Human Genome first draft

Gina Miller (nanogirl@halcyon.com)
Thu, 27 May 1999 13:53:20 -0700

The first draft of the human genome may be completed by next year The San Diego Union-Tribune

COLD SPRING HARBOR, N.Y. -- The publicly financed effort to decode the human genome, the 3 billion units of DNA at the heart of every human cell, is now 10 percent complete and is on track to meet its goal of finishing a first draft of the genome a year from now, officials of the National Institutes of Health said.

Decoding the genome, which holds the cell's genetic programming instructions, is regarded as a fundamental step toward understanding the design of the human body and its propensity to disease. Because all diseases have a genetic component, knowledge of the genome's precise sequence of DNA units should lead to fundamental advances in many branches of medicine.

Dr. Francis Collins, director of the National Institutes of Health's share of the human genome project, told scientists meeting at the Cold Spring Harbor Laboratory that the impending completion of the genome represented a
"historic time in science."

"This is the most important organized scientific effort that humankind has
ever attempted," Collins said. "It dwarfs going to the moon."

His remarks were made in the presence of James D. Watson, who with Francis Crick discovered the structure of DNA in 1953. As first director of the Health Institutes' human genome project, Watson set its completion date as 2005, a goal he judged technically feasible.

Watson's hope of seeing his project produce a complete sequence of human DNA within his lifetime faltered briefly last year when a newly formed private company, [ Celera ] , announced that it would complete the human genome by 2001. For a few days, officials at the National Health Institutes seemed inclined to cede the field to Celera and its aggressive leader, Dr. J. Craig Venter. Venter has suggested that when he succeeds, the public consortium's efforts will be seen as unnecessary.

But the institutes' efforts quickly resumed after their partner in the public consortium, the richly endowed Wellcome Trust of London, said the publicly financed effort should continue.

Wearing a canary yellow sweater and a floppy hat, Watson sat in front of the audience as the progress of the genome-sequencing project was announced. Collins projected onto a screen the first page of Watson's 1953 article in the journal Nature, noting that if the decoding was completed by 2003, as planned, exactly half a century would have elapsed between the two events.

Two-part plan

Collins also stressed the ideological difference between the two camps by emphasizing the public consortium's goal of putting the human genome sequence in the hands of the world's scientists as soon as possible, without fees or restrictions. Celera does not plan to make all its sequence data immediately available, although Venter has said scientists will have free access to parts of it.

Venter's challenge to the public consortium preceded a recent centralization of its efforts and a sharpening of focus. The various university sequencing centers financed by the health institutes have been reduced to four, and the smaller, less efficient centers have been cut out of the action.

The surviving centers now hold weekly conference calls and submit to a certain amount of central planning, which they had previously avoided.

Besides moving up its target date for the complete genome sequence to 2003 from 2005, the public consortium has said it will produce a "first draft" -- 90 percent of the sequence containing the majority of all human genes -- by next spring.

The decision to produce and publish a first-draft DNA sequence may make it harder for commercial ventures like Celera to lock up significant stretches of the genome with patent claims.

But the decision carries a certain cost in that the two-stage process of producing a first draft and then a complete sequence is less efficient than finishing the whole sequence with no intermediate stage.

Vast unknowns

Despite the progress made since 1996, when human genome sequencing started in earnest, its completion cannot be taken for granted. Both the ends and the middles of human chromosomes, the units in which DNA is packaged, consist of highly repetitive regions of DNA that may be hard to decode.

So far no human chromosome has been completed, although the long DNA molecule, which is chromosome 22, has been half-sequenced and scientists hope to finish it this year.

Sitting in his office after the meeting, Watson, who is president of the Cold Spring Harbor Laboratory, called the public consortium's progress
"extremely satisfying."

One-third of the human genome sequence is to be finished by the Sanger Center, near Cambridge, England. The next-largest contributor is Washington University ] in St. Louis. Last year the two centers finished decoding the genome of the C. elegans roundworm as a pilot project for tackling the human genome.

At a closed meeting here, where all parts of the genome were allocated to various centers, it was agreed that a French group would sequence chromosome 14, Japanese scientists would do chromosome 18 and a German sequencing center would complete chromosome 21.

"The genome belongs to the world," Watson said. "When it is being said that
this is the most important thing human beings have ever done, people want to be part of it."

This was not the case when Watson first endorsed the idea of trying to sequence the human genome in the late 1980s. Many scientists opposed the effort, in part from fear that it would divert research funds from their own projects.

Watson said he set 2005 as a conservative target date for fear that the project might not receive the necessary funds. "When we set those dates, the scientific community was not with us," he said.

Gina "Nanogirl" Miller
Nanotechnology Industries
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