WRITTEN TESTIMONY OF
GERALD M. RUBIN
before the
SUBCOMMITTEE ON ENERGY AND ENVIRONMENT
OF THE COMMITTEE ON SCIENCE
UNITED STATES HOUSE OF
REPRESENTATIVES
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
Drosophila.
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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