J. Craig Venter's Current Hot Papers, Published Since 1994 (Ranked by total citations) Rank Paper Citations 1 R.D. Fleischmann, et al., "Whole-genome random sequence and assembly of Haemophilus influenzae Rd," Science, 269(5223):496-512, 1995. 552 2 N.C. Nicolaides, et al., "Mutations of 2 PMS homologs in hereditary nonpolyposis colon cancer," Nature, 371(6492):75-80, 1994. 351 3 C.M. Fraser, et al., "The minimal gene complement of Mycoplasma genitalium," Science, 270(5235):397-403, 1995. 263 4 C.J. Bult, et al., "Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii, " Science, 273(5278):1058-73, 1996. 113 5 M.D. Adams, et al., "Initial assessment of human gene diversity and expression patterns based upon 83-million nucleotides of cDNA sequence," Nature, 377(Suppl.):3-174, 1995. 95 SOURCE: ISI'sHot Papers Database, May-June 1997

When did you come to realize it was going to be a major problem and you would have to do something about it?

   Venter: It really came to a head when we finished the first genome, the H. influenzae genome. We knew we had a major scientific discovery; it was the first completed genome in history, and Haseltine threatened to get a court injunction to block us from publishing the paper. We eventually published in Science, of course, and it's currently the number-one referenced paper in all biology. Clearly we're not talking about a paper with trivial impact. And here we were being threatened with lawsuits if we published it. So that brought the conflict to a head.

The press said you gave up $38 million to effect the break-up?

   Venter: Yes. I just walked away from more money than most scientists have in their whole careers to do research. Somebody said recently that this is going to go down as one of the smartest moves in history or one of the dumbest. What I'm doing is betting on myself and the scientists here that we'll thrive and that the research is constantly going to be at the forefront and will drive scientific innovation. I had to look at it from the point of view of deciding if I wanted to spend the next five years of my life fighting those battles versus trying to really make scientific discoveries and move things forward. And I decided I would rather fail trying than spend another five years in that situation. The fact that our one paper has been the most-cited paper in biology for a year shows that this small institute is having a real impact—and the fact that the whole pharmaceutical industry and now the National Cancer Institute at NIH habeen revolutionized by the EST approach with the cDNAs. Those are two different instances where we're driving the equation and not just responding to it.

Can you tell us where the sequencing of genomes is going to take biology over the next 5 or 10 years?

   Venter: Ten years is hard to do because things are moving so quickly. Even five years is a little bit hard. Let's just go to the end of the decade. I expect that, based on the approaches that we developed, between 50 and 100 genomes will have been completed worldwide by the end of the decade. And all of those will transform their fields; the microbial genome, for instance, is transforming the whole field of microbiology overnight. What we have now for the first time is the blueprint of life. And we'll have it for about 100 different organisms, from humans down to all these different microbes—a real diversity of life—and we're going to be able to track and start to predict real evolutionary events that actually took place.
   Each of these genomes, these millions of base pairs of genetic code, is the recorded history of life. We haven't tapped 1% of the potential of this information yet. We have to develop some phenomenal new computational approaches, because there's nothing around that can even start to deal with this in terms of tracking all these relationships. On the practical side, I see everything from new medicines to new antibiotics and new diagnostics and whole new ways to deal with things. At TIGR we've taken on a new technology—we're setting up a major gene-chip facility here. We're making gene chips to try and move all these fronts forward. But the real goal is still to put the big picture together to answer the "what is life" question.

It sounds like the kind of question where the answer will simply continue to generate new questions.

   Venter: We can come up with one definition of what life is, at least in terms of the molecular components required for it. And we can try to trace the lineage of how those components evolved. That's the goal, at least. Although, quite frankly, we don't know how we're going to get there yet.