Written Testimony Of Gerald M. Rubin

before the
APRIL 6, 2000

Mr. Chairman and Members of the Committee:

I welcome the opportunity to testify before the committee concerning my experience in working with the private sector on the sequencing of the genome of the fruitfly, Drosophila melanogaster.

Over the last year a group of academic scientists working together with scientists at Celera Genomics, Inc. determined and analyzed a nearly complete sequence of the Drosophila genome, the largest genome yet sequenced. I would like first to explain why one would choose to determine the genome sequence of the lowly fruitfly. I will then describe the history and nature of the successful collaboration between the public and private sector that allowed this goal to be achieved.

Drosophila has been a favorite of experimental biologists for over 90 years.  One measure of its key role in medically relevant research is that on three separate occasions, in 1933, 1946 and 1995, the Nobel Prize in Physiology or Medicine was awarded for discoveries made using this fruit fly. The fact that genes reside on chromosomes and that their positions can be mapped was established using fruit flies in 1912. Ionizing radiation, such as X-rays, was shown to cause mutations in 1927, and the major genetic pathways that
control communication between cells during development were discovered by genetic analysis in fruit flies in the late 1970s. For these reasons, and because of the large and active community of researchers using Drosophila, it was placed on the list of five organisms whose genomes were to be sequenced when the genome project was established ten years ago.

A remarkable finding that has emerged, both from the genome sequence and from extensive and detailed work done in hundreds of laboratories, is the amazing extent to which humans and fruitflies use a similar set of genes to construct themselves. The genome sequencing effort has revealed a number of previously unknown counterparts to human genes involved in cancer and neurological disorders. One measure of this conservation is that more than half of 289 genes that are known to be mutated, altered, amplified or deleted in a diverse set of human diseases have a counterpart in

Of the cancer genes surveyed, two-thirds have Drosophila counterparts.  Studies of these genes using the powerful experimental methods available for use in the fruitfly will provide important clues as to the mechanism of human disease.

Flies are sophisticated animals having complex structure and behavior including circadian rhythms, learning and memory. While clearly not as complex as humans, flies and humans appear to be constructed largely from the same set of parts, much as the largest supercomputers and desktop PCs are both made from similar microprocessors and memory chips. It is the nature of these parts and the simple integrated circuits composed of them that we hope to understand from our work with fruit flies. The supercomputer differs from the PC mainly in the number of copies of each component and in an increased number of cross-connections between them.

In May 1998, Celera's president, J. Craig Venter, approached me, as the Principal Investigator of the major federal grants funding the Drosophila Genome Project, with an offer to work with Celera to apply Celera's whole-genome shotgun sequencing strategy to Drosophila. At this time the publicly funded effort had only completed about a fifth of the genome and we were eager to speed up our project. In addition to this finished genomic
sequence, our contribution would be accurate clone-based genome maps and low-coverage sequence of the clones comprising the map. Celera would perform their part of the collaboration using their own funds. We agreed that in the end all the data would be made public without restriction, and we would share credit in the scientific papers that resulted from our work. Celera, in turn, would get to test the shotgun sequencing technique on Drosophila in a trial run leading up to sequencing the much larger human genome. In early 1999, with the full support and encouragement of the NIH and the DOE, I signed a Memorandum of Understanding formalizing this collaboration with Celera Genomics, Inc. (A copy of this MOU can be found on the Berkeley Drosophila Genome Project's www page: http://www.fruitfly.org.)

Many colleagues were not enthusiastic about a collaboration with a for-profit company on the genome project, despite the fact that academic researchers develop partnerships with the pharmaceutical and biotechnology industry all the time. A lot of my friends were particularly leery of a collaboration with Celera. They warned me that I was going to get into real trouble and would feel badly treated at the end of the day. And as if to
make this gloomy prophesy come true, the naysayers were widely quoted in the press.

But my interest in this collaboration was pretty simple. By combining our efforts, it seemed likely that we could get the science done better and faster than either group working alone.

When I agreed to collaborate with Celera scientists, I must admit I considered the collaboration itself a form of experiment. When people asked me how I felt about it, I'd say "Ask me when it's done."

It's done now and I am happy to be able to report that the collaboration was both highly successful and enjoyable. Celera honored all the commitments they made to me in this collaboration and they have behaved with the highest standards of integrity and scientific rigor.

Because of this collaboration, we have the Drosophila genome sequence a year ahead of our most optimistic estimates. The sequence is freely available to all, and the savings of over $10,000,000 in federal funds can be spent on the next steps in the genome project. For example, further improving the genomic infrastructure for Drosophila research by sequencing cDNA clones and providing other important tools and information to researchers.

Obtaining the genome sequence is just the beginning, not the end, of a long research process. If our work is going to have maximum impact on advancing understanding of human biology, we now need to determine the function of the genes encoded by the fruitfly genome. We began this process by setting up a larger collaboration of over 40 scientists from 20 institutions in five countries to perform an initial interpretation of the genomic sequence, which was reported along with the sequence itself in the March 24, 2000 issue of Science. This annotated sequence, freely available from the National Library of Medicine's database GenBank as well as from the www pages of the Drosophila Genome Project and Celera, will greatly accelerate the work of the 5,000 scientists world-wide who perform experiments with Drosophila. This work can be expected to facilitate the continuation of Drosophila's long history of significant contributions to our understanding of medically relevant human biology, as well as lead to a greater understanding of the biology of insects, which are themselves often vectors for disease and agricultural pests.

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Testimony by Neal Lane before the Subcommittee on Energy & Environment, Committee on Science, United States House of Representatives - April 6, 2000

Subcommittee on Energy and Environment

Subcommittee on Energy and Environment

J. Craig Venter, Ph.D. Subcommittee On Energy And Environment

Written Testimony Of Gerald M. Rubin

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