Craig Venter: 'The sequence is just our first phase'

Venter founded the nonprofit Institute for Genomic Research in 1992. Before that he was section chief and a laboratory chief at the National Institutes of Neurological Disorders and the National Institutes of Health. Celera Genomics is part of the PE Corporation. Venter was interviewed by CNN's Stephen Frazier on June 3, 1999, for NewsStand.

CNN: The first question is just a real basic one, and that is, what are you trying to do here?

VENTER: Well, our goal over the first few years is to get some basic information on several genomes, including the human genome, so we're trying to decipher the complete genetic code of the human genome, the mouse genome, an insect and the rice genome. And those genomes will provide the foundation for the future of agriculture and human medicine, so we're creating giant databases of information. We're an information company, and our goal is to provide that information to the medical community, the scientific community, the pharmaceutical community, and to individuals to understand their own individual variation and possible propensity and prevention of disease.

CNN: What's the ultimate outcome of that kind of search?

VENTER: In the last 10 years, over 5 million people have died in the U.S. from cancer. And in the last 30 years, there's been no fundamental change in the death rate from breast cancer. The statistics have been constant for 30 years. That means despite all the brilliant science that's been going on, all the discoveries, we've not made a lot of progress in some very critical diseases. Having all the genetic code, all the genetic information provides at least a new basis for starting the searches. It's like trying to work on a new complex automobile engine without a manual and without any prior experience. If you don't know what all the parts are and the components, you can't really understand the complex interactions that lead to diseases like cancer.

CNN: You're speaking in a very matter-of-fact tone, but could you help us with the scale of this kind of effort compared with earlier big science projects?

VENTER: In terms of DNA sequencing, this is about a 50-fold increase over what my previous job was as the head of the Institute for Genomic Research, where we sequenced some of the first genomes that have ever been done of life -- those of key human pathogens, cholera, tuberculosis, malaria, influenza, the bacterium that causes stomach ulcers. The human genome has 3.5 billion letters in it, in contrast to about 2 million in a typical bacteria. So if we sequenced your genetic code and gave you that information and you could read one letter a second, it would take over a hundred years to read your complete genetic code. So it's a vast amount of data, vast amount of information. Nobody ever thought it was possible in just one organization to get this much data in a short period of time.

CNN: How are you doing that? I mean you've made an announcement that you can do this faster and cheaper than the other guys.

VENTER: There's two key advances. There's the advances of the strategy and the computational effort that my team developed at the Institute for Genomic Research. The other real key advance is the new instrument developed by Mike Humkepeler's team at PE Biosystems, the other half of the PE Corporation. It's a new DNA sequencer. His company has made all the DNA sequencers that have really allowed the genome project to occur in the first place, and this new one is a fully automated machine that allows a very small crew to generate more data than we could have ever even conceived of before. We're building a huge factory here with hundreds of these machines to generate data at a scale that even in my wildest dreams two years ago I couldn't have dreamt of.

CNN: Two years ago? So this is taking you by surprise even that recently?

VENTER: Absolutely.

CNN: So how much faster and how much cheaper are you talking about?

VENTER: We're going to be producing over a hundred million letters of genetic code every 24 hours. In contrast, a major sequencing organization produced 600 million letters in the entire last year. So in one week we'll be doing equivalent to what we could have done in an entire year previously. ...

The main training that scientists will need going forward in any field is how to use the computer. It will save years and years and years of random research. So we'll go to the computer, we'll try and make an educated guess from all the data there and then we'll go to the lab to verify that data. Most of the predictions we got out of the computer tend to be extremely accurate. ... They still need laboratory analysis and laboratory verification, but just think of being able to narrow it down from millions if not billions of choices, how to go and do the right experiment from the beginning. I think this information that we're generating, the tools that we're going to provide with it are going to be so catalytic, it's going to really start to change science and medicine overnight.

CNN: When you finish the map, is your work done?

VENTER: No, in fact, the work to get the sequence is just our first phase. Getting the sequence is almost becoming trivial. When you see this factory, it's hard to say it's trivial, but it's trivial compared to what really understanding this information's going to be in turning it into treatments and cures. I don't want to make people have the feeling that cures are instantly around the corner. For some diseases, they may be. Scientists that are much smarter than I may look at some of this data and find an instant link because they've been studying a particular disease for a long period of time. There will be some instant discoveries that impact medicine, but we have a much greater problem. Our bodies are composed of about a hundred trillion different cells and each of those cells has the complete genetic code, the 3.5 billion letters of genetic code. Each of those cells use a different set of the 80,000 genes. That's why the heart is different from the liver which is different from the brain. Because different genes are expressed in those cells. So understanding how 80,000 different units constantly vary in a hundred trillion different combinations is beyond probably the best computers we will have in the world over the next couple of decades. Computing power has to expand so much for us to be able to even model human biology. So biology and disease really come from understanding all these interactive links. We're trying to understand the logic of biology for the first time by having all the information. But for some diseases, like cancer, breast cancer, it could still be the same situation 10 years from now. I hope it's not the case. I hope scientists will be able to use this information in a catalytic fashion and things will click in, but I don't want to over promise it.

CNN: Can you give us a comparison with earlier advances in science as to the importance of the map itself?

VENTER: If you look at medicine, you probably have to go back to the beginning of anatomy where we went from understanding that people aren't just physically what they seem, that when you open people up, there's a very complex organ structure, then cellular structure. As we started to understand physical anatomy that changed medicine in a very radical way. Now we're going to understand that genetic anatomy for the first time and that's going to have an even more catalytic impact, because it's going to tell us how the organs went together, why they changed, how they respond to disease, how cancer develops. It's just going to take time to sort out all that information.

CNN: One of the things I understood is that you'll be applying for patents for some of the things that you discover. How can you patent a gene?

VENTER: We consider that we are making discoveries, we're not making inventions, with the primary sequencing. In the U.S., patent law makes no distinction between inventions and discoveries. European law does make that decision -- it has to be an invention, not a discovery. So it is an important difference in different parts of the world and that's why there are different cultures with it. But you need to almost jump beyond patent law and all the basic understanding at the legal level to understand it at the human level. If you have a member of your family or if you know anybody that's a diabetic. Diabetics now can be treated with human insulin. Before a human insulin gene was cloned and patented the only way diabetics could be treated is with pig insulin, which was, pancreases were collected from slaughterhouses. Pig insulin was carefully purified from the pig pancreases, cleaned up and put it bottles and given to diabetics for injection. And what happened, because the pig gene is different than the human gene, humans eventually developed antibodies and became resistant to the pig insulin and actually their life span was greatly reduced because it took more and more and more pig insulin to get the same effect. Now diabetics have human insulin to treat their diabetes and they have that because the gene was patented and that allowed these pharmaceutical companies to develop it into a drug that you can actually buy. At a gut level, people think, gee, it's terrible that they're patenting the insulin gene. But they don't own your insulin gene, they don't mine. They don't block research, anybody can get the insulin gene sequence out of databases. They can synthesize it, they can isolate it from tissues. And they can do all the research in the world they want on it. What they can't do, you can't go just start a company and start manufacturing human insulin and selling it. Because it costs about $600 million dollars to get a drug through the FDA process, the approval process for safety. And no company would invest that kind of money if they didn't have this short period of monopoly to guarantee them a financial return. So if you look back at the system we have in the U.S., it's actually a fantastic system. Individual investors are incented to put their money at risk, hoping that a biotech company will come up with a new cure for disease, but the only way they'll ever make money is that there is actually a new treatment like the insulin gene being used to provide a treatment for diabetics. So it almost doesn't matter what the individual investor's motivation is. It can be straight monetary return, because they want to do something great for society. It really doesn't matter because the system overall works to reward people only if there's new treatments that change disease. I had my own life saved by a modern drug. I developed severe peritonitis, what you get if your appendix explodes. I was in France, giving a lecture, and my life was saved by a new advanced antibiotic developed by Smith-Klein-Beecham. In fact, at that time, I was delighted that they would make a fortune off of this antibiotic because my life was saved because I was able to get that.

People confuse patenting genes with patenting life. You know, genes and the genetic code, they're inert elements in our bodies in combination with the whole rest of the system. They're part of the functional unit. It's like having the computer program tape out of your computer. When it's out of the computer, it's just information. It's not part of human life. In fact, a lot of people get upset when they find the protein sequence of human genes and proteins is identical to those from mice and rats. We have a large number of examples of human proteins (where) the sequence of those proteins is absolutely identical to those in a rat.

CNN: That's discouraging to learn, isn't it?

VENTER: No, in fact, it's critical because it shows that we're part of this entire genetic repertoire on this planet. We didn't evolve separately from everything else, we evolved through this effort of billions and billions of years working back from single cell organisms to more and more complex organisms. We have the same genes as in the bacteria. The enzymes that correct defects, the genetic code from radiation damage, UV damage in a bacteria, are the same ones that are related to cancer in humans. Those processes are highly conserved. So in fact the best hope for understanding human biology and medicine is that we can use the genomes, the sequences from other species, to understand the human ones.

CNN: Simpler species that you can get at sooner.

VENTER: So-called simpler species, yes. We have probably the same gene set, certainly over 90 percent, as mice and rats.

CNN: This urgency that you speak of (to speed up gene research) is one that you feel personally?

VENTER: Most people call me an impatient guy. It came from the desire to really accomplish something with my life. A lot of people have major turning points in their life. Mine was in 1967, 1968, when I was sent to Vietnam. Before that I was a surfer, trying to just enjoy life in California.

CNN: Kind of a laid-back dude?

VENTER: Well, I was probably approaching surfing aggressively, but definitely enjoying the surfing lifestyle. I started with a swimming career, so it was great to be in the ocean all the time. I was a corpsman in Danang and actually turned 21 in Vietnam and it was a major turning point. You can't live through a situation like that and come out of it with the same laissez-faire attitude that you might approach surfing with before that.

I dealt with the death of thousands of young men, my age and younger, dealt with the failure of medical tools to do anything functional to help most of these people. The failure of the political system that had us there in the first place. And I felt very fortunate to survive the year and didn't want to waste any of my life going forward. I felt there was an urgency to understand human biology, maybe to improve the education system. Looking back to what our knowledge of medicine was in the 1960s ... we knew essentially nothing. At the beginning of this decade, we knew less than 2,000 genes of the 80,000 of the human genome. I feel strongly the need to do something with the period I have in my life, not just sitting back and hoping that over a decade or two, some new discoveries will be made. If I have a chance as an individual to move things forward, I'm going to do it.

CNN: I'm impressed at how moved you are by these recollections of something that happened 30 years ago.

VENTER: Well, I think anybody that was in that situation feels the same way.

CNN: And a corpsman knows an awful lot of medicine. You must have been close to a clinical physician there.

VENTER: I had probably a phenomenal crash medical education. One of the things I found is that I really thrived on learning and was a very rapid study, so I was able to participate and accomplish a lot during that year. And I was motivated. I went back and started my college education from scratch after I got out of the military. My plan was to go to medical school, but in the middle of my education at U.C. San Diego, I got introduced to basic science research and it was clearly where I wanted to go, because I realized that even though as a physician, I could very much affect a finite number of people's lives, I figured if I made some real medical scientific breakthroughs, it could have much broader impact across the board.

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