Interview: In Darwin's wake

He revolutionised the human genome project. Now, Craig Venter is hoping to do the same for our understanding of the rest of the planet. Melissa Trudinger caught up with himon the Australian leg of his voyage of discovery on his yacht, Sorcerer II.

TRUDINGER: To begin, the Sorcerer expedition -- for how long will the boat be sampling around Australia, and how long will the entire trip take?

VENTER: The whole trip started last summer, in Halifax [Nova Scotia], and we're going to be in Australia at least until the end of cyclone season which is April, and then probably even longer than that as we work our way up to the Barrier Reef and to New Guinea, then back across the top of Australia to Darwin and across the Indian Ocean, so we'll probably have at least another year to go.

It's a big trip ...

It's a big world!

...especially when you're doing it at that pace, you realise how big it is, I imagine. What's the expected cost of the project as it stands at the moment?

The sequencing cost is variable. This shaving off the tip of the iceberg that we're doing -- if we had 10 times as much money, we'd do 10 times as much sequencing, so we're still working with private foundations and the US government, and I'm meeting with Australian government leaders here in Victoria. But we expect that if we're going to do all 300 sites we've anticipated at the depth we'd like to do, we're talking about easily a hundred million dollar project.

We have good funding from the US Department of Energy's Office of Science, and we have funding from the Gordon and Betty Moore foundation, and my own foundation is funding the cost of the expedition itself, so it's mostly the sequencing and analysis funds these outside organisations are helping to work with, and what we're hoping the Australian and state governments will help finance some of the sampling in Australian waters.

How much time do you get to spend on the trip itself? Do you get to fly in and out?

Yeah, I fly in and out, and do all the major ocean passages -- the goal isn't to watch my boat from my office sail around the world. Not too many people get to sail around the world doing world-class science so I try to do as much as that as possible. But I still have to work for a living and run an institute and things, so I definitely fly back and forth.

What are your personal hopes and goals for the project? There's the big picture, but what do you really hope to get out of it?

I've done a lot of interviews, including one in the Galapagos on Darwin's birthday comparing [what we're doing] to what Darwin did. At this stage of the game, what Darwin was doing was collecting samples, and it wasn't as though he came up with his theory of evolution while sitting on the beach in the Galapagos. It was years later after putting the picture together from all the data that was collected. And that's one of the challenges we have, to see if we can come up with a new view of biology from being the first to have this massive gene collection -- a gene-centric view of the world to see what the data actually says. One aspect is collecting the data and part of it is trying to make some intelligent findings out of it, and that's a big challenge.

You'll have to come up with a new name for it because systems biology is too narrow, I think, for this.

Yeah, systems biology is sort of a catchphrase that blew in and out. It sounded good, so all of a sudden departments of systems biology cranked up everywhere, but they weren't really doing anything that was any different to what was going on before. The challenge of science is how to integrate all this information. We don't do things -- we can't afford to do things -- one discipline at a time, or one gene or one species at a time, so we have to try to integrate biology and physics and mathematics, and try and put the big picture together. If anything, I hope that will come out of it as well as just what's already happened just with our first data set -- it stimulated a hell of a lot of science, people are doing some exciting things. We get almost daily emails from scientists around the world, the findings they've had from the database and what they're doing with it. The next dataset is going to be even larger so it's exciting to be able to give a new view to biology, a new view to life on this planet from a simple set of experiments we never thought would work.

How many scientists do you think are using the data that's out there so far?

All we hear is that it's the most used database now out there, and the diversity in it is far greater than the rest of Genbank put together, so I have no idea, but I'm sure it's in the thousands. We published the Sargasso Sea paper in Science in April, and [according to] a stat from last month that someone gave us it's already one of the top three quoted papers in Science for the year. Between April and November is a pretty short period of time for that number of references -- it says it's being used pretty extensively already and I suspect it will grow a lot more. I'm finding more general interest with our environmental genomics work than I've found collectively for everything we've ever done in the human genome.

How does it fit into the broader picture of the Venter Institute? I know you recently merged three groups into one there, what role does this project play within that?

This is the ultimate extension of all the approaches I've taken, starting with the ESTs, and the random approaches, high-throughput things. The EST method led to the whole genome shotgun method with Haemophilus, that led to being able to sequence Drosophila and human and all these other species, then going up another scale our human genome sequencing has led to being able to do the environmental sequencing. It's a further extension of the same philosophical and technical approaches, so it fits in perfectly with what we're doing -- understanding that the environment's a key part of understanding genomics. The goal of the Venter Institute is to keep working on scientific projects that have particular meaning or importance to me and the other senior scientists there, so it's an institute without limitations in terms of what horizons we can work on. We want each of the projects to be incredibly significant and have a major impact.

You mentioned in your talk that you're just scraping the tip of the iceberg here, and it would seem that the human genome project was just the tip of that tip of the iceberg if you put in scale and context.

In context, sequencing the human genome was all of our genetic information, whereas we're at the very beginnings of trying to understand that in terms of the planet earth's genome collection. That's where we're at, the scrapings of the tip of the iceberg. So 10 years ago, people were working as I did to get one gene at a time, and people didn't know what was there so you couldn't measure anything. Without the genome project it would have been maybe 100 years to find all the human genes, if ever -- just looking for things one function at a time. Somehow, biologists have proceeded quite nicely up to 2004 without knowing who is in our environment. People had the notion there was more there than they thought but one of the peculiar things about science is that if you can't measure something, it largely doesn't exist. If it's not there in front of them it's not part of the thinking of their repertoire.

Where do you think this sort of project will go from here -- where would you like to see it end up?

We're hoping our global expedition will be the catalyst for governments around the world, scientists around the world adopting this approach and doing a full systematic survey of the planet. So going from an idea people were sure couldn't possibly work, to all of a sudden showing that even if we go from less than 1 per cent of the biology of the planet to 5 to 10 per cent, that at least gives us a window on what we're missing and the tools for getting there. It would be wonderful if we truly understood the biology of our planet before most of it gets eliminated one way or another.

What sort of answers or solutions do you think it might offer to the world's problems? You alluded to some of the work you're doing on synthetic organisms.

I think all the new photoreceptors certainly stimulated our imaginations, and other people's, in terms of coming up with new ways of being way more efficient in capturing energy from sunlight. If the photoreceptors really represent the complete spectrum of light there could be new ways to increase the efficiency of capturing that energy. Capturing it using biology instead of other approaches. Every major scientist we've talked to who has looked at the data set has found something really new and exciting in their own field -- some of these fields I didn't even know existed. As the studies have shown, there is more richness and diversity from our random sampling of one site in the ocean already than what existed before.

Going back a little bit to the human genome project, what do you think has been the biggest impact of that project to date?

I think the biggest impact is very similar to what the Sargasso data set is. If you go back and look at the statements that were being made by myself and my team, versus some of the others, I was arguing that sequencing the human genome was a race to the starting line, whereas others were making all these fantastic promises -- that it was the most important thing ever, more important than going to the moon. People were really pushing the self-importance of what they were doing. I think -- as somebody who laboured for 10 years to get one gene -- that the value of having all this information in a database as a starting-point means that modern science now starts with having all that information, and so it does become catalytic. Now, scientists, instead of saying they want money to go isolate a gene and having to spend a decade doing it, can do in a matter of seconds what it took me a decade to do.

It's hard to measure what impact something like that has on the future of research, because all of a sudden the field is fast-forwarded by a decade or more because scientists, students, everybody -- they have that information today, their new research is based on having that when it didn't exist a few years ago. That's a real impact because now people will make new findings and new breakthroughs that will become even more catalytic, so it could move science forward by a century just by driving the basic science in each of these disciplines. People looking for a miracle drug to come out of the human genetic code, or something else,

I think on a philosophical basis it shows us how closely related we are to every other species on this planet -- I think that's important information for people to have. You know this arrogance that we were the self-centred people on the self-centred planet in the middle of the universe -- things don't revolve around us. We're closely related to all other species, perhaps that knowledge will help us survive. I think the real impact for science is providing new information and tools that literally take decades if not more off of basic research. And we'll reap the benefits from this down the road but none of this will be instantaneous.

Has it surprised you, how fast people have moved on the data? It seems that it has sped up the pace of research even in the last couple of years.

Yes, it certainly has changed the pace of research. But things never seem to move fast enough for me -- it still seems to be moving awfully slow compared to what I would like to see done, just because it's hard for governments and government agencies to turn around and change funding priorities, change review processes, get out of the old mould and really use the new information in creative manners, instil them in major innovation around the world.

So it's still in a transition period?

Sure. But it has also been a silent revolution -- students today just take it for granted that they can look up the sequence and get it in seconds off the database, versus what science was like a decade ago, And I think maybe because of that, on one level it has been truly catalytic and on another level scientific leadership hasn't made fundamental changes to be ready for it. Most biologists think they don't need computers. Just to analyse this environmental sequence data, or understanding evolution, we can't do it without massive computing.

I've got one cheeky question for you -- what's it like knowing your own genome sequence? Is it something that you think about or go and check to see if you've got one of the diseases that have been showing up in the databases?

I don't think that's so cheeky. I think people have so many confused views and fears over genomics -- it's not what people anticipate that it is. Understanding probability of statistics of what it means to have a 15 per cent increased risk of cardiovascular disease based on certain factors -- there are very few yes/no answers in the genetic code. You don't look at it and go "Aha! now that explains this quirky bit of my personality" -- that's just not how it works. But I think that's the lay view, including among many scientists, of what it is. Even when I poll medical school classes, roughly half of each medical school class doesn't want to know their own genetic code, they're afraid to know, it's going to give them some defined principle of their lives they don't want to know about. And so I think we're reading way, way too much into what it gives you. To me it's a scientific curiosity, it's a point of analysis. I'm happy to have it on the internet because it doesn't provide what everyone, in their deep dark fears, fear that it would provide. Or if it does, there is nobody out there yet that's smart enough to read it.

So it's not an invasion of your privacy?

Maybe someone will make a discovery and I'll go "Oh shit, I shouldn't have put it out there after all!" I can't imagine what someone would find reading my genetic code that they couldn't already find on the internet anyway.