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Venter's DNA Major Source of Celera's Database
dh003i writes "According to this article, Dr. Craig Venter's DNA is the major source of Celera's database of the human genome. Interesting stuff." Includes interviews with lots of aggravated geneticists.
Scientist Reveals Genome Secret: It's Him
By NICHOLAS WADE
When scientists at Celera Genomics announced two years ago that they had decoded the human genome, they said the genetic data came from anonymous donors and presented it as a universal human map. But the scientist who led the effort, Dr. J. Craig Venter, now says that the genome decoded was largely his own.
Dr. Venter also says that he started taking fat-lowering drugs after analyzing his genes.
Reactions among scientists range from amusement to indifference, most saying that it is unimportant whose genome was sequenced. But members of Celera's scientific advisory board expressed disappointment that Dr. Venter subverted the anonymous selection process that they had approved.
Dr. Venter, a pioneer in the use of new DNA sequencing machines, challenged the government-supported effort to decode the human genome and held his academic rivals to a draw in June 2000, despite starting years later in the race.
Both teams said their DNA sequence was based on the DNA of anonymous donors, with Celera's being drawn from a pool of 20 donors from 5 ethnic groups. But in an interview this week, Dr. Venter elaborated on his brief mention on "60 Minutes II" on April 17 that the Celera genome was based principally on his DNA.
In making this known, he has abandoned his genetic privacy in the most thorough way possible, even though for now only subscribers to Celera's genome database can browse through his genetic endowment.
Though the five individuals who contributed to Celera's genome are marked by separate codes, Dr. Venter's is recognizable as the largest contribution. He said he had inherited from one parent the variant gene known as apoE4, which is associated with abnormal fat metabolism and the risk of Alzheimer's, and that he was taking fat-lowering drugs to counteract its effects.
Dr. Venter's reason for having his own genome sequenced, he said in an interview this week, was in part scientific curiosity -- "How could one not want to know about one's own genome?" -- and also a sense of responsibility that because he was asking other people to donate tissues, risking invasion of their genetic privacy, he should be first in line.
He did not make this known at the time, he said, "because I didn't want it to be the issue or the focus."
"Now, after the fact," he said, "I don't think it matters."
As to opening himself to the accusation of egocentricity, he said, "I've been accused of that so many times, I've gotten over it."
The academic consortium expressed no great emotion at the news that their rival had sequenced his own genome.
"That doesn't surprise me; sounds like Craig," said Dr. James D. Watson, the co-discoverer of the structure of DNA. Dr. John Sulston, former director of the Sanger Center in England, said, "It doesn't have any great significance." Dr. Francis Collins, director of genome research at the National Institutes of Health, declined through a spokesman to comment.
But members of Celera's scientific board of advisers expressed regret that the process they had approved for choosing anonymous donors had been subverted.
"I think the original idea, to keep everything anonymous, was not a bad one," said Dr. Richard Roberts, scientific director of New England BioLabs and a board member.
Another member, Dr. Arthur Caplan, a biomedical ethicist at the University of Pennsylvania, said, "Any genome intended to be a landmark should be kept anonymous. It should be a map of all us, not of one, and I am disappointed if it is linked to a person."
The drive to sequence the human genome was an opportunity for personal glory as well as scientific discovery, and Dr. Venter's action emphasized the first motive, Dr. Caplan said.
It seems that Celera's intended process of choosing randomly among anonymous samples must have been overridden at some stage so that Dr. Venter's became the one selected. A Celera spokesman, Robert Bennett, would not confirm or deny Dr. Venter's claim and declined to make available Dr. Sam Broder, the company's vice president for medical affairs, who oversaw the donor selection process.
Dr. Venter, however, said that "I made the selection with a team," and that "only me and two other people" know the codes to Celera's five donors.
Because the human genome decoded by the academic consortium is a mosaic of different individuals, Dr. Venter is at present the only person whose genome has been largely sequenced, and may remain so for many years. In his person, he offers a unique way to connect a human genotype with its phenotype, as biologists refer to a genome and the physical form it specifies.
Is his body now particularly valuable to science? "You mean for dissection?" Dr. Venter said. "I haven't thought that far ahead. You have given my critics a chance to dissect me."
Dr. Norton Zinder of Rockefeller University said he saw some value in less drastic investigations to study the link between Dr. Venter's genotype and phenotype. "You would have to do experiments on him," Dr. Zinder said. "Craig would become an experimental animal. He's certainly made himself liable for that."
But Dr. Kenneth Kendler, a psychiatric geneticist the Virginia Institute for Psychiatric and Behavioral Genetics, said that science was not advanced enough to read off a person's personality from their genome and that, as a sample of one, Dr. Venter and his genome were not of much help to scientific inquiry.
The same verdict came from Dr. Stephen Warren, editor of the American Journal of Human Genetics.
"I think it's of much more interest to him to know his genotype than for other geneticists to know it," Dr. Warren said. But he praised Dr. Venter's drive and ambition for forcing the public consortium to speed its efforts.
As for the idea that Dr. Venter's body should somehow be preserved along with his genome, Dr. Warren said, "That would be his wish, no doubt, to be prominently displayed in the Smithsonian."
The celera human genome effort consists of DNA from 6 individuals, from which Venter was one.
They did at least a 6x oversampling of the whole genome and are still in the process of assembling the fragments to contigs. They are also using their mouse genome data (two strains) to assist in the assembly of the human data and vice versa.
The celera effort is as serious as the public one.
Besides, scientists have always had a history of experimenting on themselves: Newton died of mercury poisoning from his experiments, Kevin Warwick has been having chips implanted in his body, and where do you think Antony van Leeuwenhoek got the sperm he observed under his microscope?
Though the fact that Ventner relied heavily on his own genetic material certainly increases the chances for mistaken conclusions (given its being very limited input), but the results of Celera's "decoding of the genome" represent limited output by design.
While Celera's accomplishment may have gained *Press Acclaim*, and while it in some ways has validated the so-called "shotgun" sequencing technique (which has been around since before the days of Celera), Ventner and Co. didn't claim to have resolved the full sequences (and their variations between individuals) of the human genome as many are mislead to believe. Rather, Celera claimed to map the loci of human genes to the chromosomes (loci ~= regions that code genes). Further, it claimed to discover regions that are possible or even likely to be loci for genes not yet characterized, based on sequence patterns that are generally considered to be "flags" for gene loci. Given that loci characterize a set of alleles (allele ~= version of a gene, for example, you may have an allele that codes for connected earlobes, or disconnected earlobes, or both [ humans are diploid, meaning they recieve one allele form your father and one from your mother, barring crossing-over events, in which case you can recieve 2 alleles from either your father or mother exclusively]), and given that sequence patterns and homologies between species were mostly used to identify the loci, the fact that Ventner used Ventner's DNA seems an acceptable way to get a rough map of the gene loci, and Celera freely admits that further characterization is necessary to identify alleles, and to refine the definitions of the loci.
If you aim to sketch a rough outline of the gene locations, it really doesn't matter whose DNA you use to start it, because you anticipate that it will be refined with the DNA of others.
All of this has been thoroughly reviewed by genetisists the world over, and none of them to my knowledge are up in arms about this.
A popular misconception is that Celera accomplished in a short time what other bodies have failed to accomplish. Celera used a different approach to get a full rough outline of gene loci completed, whereas other researches have taken a step-wise approach to gain information about regions in greater depth. The rough outline in itself is a useful accomplishment, because it allows researchers to focus on areas of the genome that appear to affect specific genetic phenomena of interest, but it's not the key to the kingdom, and there is much work to be done even to characterize regions that *look* like they code for proteins, much less characterize genetic diversity amongst humans.
The Human Genome Project, which makes up the bulk of Celera's "competitors", uses a more elegant, and painstaking approach to sequencing DNA (relying heavily on a technique known as "primer-walking"). Their approach generally begins with the "shotgun" approach applied to moderately-sized regions to gain an outline, and then uses "primer-walking" down the assemblies to verify that they are correct, and to gain information about gaps in the assembly. In many cases, primer-walking validates shotgun sequence assemblies, but sometimes, it indicates errors. The process of validating sequence using this approach is more expensive, more time consuming, and absolutely necessary to refine the genetic map, and to obtain sequence information for certain "hard to sequence" regions of the chromosome.
If share holders want to worry about their investment in Celera, they should be think about the fact that genetic sequences have been declared "unpatentable" in the U.S., which makes Celera's real goal (making money) much more difficult.