杏吧原创

Craig Venter has scorched a trail through genomics 鈥� cracking the human genome along the way 鈥� and now aims to synthesise life itself. Often a controversial figure, he explains why he chose to defy the scientific establishment and go it alone.

If you had to be known for only one achievement, what would it be?

My truly unequivocal first was the first genome derived from a living organism, the bacterium Haemophilus influenzae. Technologically, Haemophilus and the fruit fly Drosophila were the most important. After Drosophila, the human was obvious. But I will be remembered for the human genome, along with Francis Collins, who led the public project. We were numbers four and five in USA Today鈥榮 most influential people of the past 25 years. We outscored bin Laden.

One article in The New Yorker from 2000 began: 鈥淐raig Venter is an asshole. He鈥檚 an idiot. He is a thorn in people鈥檚 sides and an egomaniac.鈥� Why have you been so controversial?

It has almost all been around the human genome. My work on expressed sequence tags started it all because it was such a powerful tool that people got very threatened by it. I鈥檓 not a human geneticist and you were either in that hierarchy or you didn鈥檛 survive. But I had independence. After facing death in Vietnam, I was not afraid to take risks. That鈥檚 not typical of scientists. It鈥檚 a group that follows much more than it leads. Maybe being outspoken is one thing that made me controversial.

To call you an idiot is silly, but comments about your ego crop up repeatedly. How do you respond?

That鈥檚 the one I understand the least. I鈥檝e made a lot of big promises, but I feel I鈥檝e delivered on every single one of them. I鈥檝e been trying to survive outside the traditional funding system. You don鈥檛 do that through false modesty, but you don鈥檛 gain anything through false bravado, either. Are things built around personality? Sure. I鈥檝e not known anyone to be truly successful in any field that was immensely modest.

Some of the attacks must have hurt, though.

What hurt more than the emotional pain of being attacked was having people that you looked up to, and who represented the system, behave so badly and non-intellectually. It鈥檚 more like a profound disappointment.

You are particularly critical of James Watson, an intellectual hero of yours. Did you feel betrayed when he attacked you for your role in gene patenting?

That鈥檚 a great way to describe it. I don鈥檛 dislike him, but I resent some of the things he鈥檚 done. I resent Watson and others for using the patent hook. That way they didn鈥檛 have to attack the science, they could just attack me.

Watson, too, has a book coming out, in which he says: 鈥淒on鈥檛 use autobiography to justify past actions or motivations.鈥� Are you guilty of this?

I don鈥檛 think so. I certainly wanted it to be obvious to the reader that, by the time it came to sequence the human genome, my choice was either to do it outside of the Human Genome Project or not to do it at all. It wasn鈥檛 as people tried to portray it: a financial grab. I was forced out by groups who didn鈥檛 want to try new approaches.

I鈥檝e tried very hard in the book to give a straight regurgitation of things. Some of the stuff was so emotional that I鈥檇 have tears running down my face. But I didn鈥檛 start with a view of how I wanted to portray myself and how I wanted to portray Watson.

Would you rather have pursued your work under the Human Genome Project?

That short period of time at Celera was about as close as you can get to scientific ecstasy. I wouldn鈥檛 give that up for anything. But we could have had that same quality of science experience without the crappy business aspects, without the politics and the name-calling. I鈥檇 rather have done it at the National Institutes of Health by introducing new ideas and new approaches. And I tried to cooperate, but people were incensed at my proposal to have the public project sequence the mouse while Celera did the human.

But you must have realised that this would provoke outrage.

It would have been the right scientific thing to do. Emotionally, OK, it was dumb. But if the response had been 鈥淲hy don鈥檛 we each do half of the human and half of the mouse?鈥�, then maybe things could have been different. In the end, perhaps it鈥檚 telling that there we were, decoding our own species, and the process proved how flawed we are as a species.

Will history record that Celera won the race to sequence the human genome?

It depends on what you define as 鈥渢he race鈥�. The race stopped for me at the White House in June 2000, when Celera and the public project announced that we had each produced a draft sequence. It was a truce, but one party had clearly won. At that moment, the Celera version was substantially better.

So do you regret that the White House event declared the race a tie?

One scientist said it was like doing a marathon and I was jogging on the spot waiting for the other guy to catch up so that we could cross the line together. Colleagues were really angry with me. But I don鈥檛 regret it at all. I think it was seen as an absolute defeat for the government-funded project because, after everything, the head of the government wanted to share the event with an outsider. President Clinton said it was one of the highlights of his presidency.

Did you ever doubt that your 鈥渨hole genome shotgun鈥� approach would work?

I knew it would work ultimately, but not whether it would work in that time frame, with these guys having to write half a million lines of computer code. The system was not tested until we assembled the Drosophila sequence. It was like testing the first parachute by jumping out of the aircraft.

What about complaints that Celera鈥檚 human genome used data from the public project?

It was a mistake, because it gave them that excuse to attack us, and it screwed up our data. When we sequenced the mouse, with just Celera data, it assembled so much better. But it drove them insane, the notion that we could use their data, and sometimes you have to enjoy torturing your enemies.

鈥淪ometimes you have to enjoy torturing your enemies鈥�

When can we expect you to unveil the first bacterium with a synthetic genome?

The chances are, relatively soon. There are two components to it. One is: can you make these large molecules, on the scale of entire genomes? And the answer we hope to be publishing soon is 鈥測es鈥�. The other aspect is, once you have this large molecule, can you 鈥渂oot it up鈥�? We鈥檝e already answered that question, when we showed that we can transplant a genome from one bacterial species to another.

Assuming you can make synthetic bacteria, what will you do with them?

Over the next 20 years, synthetic genomics is going to become the standard for making anything. The chemical industry will depend on it. Hopefully, a large part of the energy industry will depend on it. We really need to find an alternative to taking carbon out of the ground, burning it, and putting it into the atmosphere. That is the single biggest contribution I could make.

So we shouldn鈥檛 expect you to retire any time soon鈥�

I equate retirement with death. If the book is not a dismal failure, I hope to write another one about synthetic life. I鈥檇 also like to end my career having 10,000 human genomes in a database and really being able to answer some basic questions about nature versus nurture.