Testing, Testing

Patents in July 2000 have already led to more than 740 genetic tests that are on the market or being developed, according to the National Institutes of Health. These tests, however, show how far genetics has to go. Several years after the debut of tests for BRCA1 and BRCA2, for instance, scientists are still trying to determine exactly to what degree those genes contribute to a woman’s cancer risk. And even the most informative genetic tests leave plenty of questions, suggests Wendy R. Uhlmann, president of the National Society of Genetic Counselors. “In the case of Huntington’s, we’ve got a terrific test,” Uhlmann avers. “We know precisely how the gene changes. But we can’t tell you the age when your symptoms will start, the severity of your disease, or how it will progress.”

Social issues can get in the way, too. After Kelly Westfall’s mother tested positive for the Huntington’s gene, Westfall, age 30, immediately knew she would take the test as well. “I had made up my mind that if I had Huntington’s, I didn’t want to have kids,” declares Westfall, who lives in Ann Arbor, Mich. But one fear made her hesitate: genetic discrimination. Westfall felt confident enough to approach her boss, who reassured her that her job was safe. Still, she worried about her insurance. Finally, rather than inform her insurer about the test, Westfall paid for itsome $450, including counselingout of pocket. (To her relief, she tested negative.)

The HGP’s Collins is among those calling for legislation to protect people like Westfall. A patchwork of federal and state laws are already in place to ban genetic discrimination by insurers or employers, but privacy advocates are lobbying Congress to pass a more comprehensive law. In February 2000, President Clinton signed an executive order prohibiting all federal employers from hiring, promoting or firing employees on the basis of genetic information. It remains to be seen whether private companies will follow suit.

In the meantime, Celera is now ready to hawk its Homo sapiens genome, complete with crib notes on all the genes, to online subscribers worldwide. “It’s not owning the datait’s what you do with it,” Venter remarks. He envisions a Celera database akin to Bloomberg’s financial database or Lexis-Nexis’s news archives, only for the genetics set. Which 300 genes are associated with hypertension? What, exactly, does each gene do? These are the kinds of queries Celera’s subscribers might posefor a price. As of this writing, Celera planned to offer a free peek at the raw genome data online, but tapping into the company’s online toolkit and full gene notes will cost corporate subscribers an estimated $5 million to $15 million a year, according to Gilman. Academic labs will pay a discounted rate: $2,000 to $15,000 a year.

Internet surfers can now visit GenBank for free. With all this information available, will scientists really pay Celera? Venter thinks so. “We just have to have better tools,” he says. For genomics, that is becoming a familiar refrain.

Thousands of people have contributed to the Human Genome Project (HGP). Their efforts must be paid for, collated, reviewed, corrected, and combined with the contributions of others, if the project is not to degenerate into chaos. As with any major undertaking, this requires a well-conceived organization and a management hierarchy. In the case of the HGP, there happen to be two such: the National Human Genome Research Institute (NHGRI) and The Institute for Genomic Research (TIGR), also known as Celera Genomics. This is a good thing, because the two organizations provide a cross-check on each other and thereby greatly diminish the number of sequencing errors. It is by no means a duplication of effort. Inevitably, however, it also engenders a competitive atmosphere, particularly for scarce resources. This may or may not be such a good thing, although so far it has kept things lively and moving right along. Not surprisingly, both projects are headquartered in the Washington, DC area, which is where the funding is located.

The heads of these two organizations are Francis S. Collins and J. Craig Venter. Both are staggeringly brilliant but quite different in their approaches to sequencing the Homo sapiens genome. The following two essays profile these two men and tell us something about what inspires them.