The Corner

The Human Genome and the Human Being

In a characteristically spirited — combative, even — interview with Der Spiegel, biologist and entrepreneur J. Craig Venter pooh-poohs the scientific achievement that helped catapult him to international celebrity more than a decade ago: the sequencing of the human genome.

Venter: . . . From the time of the first few discoveries of gene defects — Huntington’s disease, for example — everybody thought that if you knew your genome, you would know when you would die and what you would die from. That is nonsense.

SPIEGEL: So the significance of the genome isn’t so great after all?

Venter: Not at all. I can tell you from my own experience. I put my own genome on the Internet. . . . And what . . . have I learned from my genome? Very little. We couldn’t even be certain from my genome what my eye color was. Isn’t that sad? Everyone was looking for miracle ‘yes/no’ answers in the genome. “Yes, you’ll have cancer.” Or “No, you won’t have cancer.” But that’s just not the way it is.

SPIEGEL: So the Human Genome Project has had very little medical benefits so far?

Venter: Close to zero to put it precisely. . . . [W]e have, in truth, learned nothing from the genome other than probabilities. How does a 1 or 3 percent increased risk for something translate into the clinic? It is useless information. . . . [For there to be practical medical applications] we need a lot more information: Information about your body’s chemistry, your physiology, your complete medical history, your brain and your entire life. We would need to do that a million times on different people and correlate that data with their genetic information.

SPIEGEL: Will that lead in the end to the kind of personalized medicine that genetic researchers have always touted? Each person would get his or her own personal treatment that is tailored precisely to that person’s genetic make-up?

Venter: That was another one of these silly naïve notions that was out there. It’s not, “Oh, we know your genome, we’re going to make this drug for you.” That will never happen. It is more important that you use the information in the genome about your personal risks and reduce them through intelligent behavior.

Venter is the just the latest prominent scientist to remark on what Fortune magazine has dubbed “the great DNA letdown” — the failure of the multi-billion-dollar, public-private genome-sequencing effort to produce any noteworthy practical applications so far. That failure is especially remarkable in light of the hyperbole surrounding the genome a decade ago. Bill Clinton described the genome sequencing project as “the scientific breakthrough of the century, perhaps of all time,” and said that “it is now conceivable that our children’s children will know the term ‘cancer’ only as a constellation of stars.” Venter echoed that point at his famous press conference alongside Clinton, Tony Blair, and geneticist Francis Collins, speaking of “the potential to reduce the number of cancer deaths to zero during our lifetimes.” The New York Times wondered if we had “broken back into” the Garden of Eden “for a second bite” of its fruit. The Clinton White House said that using genomic research to fight disease would be “the single biggest challenge to humankind.”

All that seems so long ago. The greatest non-story of the last decade — the dog that didn’t bark — may be the lack of practical results to flow from the sequencing of the genome as yet. Still, a few concrete clinical applications are finally on the horizon: the first drugs based on genomic information are now about to hit the market, with several more in the development pipeline. And promising new areas of therapeutic research are just beginning to open up.

For better or for worse, our limited genomic knowledge is already influencing people’s decisions about important matters. Some women who learn from DNA tests that they have a genetic susceptibility to breast cancer are electing to undergo mastectomies even though they don’t yet have, and might never develop, the disease. A prenatal genetic test for cystic fibrosis seems intended to encourage parents to consider abortion if their unborn child tests positive. And even though Venter cautions that our partial genetic knowledge remains essentially “useless information,” the arrival of affordable personalized DNA tests — like these spit kits selling for a few hundred dollars — might soon lead more people to make practical decisions about themselves, their mates, and their children based on mere genetic hints and whispers.

Why has it taken so long for practical results to flow from the sequencing of the genome? One reason is the deepening realization that the genome ain’t what it was cracked up to be. A decade ago, it was still routinely described as “the book in which all human life is written” or “our own instruction book,” all in keeping with Watson and Crick’s description of DNA as the very “secret of life.” But in the past few years, researchers have come to recognize how grossly oversimplified was the so-called central dogma of molecular biology — the notion that DNA makes RNA, RNA makes proteins, and proteins make us. In particular, a new field called epigenetics suggests how much context matters, and reminds us that the mere code of our genetic sequence cannot explain who we are and who we will become.

The findings of epigenetics don’t mean that our genomic knowledge won’t soon have many useful therapeutic applications, improving the lives even of the profoundly sick. Nor do the findings of epigenetics mean that the more distant dreams and nightmares of a biologically reengineered human future can simply be dismissed. But the reductionist assumptions about DNA underpinning those dreams and nightmares are being fundamentally challenged. We should take the exciting findings of epigenetics as an invitation to better understand the peculiar kind of creature we are — recalling that the answers to the deepest questions about being human lie not in our genes but in ourselves.

— Adam Keiper is editor of The New Atlantis: A Journal of Technology and Society.

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