This article was taken from the July 2012 issue of Wired magazine. Be the first to read Wired's articles in print before they're posted online, and get your hands on loads of additional content by subscribing online.
There is one version of Craig Venter's life story where he would've been a dutiful scientist at the US National Institutes of Health (NIH), a respected yet anonymous researcher in genetics, perhaps.
Thankfully, Venter saw that storyline developing -- and set about making sure it never happened.
Instead, in 1992 Venter left the NIH to head the nonprofit Institute for Genomic Research. Six years later he founded Celera Genomics, a brash rival to the NIH project that aimed to sequence the full code of the human genome. Venter had come up with a better technique -- known as shot-gun sequencing -- to get the job done, and it changed the way we translate genetics from proteins into code. Not incidentally, it also served as a model for today's Big Data explosion in science and research.
In 2001 Celera officially "tied" the NIH to the genome finish line, though the company's sequence was more than a bit further along. (Celera's model genome, it just so happened, included Venter's own DNA.)
In the decade since, Venter has been on a tear of invention and exploration. In 2004 he sailed around the world, discovering thousands of new species and sequencing millions of new genes. In 2007 he unveiled his own genome, unexpurgated. And in 2010 he announced the first successful synthesis of life -- a unique critter borne from two distinct organisms, thus proving that it is possible to create new organisms for specific purposes. He is a figure who has pushed science forward, sometimes by sheer force of will.
Wired spoke to Venter at an event in San Francisco hosted by [City Arts &
Lectures](https://www.cityarts.net/) and the California Academy of Sciences.
You first made your mark on the international stage when your company, Celera, sequenced the human genome. Ten years on, what do you make of that work?
The last decade has been pretty successful on the technology front. Think about it: the human genome project started as a $3 billion (£1.8 billion) taxpayer initiative in the US with a couple more billion coming from foundations and governments overseas, so a total of about $5 billion. Celera's breakthrough was that we sequenced the human genome for a mere $100 million -- we had a giant building full of sequencing machines. And now that giant building is condensed to something the size of this table, and that $100 million has been reduced to $1,000 or $2,000.
But what most people think about when it comes to genetics is personalised medicine. If we sequence your genome or my genome, what can we interpret, what can we predict for the future, what can we change? That's in its absolute infancy. We're at the point where we don't need one genome or just a few genomes to interpret your genome. We need tens of thousands of genomes as a starting point, coupled with everything we can know about their physiology. It's only when we do that giant computer search, putting all that DNA together, that we will be able to make sense in a meaningful statistical manner of what your DNA is telling you. We're just at the start of trying to do that.
So the fact that it's ten years out and we're able to start on that project -- that is exciting.
There is some perception that in terms of human health the genomics revolution has overpromised and underdelivered. Well, it depends on whose promises you're talking about.
Some people were saying that ten years out we'd have every single disease cured. I think that was overpromising. I have always said that it was a race to the starting line. Once we got the first genome, that's when genomics would really start.
**What about your own interest in human health?
Where does that stand on the spectrum of what you're doing?** I turned 65 last year, and each year I get more and more interested in human health. For most people it happens around the age of 50, but I've always been a slow learner.
It's critical in terms of the cost of healthcare. If we can actually do this experiment of getting at least 10,000 human genomes and then get the corresponding phenotype information, we can show that this data set could make preventative medicine possible and thereby reduce healthcare costs. And one of the things about genetics that has become clearer as we've done genomes is that we're probably much more genetic animals than we want to confess we are.
What do you mean by that?
We're much more genetically determined in terms of our physiology.
We have 200 trillion cells, and the outcome of each of them is almost 100 percent genetically determined.
So on a cellular level, since the genes control the function of the cell, no matter what happens in that cell's environment, we're more the product of our genes than our environment. Yes. And that has important consequences when it comes to reading our genomes, trying to understand the basis of disease, and then trying to alter those features. We're a country that seems to love drama and disasters. We're not so good at preventing them. But preventing disease is the future of medicine.
Another area that you have helped pioneer is synthetic life. It's built on the same raw material -- DNA -- as your work on the human genome, but it leads us in a very different direction, toward energy solutions, things like that.
"Synthetic life" means different things to different people. For some it's green monsters, for others synthetic means plastic. Most people didn't know what to make of it when we announced that we had created synthetic life. We're talking about chemical synthesis.
You started with a mycoplasma, one of the simplest bacteria.
In 1995 we sequenced the first genome of a living organism -- in fact, we sequenced two. For the second, we chose the smallest cell that we could find, with the smallest genome. It was a species called Mycoplasma genitalium. It has only about 500 genes. Then we asked: could there be an even simpler lifeform? Could we get down to a minimal cell? And we set up all kinds of experimental ways to knock out genes and eliminate them from mycoplasma itself, whittling away. But due to a lot of complexity, you can't get there experimentally. We decided that the only way to get there was to make the chromosome -- synthetically.
We had to develop all the technology and ability to do it, and it took us 15 years. We ended up converting the digital code in the computer into biochemistry.
Starting with four bottles of chemicals, we rewrote the analogue molecule of DNA. And then we transplanted that synthetic DNA into a regular cell and booted it up, the same way you boot up software on a computer. We call this genome transplantation.
So now we had a cell of one species outfitted with the genetic software of another. In a very short time the cell converted into what the genetic software told it to do. There was no trace of the original species. Every protein in the cell came from the DNA we'd inserted. So we completely converted one species into another simply by swapping out its software.
**And this wasn't just an academic exercise.
You see a clear benefit in this ability to synthesise life for a specific function.**
What we published was only a proof of concept. A lot of people say, well, the cell doesn't have any uses. But before we did that experiment most people thought it was impossible, so I think it was a pretty useful experiment as a proof of concept. And now we're working on trying to get cells to do what we want them to do.
But surely you're trying to get them to do something that's close to what they already do naturally.
Right. We're trying to harness photosynthesis. A key part of photosynthesis is what happens when the Sun goes down.
Cells convert CO2 into sugar and fat molecules. And they store the fat to burn as energy to get them through the night -- the same way we store fat, only that's just to get us through TV shows. We're trying to coax our synthetic cells to do what's happened to middle America, which is store far more fat than they actually were designed to do, so that we can harness it all as an energy source and use it to create gasoline, diesel fuel and jet fuel straight from carbon dioxide and sunlight.
Energy is just one of your targets. You believe DNA can be used to solve all sorts of problems: health, energy, food...
I think of it as an equation: water equals food equals energy. If doesn't matter where you start in that equation, you need cheap renewable energy to produce food and clean water, and vice versa.
Biology is a natural part of many of those, certainly the food part. And it's been a part of energy. Oil is ancient biology, as is coal, but we need to not take that ancient biology out of the ground, burn it and put it into the atmosphere. We need a way to recycle the biology. So biology will be a key part of the solution.
Will it be the only solution? No. We need lots of solutions. We can now start with the code, the digital code of DNA, convert that into chemical DNA, and convert that into new living organisms that have the potential to do what we need them to do. Producing these very necessary things for society.
Just to touch on the ethics of this, why do you think it strikes a nerve in people that you're doing this with life, with organisms, compared to the tinkering and manipulation that's being done with, say, silicon? What is it about biology that is different? I think because we're a part of biology and we relate to that. But the amount of fear this arouses depends on our education, it depends on people's religion. You see it in literature, the idea that "if you alter life forms it's going to lead to no good end". That goes back to Mary Shelley's
Frankenstein, and you see it in movies -- it's part of our culture. Perhaps it's an innate fear because we're a part of biology, so we're afraid of making things better or making them worse. But I think it's the most powerful technology we have at our disposal to change the outcome of humanity.
Let's end with a big question: in 1990, Carl Sagan wrote that "We live in a society exquisitely dependent on science and technology, in which hardly anyone knows anything about science and technology." That seems even more true today. Do you think we respect science enough as a society? The new anti-intellectualism that's showing up in
[American] politics today is a symptom of our not discussing these issues enough. We don't discuss how our society is now 100 percent dependent on science for its future.
We need new scientific breakthroughs -- sometimes to overcome the scientific breakthroughs of the past.
A hundred years ago oil sounded like a great discovery. You could burn it and run engines off it. I don't think anybody anticipated that it would actually change the atmosphere of our planet. Because of that we have to come up with new approaches. We just passed the seven-billion population mark. In 12 years, we're going to reach the eight billion mark. If we let things run their natural course, we'll have pandemics, people starving. Without science I don't see much hope for humanity.
This article was originally published by WIRED UK
