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TR: So one issue is understanding how many genes there are?
Gilbert: We can’t do that yet in a totally convincing way. I would think we would be able to within a few years. And I think we will in fact also work out the two next major problems in biology. One is the problem of how proteins fold up into their specific three-dimensional shapes-how to predict that from their DNA sequence. And the other problem is deciphering the program of how the egg develops into the complete organism.

TR: And are those problems being solved by the companies you invest it?
Gilbert: The scale of these problems is beyond the reach of the average small company. They’re very large problems. And if they’re solved, then it’s difficult to sell the result. Is it useful for a company to try to solve the protein-folding problem? In some ways it’s questionable. It’s very hard as a company to sell that as a useful approach. There are companies trying to do that. Would I invest in them? Probably not.
Metcalfe: Well, I’m involved with a company that uses peer-to-peer software for doing protein folding. And it seems to me that there is a way to make this kind of work profitable. Couldn’t you just run through the human genome, which has now been catalogued, and fold every protein, and create another database of the foldings of every protein implied by the genome?
Gilbert: You could in principle, but you can’t in practice, because you can’t do the calculation.
Metcalfe: Well, let’s assume that in the fullness of time, they will solve the problem, so now we have a complete database that is not the human genome, but it’s all the expressed proteins of all the genes of the human genome. What could you do with that?
Gilbert: Well, you could sell it to somebody. But can you sell it for enough to have made the whole thing worth doing? It’s like with Celera. Are the companies they sell their DNA sequences to going to offer enough to make the half-billion dollars in Celera’s costs to do the genome worthwhile? Are they actually going to get enough income to match that? I don’t think so.

TR: So those problems will be solved in the universities or by government funding?
Gilbert: Well, the big problems, the fundamental problems, get solved in the university. And we need the government-funded projects for things that are far out. Celera would never have been able to sequence the human genome without a massive initial public investment.

TR: So does that mean we have to wait until these huge problems are solved to get a return in biotech?
Gilbert: No, not at all. The individual drugs will be profitable, not the whole database of information. In many areas we can already find specific molecules that will have important effects. I mean, the exciting subfields are things like neurobiology-can one enhance memory? I’m involved in a company trying to enhance memory, so I think that’s a perfect example. With Eric Kandel of Columbia University I helped to found a company called Memory Pharmaceuticals.

TR: What is the company doing?
Gilbert: They develop small molecules to use as drugs that affect memory. We already know enough about what goes on in the hippocampus [a brain structure that plays a central role in memory] to enhance the way that the cells talk to each other. And one can study the process of memory further by turning genes on and off in the hippocampus of mice. You can make dumb mice smart and vice versa by switching the right genes off and on.

TR: Well, thank you both very much for speaking with the readers of TR. One of the things that’s most interesting to me in this conversation is that although you come from different backgrounds-in infotech and biotech-there is so much overlap in technologies these days that you may wind up in your new role as venture capitalists competing for the same companies.
Gilbert: Well, my general reaction to the discussion we had is that we may be potential coinvestors.
metcalfe: It’s a win-win situation.

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