Extended Interview: J. Craig Venter
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SUSAN DENTZER: What was deemed to be in it to take on the public project in effect in this way?
J. CRAIG VENTER: Well, you have to, again, go back two years to understand where the public project was. There was an article just before our announcement in May of 1998 by Elizabeth Pennisi, a science writer for Science magazine, who did a fairly in-depth assessment of where the public genome project was, and basically concluded that it was way behind schedule, things were going much slower than anybody thought they would go, and it wasn’t clear when if ever the genome would really come together and get sequenced. I mean, that was the context where we made this decision. It wasn’t, “Gee, you know, they’re going to be done in 18 months. Let’s see if we can beat them to it.” We had a clear-cut new technology, and wanted to do the experiment of trying the whole genome shotgun method that we used for the first three genomes in history on a larger scale.
We had actually approached the head of NIH at the time, Harold Varmus and Francis Collins, and you know, offered to collaborate with them, but I think they were fairly sure this approach wouldn’t work, you know. The same critics over and over again saying things would not work, and they weren’t very concerned about trying to collaborate. You know, they were locked into where they were going, or so it seemed at the time.
We said it would take two to three years to sequence the genome if this new experiment worked, but to make sure it worked, we were going to sequence a smaller genome first. Well, it’s not so small. It’s the Drosophila genome, the fruit fly, that’s now been the largest genome completed in history, and it took less than a year from start to publication in Science. So we actually sequenced the Drosophila genome faster than we sequenced the hemophilus genome, even though Drosophila’s about 80 times bigger than hemophilus. So it was a pretty big change in technology and what a small group of people could do in less than 4 or 5 years from the development of a method when they published the first genome.
J. CRAIG VENTER: I think people, particularly some of our biggest critics, are heads of labs associated with the public effort, so they were some of the ones that said the hemophilus genome method wouldn’t work on hemophilus or any of the 15 genomes done since them by us and 15 by other groups, and they said that it wouldn’t work at the scale of Drosophila for sure, you know. It’s a moving bar, that each thing we do, they say, “Well, they did that, but it won’t work the next time.” So it’s been a handful of critics, but I think the public doesn’t understand how the scientific community really works, that it’s a very conservative community, that funding is very precious to scientists, and they’ll do anything to keep their funding. And once you establish a funding source and a funding mechanism, scientists work very conservatively to maintain that, and so we’re no different as a community than any other human endeavor. People want to protect the territory that they have, and they’re very threatened by change. That’s not true for all of scientists, but you know, fortunately the scientific community moves forward in a conservative fashion.
This was a big experiment that we were proposing. The reason a government agency wouldn’t fund it is because there was no guaranteed answer. We couldn’t guarantee or show proof that this would work on this scale because it hasn’t been done.
We went ahead and did the experiment with Drosophila, and it was a spectacular outcome. I think it worked even better than we thought it would, but none of the methods that we ended up using existed 18 months ago. Nobody’s ever set up to make this much DNA with a small team of people. We don’t have 3,000 scientists doing this. We have 50 that do everything.
That’s because of the new automation methods we’ve developed, the new process methods we’ve developed, and new algorithms, some exciting new cloning methods, new ways to process DNA, none of which we knew how to do 18 months ago. With the smaller genomes we did, they were much more like the public program, a very manual-labor intensive kind of process, which makes it very expensive. The hemophilus genome, that took us a year to do, we could now do in two hours with this new facility. It took 11 days of calculations to assemble the hemophilus genome at TIGR [The Institute for Genomic Research] in 1995. Today, with our new algorithms and our new super computer, we can do it in under 5 minutes, so there have been very dramatic change. And hemophilus took 10 years off the process at a time.
So we’ve gone from something that earlier, last decade, in the 1990s, would have taken 12 years to do something, to something we can do in two hours now. That’s a big difference, that’s a big advance. But thinking conservatively, until that’s proven, you know, the assumption is it can’t work. But if all science worked that way, we wouldn’t have much progress in science or medicine. You have to be willing to take risks at some time to go out and do something new.
SUSAN DENTZER: The stated reason that these efforts, however ambitious or sincere they in fact were, the stated reason for the public side that they fell apart, was their impression that you, Celera, wanted to patent a number of gene systems.
J. CRAIG VENTER: Well, I don’t think that’s–I’m not aware of anybody stating that as the reason that they didn’t want to collaborate, number one, and number two, you know, I don’t think we filed as yet any patents on human genes. You know, there’s a recent study published in the Wall Street Journal of who the top ten human gene patent holders were. Number one was the US Government. Number two was Incyte Pharmaceuticals. Celera’s not on the list. And so this is really a false issue. I think in the past with ESTs [Expressed Sequence Tags], when the government filed a patent on the ESTs that I discovered and the method, it created a lot of controversy, and some scientists learned that it was a weapon they could use to attack what was being done, arguing about patents, because they didn’t want to be seen arguing about the science.
So even though there are companies and groups out there that take the public data every night, download it–they don’t generate it themselves; they do a quick computer search and they file patents on it–NIH is not criticizing them. Francis Collins is not attacking them. Because he feels he’s in competition with us, he’s tried to use patents as a weapon, even though Celera probably has the most conservative patent stance of any genome company.
In fact, at the congressional testimony, I think it became clear to everybody that Celera and the US Government have the exact same philosophy on gene patents, that there should be a very high bar, that you need to know something what the gene does that has real purpose of going into to do something about medicine. So patents are a bogus issue that are being used as a political weapon to try and fool people.
You know, I think Incyte’s actually upset that they’re not getting more press attention over all the patents. They keep issuing press releases that they’re filing 2,000 patents a week. Celera hasn’t filed a human gene patent yet, to my knowledge. We do plan to file some on very exciting discoveries that we’re making with our pharmaceutical partners. But the companies that are dying for the press attention, they’re saying, “Please attack me”, were filing 2,000 patents a week.
You know, people think that Celera’s trying to patent the whole human genome because it’s been used as–I guess people in Washington learn how to do political attacks, and so it gets used as a political weapon, not as a factual one.
I didn’t change my opinion of how to do science because we were forming Celera. I wrote an editorial piece in Science about the nightly data release and how I thought it was bad for science as a field, I think a few years before Celera was formed.
But does Celera have proprietary interests? Absolutely. You know, Celera is a business. It’s funded with private money, a substantial amount of it, over $300 million in the initial funding, as we talked about, to build this entire enterprise. We have 50 million shares out there owned by the public that have invested further, further investment of approximately $1 billion went into building the next stages of what we’re doing with this business. And, you know, Celera did not set up to sequence the human genome as a public charity, because we could have done that through TIGR as a charity. PE wanted to do this to build the next phase of a business of understanding the human genetic code and how it’s going to fundamentally change medicine.
SUSAN DENTZER: What will be the timing under which you will make your information about the sequencing of the human genome public at this point?
J. CRAIG VENTER: It, it, it’s very easy. As soon as the genome is done in terms of the three phases are finishing the sequencing phase–that’s what we recently announced. We had over 20 million pieces that are all being assembled right now by our supercomputer system. As soon as that is done and validated, and we hope to know this week, by the end of this week really where we are in that process. It’s so much data, it’s so much information, it’s not something you can just scan through a printout and say, oh, it’s done.
I mean it takes–either once the assembly algorithm is finished running in the computer, it’s going to take a couple of weeks to really know for sure, you know, do we have all the chromosomes? Are they all in the right order? We have to check that with billions of pieces of little data, from all kinds of places, we’ll compare it to the public data. Then we will, as we did with Drosophila, we’re going to have an annotation jamboree where we have top scientists from around the world come here to start this exciting process of interpreting the genetic code.
There’s been some crude attempts of this with the rough data in the public but it can’t be done systematically until the complete sequence is there in the proper order. It’s been done with chromosome 22. Chromosome 21, I think is going to be published in a week or so.
So, these small chromosomes, there has been tremendous progress in the public effort on and it’s really gone in the right direction. Our goal is to have the genome put together and published in a scientific journal by the end of this year, hopefully much sooner.
SUSAN DENTZER: And at that point, all of the information, in effect, will be public?
J. CRAIG VENTER: It will be available through our Internet site, Celera.com, just as the Drosophila genome is now, for free to the public, to the scientific community, to anybody to do anything they want with it except just take our entire data base, copy it and resell it.
SUSAN DENTZER: As far as this company’s business plan going forward, you have said you want this company to be the Bloomberg, in effect, of genomics. What do you mean?
J. CRAIG VENTER: Well, and Bloomberg seems to like that. One of the people at Bloomberg told me they were going to start saying they were the Celera of the business world. Bloomberg’s, you know, for people who don’t use the service, provides through the Internet, through specialized computers information about the financial world. It’s a very large data base. I think they have on the order of a billion dollars or more a year in revenue. I could be way off on that.
But it’s, it’s an example of how the model is you don’t own the data, it’s not secret information. It’s such a large data set that making it useful, making it interpretable, making it so that pharmaceutical companies, scientists, universities, scientists government, scientists can use the human genetic code and understand what it means and how to understand cancer. How to come up with new treatments for disease.
Our data base right now has over 80 terabytes of information. That’s about five equivalents of the National Library of Congress. It’s not something you could just print out and flip through. Just printing the human genetic code that we now have in our data base would be a stack of paper 100 feet taller than the Washington Monument. It’s a huge amount of information. I think that’s what’s really hard for people to grasp.
Just printing the Drosophila genome in very tiny print, 8 font print covering the entire sheets of paper is a stack of paper about 5.5 feet tall. That’s the genetic code. That’s just the As, Cs, Gs and Ts. That’s not the interpretation. That’s not the linkage out to tens of thousands of scientific articles in the literature linking it out to disease information, linking it out to what does this mean with the changes in genetic code?
So, it’s a huge amount of data that we’re making available on subscription but we’re proving it’s not the genetic code. We’re going to get that to you and everybody else that wants it for free because it’s the interpretation, it’s correlating all this information together that makes it useful to people and that’s what we’re trying to do as a business. But it benefits everybody because instead of a pharmaceutical company having to spend $100 million to build a computer facility to try and do it themselves, for a tiny fraction of that they can get access to our facility and using it.
SUSAN DENTZER: Just finally, recognizing that this is a purely speculative question, where will this entire field of genomics be 10 years from now and what will Celera have accomplished 10 years from now?
J. CRAIG VENTER: Those are very tough questions to answer. Mainly because it’s hard to predict the time course. But I can tell you what the future will bring in part but I can’t tell you how fast it will happen, whether it’s in two years or 10 years.
But the goal is to start to understand the differences in the genetic code of all of us. In fact, it’s to bring power to individuals. If we help you understand your genetic code, and how the changes in you, you have 3 million differences in your genetic code than I do. We differ from each other in 3 million out of the 3 billion letters. Most of those don’t mean anything but probably 10,000 of those letters are why you are very different than I am in lots of respects. You have more hair, for example. Those are determined by changes in the genetic code, in genes and the regulatory regions.
We’re trying to understand those to individuals to help them predict and give them power over their own future. For example, we were involved in the middle of the last decade with the discovery of three genes associated with colon cancer. This was working with Bert Vogelstein [ph] at Johns Hopkins University. And now, if measuring people’s genetic code we find those genetic changes that would indicate a much higher risk of getting colon cancer, that’s something you can actually do something about instead of waiting just for symptoms to appear or waiting until you’re age 50 to get a colonoscopy.
If you know you have a greatly increased risk you can get checked much more frequently and if you catch colon cancer in the early stage, it’s essentially totally treatable, it’s curable. But if it’s, if it’s too late and you wait until some severe symptoms appear, there is a high mortality rate with it. So, this is one way, one example of severe disease, colon cancer, to give people more power over their own lives.
But there’s thousands and thousands of ways this will manifest itself. Most drugs work on 30 to 50 percent of the population and they have rare side effects that work very adversely on a very small portion of the population.
There was a recent Type II diabetes drug that was taken off the market because 1 in 10,000 people developed very severe liver toxicity and, I think over 100 people actually died directly or indirectly from taking that drug. We think those kinds of changes will be predictable.
So, the future of personalized medicine is making sure in the future when you get a prescription for a drug that it’s one that will actually treat your disease, not be neutral. You’re not one of the people it has have no effect on or even worse, you’re one of the people that it has toxic effects on.
If we can predict those, medicine will be very personalized. So, it will be tailor-made for the first time to you and your physical, your genetic makeup, not what works randomly on a population. I think that will be such a powerful change in how medicine is practiced, it’s hard to imagine all the implications from it.
That’s where Celera wants to be, that Celera is going to help drive that through the information, providing the information, helping you and others understand their own genetic code, explaining what this means through our Web site, educating physicians through our website and through subscription services.
This information is not taught in medical schools yet, so, how can our physicians possibly know how to deal with this information as it comes out? So, there’s a tremendous challenge as this begins to transform medicine. But it’ll certainly begin to happen within that 10-year period.