The Secret of Life

The mapping of the human genome, says Craig Venter, will change science, research, medicine, politics, health insurance, and the way biology looks at the last 3 billion years of evolution. And that's just the beginning.

Craig Venter, president and chief scientific officer of the Celera Genomics Group, is the kind of man who inspires stories — like this one from five months ago: Venter, now 53, is speaking at Harvard Medical School. He announces that Celera's next great undertaking will be to map the roughly 1 million proteins in every human being. He goes on to say that Celera hopes to complete its so-called proteomics project in just three years.

There are people in the audience who have spent up to 15 years trying to discover and understand the function of a single protein. And here is this nervous bald guy telling them that they really needn't have wasted their time. His company will do it all — in 3 years. And the most unbelievable thing of all is that he's probably right. Given its track record, there's every reason to believe that Celera Genomics will eventually identify, and provide the architecture for understanding, most of the proteins in the human body.

Celera Genomics may be the fastest company on Earth. The company opened its doors in May 1998. Since then, Venter's team has tackled the genome sequencing of the fruit fly and of five different human beings, and by the end of the year, it will have sequenced one strain of mouse. Each one of these scientific accomplishments is worthy of winning a Nobel Prize. The fact that one team of scientists has done all of these things in such a brief time is nothing short of astonishing.

In his younger days, Craig Venter was an indifferent student with a bad attitude. His main interest in life was catching the perfect wave on his surfboard. Then he was drafted into the Navy and served as a corpsman in Vietnam. The year that he spent in the intensive-care unit in Da Nang changed his outlook on life.

Venter returned to the United States determined to make a difference in the world. He enrolled in junior college at the College of San Mateo and then transferred to the University of California at San Diego, where he ultimately earned a PhD in physiology and pharmacology. Later, he entered the world of scientific research, receiving sponsorship from the National Institutes of Health. In 1992, frustrated by the glacial pace of genomics research, Venter started the Institute for Genomic Research (tigr) with his wife, Claire Fraser. In 1998, he joined forces with PE Corp. to create Celera Genomics. And on Monday, June 26, 2000, a mere two years after Celera opened its doors in Rockville, Maryland, the company announced that it had successfully sequenced the human genome.

In an interview with Fast Company, Venter discussed his work — the consequences of which are sure to reverberate across the decades of the new century. What he says here is science, not science fiction. It marks the beginning of the Age of Genomics.

You've been critical of the Human Genome Project and of some of your colleagues in the field. What's wrong with traditional gene research?

Somehow, "the discovery gene" took over as the major currency in genetic science. If you discover a gene and you sell it to the pharmaceutical industry, then you get to write a major paper, you get a major promotion, you get a big-name professorship, you get a big prize — and perhaps you get a lot of money. Traditionally, that's how the genetics field has operated.

But we changed all of that with genome shotgun sequencing — a technique that blasts apart the whole genome and then puts it back together, like a mosaic, rather than using the brick-by-brick method of looking at individual genes. A Nobel laureate came to visit me yesterday, and he said that our publication of the Drosophila (fruit-fly) genome ruined several doctoral theses that he knows of. People in this industry used to make their living by cloning and sequencing individual genes. Fundamentally, we have put them out of business.

If you're on the outside of the scientific community, it's hard to understand how much hostility there is toward Celera and toward me.

Why is the sequencing of proteins an important next step?

Sequencing the human genome is an enabling step toward the next stage — which is understanding all of the proteins. We're setting up a facility that will be able to sequence a million proteins each day. This project wouldn't have been feasible — you couldn't have even considered it — without having the genetic code sequenced and reassembled.

What's really key, what's really important, though, is the integration of this information. Think of yourself as a construction site. Your genetic code is the master blueprint. This code controls the timing mechanisms that deliver piece X to place Y in exactly the right order at exactly the right time. Proteins are the tools, the bricks, the mortar — all of the building material on the construction site. DNA controls the timing of how those pieces come together. If the pieces arrive on the construction site in the wrong order, chaos erupts, and the building doesn't get assembled: The steel isn't supposed to be the last thing that's delivered.

So the genetic code handles the timing. We don't know how this works yet. We do know that the code is saying, "These parts have to be delivered to make this cell over there, instead of that cell over there." Now, once we understand how proteins and genetic code work together, we can move on to the next stage. Celera wants to work to develop cancer vaccines. If we can understand how the code interacts with the proteins, we can go a long way toward finding a cure for cancer and for other terrible diseases.

Is your breakthrough the result of a different approach to research? It's the result of a different kind of research tool. I believe that the right tools make all the difference in this business. At every stage in the history of science, fundamental breakthroughs have happened after a new set of tools have been developed and when those tools have been used to gain a new way to look at the world. The creation of the telescope allowed Galileo to discover that Earth wasn't the center of the universe. The creation of the DNA sequencer allowed geneticists to prove once and for all that human beings are not at the center of the biological universe. In both cases, it was a tool that made the breakthrough possible. In some ways, science hasn't changed much in nearly 400 years.

A question that lots of people are now wrestling with is, What are the implications of genomics? What do you think the breakthrough in genomics will mean for human life?

The biggest immediate change will be in the way that genomics dramatically increases our understanding of disease. And that understanding will lead to new approaches to creating drugs and to treating disease. Right now, doctors and pharmaceutical companies have an economic problem. In order to maintain their business goals, they will have to develop and introduce new drugs three to five times faster than they have previously. Wall Street has set these expectations for financial success: Companies have to grow at least 25% a year, or they're not succeeding. That requirement would create a lot of pressure for any business. It means that pharmaceutical companies can't just settle for 2 or 3 or even 6 new drugs a year; they have to introduce 10 to 20 new drugs a year.

Drugs are increasingly being discovered using rational, scientific approaches. But those approaches are still highly limited. A lot of people think that the process of moving from gene sequencing to drug development is a simple one: You get a gene sequence, you look at it, and it tells you what to do; a cure for a disease is instantly apparent. But in fact, the opposite is true. You have to start by figuring out the gene's context. That's what genomics does: It shows you how everything fits into a larger context. Genomics helps you understand the architecture of disease.

The second big implication of genomics is this: Research is going to take an exponential leap forward. As information becomes more and more available, scientists will be able to determine how to use that information, and the circle of knowledge will broaden.

This past April, Celera published the Drosophila genome. There are 6,000 scientists in the world who study Drosophila. It's important work, because the genetic structure of a fruit fly is similar to the genetic structure of a human being. Now, instead of taking 10 years to find and characterize a gene in the Drosophila genome, these scientists can get that data from computer searches in 10 to 15 seconds. We already have a cascade of people doing research that they couldn't have imagined doing a year ago.

As scientists publish their results and move to the next stage in their work, the rate of progress will build exponentially. And it's already helping the pharmaceutical industry to target its drugs more effectively. The human genome is going to refocus the energy of researchers around the world — and that redirection will lead to the discovery of new diagnostics.

However, we can't predict that this approach will lead to a cure for breast cancer in, say, three years. I'm very confident that the genome work that we've done will lead to a cure. But there is no way to put a timeline on a discovery — beyond knowing that eventually it's going to change everything across the board.

Where does Celera fit into all of this?

For Celera, the future is more and more about interpreting information. It's a business that reaches from pharmaceutical companies to each of us as individuals. My long-term vision — and I don't know if the long term is 3 years or 10 years — is basically this: We will help people sort out their own genetic code, and we will help them understand what that code means for their life and for their future. Once they have that information, we will tell them what medical and prognostic choices they have.

Over the next 10 years, we should see a dramatic increase in new pharmaceuticals, and we should start seeing new ways to understand the disease process as well. That shift is going to have a huge impact on Celera's business. Celera will be the driving force in this new way of looking at disease — even if other companies are having breakthroughs of their own.

Where do you stand on deciphering and publishing the genetic code?

In April, we announced that we had finished the sequencing phase of the project. Once our computers had all of the components necessary to start the assembly phase — the phase when we put all of those components together — we started trying to solve the world's largest jigsaw puzzle. That puzzle has more than 20 million pieces, and each piece is a string that is 600 letters long. Our task was to put all of them in the right order, to find out which letters go in which sequence and which letters overlap. We finished that phase this past summer, and we are now having an annotation jamboree, just as we did with the fruit-fly genome. Publication will follow soon after we're done with that.

Finishing the sequence in the assembly is the end of the beginning. It's sort of the end of the grunt work. Then we can start to interpret the genetic code.

What do you expect to learn from this data?

We will probably work for the rest of the 21st century to understand what the data means. But we will learn much more about who we are and about where we came from. We'll also come to understand evolution better, and we'll gain a deeper understanding of our own history as a species.

We now have the means to answer a lot of the key questions that we've always had. That fact will surely have as profound an impact on our society and on our species as Galileo's work had when he showed us that we weren't the center of the universe. We have a human-centric view of biology that's out of sync with what we know about the way life has progressed over the past 3 billion years.

Do you foresee a time in the near future when everyone in the United States will have his or her own genetic-identification card?

Again, the exact timing of these developments is hard to pin down. I have an unusual curiosity about my genetic makeup — and I assume that everyone else has a similar curiosity. I can't imagine not wanting to know about the makeup of my own genetic code, or what it might mean in my own life. By knowing my risk of getting a certain type of cancer, for example, I could prevent the onset of that disease. I want to know what my genetic code means for my physiology.

I am betting that the rest of the world shares the kind of curiosity and desire for self-preservation that I have. That hunger for knowledge will make people want to know about their genetic code, and it will allow them to take effective advantage of that knowledge. People are already starting to ask about their genetic makeup, and we hope to make that information available to them within the next few years.

We also have to make sure that we get the technology right so that it works without causing people harm. How can we do that? How can we open up the technology while making sure that information can't be used against people? Who owns your genetic information? Do you own it, or does your insurance company own it? For example, many life-insurance companies have statements in tiny print at the bottom of their application form saying that you must provide them with any information that you have about your health. But if that information is something that you paid for, if it's your own genetic information, are you contractually obligated to deliver that data to your insurance company?

So one outcome is that we end up losing our health insurance?

A lot of people don't realize that we would all become uninsurable very quickly if we knew the construction of our own genetic code. What really needs to happen is the implementation of universal health insurance. We need to get back to a system of shared risk. The way that our system works now means that universal health insurance won't be easy to implement. But it's essential that such a system is put into place. Otherwise, discrimination will become more and more prevalent — and discrimination will become more and more insidious. We don't necessarily need to have a health plan that's administered by the government, but we do need to have a plan that involves a shared-risk paradigm.

What are the benefits of having your own genetic-information card?

Think about drugs. What many people don't realize is that most drugs are effective for only 30% to 50% of the population. Consider the notion that taking one baby aspirin a day is effective in preventing heart attack and stroke. It's true — but only for about 33% of the population. One gene, one letter change, determines whether you're part of that 33% or not. Our medical establishment tells all of us to take a baby aspirin a day — mainly because, without genetic testing, there is no way of knowing who belongs to the category that the drug works for and who doesn't belong to it.

The baby-aspirin example highlights the way medical decisions are made today: They aren't made with you or me in mind as individuals; they're mere guesses about statistical populations. For instance, there's a Type 2 diabetes drug that's very effective. But in one out of 10,000 cases, it's lethal, so it was recently taken off the market. In that one case, it's clearly not very effective. In future diagnostic tests, genetics will allow for advance screening to determine whether you're the one in 10,000 for whom that diabetes drug is lethal. Soon medical decisions won't be about statistical odds — they'll be about you.

Your personal genetic-information card would not only identify your individual reaction to a specific drug; it would also be a digital record of your personal health information: what other drugs you're on, and what the implications are of drug interactions. Taking two different drugs together may not affect me, but taking those same two in combination could be lethal to you. Your card would serve as a digitized health record. And the foundation for this advancement is the human genetic code, because it's the only thing that's truly unique to each of us.

In your view, what kind of political reaction is the Genetics Revolution likely to generate?

The politics are hard to estimate. In Europe, and in England in particular, the reaction has been almost hysterical — in part because of a distrust of government that stems from the mad-cow disease incident. It wasn't exactly a confidence builder, and it was handled poorly. Should people have an inherent distrust of government officials, especially when those officials say that everything is fine? Yes. I think we all should, to some extent.

Yet there are other people who have a very different view of things — particularly in societies where people are not overfed. In some countries, eating is almost a recreational sport. But I've been to parts of Africa where there are droughts and massive starvation. Somehow, I don't think that those starving people would be too worried about the perceived dangers of genetically modified foods.

With disease, it's a different situation, because disease is very personal. People who live with cancer want to try anything that might help them. When something affects your own health, your political views and attitudes tend to change.

When people talk about the Web, they argue that knowledge is power. Does that opinion apply to the Genetics Revolution too?

Giving people information about their own genetic code is the most important thing that we can do to alter the balance of power between the individual, the government, the insurance industry, and the health-care establishment. Once you have information about your genetic code, you have power over your own life. You're no longer just some statistical aberration in somebody else's study. If you know that you have an increased risk of colon cancer, for example, you can go do something about it. You can be aware of the possibility and watch for early symptoms — because, if you catch colon cancer early, it's totally treatable and curable. There are millions of different attributes linked back to genetic code. By using Web sites and certain information services — which Celera plans to provide, by the way — you can look up that information.

Today, you can tell Amazon.com which kinds of books you're interested in, and the company will notify you about new books on those topics when they become available. In the future, you'll be able to specify to a research company the diseases that you're concerned about, and when a new study on, say, diabetes comes out, you'll be able to have that study sent to you automatically by email. Instead of relying on physicians, hmos, and governments to provide you with information that you need to have about your health, you can personally make sure that you have that information. After all, what's right for 99% of the population may not be right for you. And the government may not really be interested in that point. It's not that the government doesn't care — it's just that individuals don't happen to fit within its statistical paradigm.

Having access to such information gives you power over something that is uniquely yours: your genetic code.

How do you imagine people tapping into this new world of personal genetic information?

We're seeking a pure, tight genetic code, and we're already getting that for several subjects inside Celera. In the future, you would get a DVD with your version of that code on it — a complete map. Each week, you'd log onto the Celera Web site to get an update on your code and to find out what the latest research means for you. For example, you could look on the site to see the latest research on codes that have an indication for a specific disease or for some trait. Either you have that code, or you don't. If you don't have it, you don't have to worry about it. And if you do have it, then you'll want to know more about what that means. This is the kind of information that changes the outcome of people's lives. By using genetic information intelligently, people can alter their lives for the better.

John Ellis (jellis@fastcompany) is a Fast Company contributing editor. Visit the Celera Genomics Group on the Web (www.celera.com).

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