Whitehead scientists enjoy genome sequence milestone


The Whitehead/MIT Center for Genome Research enjoyed much more than 15 minutes of fame in late June, as the Human Genome Project and Celera Genomics announced their first assemblies of the human genome, the genetic blueprint for a human being.

Whitehead was the single largest contributor to the Human Genome Project, providing roughly a third of all the sequence assembled by the international consortium of 16 laboratories involved.

Whitehead also laid much of the groundwork needed for the project, by scaling up 20-fold and launching the project's final phase -- sequencing the three billion base pairs that make up the human genome. Over the past year or so, Whitehead's sequencing center produced more than one billion base pairs or DNA letters that went toward assembling the "book of life" announced on June 26.

BETTER, FASTER THAN EXPECTED

Production of genome sequence has skyrocketed over the past year, with more than 60 percent of the sequence having been produced in the past six months alone. During this time, the project consortium has been producing 1,000 bases per second of raw sequence -- seven days a week, 24 hours a day.

The consortium's goal for spring 2000 was to produce a "working draft" version of the human sequence, an assembly containing overlapping fragments that cover approximately 90 percent of the genome and that are sequenced in "working draft" form, i.e., with some gaps and ambiguities. The consortium's ultimate goal is to produce a completely "finished" sequence, i.e. one with no gaps and 99.99 percent accuracy. The target date for this ultimate goal had been 2003, but the final, stand-the-test-of-time sequence will likely be produced considerably ahead of that schedule.

The Human Genome Project consortium centers in six countries have produced far more sequence data than expected (more than 22.1 billion bases of raw sequence data, comprising overlapping fragments totaling 3.9 billion bases and providing seven-fold sequence coverage of the human genome). As a result, the working draft is substantially closer to the ultimate finished form than the consortium expected at this stage.

Although the working draft is useful for most biomedical research, a highly accurate sequence that's as close to perfect as possible is critical for obtaining all the information there is to get from human sequence data. This has already been achieved for chromosomes 21 and 22, as well as for 24 percent of the entire genome.

In a related announcement, Celera Genomics announced that it completed its own first assembly of the human genome DNA sequence.

The public and private projects use similar automation and sequencing technology, but different approaches to sequencing the human genome. The public project uses a "hierarchical shotgun" approach in which individual large DNA fragments of known position are subjected to shotgun sequencing (i.e., shredded into small fragments that are sequenced, and then reassembled on the basis of sequence overlaps). The Celera project uses a "whole genome shotgun" approach, in which the entire genome is shredded into small fragments that are sequenced and put back together on the basis of sequence overlaps.

TRIUMPHANT FEELINGS

Behind all the publicity hoopla was the personal triumph and exhilaration felt by every Whitehead person involved with the project. In fact, for most of them, including the eight representatives from the Genome Center who went to a White House ceremony in Washington, the pride and excitement about a job well done far surpassed any appearance on the "Today" show.

Eric Lander, professor of biology and director of the Whitehead Genome Center, and Lauren Linton, co-director of its sequencing center, as well as sequencing center team leaders were in the White House East Room as President Clinton and Britain's Prime Minister Tony Blair made the historic announcement -- that the "book of life" had been decoded. The room was electric with anticipation as the band played "Hail to the Chief" and announced the President's entrance.

Remarks by President Clinton, Francis Collins (director of the National Human Genome Research Institute) and Craig Venter (president of Celera Genomics) recognized the work of the thousands of scientists who helped the world reach this milestone.

"We are incredibly happy and feeling a sense of triumph. This is an exciting day, and the credit goes to all the people who worked day and night at a feverish pace both to create the sequencing center and to sequence every last bit of DNA to achieve the goals that we had set for this milestone," said Dr. Linton.

"It's very exciting to be here, to stand here in the White House and be recognized for our accomplishments. It was impressive and overwhelming and totally thrilling," said Nicole Stange-Thomann, leader of the clone preparation and library construction team.

She and several team leaders from Whitehead, including Kevin McKernan, Mike Zody, Lisa Kann, Jim Meldrim, Ken Dewar, Will Fitzhugh and Paul McEwan, attended the White House event and the press conference that followed at the Capital Hilton.

MEDIA BLITZ

Back in Cambridge, sequencing center assistant directors Bruce Birren and Chad Nusbaum rallied the troops for a celebration at the Whitehead Genome Center. They also faced huge and unprecedented media interest in the topic, handling dozens of interviews and television broadcasts that followed the announcement. WHDH-TV Channel 7 (the Boston affiliate of NBC) broadcast live from the Whitehead party, and Channels 4 and 56 also descended on the Whitehead sequencing center.

CNN, ABC, NBC, CBS, the Discovery Channel and many other national and international TV stations had prepared in advance, taking footage of the sequencing center and conducting interviews in the past several months, and were ready with stories featuring Whitehead soon after the June 26 announcement.

Whitehead was also featured in the New York Times, the Boston Globe, the Boston Herald, the Washington Post, the Los Angeles Times, Newsday, USA Today, the Wall Street Journal, the Dallas Morning News, Time, the Associated Press and many other newspapers and magazines.

While the media attention focused mostly on the sequencing center, some of it also trickled down to the Genome Center's Functional Genomics Group and the main Whitehead Institute on questions regarding functional genomics and other applications of the genome sequence. Media calls came at a frenzied pace as news outlets frantically tried to get Whitehead scientists to appear on shows on short notice.

MIT Professor of Biology and Whitehead member Richard A. Young appeared on MSNBC; Professor and Whitehead director Gerald Fink was on Greater Boston with Emily Rooney; and Kevin McKernan (a team leader at the sequencing center) and David Altshuler (a research scientist at the Genome Center and Harvard endocrinologist) were on the Geraldo Rivera show on CNBC. All this happened within the span of just one day (June 26). Media calls continued to pour in all week as reporters did follow-up stories about the Genome Center's accomplishments.

"We deserve to be proud of our accomplishments and bask in this glory as the world's attention focuses on us. The credit goes to all the individuals at the Whitehead Genome Center who have worked hard to make us the flagship center of the Human Genome Project Consortium. Everyone associated with this project should feel proud," said Professor Lander.

A version of this article appeared in MIT Tech Talk on July 12, 2000.


Topics: Genetics, Innovation and Entrepreneurship (I&E)

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