In the late 1990s, the Human Genome Project whooshed into public consciousness with the promise of individualized designer health care–medicine that fit like a tailored Armani suit rather than like a one-size-fits-all burlap sack. The reality of this revolution has been slow in coming, with a few genetic tests here and there that can verify rare diseases such as Down’s syndrome and Tay-Sachs or breast cancer in the small percentage of patients whose condition is caused by the BRCA I and/or the BRCA II genes.

Nearly all of these tests involve testing for a single gene or a DNA marker known as a Single Nucleotide Polymorphism–an SNP–that is a single letter in one’s DNA that is different in those with a disease than in those without it.

The single-gene- or single-SNP-causing-disease model never worked well for most common diseases such as heart disease and cancer, which seem to involve complex cocktails of genes and parts of genes, combined with influences from the environment that act on genes or on cells and tissue. In 2004, the idea of multiple-gene tests for a single disease became commercialized with great fanfare when a diagnostic test called Oncotype DX, developed and sold by Genomic Health, of Redwood City, CA, went on sale. This 21-gene test costs $3,400 and runs results through a complicated set of proprietary algorithms to determine the probability of a recurrence of the cancer in a breast-cancer patient. For some patients the test also assesses the benefits of certain chemotherapies.

Genomic Health says it spent $100 million on clinical trials to validate the accuracy of its test–and published the results in a 2004 article in the New England Journal of Medicine.

This all sounds very Armani to me, and it gets more so when one realizes that the multiple-gene tests have exposed a little-known fact about genetic tests: they are largely unregulated. The thousand or so genetic diagnostic tests available in the United States right now are considered laboratory-based tests, which means that only the laboratories where the testing is processed are regulated. Only six diagnostic genetic tests have been designated as “medical devices” by the Food and Drug Administration (FDA) and are subject to regulation.

Some genes, like the BRCAs, have been validated for the risk they cause by millions of patients being tested for the genes who are then followed to see if the gene was an accurate predictor. Other genes have a very high rate of “penetration”–that is, you have the gene, and you almost certainly will get the disease. Huntington’s is an example. But most of the hundreds of genetic markers out there in labs have not gone through a rigorous trial to see how well they work to predict disease. Never mind multiple-gene tests, which by their nature require complex equations for researchers to understand what risks the genes pose.

This is why the FDA recently announced that it is stepping in to investigate. Right now, up until March 5, 2007 the FDA is taking public comments about tests that use proprietary algorithms to predict risk. This is how Genomic Health and other gene testers make money, since any lab worth its genes can detect the genes and other markers. But this is less than useful without knowing one’s risk.

But how accurate are these predictions really? Genomic Health has published results of clinical trials using its still secret numeric formula, which has helped doctors adopt the tests and accept their prognosis. Insurance companies are also beginning to pay for the Oncotype DX. Both parties, however, have been slow to come on board given the track record of many genetic tests, which don’t have extensive clinical science behind them to demonstrate how accurate they are.

Predictably, diagnostic companies are complaining that if the agency decides to regulate genetic tests, costs will climb, stocks will be roiled, and diagnostic businesses will become more like drug companies that must deal with complex regulations and long testing periods. Yes, but regulations will also create a base assurance that these tests mean something to individuals like you and me and are able to assess risk for disease and treatment.

It also may mean that a world like the one depicted in the 1997 film Gattaca, where all important decisions were made based on one’s genetic profile, just got a tick closer.

In short, personalized medicine may have arrived for real this month with a bureaucratic hiccup–which is, I suppose, the ultimate validation that a promised revolution is passing from hype to reality.

Check out details on the Web in a review article in the January 25 issue of Nature.