NOVA Online | Cracking the Code of Life

Dr. Craig Venter

Meet the Decoders
Dr. Craig Venter

Krulwich: Do you know anybody in this original group [of people selected to have Celera decode their genome]? Any of your employees, or are they all found objects?

Venter: No. Some of them are employees.

Krulwich: I have to ask, because everybody does: Are you one of them?

Venter: I am one of the volunteers, yes.

Krulwich: Do you know whether you're one of the winners?

Venter: Of the lottery? Or the losers? I have a pretty good idea, yes, but I can't disclose that, and it's important not to in terms of -- because it doesn't matter.

Krulwich: If you're the head of the company, and you're watching the decoding of moi! That has a little Miss Piggy quality to it.

Venter: Well, any scientist that I know in this field would love to be looking at their own genetic code. I mean how could you not want to, and work in this field? So we had lots of volunteers of scientists that wanted to be amongst that group.

Krulwich: Why is that? I don't know -- I'm trying to think. People ask you, "Why do you go on television?" I think, I don't know, because I like to tell the stories. I don't like the looking at myself part.

Venter: Then you wouldn't be interested in seeing your own genetic code?

Krulwich: Hmm!

Venter: Understanding how you differ from the rest of the six billion people on the planet?

Krulwich: If all my friends and neighbors could look at theirs, and we could compare, but the thing itself?

Venter: Oh, you want to beat somebody? [Laughter.]

Krulwich: Well, I don't know. The chances are I'd lose as often as I'd win. Right? No. I think I'm scared. I think I'm scared to see some kind of critical reflection of myself written down in chemicals. You're not I guess?

Venter: Well, a lot of people do have that concern, and our concern is genetic discrimination, that's part of why we went through this review process.

Krulwich: It's just like, "Oh, man, you've got six C's, and I only got five? I don't know what that means, but I feel like maybe like that -- maybe I'd feel like I'm sort of losing a track meet.

Venter: How can I ask other people to volunteer to do this if I was not personally willing to do it myself? If other people leading this team were not -- because it is a risk. Because it's a perceived risk. People have lost their jobs. They have lost insurance, because of some of those minor genetic differences.

Krulwich: How did this begin? Did you put a want ad on some -- I mean how do you decide to get the donors?

Venter: Yes. The early part was very complicated in terms of human subjects and getting the approval and all the kinds of process we have to go through, and so the legalities of it. We set up a huge committee of some of the best ethicists in the world, people familiar with the biology of ethnicity, experts on race, use of human subjects in research, and we had to write all new rules, all new terms, because nobody has ever sequenced somebody's genome before.

Krulwich: So the purpose of this is to take basically a read on a typical human being?

Venter: That's right.

Krulwich: Whether you're African or Norwegian or men or women or dumb or smart or athletically able or no, it doesn't --

Venter: We didn't screen -- we screened for some of those things. We screened for men or women. We sequenced three women and two men. And we tried to have some diversity in terms of we had an African American, somebody with self-proclaimed Chinese ancestry, two Caucasians and a Hispanic.

Krulwich: So you get kind of a human soup going?

Venter: Sort of, but they're kept individually. We track the data separately so we know what the differences are with whom. Think about it, if you were here a year and a half ago, you'd have been having blood drawn from your arm. It's very simple, because every cell in our body has DNA.

Krulwich: Right. By the way, when the people were chosen, did they know that their blood or their semen or their whatever was going to become part of this project, or were they part of a much larger -- that it would only be some of them?

Venter: No. They had to go through a training course to know precisely.

Krulwich: Really?

Venter: We educated them about the genome project, what we were doing. What the uses would be, and the potential risks. The potential risks are, you know, having everybody know your genetic code, when people are worried about genetic discrimination, worried about losing their jobs, losing their health insurance.

Krulwich: But this is like being elected Miss Universe in a way, right?

Venter: Except it's anonymous, like Miss Universe with a paper bag over her head.

Krulwich: I see. Interesting. Did people balk, and say, "No. I don't want to do this?"

Venter: No. It's all volunteers and, in fact, we had a lot of volunteers, and so some of the volunteers were here on the staff, and we also had an ad in the Washington Post, which people responded to.

Krulwich: What did the ad say?

Venter: It didn't say very much. It just said, "Looking for subjects for human use for DNA sequencing." We didn't do it on Page One, because we would have a couple of hundred thousand people.

Krulwich: How many people respond to ads like that?

Venter: It's interesting isn't it? There was a large number of people that responded.

Krulwich: Like tens?

Venter: No. It was in the hundreds.

Krulwich: Why do you need so many copies [of DNA from a single donor]?

Venter: Because we need a certain concentration of the purified human DNA to be able to actually detect the letters of genetic code.

Krulwich: Because this stuff is so small that unless you have multiple copies, exact copies, you might not be able to see what you're looking for?

Venter: Exactly.

Krulwich: How small is it? We all know that shape. You've got it all over the office. You've got it on the lamps. You've got it on your carpet.

Venter: You can't see it with a microscope.

Krulwich: It's that small?

Venter: You'd need a very specialized electron microscope to get down to the level to actually see a single strand of DNA.

Krulwich: The classic picture is I've got this little [inaudible], and there's little ladders in there.

Venter: Yeah.

Krulwich: The distance between one side and the other is that a few atoms' width across?

Venter: Yes. Yes. And so what we're determining is the order of all those letters on that ladder. And there's three billion different letters on that ladder. So the pictures everybody shows of the DNA structure is only about 10 letters.

Krulwich: So that's as much as you usually see -- a chunk?

Venter: That's right.

Krulwich: But the chunk that you're breaking it up into --

Venter: They're much larger than 10. We have pieces that are 2,000 letters, 10,000 letters, 50,000 letters and 150,000 letters. So we have different size pieces, and they're very important and the end strategy for reassembling the jigsaw puzzle.

Krulwich: That's my next question, which is if you took a strand of DNA, and went chop, chop, chop, chop, and get about 50 different pieces, then you want to be able to put them together again in the right order?

Venter: That's right.

Krulwich: This will become a problem which we'll get to in a moment.

Venter: Yes.

Krulwich: Okay.

Venter: In this room [at Celera] the way we read the -- what we do in this room is so we can read the letters of DNA, because even with the amount of DNA that we get that's this amplification, we still need a stronger signal.

Krulwich: A strong signal means you need something you can see?

Venter: That's right. So we attach four different color fluorescent dyes, one color for each letter of the genetic code.

Krulwich: So the color floats in and sort of stops where there's a G, and the next one floats and stops where there's a T or something like that?

Venter: In fact, we add them on during the PCR [polymerase chain reaction] process. As we make copies, we add in the single letters, and they get incorporated by the DNA polymerase as we make more and more copies. The colors get incorporated in to the DNA while we're making the next copy.

Krulwich: What do the colors tell you, that the last letter in the sequence is something or the first letter is something?

Venter: It depends on the sequencing technology that's used, but it's usually the last letter in a ladder of pieces that you see.

Krulwich: So it's called "the caboose effect?" I mean, you look to the end, and there you should find if it says "green," you'll find a certain letter. If it says "blue," you'll find a certain letter.

Venter: Yes. So with this sequencing technique what we do is every place there's a new letter three billion times in the genome it stops at one of those letters. So each place that it stops you know the letter that's on the end.

Krulwich: So you have three billion stops, three billion final letters, then you add them all together, and you get the right thing?

Venter: In fact, we had to do it 15 billion times to get enough redundancy on doing this.

Krulwich: Is this as boring as it sounds if you're a thinking human?

Venter: If you're a thinking human you wouldn't. That's why we have robots that do this. It was initially thought it would take 3,000 scientists to do this over 15 or 20 years. We did it in nine months with about 50 people. The robots would do the boring pieces, and the people would do the exciting ones.

Krulwich: So when this whole business got started, it's a business that seems to me just from eyeballing it to be built from very finely-tuned machines.

Venter: Exactly. And a very finely-tuned process, when you sequence DNA, you only can get about 500 letters at a time. So the conceptual strategy -- how do you get three billion letters in a row, when you're only getting 500 at a time? -- you know, that's the challenge of the entire process.

If you could read down, that would not be the problem. If you could read pieces of DNA in a million or a billion pieces long, but you can only get 500. So all this is designed to feed into the information. So it's a giant jigsaw puzzle, where we can deconvolute all of the information from tens of millions of columns in the end, and the computer to put it back together again. So we use very precise robots at each stage, to get very precise replication of this whole thing, but the human genome, we did it 27 million times.

Venter [walking through Celera]: Actually here's -- we sort of have to catch these as we do, so here's one of the robots, automatically loading samples. So it's picking samples out of that tray and loading them into capillaries, and we'll go through more.

Krulwich: How much is one of these?

Venter: These are the $300,000 machines.

Krulwich: These are $300,000. Who makes these?

Venter: Dr. Hunkapiller's company, my sister company.

Krulwich: Look how many you've got. You've got like a dozen of them.

Venter: We have 300 of these.

Krulwich: Three hundred?

Venter: Yes.

Krulwich: Three hundred at three hundred G's, that's a lot of money.

Venter: Yes. But normally people would have to do all of this work manually, so before this instrument, this was a manual process. Now here you're seeing this robot rapidly lower the number of samples...[inaudible]... It's going to start a run and start reading the DNA from the exact sequence of 96 pieces of DNA. In a few hours it will start this all over again, and repeat the process.

Krulwich: When you went to the company, were you their first customer for this product?

Venter: When we decided to sequence the human genome and formed Celera as part of this organization, this instrument was just a breadboard device. It didn't look like this at all. It was just different pieces scattered on the counter.

Krulwich: Oh, really? It was just a concept and all the parts had not been attached?

Venter: That's right. But it was clear that it was a breakthrough concept in terms of the automation, and more importantly the accuracy of the data that we could get. The previous sequencing techniques were just a large slab gel, you've probably seen pictures of these?

Krulwich: Right.

Venter: And DNA samples could cross over and run into each other, and you'd get mixed data. This happened 30 or 40 percent of the time, which would make it impossible with our mathematical approach to the genome to sequence it this way. So we had to have much more accurate data, much more precise technology. And it was clear that this new technology provided that. But it was not an instrument. It did not look like those fancy boxes.

Krulwich: You must be like the machinist's ultimate customer? You can walk in and buy on faith. You don't have the newfangled prejudice apparently, and you even buy one when it's not actually assembled. You buy conceptually.

Venter: But it was clear and I had faith in the engineering capabilities of this team.

Krulwich: And the fact that they're related to you does it not enhance your faith?

Venter: At that time they weren't.

Krulwich: Oh, they weren't. Are you the only customer for the first year of the run of these things?

Venter: No. In fac, that's what led to the genome race, because we had this new technology, all our -- the teams in the government ran out to buy the same instruments.

Krulwich: Oh, my lord! And you know what's interesting is there's almost nobody here.

Venter: Yes. It's all automated.

Krulwich: So in the course of every minute, how many sequences could this room sequence?

Venter: We'll have to sit down and calculate it, but it's a very big number.

Krulwich: It is.

Venter: So each one of these machines every hour and a half or two hours does 96 samples. Each sample gives us around 500 to 600 letters, and we have that going around the clock, 24 hours a day, on 300 machines.

Krulwich: So they're could be human genomes going through here, cat genomes, dog genomes, mice genomes?

Venter: We've done them sequentially. We've done the fruit fly to prove that this approach really worked, because it was so radical. Then we did humans. So the fruit fly took us four months, while we were still scaling up. We only had a few of these machines. If we were going to do the fruit fly today, it would take two and a half weeks.

Then we did the human genome, the human genome took nine months, not 15 years, but nine months. And when we were still scaling up the process. We just did the mouse genome and finished up last October in four months. And the mouse genome is essentially the same size as humans. So we've done now in four months what just a few years ago we thought would take 15 or 20 years to do.

Krulwich: Is that the plan, to go through all of God's creatures?

Venter: There's tremendous benefit from doing this, because we need, in fact, to compare our genetic code to those of other species, to help interpret it, so we know what's conserved through evolution. What's unique to humans. What might be in chimpanzees. What might be in mice.

Krulwich: If I'm a yeast specialist, and I find that this particular part of the yeast genome, I don't know, allows the yeast to grow and healthy growth. I mean, I notice that the yeast gets sick and doesn't grow, that it's because of the problem right there. Is there a chance that I could find a dog or a human or a chimp with a growth problem, and the gene for growth would be the same one as the yeast?

Venter: Let me give you a very exact example. The enzymes that repair DNA, they're called mismatched DNA repair enzymes. When we sequence a bunch of genes from humans with the new technique that I developed in the early `90's, we compared those back to yeast and E. coli and found almost an exact match between the human gene and the ones from yeast and E. coli, so that the genes and the proteins in our cells that repair DNA are virtually identical to those in yeast that we use to make beer and bread with and in E. coli.

Krulwich: You mean like those little things that fly through the air and make beer beery. You know, if it's wild beer or yeast can be like baking yeast?

Venter: Like baking yeast.

Krulwich: So the-- Really?

Venter: All our functions are conserved through probably 4.2 billion years of evolution. So comparative genomics, the technique, it doesn't matter whether it's a yeast gene, a human gene, a bacterial gene, a fruit fly gene, the same thing works, because we have the same chemistry, the same structure.

Krulwich: So if I'm trying to find out what does this particular stretch of DNA do in a human, I could look it up for a mouse, look it up for a clam or look it up for a yeast, and I might discover the answer to a human's?

Venter: Exactly. And that's why a fruit fly was important. We can do genetics. We can do experiments on fruit flies. We can do experiments on yeast. It's not so easy to do experiments on humans. So, in fact, it helps us to interpret our own genetic code, to have the genetic code of the other species. The single most important one that we have right now is the mouse genome. It's helped us identify the human gene, because we only have a few hundred genes difference between us and mice.

Krulwich: Because they're mammals?

Venter: So a few hundred, it's actually quite startling in terms of --

Krulwich: Because they look so different -- I mean I do.

Venter: [Laughter.]

Krulwich: So that's ultimately the business strategy then, right? I mean, ultimately you want to be a business where people can look up a sequence, and then see and understand anything.

Venter: That's right.

Krulwich [looking at machine]: Now this array of color that's popping up here is telling us what?

Venter: That each one of these little boxes -- see that little green box there?

Krulwich: Yes.

Venter: That means right at that position of that genetic code there's an A and there's another A behind it. Then there's a red box and another red box, so that's two A's and two T's.

Krulwich: So this is light bouncing off--

Venter: It's hitting--

Krulwich: So these little chemicals--

Venter: As the DNA runs down these very tiny fibers, they get separated one letter at a time, and as they come off the end of the fibers, a laser beam hits the DNA, activates the dyes, the dye flows, and it's read by a very tiny, very specialized TV camera.

Krulwich: Oh, so these are TV pictures of lights bouncing off of almost atomically small substances.

Venter: Except we have enough of it there, that's why we had to magnify the amount of DNA, so there would be enough signal to actually see.

Krulwich: I see. How do we break out all of these colors into particular order? This is a very hard order to read? Oh, there you go.

Venter: It's all done automatically by the computer. But here's this, looking at a single lane. So now you can see clearly the peaks.

Krulwich: Yup.

Venter: So there's just a blue one coming up, so that's a C coming up. You could read this, and you could write this all down.

Krulwich: So blue, yellow, red, red, yellow--

Venter: So that's--

Krulwich: C, G, T, T, A.

Venter: So you could sit here every second and write down a new letter, but you have to do it 96 times on this machine and 96 times on every other one every second.

Krulwich: This could be like the book of Revelation. I mean, the answers to our questions are being revealed to us as bouncing light, color, and here's the answer?

Venter: Yes. And it then converts that color peak into a letter. So we have a computer program that just calls us says, that's a C, and when we transfer the data over to the computer, we then will transfer out, convert this to color into a 600-letter piece of genetic code.

Krulwich: And how many machines, this is a very big room?

Venter: There're 300 machines.

Krulwich: Three hundred machines somewhere up in this floor? And it's quite cool here.

Venter: Yes. This room needed three key things; it needed a massive amount of air conditioning because the lasers on each of these machines generate a lot of heat.

Krulwich: What's your air conditioning bill?

Venter: It's about a million dollars a year.

Krulwich: Really? A million dollars a year?

Venter: Yes. We've substituted electrons for people and--

Krulwich: Are you Potomac Power and Light's No. 1 customer?

Venter: They love us.

Krulwich: You and the Pentagon. Do you have electricity -- do you have to build special conduits to get --

Venter: Yes. In fact we had to bring a whole new power grid in to provide sufficient power to these buildings.

Krulwich: We really are made of interchangeable parts?

Venter: That's right.

Krulwich: Do you have to salt and pepper it or something before it makes the transition from one creature to another?

Venter: Some of the genes going from fruit flies to mice to humans--There's one that causes [inaudible] -- the fruit flies don't have eyes. We can take the same gene from a mouse or humans and it will rescue the phenotype, and the fruit flies will have normal eyes. So it's the same gene, the same function, that's related to eye physiology. So that's how we got to be. The parts have accumulated through these 4.2 billion years. Each one has gotten refined and better and better. So, in fact, we may not have any human specific genes at all. The 200 that aren't in mice may also occur in chimpanzees or some other species. So there may not , in fact, be any genes--

Krulwich: Original to us?

Venter: Original to the human race.

Krulwich: So we're just a special mix of everything else?

Venter: It's the combination.

Krulwich: It's the image of God ... [inaudible] ... that we have to work with. There must be a little extra or maybe not?

Venter: There's no evidence of that in the genetic code.

Krulwich: By the way, where do you rank in the number-of-machines-under-the-same-roof world?

Venter: On the computing side or the DNA side?

Krulwich: On the computing side.

Venter: On the computing side, we've been told this is, if not the largest, certainly one of the largest supercomputer facilities in the world.

Krulwich: Bigger than one of those atom-smashing kind of places?

Venter: Yes.

Krulwich: Bigger than a war -- like in Moscow or America's war machines?

Venter: No. The ones in the Department of Energy, for example, for simulating nuclear weapons blasts are much bigger.

Krulwich: Good. Where do you get then? You're No. 2?

Venter: We're in the top 10 or 20 in the world. And Compaq tells us we're basically the No. 1 civilian computer.

Krulwich: So when you walk to a vendor of computers anywhere in the world, do they start to dance or shiver?

Venter: [Laughter.] Well, in fact, it was very interesting. I'm not an expert on high-end computing. I've had to learn this in real time as we did it, and I did not know how to sort out-- You know, it's not different than claims from car salesmen, you know?

Krulwich: Right. Exactly.

Venter: You have to test drive them, right? To really sort out--

Krulwich: Not if-- It's like, it's worse than that, because these are cars that have never been driven by anybody.

Venter: That's right. So I'm an experimental scientist, so I gave the computer companies a problem to solve. And then we ranked them by who could solve it, and who could solve it the fastest, so we knew which computers were going to be fastest for these purposes.

Krulwich: So when you bid out a job how many people are trying to build what you want to have built?

Venter: Well, there's not really that many high-end computer vendors.

Krulwich: Two?

Venter: Well, it ended up being only two that could run the experiment and that was Digital and IBM. Digital then being acquired by Compaq. And so we chose the Compaq alpha chip for the high-end purposes, because it was going to be such a big calculation.

Krulwich: So the Compaq alpha-chip salesman is in Hawaii right now and is just recovering from his drunk probably.

Venter: [Laughter.] And he's been there for two years.

Krulwich: They [the huge number of computers at Celera] didn't break each other? The idea of linking them together or the simple-- adding that much, plugging in that many plugs didn't--

Venter: No. We were worried about the harmonics of having hundreds of machines. We were worried even with all the robots, if they were synchronized, that the building could start to sway or something.

Krulwich: Oh, really? But you were worried a little about-- Surely, it was a huge gamble.

Venter: Right. All the things that we used for sequencing the genome, none of it existed in 1998 when we started this. The algorithms were all new. All the technology that we saw processing the DNA samples -- we've developed all new techniques here to do it at this scale. The instrument was a [inaudible].

Krulwich: And you don't have the worst-night-of-your-life problem? You don't have like the worst-night-of-your life story from this?

Venter: Actually, we didn't. I had no trouble sleeping the entire period of time, because we had five teams, some working on the supercomputer, some working on the instruments, some working on the algorithms, some working on processing the DNA samples. Some of the top scientists in the world, top engineers in the world, their job was to actually work nights, so that I could sleep.

Krulwich: I see.

Venter: And as long as they were having sleepless nights, I felt fine.

Krulwich: You could sleep like a baby?

Venter: That's right.

Krulwich: Okay.

Venter: But it was a system that, if any one of those teams failed, the whole thing failed. So it was an interdependency, you know. You've got the best computer in the world, and if there's not accurate, incredibly--

Krulwich: Did you hear about one?

Venter: Oh, we had problems all the time.

Krulwich: I mean, falling off the cliff kind of problems?

Venter: We had a few stomach-churning events. Not being clear whether there was fundamental flaws in all of the pages of things. Nobody has done this before. It's all new. And most processes take awhile to debug. There was no question in our minds that this technique over time would work fantastically.

We set kind of a demanding time schedule. We said we would have this done in 2002, but we got it done in the year 2000. So even with all these problems, with all the building company from scratch, new technology, new instruments. If you'd asked me in early `98, could we sequence the genome in nine months, I would have said no. Absolutely not, impossible.

Venter: I like these, these are our own computers. We needed such high-end computers, we bought the computer company.

Krulwich: Before I even ask what they do, I really think they're gorgeous.

Venter: Aren't they beautiful?

Krulwich: I like the purple. I like the high -- is this necessary or is this just for the excitement to look at part?

Venter: It's mostly cosmetic.

Krulwich: What do they do?

Venter: This now a Celera product; we bought [inaudible]. They designed their own massively parallel computer chips for interpreting the genetic codes. So these are custom-built supercomputers, literally hundreds of thousands of chips.

Krulwich: The looked stacked to me, right?

Venter: Yes. You can have one or you can create an infinite stack. See we're building one that has a million computer chips in it.

Krulwich: Now is this the part that you were mentioning before that the real trick here is after you slice up all of the DNA, and after you've sequenced it through, and you now know what all the constituent parts are, now in order to get an accurate picture of a human or a dog or a yeast, you have to put everything back together in the right order?

Venter: Imagine these beads like they have down in New Orleans for the Mardi Gras.

Krulwich: Right.

Venter: If each bead was a different letter of genetic code, imagine having beads 500 feet long, you know, these necklaces 500 feet long, and then imagine 27 million of them piled on the floor, and your job was to go compare-- And the order of the beads was different on every one. Your job is to go sort all of those 27 million necklaces out in the right order.

Krulwich: This is the rough stuff, that's the hard stuff.

Venter: This stuff right there. That's what's very difficult for people to understand, even senior scientists in this field. It's so beyond what people can actually imagine. That's why everybody said this was absolutely impossible, that you couldn't break the chromosomes apart and solve this jigsaw puzzle with 27 million pieces, when the pieces are these beads 500 letters long.

Krulwich: What do you do when you finish sequencing whatever you want to sequence?

Venter: It will never be finished, because scientists will be trying to interpret our genetic code for 100 years. And we'll always be making new discoveries with this information. This would be a field that would not exist without this level of-- In fact, our problem is we need 10 times the compute power.

Krulwich: Than this?

Venter: Our biggest problem the scientists find over here is the not enough compute cycles for all the experiments we want to do. So if we had a ten-times bigger computer, there's even that much more to do. So biology for the first time in history has surpassed the level of compute capacity.

This our hard drive. These are our hard drives. So we have very fast optical links. You know the hard drive on your computer? This is the hard drive for our computer. It's over 100 terabytes of data.

Krulwich: What is a terabyte?

Venter: A terabyte is a thousand gigabytes.

Krulwich: And a gigabyte is --

Venter: Is a thousand megabytes.

Krulwich: You're being coy here. What's a megabyte?

Venter: Okay. It's a million bytes.

Krulwich: So how many zeroes are there behind that one, the big number?

Venter: Well, with a million -- think of your salary-- [Laughter.]

Krulwich: Yes.

Venter: The one with six zeros.

Krulwich: Yes. But now the biggest number, that tera thing, that's like--

Venter: For each level you add three zeros.

Krulwich: How many zeros do we come up with for the capacity of the whole room?

Venter: The capacity of the whole room in terms of 100 terabytes, so oh, 14 zeroes, if I'm doing it right on the spot here.

Krulwich: Fourteen zeros, that's a lot of power.

Venter: Yes. So let me show you our main computer. That's in the next room.

Krulwich: Oh, there's another room?

Venter: This is still the hard drive.

Krulwich: So this is the calculation part.

Venter: There's two computers that we used. This was the latest one. This came to us at the last minute. This is called the Wildfire computer. It's a new supercomputer from Compaq. So this was a key part of the human assembly. But here's the main computer that we used. It's this whole set here.

Krulwich: This whole wall?

Venter: This whole wall. So each one of these boxes can hold five computers. Each of these computers would be more than enough to run any university, any major department. You can see we have a lot of these.

Krulwich: Now when you have one of these Master-of-the-Universe moments, which I'm sure you do from time to time, called, "Look what I've built," is the computing power that you have assembled as much of a satisfaction to you as the knowledge running through it?

Venter: No.

Krulwich: No.

Venter: To me, this was an absolutely critical tool that we had to have to get it. Perhaps because my knowledge of computing is not sufficient to really appreciate all of the brilliance that went into this, but to me the goal was to get the genetic code. We couldn't do it without this. So I appreciate the technology, but we have people who live inside these computers, this is their life, and they would feel differently about it.

Krulwich: Right. So the eloquence of this-- If it were a hamster running on a wheel, that it could turn out the same amount of information, that would be cool with you?

Venter: Yes. That would be a lot cheaper.

So each of these have four of the big alpha chips in it, and I can show you one of these later. And so we have literally hundreds of alpha chips in all of these computers. And this is a network. We can address things on the control room, all of the different bars changing. We can send a process to one of those chips, or we can use all of them together. For assembling the human genetic code, it took 20,000 CPU hours. So a CPU hour would be using one of those chips for an hour. So we did it on one shift.

Krulwich: I'm trying to think of what other project would take up that kind of power?

Venter: Simulating nuclear weapons blasts would certainly have done that and bigger. Trying to do massive chaos and weather predictions on a global scale could do it, but not much. It's a very big calculation. We've now done it several times to make sure that it's done right. But just think if we had the ability to sequence the genome of all six billion people on the planet, if each one took us 20,000 hours to reassemble, and that's not even to compare them, to understand them. You have to start to understand when you get to these huge numbers why computing is the limitation.

Krulwich: If you wander around all those machines, you could think, someone famously said, that monkeys could do this; it just goes on. I mean, once you've got the machine set up it just takes care of itself. So let me ask you about the grainy part of it. What is the hardest part of this?

Venter: I think having the whole thing come together and actually work well. Each of the components have their own problems, from the technology working right, the engineer designing it right, and all the things working. My role and my job in this was really -- I was the integrator. I can see large pictures better than many, and don't have the skill sets to do all these other things that some of the team does.

Krulwich: But you seem to be a pretty good picker, though. You seem to be able to find talent when you need something done.

Venter: I've had a philosophy of just hiring the best people and then giving them complete license to go do their job. I don't micro-manage. We get the best people, people who have been working 18 hours a day for the last two years to do this. You know, people are not driven by the excitement of what we're doing. Obviously, they wouldn't select to come here. But each step is very complicated on its own, so we need the world's experts. If we don't have the best computers, if we don't have the -- you know, we have a Nobel laureate, Cam Smith, who with his own hands makes these libraries at the first step. If that's not done with incredible precision, where the DNA really represents the species or the humans that we're sequencing in a completely random fashion, it can never be put back together again.

Krulwich: Let me see if I understand metaphorically what the math is doing. If I took a dictionary page, just a random page out of the dictionary, and I ripped it up into many many pieces and they're in -- I took a piece that says, I don't know, it has the word "verb" in it, a very common word in the dictionary, and a little bit of something on the left, and a little bit of something on the right. The question is, could I reassemble the page? Is there some way that I would know how to tuck that fragment and all the other fragments right back in the same order? Is that the first piece of business?

Venter: It's a good way to think about it. So you can think of a bacterial genome as maybe one page of the dictionary. And the way you do that, you don't just take that one page. Maybe you Xerox the page, and you shred randomly all the Xeroxed pages differently. So in some cases you're have "verb" with a part of a word on the right-hand side; some pages you'll have "verb" with another word on the left-hand side.

And so what the computer does is searches through these. And it will find "verb" and line up all those "verbs," but only a few of them will have the right stretches on both sides. And eventually you can, by doing these massive comparisons, find the exact right order, because the pieces on either side place it precisely on that page where it goes.

It's the same thing with the genetic code, only instead of the alphabet that we have for our language, the genetic alphabet is only four letters, and the words are roughly 500 letters long. So we're dealing with stretches that are 500 letters long with just four different letters in them.

Krulwich: But the principle is the same. You take a page, rip it up, and then you copy that page and rip it up and another copy and another copy. And basically the computer gets used to finding comparisons so they can imagine the thing.

Venter: So the randomness is the key part, because each page gets torn differently. So in some cases it will fractionate here and in some cases it will fractionate here.

Krulwich: So you're sitting there thinking, gee, we could reassemble a whole creature from all those little parts?

Venter: That's right.

Krulwich: And the reaction was?

Venter: No we can't; it won't work.

Krulwich: Then you do it and then what's the reaction?

Venter: It was buried. I mean, I think most scientists in the world got just very excited about it, seeing the complete genome of a free living organism and all 1,800 genes laid out. In fact, it was overwhelming for most of us trying to understand how that cell functioned looking at this information for the first time. My critics said, "Well, he lucked out. It worked for some reason with this type of organism; it won't work with the next one."

A few months later we did the next one and a few months later we did the next one. We did the first three in history in a matter of a year or so.

Krulwich: Now I see there's one thing we have, which is this big -- is the fruit fly part of his party?

Venter: Yes. But that didn't come until much later.

Krulwich: So you're just scaling up your organisms; is that what's happening?

Venter: Well, we found that we could get this information very quickly, and we started just making -- it wasn't planned. We made such major discoveries looking at this information that we just kept switching from organism to organism; actually fascinating organisms.

We found one from the bottom of the Pacific Ocean that was in one of these hyperthermal vents. At our body temperature it's frozen solid. It comes to life about 80 degrees Centigrade -- or about 60 degrees Centigrade. At 85 degrees Centigrade, that's its optimum for growth, and it's happy in boiling water temperatures. And it makes everything it needs for life from carbon dioxide and uses hydrogen as an energy source. Its genome uses the same letters of the alphabet, a lot of the same constructs, but most of the genes were new. Science had never seen anything like them before.

We did another organism that can take 3,000,000 rads of radiation. Its chromosome gets blown apart into little pieces, and over 12 to 24 hours--

Krulwich: What are you, wandering around the zoo of little creatures and making -- let's try this one, let's try that one?

Venter: Exactly. It's fascinating. We're uncovering the basic concepts of life by doing this.

Krulwich: All right. So let's scale this up. If you get to bigger and more complex creatures, I believe you now introduce another, even more ambitious technique. Tell me if I'm -- I don't know what this is called.

Venter: No, it's the same.

Krulwich: Same technique.

Venter: Except it's a different scale. And scale is important.

Krulwich: So I don't actually have to go and rip up my entire dictionary really.

Venter: Well, we were dealing with one page of the dictionary. And now we're expanding to the whole dictionary for Drosophila, and the human genome you can consider the Oxford Dictionary.

Krulwich: But it's the same deal. So on a human being if you rip up the entire dictionary so there's trillions of fragments all over the place, and you're stuck with this word "verb" -- a little bit of something here and a little bit of something here -- you had the notion that you could not only find where this particular fragment goes, but you could put it in the right order for the entire dictionary. Think how weird that is.

Venter: But there has to be a single mathematical solution for it or it wouldn't have been a unique page in the first place.

Krulwich: Yeah, known to God perhaps. But for a human to assemble it from all of its little fragmentary parts --

Venter: But the principles are no different than reassembling the dictionary. If every page of the dictionary was the same with just maybe one or two little differences, it would probably be much harder, if not impossible. But each page of the dictionary is unique. Each part of our genome is unique. We would not be alive if there was not a single mathematical solution for our chromosomes. We would just be scrambled goo.

Krulwich: I know. But you're saying that belief in math led you to believe that you could climb this mountain?

Venter: And I'm not a mathematician. It was belief in the techniques. I'm an experimental scientist. We did the experiment; it worked. We did it again; it worked. We did it on another species.

Krulwich: But I could say to you, "Look, I can climb a hill." Then you could take me to a mountain, and I could look at the mountain, and I'd say, "Well, maybe I can climb the mountain." Then you could take me to Everest, or you could take me to something on Mars that's three times the size of Everest. I might lose the ambition to make the climb.

Venter: You have to have different tools for each one. And so we had to develop a whole new tool set to do the Everest project. We couldn't do it with the same tools that we used for climbing the hill. But the principle is exactly the same.

Krulwich: You act as though you thought that you just plunged in with the certainty that you would come out with an accurate read of the human being. But the truth is you didn't know; you just felt you had to try?

Venter: We didn't have -- all the tools that we used in the end didn't exist two years ago. Necessity is sort of the mother of invention in our experiences, if there is a problem. That's why it helps to have, and it's critical to have, the top people.

Krulwich: Were you scared, or did you think somehow that you -- why weren't you scared, or were you?

Venter: I'm not afraid to take risk. I mean, I said at thee beginning that either this would be one of the most spectacular success stories in history or the biggest flame-out in history. There was clearly a risk element to this. In fact, when I look at all the things that could have failed and could have gone wrong, it's stunning perhaps that it did work as well as it did.

Krulwich: One of the things that's a problem, I think, for humans is the genome itself is a little bit more complicated than it might be for some of those early bacteria, because maybe there's a working part, a recognizable part, and then a lot of kind of stuttery stuff, and then something recognizable again. So there's like these -- we're built with a lot of garbage in us to begin with, so it may not be as easy.

Venter: In fact, there was a key experiment we did. And so we didn't jump from the microbial genomes to human. We did the experiment to test whether all this was really feasible. And we did the fruit fly. So that was the key demonstration project that not only convinced me and convinced our team, but convinced the rest of the world that this would really work.

Krulwich: The fruit fly is much closer to us than the bacteria?

Venter: Yes. And in size the bacteria is 1.8 million letters; the fruit fly was 120 million. So it was a big increase in the scale of the experiment. The same critics were certain the fruit fly wouldn't work.

But when I look back, and I'm asked, what were the key experiments, there were three. It was developing the EST [expressed sequence tag] method itself that led to the next step. The Haemophilus genome and the fruit fly genome were the two really key steps. If the fruit fly genome had not worked human would have been impossible. The fruit fly genome working so spectacularly gave everybody absolutely immense confidence that it was actually doable. Some of the people on my own team probably did not believe it until that experiment was done.

Krulwich [asking about Venter's experience working in a Navy field hospital in Vietnam]: You tell a story about two kids who come in. One holds on for about two weeks and the other not. Tell me that story.

Venter: Well, I learned that there was more to medicine than just physical situations. There was one young man who had this massive gut wound. And the surgeons basically said that by morning he won't survive. But this guy so wanted to live that just through sheer determination he survived for a very long time. He survived there for a couple of weeks in my ward.

Krulwich: Where were you? You were right with him?

Venter: Yes. And then he was Medivacced to the Philippines finally, because people were just stunned that he was able to do so well. Eventually he died because he couldn't overcome at some stages the real physical damage that was done.

There was another soldier who was slightly older -- he was in his 40's -- with a fairly mild wound that he should have survived. And basically he gave up.

Krulwich: What did that teach you?

Venter: That there was much more to us than just the physical aspects of things. The human spirit plays a very important role in what we do and what we can do.

Krulwich: So being a fairly willful person yourself, there's going to be a double lesson in it. Maybe it pays to be tough, or it pays to refuse to give up, or it pays --

Venter: There is no question about it.

Krulwich: So that's-- Seeing the kid who lasts and lasts and lasts became wind at your back ever since in some way?

Venter: It was clearly motivating. I mean, he was clearly representative of a lot of -- there were an awful lot of casualties there. But most people just wanted to go home.

Krulwich: Is this in some sense, when you're young, and you see a lot of people die, and they all could be you, do you then feel that you sort of owe them cures, cures that they'll never get? Or am I over-romanticizing?

Venter: The motivations become complex. That's certainly a part of it. Also I think surviving the year there was -- I'm trying the think of the best way to put it. I felt it was a tremendous gift. I think it more than anything made me risk-adverse. You know, it's one thing when my critics now are shooting criticisms at me. It's very different when somebody is shooting rockets at you. It sort of puts things in perspective, I think. If you're not in that situation you can never truly have that perspective.

Krulwich: The question is, this thing we were just discussing does this impulse in you account for your impatience? I mean you were sitting there, raring to go. By your description, you've got the loudest motor purring all the time. Why?

Venter: It's hard to actually know. I'm driven to want to accomplish something perhaps because of the events in Vietnam that really influenced my life. I've been worried at every stage of my life since Vietnam that I would die before I accomplished what I wanted to. And so I felt this sense of urgency constantly, this sense of timing, not being willing just to sit around.

Krulwich: Why die? Because you saw other people die or because you were worried that you would get a disease?

Venter: No. Because you learn the finality of life. And I knew that there was a finite period that I had. My own father died at age 59 from sudden cardiac death, so I knew that even potentially genetic factors might have it be a shorter period of time, but it was-- It didn't matter whether it was going to be 30 years or 80 years, that's a very short period of time.

Most people, I think -- or I certainly did when I was sitting on my surfboard at age 18, felt a certain amount of immortality. I think, as far as I know, most young people feel that way. I stopped feeling that way when I was 20.

It's probably a very good lesson in terms of, you know, not going forward with this false sense that things really go on forever. So I felt it was really a finite period of time to do something, and a chance to really accomplish something was far more important to me than building some social structure to come out of a competitive hierarchy as, you know, the top professor in an elite school of guys that went to elite schools all their lives. I wanted-- It was far more important to me to do things.

Krulwich: Is there something lurking inside you like, you know, these guys go to these Ivy League schools and sort of have a head start, and you don't like them?

Venter: Not at all. In fact, I think I've proven that it doesn't matter. It matters what you do, so there're no excuses. It's based on your own intellect, your own skill set, and I think--

Krulwich: Why do you get in so much trouble all the time? Why are you fighting with everybody?

Venter: I am competitive, but when the social order doesn't allow you to make progress, and it doesn't for most people, I said, "The hell with the social order. I'll find a new way to do it." And so I don't think it's threatening to some of the people in this field that I sequenced the genome; it's that their social order that they spent a long time establishing so they knew who was at the top of the tree and who wasn't, I just said, "I don't like your tree, because it's just going to block us from making progress."

When we heard "No" from NIH that we weren't going to fund your research, because it wouldn't work, a lot of people said, "Okay. It won't work. I'll go drive cabs or do something else with my life." I knew it would work. I think that happens to a very large number of people, but very few get the chance to break through and actually prove it.

Krulwich: Let me talk about the business of this. Just the word "business" already got a lot of people upset way back, back in the day-- You apparently have a good business sense, but do you consider yourself a businessman?

Venter: No. In fact, I still sort of bristle at the term for some reason. My goal in life wasn't to make money. I've been trying to find ways to enjoy some of the money that I've made, but--

Krulwich: You got your boat.

Venter: Yes. But it was never the goal; it's been a nice side effect, and, in fact, it's led to my philosophy for business. I'm in business, because it was a necessary part of doing this. The government was offering me a $300 million dollar grant to sequence the human genome. You know, Applied Biosystems, which had developed the technology that everybody in the world uses for genome sequencing, wanted to expand its business into the information side and offered me the opportunity and the means to sequence the human genome, but they wanted to build a new business to do it.

But my philosophy is if you do good science, just as if you do good medicine or create new medicines, profits will follow. They have for me personally without-- My focus is not on making money. I've made money by just trying to do world-class science. That's the goal that we're setting at Celera. If we do world-class science and create new medicine paradigms, the money will more than follow at a corporate level and at a personal level.

Krulwich: If you bristle at the word businessman, that might be because in some part of your soul, you may think as some do, that the business of science and the business of business are fundamentally incompatible for one simple reason: that the business has to sell something, and the science has to learn or teach something. And that sometimes learning and teaching and business just can't fit.

Venter: But in the case of developing treatments for disease, they more than fit. I think I bristle at it because it's used as an attack, used as a criticism. In this case, if the science is not spectacular, if the medicine is not spectacular, there will be no profits.

Krulwich: So you're going to go and treat the whole tree of life as a sort of knowledge base, and you're going to ask yourself, you and your company, what is a tree? What is a clam? What is a human? And then if I'm interested in any of those creatures or anything about the relationships between them, I will go to you as sort of the library of that, and pay you a subscription?

Venter: That's part of the business model. And that's the part that's going extremely well right now.

Krulwich: What does it cost by the way to be a subscriber?

Venter: It depends on who you are. If you're a pharmaceutical company, it's in the millions of dollars. If you're an academic researcher, it's a few thousand dollars.

Krulwich: Is this a Yahoo kind of thing if you get there first, and no one else will follow, you hope to be the portal for this kind of stuff?

Venter: Yes. Not from just getting there first, the first mover advantage is a tremendous benefit. Building the integration, building these tools, could somebody else get there if they went out and spent one or two billion dollars right now, building all of these databases and technical capabilities? Sure. Not too many people are likely to do that.

Krulwich: So you want to be a drug company?

Venter: I'm not content to sit back and just hope somebody else will do that.

Krulwich: So you want to be an encyclopedia -- a wannabe pharmaceutical company in the front room? So then if you're a pharmaceutical company with an encyclopedia in the back room?

Venter: What we're trying to is drive medicine forward in two ways. We're making the information and the tools broadly available to make the other people come up with discoveries faster. We're trying to set up a massive program. We're going into proteomics. We're setting up to do over a million protein sequences a day -- that's more than have been done to date in history -- to understand the next stage in the human genome. The genetic code--

Krulwich: So if you find a really interesting protein, you could maybe make some money from, are you going to try to own it?

Venter: Are we going to patent it?

Krulwich: Yes.

Venter: A patent is not ownership. It's the right to commercially develop something.

Krulwich: Are you trying to do that?

Venter: Absolutely.

Krulwich: How can you be selling information to drug companies and being a drug company at the same time?

Venter: They're not incompatible.

Krulwich: They aren't? If I were a drug company, I'd begin to worry if I saw you looking through the information and grabbing some of the good stuff.

Venter: They have all the same information at the same time we do, that the rest of the world does. Here's the notion that it's very simple to do. The information content that we have in our genetic code is so vast, there're not enough scientists alive today with enough resources to make more than a tiny dent in it. It would be phenomenal if everybody could use it, and it was as simple as whoever has it first, that's all there is to it.

Our biology is complex. Why are the drug companies really struggling to come up with massive new treatments? Why has breast cancer therapy not really changed dramatically in the last several decades? Biology is complicated. Solving these diseases is very complicated. So the worst thing morally and in terms of changing medicine would be for any company to try and tie up the information just for their own purposes, because there's no way anybody could use more than a tiny fraction of it. So that they are not incompatible.

Krulwich: If I have a sick person who's got some genetic illness, let's make it cystic fibrosis or something. If this person is sick, I could-- I even know the reason why he is she is sick, because I can say, "Oop! There's the mistake. This person has cystic fibrosis, because I see it in the genes." I can either fix the gene or failing that, could I fix the protein?

Venter: Let me deal with your basic premise, because it's wrong.

Krulwich: Okay.

Venter: But it's what most of the scientific community has believed for the last decade or so: that we know these genetic changes in specific genes, and we know which diseases they cause. And this has been-- We say the analogy is like looking under the lamppost for your lost keys. You know, why do you look under the lamppost? It's because that's where you can see. So if you measure the genetic changes in people with diseases, you say, "Ah! There's this absolute correlation if you have these changes, you'll have the disease."

But that's not measuring the whole rest of the population. When you measure the rest of the population, you find that many people have those same exact genetic changes, but they don't have cystic fibrosis. Some of those people with those same changes get chronic lung disease. Some get chronic pancreatitis. Some just get male sterility with the same changes. Some get asthma, and the latest paper that was published just late last year was that some people get chronic sinusitis. Again with genetic changes in the same gene. And more disturbing to a lot of people is that a number of molecules have no disease whatsoever.

Krulwich: And still have the same--

Venter: And still have the same changes.

Krulwich: I call them "mistakes." You call them "changes."

Venter: Well, in the person with no disease, what's the mistake?

Krulwich: Got it. Yeah. Okay. I didn't know that.

Don't you think, though, that over time with enough data and enough instant-- enough experience, that we'll be able to say, "Sixteen repeats of this equals that disease at an 80 percent probability between your 40th and your 55th year," is it that kind of thing?

Venter: With rare diseases-- In the case of Huntington's disease, which is a rare exception to the rule, yes.

Krulwich: But only then?

Venter: Even then it was a probability still. I mean the probabilities will change to, you know, a fraction of a percent to maybe 50 percent likelihood or something. But it's all these other levels of the information that provide our degree of complexity. How could the [inaudible] in some cases cause cystic fibrosis, in other cases asthma? It's because of the different protein-protein interactions that take place in the development of the cells, and the development of our body.

You get a little spelling change in another protein that interacts with that [inaudible] channel could totally change the developmental cycle. Environmental elements could affect it as well. You know, we're products of the environment and our genes.

Krulwich: So genes will always produce certain proteins. That's their job, and that's expected. But then the proteins will have a conversation with the other-- and with life--

Venter: That's right.

Krulwich: And you can't be sure of the outcome.

Venter: That's right.

Krulwich: So what kind of business could the protein business be? Messy, messy, messy.

Venter: Absolutely. You could not do it without having the human genome done first. That's one of the reasons why we wanted to get the genome done, so we could understand the next level of biology, trying to understand-- It may not even be a single protein that we can say, "This will tell you whether you have colon cancer."

It may be this complex array that we see these proteins change all the time, and this indicates an early indication of colon cancer. Those early findings, if we can make them and make them routinely, will have a profound impact on medicine. Colon cancer can be treated.

Krulwich: You mean you're going to watch proteins behave and sort of look at them like Balanchine, learn their ballet? And then you'll learn whether they're off a step or two or whether you can get them back into shape or--

Venter: We're in the process of sequencing all the proteins in the blood, in the urine, in spinal fluid as well as the different tissues. But blood and urine are the most important, if we can do easy diagnoses.

When a cell dies-- If you have colon cancer and a cell dies, the proteins associated with that colon cancer cell, some of them will end up in the bloodstream. With the new technology and because we have the genetic code now, we can now for the first time in history do a comprehensive survey of what's in your bloodstream, what proteins are there.

And if we do these in large numbers of people, we look at people with colon cancer and people without, then we find ones that associate with being able to predict whether you've got colon cancer or not. So we need this huge throughput, the same scale that we did with the genome, only it's going to be in terms of protein sequences.

But it needs even 10 times larger compute capacity than we already have. And it needs the complete accurate human genetic code to do the interpretation. That's one of the reasons why we're in a hurry to get the genetic code. It enables all these next steps in biology. And if we find those, we'll turn these into new clinical diagnostics, new clinical treatments.

Krulwich [referring to the dual announcement with Francis Collins of the Human Genome Project about the sequencing of the human genome]: Now let's take you to the White House. Did they give you the full treatment with the guys with the Marines and the gloves, playing violins on the staircases and everything, because it was a daytime affair?

Venter: It was a very terrific occasion. I've discussed on various occasions the genome project with President Clinton. He was very excited about it, very supportive of it. He wanted to be involved in the announcement of the completion. There was this competition going on with some of his employees at the time, and it was not the best for science, or for the public.

Although looking back, it had this odd sense of hoping to interest the public in the genome. So more people know about the genome probably because of the so-called genome wars and race than they would have if we just said, "This is all great. Let's try to explain it." But he helped bring about a detente.

Krulwich: Did he want this detente?

Venter: Yes. I think he very badly wanted it and helped bring it about from his side. Regardless of pressure from his bosses, if Francis Collins also didn't want to have it, we probably wouldn't have had it.

Krulwich: Did you get like a call saying, "Please come in peace?" or whatever way they signaled it?

Venter: It was a long, arduous negotiation process for us to decide, you know, whether we could actually achieve some sort of detente.

Krulwich: Were you arguing about who stands next to whom? Who speaks first?

Venter: No. We were trying to do this regardless of whether there was going to be a White House event. I think the White House sort of held it out as a carrot, "If you guys can get your act together, it would be really nice to have a big joint announcement." But it was never a promise or a guarantee.

I think because we made good progress, my understanding is that the president viewed the fact that the genome was sequenced during his administration, and that it was a historical event, that it was worthy of such an announcement.

But it was quite interesting in terms of all the things that went up to it at the end. It was a situation where I was being given a live open microphone at the White House in the East Room, with the president there and the prime minister of England linked in from video on live international television. The president was a fairly brave man in the sense that--

Krulwich: He didn't know what you were going to say.

Venter: They had a rough idea. They called multiple times, asking for a copy of my presentation. But I felt with the opportunity that I was my own speechwriter, and I decided it was an opportunity for me to say something very personal about what I was doing, and I was still in the process of doing that up until the morning that I went down to the White House.

Krulwich: The last question about this. The president used a rather interesting analogy. He said he recalled the moment when Tom Jefferson, Thomas Jefferson came and sat down I believe in that very room with the two men he had sent across the United States to open up the west. Did you think that was an apt analogy?

Venter: I thought it was an interesting one. And what I learned afterwards is I have a family linkage to one of those early explorers.

Krulwich: Lewis or Clark?

Venter: I think it was Lewis. It wasn't a real close relative. [Laughter.] I wish I'd known it earlier. I would have included it, and I would have thanked him for mentioning one of my relatives.

Yes, we're explorers of the unknown. In fact what people don't realize is how little of science really explores the unknown. This is one of those pretty rare situations where it was. We had really no idea where it was going to take us, what we'd find when we got there. In fact, whether we'd get there at all. So I don't think it's been unlike other great explorations, because it was just into the inner universe instead of the outer, physical--

Krulwich: Have all the things that have happened to you from Vietnam right to this moment, which goes on, was there any moment or any turn that gave you a bigger thrill than all the rest?

Venter: Probably the single-- You know, making these discoveries, having a successful completion is incredibly satisfying and incredibly enjoyable, more so than any outside affirmation could ever be. In fact, if that wasn't true all the criticisms I've gotten in this past decade probably would have destroyed me. But doing the first genome in history was so truly enjoyable, and just the thrill of making that level of discovery, and the same with the human genome and the Drosophila genome, I think it's-- I've just been allowing myself recently to think about it and enjoy some of the level of some of the discoveries that we've made, and--

Krulwich: Are you talking about beauty and elegance, or are you talking about meeting a challenge? Are you talking about opening a door?

Venter: All of the above. It's, you know, early in my childhood when I was ignoring those spelling tests and things, I was building boats. I liked creating things and doing that with your own hands is a self-satisfaction of completing something, along with the self-satisfaction of taking something that was theory and turning it into reality, and knowing that it's going to change the world is extremely self-satisfying.

I mean, one of the decisions that I made very early on, when I switched from a career in medicine to go into science, was the hope that if I made a major scientific discovery, it would affect far more lives than I could ever do in a one-on-one basis in medicine and treating people. And so making those levels of discoveries is a joy that unless you've done it, you know, you wouldn't trade anything on Earth for it.

Interviews: Collins | Lander | Venter

Photo: WGBH/NOVA.

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