William, CRA, news coming this week?!
May 7, 2000
Rivals on Offensive as They Near End of Genome Race
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Genetics: The Human Genome Project
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By NICHOLAS WADE
he 10-year project to decode the human genome is entering its end game, but the high goal of unlocking the secrets of human heredity is ending in a fractious exchange of claims and countercharges.
Within a few weeks, both contestants in the genome race plan to declare victory, but in different terms, each already judged imperfect by the rival team.
The genome is an instruction manual containing the 100,000 or so genes that govern human development, operation and maintenance. Defects in various of these genes cause or contribute to almost all human disease.
At stake is academic glory for the genome researchers, an eventual gold mine for the companies that are first to develop useful drugs from the genomic information, and a landmark in scientific history as the foundation for human self-knowledge is put in place.
One contestant is a consortium of largely American and British academic centers supported by the National Institutes of Health and the Wellcome Trust of London. The other is the Celera Corporation, an upstart
whose formation just two years ago turned the centers' unchallenged pursuit of the genome into a furious race.
Since then, each side has made remarkable progress. The consortium, despite its unwieldy organization, responded to the Celera challenge, scrapped its target date of 2005, and focused on providing a rough but usable human genome sequence as early as possible. Its rough draft -- some 90 to 95 percent of genome including most of the genes -- may be ready as early as June.
Washington expects to have invested more than $3 billion by the time the project is complete and Celera about half a billion dollars.
Celera -- the name is the female form of the Latin word meaning "quick" -- has indeed been strikingly nimble. In just two years it has built a plant with 300 DNA sequencing machines, decoded the genome of the fruit fly -- a widely studied laboratory organism -- as a pilot project and, said its president, Dr. J. Craig Venter, is within a few weeks of decoding almost the entire human genome.
Although the two sides have discussed collaborating in a joint publication, talks broke down in December amid charges of "antagonism and excessive competition" made by Dr. Francis Collins, head of the National Institutes of Health part of the Human Genome Project, in a letter to Dr. Venter and others at Celera.
In any agreement, Dr. Collins wrote, referring to what he evidently considered past lapses by the Celera side, there would have to be "honest and straightforward responses to scientific inquiries, but avoiding disparaging the other party, sowing discord or undermining the collaborative spirit."
The intense pace of competition has been heightened by personal and institutional factors. Dr. Venter's ideas for decoding genomes have several times been dismissed as unworkable by the consortium's leading experts, and he has not hidden his satisfaction in proving he was right. His overall strategy for decoding the human genome, called a whole genome shotgun, was considered and rejected by the consortium but in Celera's hands has so far worked, at least with the fruit fly.
Consortium scientists say Dr. Venter has unfair advantages, notably in that Celera can use all the genome data that the consortium makes publicly available through GenBank, the government's computer data base for genome information.
In its public statements the consortium, which seems to have chosen a workable but less efficient decoding strategy than Dr. Venter's, has aimed to seize the high ground on data release. Though scientists usually harvest the first fruits of their findings, the consortium's centers publish their genome data immediately on the GenBank data base, where it is free for any use.
On March 14 President Clinton and Prime Minister Tony Blair were persuaded to issue a statement saying the genome "should be made freely available to scientists everywhere." They praised the consortium's data release policy and, at least in Dr. Venter's view, indirectly criticized Celera. The statement inadvertently devastated biotechnology stocks, including Celera's, when it was misinterpreted by the markets as meaning the two governments would oppose patenting human genomic data.
Celera has said it will make its human genome sequence available on a DVD disk, with no control over any discoveries that other scientists may derive from it.
But the company has refused to deposit its data in GenBank without safeguards to prevent its commercial rivals, such as Incyte and Human Genome Sciences, from downloading the data and selling it as their own.
Although the consortium wants everyone to use its data, that resolve is less intense when the user is Celera. Dr. Collins has said it would be "a breach of scientific ethics" for Celera to include the data in its article describing the human genome.
This charge has not resonated well. "I strongly disagree with that," said Dr. David Lipman, director of the National Center for Biotechnology Information, which runs GenBank. "These groups understood when they deposited their data that the whole goal was to make it available without restrictions immediately."
But Dr. Lipman supports another position taken by the consortium, that journal editors should not accept Celera's article on its human genome sequence until the company has first deposited its data in GenBank.
Genome sequences are mind-numbing rows of A's, T's, C's, and G's which would take hundreds of pages.
Many journal editors require genome article authors to deposit the sequence in GenBank's computers.
Dr. Lipman said GenBank did not have the resources to accommodate Celera's request that its data, if deposited in GenBank, should receive legal protection from copying by its commercial rivals.
The two teams are negotiating with rival journals to publish their descriptions of the genome -- the consortium with Nature of London, Celera with Science of Washington.
Despite the customary scientific practice of waiting for publication until announcing a new discovery, the two sides are likely to issue claims of success well before their articles appear in print.
To pre-empt Celera's article in Science, the consortium may hope to enlist Mr. Clinton and Mr. Blair again in an announcement, perhaps early next month, that it has achieved its rough draft of the human genome.
To pre-empt the consortium's declaration of victory, Dr. Venter may make it known, perhaps this week, that he has successfully assembled the human genome, the final stage in decoding and in principle a large step ahead of the rough draft stage reached by the consortium.
Both sides have already found fault with the other's victory plans.
The consortium's data is in a mixture of states. Though some regions of the three-billion-unit human genome are essentially complete, much of the rest is in the form of millions of short pieces of DNA, most of them about 10,000 units of DNA in length. Although the consortium knows roughly where each piece should go on its parent chromosome, it does not know exactly enough to place all the pieces in correct order.
Dr. Venter has said that anything worthy of being called a human genome sequence needs to be arranged in correct order, which the consortium's rough draft is not.
If Dr. Venter's whole genome shotgun approach works as well with the human genome as it did with the fruit fly, Celera's version of the genome will all be in correct order.
Celera's genome is likely, however, to have lots of gaps. The gaps in its fruit fly genome sequence were mostly small holes of known length and position that could be filled in later and were of minor significance. But Dr. Robert Waterston, head of the sequencing center at Washington University, St. Louis, a leading component of the consortium, has calculated that there could be 100,000 gaps in Celera's human genome sequence, with an especially large number in regions where Celera has no consortium data to rely on.
Even though the consortium's rough draft will not be completely ordered and will contain many gaps, it will nonetheless be of great value to researchers. Most of the genes are contained within the decoded regions and can be fished out by computer search programs, Dr. Lipman said.
With Celera's fully assembled genome, it will be possible to search for genes and to compare the human with other genomes, an important step in understanding how the human genome works.
In the battle of rival claims, one certain winner will be the public. Because of the competition, the human genome sequence and all the benefits from it will be available to researchers and pharmaceutical companies more than four years before the original target date of 2005.
"I think they both represent remarkable achievements," said Dr. William Haseltine, president of Human Genome Sciences. |
