Eric Lander, founder and director of the Whitehead Institute/MIT Center for Genome Research, gave a stirring lecture to the MIT community to celebrate publication of a draft sequence and an initial analysis of the human genome, the set of DNA-encoded directions that defines an individual person.
The Whitehead-MIT Center was the single largest contributor to the Human Genome Project, a publicly funded international consortium.
The global group began work in 1990 and announced in June 2000 that it had assembled the human genome. It has taken since that announcement to analyze their findings, published in Nature last week (MIT Tech Talk, February 14, 2001).
Professor Lander's lecture praised scientific progress and the scientific process and noted the cultural context in which these unfolded. He expressed delight in the teamwork of the genome project around the world and pride in each collaborator's "absolute commitment -- that the data be freely released and available on the web every 24 hours."
His voice hoarsened by many recent speaking appearances, Professor Lander declared, "Nobody could do this alone, and nobody can take personal credit for it. About 250 people have completed this remarkable project, the first collaborative effort in biology but not the last. If we at MIT had not pulled together, it would not have gotten done."
Many of Professor Lander's students attended the genome talk, pads and pens in hand, and he asked members of the genome project team to stand for applause acknowledging their work. Rm 10-250 was filled to its 475-person capacity; nearly 200 more watched the talk on video in overflow rooms nearby. The event was also webcast.
PROJECT ORIGINS
Professor Lander's brief history of the consortium's genome research began in the dawn of time -- in genome-mapping terms, 15 years ago.
"Back in 1984 and 1985, it was an absolutely ludicrous notion to think that we could do this. DNA sequencing was so inefficient, there was this debate: was it even worth it? We had no clue what to do or how to do it. But that's the marvelous process of a scientific project," he said.
Professor Lander has likened the genome project to taking the large book of genomic information, breaking it into chapters, shredding each chapter, putting the scraps on the floor, and then reassembling it all, scrap to page to chapter.
He has also used a metaphoric description to portray the limitations of the project, calling the information contained in the human genomic code a "parts list. A Boeing 777 has 100,000 parts in it. Having a parts list doesn't tell you how to put it together or how it flies."
Turning to a series of slides, Professor Lander showed images of the Whitehead facility, computers in pristine formation, robots and segments of maps of the genome.
The human genome is expressed in four chemical symbols: A, T, C and G, representing the nucleotide bases adenine, thymine, guanineand cytosine. At full length, the genome is more than 3 billion letters, equalling about 75,500 pages of the New York Times. The interpretation of the genome is expected, over time, to clarify the causes of diseases such as cancer and to generate new treatments.
Noting that science progresses both in real time and relative to technological change, Professor Lander said there was a "dramatic scale-up" in the project in spring 1999 due to the development of more efficient "picking robots." With these robots processing 120,000 clones every day, the project went from mapping 10 percent of the genome in May 1999 to mapping 90 percent of it in May 2000.
"There are still gaps. It's not perfect. It's not finished. There's still about a year and a half to go before the finished state. But the order of accuracy keeps growing," he said.
REVELATIONS
As the accuracy of the map grows, startling facts about the territory have emerged. Chief among these so far is that "humans have surprisingly few genes -- between 35,000 and 40,000, not the 100,000 figure we have used," Professor Lander said. "We look like we have a small founding population of about 10,000."
He defined several goals for genomic sequencing and further research. The first is to "create for biology a periodic table of the elements," he said.
The next goals for genomic sequencing will be to complete maps (or books or parts lists) for the mouse, rat, zebra fish, puffer fish, seal and chimpanzee.
He reminded the group that while the human genome project may give us the entire sequence of our DNA, scientists must still determine how all the encoded proteins work.
Throughout his talk, Professor Lander demonstrated not only happiness with his work and with the consortium's success, but also his devotion to his students.
Describing the human genome map to them, he said, "This is the greatest lab notebook in history. Look at it this way: evolution has been taking notes for three and a half billion years, and we are getting a chance to look at its notes. The problem is, it's only been taking notes on the successful experiments."
Professor Lander focused his talk on the excitement of completing this initial genomic map, its implications and his enthusiasm for the consortium's practices and philosophy of "winning by giving it all away free on the web."
But he did not shy away from the context in which this "marvelous process" occurred. Of one slide, a montage of newspaper front pages declaring victory for the genome project months in advance of last week's Nature article, he quipped, "This was not being left alone to do science." He noted his preference for practicing "science by peer review over science by press release," a comment on how an exhilarating advance in research can be ratcheted to giddiness by the media.
And Professor Lander also acknowledged a private firm, Celera, whose successes in genomic sequencing paralleled the Whitehead-MITteam's, thanks in part to the public consortium's data availability on the web. The announcement made in June 2000 that each team had finished assembling the genome was made jointly by both teams. Last week's announcements were made at the same time in different journals.
A geneticist, molecular biologist and mathematician, Professor Lander is a member of the Whitehead Institute for Biomedical Researchand a professor of biology at MIT. He founded the Center for Genome Research in 1990 and described the completion of the draft sequence as the culmination of 15 years' work.
Professor Lander and his research group have developed many of the tools of modern genome research -- including genomic maps of humans, mice and rats in connection with the Human Genome Project and techniques for genetic analyses of complex multigenic traits. He has applied these techniques to the understanding of cancer, diabetes, hypertension, renal failure and dwarfism.
A version of this article appeared in MIT Tech Talk on February 28, 2001.
