papers, demonstrating the use of P-elements for engineering transgenic flies.
“This enabled people to conduct genetic engineering of an animal, for the first time,” Rubin said. The use of P elements for selectively modifying the fly genome opened up countless possibilities for the field, while for Rubin, it offered him the intellectual freedom to take on big, ambitious projects that would transform the field yet again.
This included Rubin’s effort to sequence the fly genome, a major venture that, at the time, many believed was too hard and too expensive, all for a sequence of bases that no one would know how to interpret. “Nobody now doesn’t think it wasn’t worth it,” Rubin said, but at the time, it was a massive undertaking that many people feared would be a waste of money. Of the experience, Rubin noted that “it taught me how to carry out projects where you had to get people to work together, who wouldn’t normally work together,” he said. “I found that I enjoyed that.”
After the fly genome was sequenced, Rubin was offered the opportunity to become the director of the Janelia Research Campus, which is the Howard Hughes Medical Institute’s research center in Ashburn, Virginia, an undertaking that he describes as a “sociological experiment” in research. “Science had gone in a direction that was much harder for young people,” Rubin said. “We wanted to see if we could do a different kind of science, that would make a difference.”
As part of this venture, Rubin decided to embark upon mapping the fly connectome and developing genetic tools to manipulate individual cell types, massive undertakings that would map the various circuits of the fly brain, down to the last neuron, and offer researchers tools that could help them understand how the brain’s wiring correlated to behavior. This venture, which would take ten years and $60 million, would come to define the field of Drosophila neuroscience, by offering a powerful tool that could yield countless valuable insights into the circuitry of behavior.
Of his efforts to map the connectome, Rubin notes that his efforts were similar to that of a venture capitalist, which included creating the vision for the project, recruiting the people who had the skills to accomplish the venture, and also finding the funds to make it possible. “I had to use my scientific credibility as collateral, to get the money to back the project,” Rubin said.