Reading the Book of Jim

If Rothberg is right about the $1,000, that would be cheaper than a battery of genetic tests, which cost between $300 and several thousand dollars each. A personal genome offers another advantage. Most conventional genetic tests probe for known mutations. "If yours is one of the rare ones you're out of luck," says geneticist Richard Gibbs of Baylor University, who first suggest-ed that 454 approach Watson about sequencing his genome. A full sequence, in contrast, can be compared to the benchmark genome—sort of an average of the genomes of the people who ponied up DNA samples for the human genome project—so if you have any misspelling at all it will be detected.

The biggest potential benefit of having your genome fully sequenced is likely to come from the fact that no gene is an island. With the exception of diseases that arise from defects in a single gene, such as Huntington's and cystic fibrosis, the effect of one gene depends on your other genes. "We know it's not just your genes or your environment" that determines your health, says 454's Rothberg, "but the other genes in your genome." After all, the fact that identical twins—who have identical genomes—are identical for disease only 60 percent of the time (on average) shows that having a particular DNA sequence doesn't mean you will definitely develop the disease. One reason not every woman with a BRCA1 mutation develops breast cancer (some 30 percent do not) is almost certainly that some carry "modifier" genes that weaken the effect of the disease genes. A full genome sequence would pick up these modifier genes. "I think if we can identify those modifiers," says Baylor's Gibbs, "we'll be able to tell if you're in the 30 percent or the 70 percent," which today's genetic tests cannot.

The value of a personal genome depends on its accuracy, of course. At this early stage the error rate is a huge unknown. Watson's biggest concern is that he'll be told incorrectly that he has one chemical letter instead of another—a C instead of a G, say—somewhere and that the misspelling is associated with a disease, raising alarms unnecessarily.

An equal problem is that gene-disease claims have a lousy track record. Of those for complex diseases involving multiple genes, notably mental illness, few have been confirmed. And when scientists have tried to validate a claim the results have been sobering. Geneticists led by Thomas Morgan of Washington University recently examined 85 variants (that is, "spellings" of A, T, C and G that are different from the norm) in 70 genes that studies had linked to an increased risk of cardiovascular disease. Exactly zero of the variants were more frequent in heart patients than in healthy people, they reported last month in the Journal of the American Medical Association. That means the variants do not increase risk of heart disease as claimed. Yet companies offer genetic tests for at least seven of them. "An unfortunate number of claims based on candidate [disease] genes have not held up," admits Francis Collins, who led the human genome project to the finish line in 2003 and is now director of the genome institute at NIH.

Even assuming the sequencing is accurate and the link to disease correct, the value of a personal genome sequence is debatable. At least 90 percent of the human genome is "junk DNA" that has no clear function. An even higher percentage seems to have nothing to do with health. Genetic variations linked to disease are sprinkled across 0.01 percent of the genome, estimates George Church of Harvard University, who has been pushing technology to make genome sequencing affordable. Those regions could be sequenced for $1,000, he estimates, "and would give you 95 percent of the heavy-hitting mutations" linked to health.

Watson hopes that if people learn they harbor genes that raise the risk of any diseases, they will take steps to minimize that risk starting from birth. That way, a kid at risk for type-2 diabetes, say, will keep her weight in check and thus her diabetes risk lower before she becomes even a pudgy toddler. (Watson, though, concedes that if he has a gene variant that raises the risk of some disease 20 percent, and that the risk can be lowered by giving up chocolate, count him out.) But it is not at all clear how people will react to knowing their genetic blueprints. Many are genetic fatalists, says Angela Trepanier, president-elect of the National Society of Genetic Counselors. That is, they believe that health and even intellectual and emotional destiny is written in their DNA. Rather than reacting to the news that they have genes that raise the risk of colon cancer by having regular colonoscopies, some will say, "To hell with it, I'm doomed anyway. Where's the cheesecake?"