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Interview: Sleep when you’re dead

As if cracking the human genome was not enough, Craig Venter aims to synthesise life itself

Craig Venter has scorched a trail through genomics – cracking the human genome along the way – 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‘s most influential people of the past 25 years. We outscored bin Laden.

One article in The New Yorker from 2000 began: “Craig Venter is an asshole. He’s an idiot. He is a thorn in people’s sides and an egomaniac.” 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’m not a human geneticist and you were either in that hierarchy or you didn’t survive. But I had independence. After facing death in Vietnam, I was not afraid to take risks. That’s not typical of scientists. It’s 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’s the one I understand the least. I’ve made a lot of big promises, but I feel I’ve delivered on every single one of them. I’ve been trying to survive outside the traditional funding system. You don’t do that through false modesty, but you don’t gain anything through false bravado, either. Are things built around personality? Sure. I’ve 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’s 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’s a great way to describe it. I don’t dislike him, but I resent some of the things he’s done. I resent Watson and others for using the patent hook. That way they didn’t have to attack the science, they could just attack me.

Watson, too, has a book coming out, in which he says: “Don’t use autobiography to justify past actions or motivations.” Are you guilty of this?

I don’t 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’t as people tried to portray it: a financial grab. I was forced out by groups who didn’t want to try new approaches.

I’ve tried very hard in the book to give a straight regurgitation of things. Some of the stuff was so emotional that I’d have tears running down my face. But I didn’t 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’t 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’d rather have done it at the National Institutes of ҹ1000 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 “Why don’t we each do half of the human and half of the mouse?”, then maybe things could have been different. In the end, perhaps it’s 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 “the race”. 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’t 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 “whole genome shotgun” 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’s 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.

“Sometimes you have to enjoy torturing your enemies”

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 “yes”. The other aspect is, once you have this large molecule, can you “boot it up”? We’ve 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’t expect you to retire any time soon…

I equate retirement with death. If the book is not a dismal failure, I hope to write another one about synthetic life. I’d 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.

Profile

Craig Venter joined the US National Institutes of ҹ1000 in Bethesda, Maryland, in 1984. He left to form The Institute for Genomic Research in 1992 and in 1998 launched the company Celera to sequence the human genome. Today he heads the J. Craig Venter Institute in Rockville, Maryland. His new book, A Life Decoded, is published by Viking in the US and Allen Lane in the UK.