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Whitehead receives $35m for genome project's next phase

The Whitehead Institute for Biomedical Research will receive approximately $35 million from the National Human Genome Research Institute (NHGRI) of the National Institutes of Health to participate in the first year of the definitive, full-scale effort to sequence the human genome.

An international consortium announced on Monday (March 15) the successful completion of the pilot phase of sequencing the human genome and the start of the large-scale effort to read all 3 billion DNA letters (referred to as DNA bases) that make up the instruction book for a human being.

Based on experience gained from the pilot project, the international consortium now predicts they will produce at least 90 percent of the human genome sequence in a "working draft" form by the spring of 2000, considerably earlier than expected.

The five major sequence producers in the international consortium will be three US laboratories funded by NHGRI (the Whitehead Institute, Washington University School of Medicine in St. Louis and the Baylor College of Medicine in Houston); the Joint Genome Institute of the US Department of Energy (DOE); and the Sanger Centre, supported in the United Kingdom by the Wellcome Trust. The NHGRI awards total $81.6 million; the Wellcome Trust has announced that they are adjusting the funding of the Sanger Centre to make available approximately $77 million for human DNA sequencing over the next 12 months.

"The rich academic environment of MIT has contributed significantly to Whitehead's leadership role in the Human Genome Project," said Dr. Eric S. Lander, director of the Whitehead/MIT Center for Genome Research and a professor of biology. "Our progress over the past three years reflects the involvement of dozens of MIT undergraduate and graduate students in biology, engineering, computer science and other fields.

"In the pilot phase, we and others designed and tested new technologies and strategies for scaling up DNA sequencing; the results were tremendously positive. We showed that we could generate highly accurate, continuous DNA sequence in a cost-effective manner. Now we're ready to move ahead," Professor Lander said.

During the pilot phase, eight scientific teams supported by NHGRI, DOE and international collaborators completed the sequence of more than 480 million bases, of which 260 million (or close to 10 percent of the human genome) are in high-quality finished form.

The finished sequence produced by the pilot projects met or exceeded the international accuracy standard of no more than one error in 10,000 bases. In fact, the most recent assessment showed that leading sequencers are 10 times more accurate than that, producing fewer than 10 errors for every million bases sequenced.

Pilot project participants also drove down the cost of sequencing, from approximately $2 per base when the pilot project started to an average of 20 to 30 cents per base today. The consortium members expect to reduce the cost even further as the project progresses.

The consortium's goal is to produce a working draft covering at least 90 percent of human genome sequence within one year. In plans drawn up last fall, Genome Project leaders projected completing the working draft by December 2001. The new consortium goal advances this timetable by more than a year and a half.

The working draft will then serve as the scaffold for the painstaking but critical work of finishing, which involves closing gaps and correcting errors, leading to completion of the final high-quality, continuous human DNA sequence by 2003 at the latest.

The NHGRI-funded laboratories will be responsible for producing approximately 60 percent of working draft sequence. DOE's Joint Genome Institute and the Sanger Centre will be responsible for producing approximately 10 percent and 33 percent, respectively.

"The consortium is committed to releasing all DNA sequence into DNA databases within 24 hours and will not patent any of the sequence generated," Professor Lander said. "Thus, the information will be available immediately to academic researchers answering critical questions about human disease through basic biomedical research, and to corporate scientists engaged in drug development to fight human disease."

"Through this major publicly funded effort, we can ensure that sequence data remains in the public domain for access by all researchers for the development of future healthcare treatments. This is crucial for the real medical benefits to be realized efficiently," added Dr. Michael Morgan, chief executive of the Wellcome Trust Genome Campus.

The sequencing effort is also designed so it can take advantage of any sequencing work done in the private sector. This may allow completion of the final sequence far sooner than 2003. "The Human Genome Project looks forward enthusiastically to cooperating with all parties that can contribute to more rapid public availability of the human genome sequence," said Dr. Collins.

He added that the three new awards to Whitehead, Washington University and Baylor were based on a peer review process that evaluated the largest of the pilot projects -- those that had completed 15 million bases of high-quality, finished sequence by December 1998. NHGRI will review additional applications in March and plans to award additional funds for large-scale human DNA sequence production in May.

"We are very proud to be part of this international effort," said Dr. Gerald R. Fink, professor of biology and director of the Whitehead Institute. "The complete human genome sequence will be the foundation for all biomedical research in the 21st century. Just a decade from now, our students will be unable to conceive of a time when researchers lacked this critical tool for advancing knowledge of human health and disease."

A version of this article appeared in the March 17, 1999 issue of MIT Tech Talk (Volume 43, Number 23).

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