Today's date:
  Global Viewpoint



Genetic scientist J. Craig Venter led the private research team that first mapped the complete human genome. He is now on a scientific mission to map the biological diversity of the world's oceans. He spoke recently with Michael Milken, the medical philanthropist and financier, at the Milken Global Conference in Los Angeles.

By J. Craig Venter

Michael Milken: What are the challenges ahead in genetic engineering?

J. Craig Venter: With genetics we have entered a field of such complexity that we don't know exactly what lies ahead. Progress in this realm is not linear. Just a few years ago, when we mapped the human genome, we discovered that we had 20,000 some odd genes instead of 300,000. That meant our biology was much more complex than we once thought, with different genes and combinations of genes in conjunction with environmental influence creating different results for different people.

Today we have the technology for measuring and mapping the genomes of many species, but that is not the same as understanding our biology. I have mapped my own genome sequence. I am trying to understand it. If I can thoroughly understand it by 2025, and I am still here, that means science will really have progressed.

If we progress at the rate we are today in massive computing capacity, it is quite possible that every individual could have their own genome sequences for about $1,000 or less within 10 years.

But more importantly, we are now trying to engineer biology. To do so, we must follow the same lines as chemistry. When chemists thought they understood a chemical compound, they had to then synthesize it to prove their knowledge. We are now trying to push biology to understanding first principles so we can replicate chromosomes for simple cells. We have done viruses. We are trying now to make the first synthetic chromosomes for living cells.

Bacterial genomes are pretty straightforward to decipher. When we get into multi-cellular organisms — we humans have 100 trillion cells — it is not linear.

So it is a question whether society in time will progress fast enough that we can go beyond engineering single cells, maybe to produce energy, maybe to produce new pharmaceutics, where we could engineer and understand the complexity of our bodies. If that happens in the next 20 years, it will be truly one of the biggest miracles in science.

Milken: How do you think this will play out 20 years from now in the clinic for the typical patient? What will it be like?

Venter: The most important contribution to the patient will be the possibility of preventive medicine. Take the example of colon cancer. We know various genes are associated with colon cancer. If you know your genome, you can work out whether you have a genetic probability of getting colon cancer. If you know that, you don’t wait until age 50 for a colonoscopy. The practice of medicine, the control of our own biological destiny, will thus shift more and more into our hands with this information.

About 30 percent of cancers are due to somatic changes in our genes, gene changes that occur after we are born. We cannot predict or control life just on the basis of genes. We cannot do that at a single-cell level, and we certainly can’t do it with our 100 trillion cells. So, hopefully, in 20 years we will understand the importance of the environment and we will have new technologies that will allow us to measure these environmental influences whether they be diet, sun exposure, x-ray exposure or toxins. In conjunction with our genes, we need these kinds of databases to make sense out of our bodies. It can’t be found in the linear way science has proceeded.

Early detection is part of the preventative paradigm. What we have to do is change mostly conditions in our society. We are great at dealing with disasters as a country, as a military, after they occur. We are willing to pay for health care after disease has occurred. We don’t have a paradigm of paying for prevention, predicting things in advance.

This is important because genetic engineering of humans should not happen in the next 20 years because our knowledge of our own genetic code will not be sufficient to do that.

Milken: Cloning is the most controversial biological issue out there today. What are your views on that?

Venter: The biggest problem is that the public gets its science education from Woody Allen and Arnold Schwarzenegger movies. People seem to think that cloning means making a duplicate copy of a sheep, a dog or you.

One of the things that is clear now about genetics is that even twins and triplets don’t have the same fingerprints. They don’t have the same physical body structures because when we go from one to 100 trillion cells, there are so many random events that you don’t end up with the same experiment twice. They have different personalities, different life outcomes. Every multi-cellular species, including clones, will have these differences.

There is no value or rationale for human cloning. It is the part of the technology that seems to fascinate people most in the science-fiction mode. But you have a baby son that would have a very different physical structure from you. It might look similar but would grow up in a totally different environment than you did and would have a very different life outcome.

We are not going to do it. It is spending a lot of energy in the wrong direction.

Milken: What are the most significant advances today in using genetic engineering?

Venter: One of the most exciting things going on, in the U.S. at least, is the stem cell research fund being set up in California. We will never understand how our genetic code leads to the creation of 100 trillion cells for each of us, each with their own function, if we don’t understand stem cells.

Regenerative medicine — when we can engineer our body to repair itself — will only be possible when we know why and how stem cells function. The single most important area of science is understanding our physiology — how we go from our genes to our biology.

Milken: Why are you out there traversing the ocean, collecting species? What are you going to find? How is that going to help all of us?

Venter: It is part of understanding the environment around us, the other part of genomics. What we are finding is that each millimeter of seawater has millions of bacteria and 10 million viruses. You have to think about that the next time you swim in the ocean and you swallow a mouth full of seawater.

Until this expedition, we didn’t even know these species were there. We understood only 5,000 micro-organisms, usually ones we think are associated with disease.

In just one year we have doubled the number of genes in the public database. We found 50,000 new species in just one barrel of seawater and found most of the biology in the surface of our oceans is driven by sunlight to be photo-receptors. Previously, we only knew one existed, and now we have thousands of them. They are probably the most prevalent gene family on the planet.

As for the significance of this effort, it is very simple: There is no point in trying to cure cancer if we don’t do something about the destruction of the environment because we won’t be here as a species to do it.

Sailing around the world, it is hard to go a mile in the ocean without interacting with trash. And it is getting harder and harder to catch fish. Off of Costa Rica, where currents converge, we recently came across several oil drums, literally tons of plastic and even a floating refrigerator.

We tend to treat our environment as though it is infinite. You think it goes somewhere else. But it doesn't. Of one piece, it just flows and blows to a different part of the globe and takes pollution with it.

For example, scientists are now tracking huge clouds of pollutants that come out of India and China that possibly may remain in the atmosphere for up to 50 years and could halve the amount of rain and snowfall across the Pacific in California. It will have tremendous economic consequences if we lose our farming due to losing this water. In some ultimate sense, our health depends on these environmental factors we know virtually nothing about.

We are finding that, every 200 miles, the biological diversity is 85 percent unique. We think we have 100 trillion cells in our bodies, carrying within us our own microbial systems. Now just  imagine, with this kind of diversity, that there are also 100 trillion different organisms in our environment that we engage with and that affect our personal chemistry. When we understand these organisms, we will better understand, for good and ill, the human interrelationship with the environment.

As I mentioned, much of our environmental systems we are discovering are photosynthetic processors. What can we learn from them as we try to engineer photosynthesis to produce hydrogen directly from sunlight? Knowing this biology can change our dependency on fossil fuels, taking billion-year-old biology out of a hole in the ground, burning it over decades, putting it into the atmosphere and possibly extinguishing our future on this planet.

This understanding of ocean species is therefore critical. All the best models for reducing C02 in the atmosphere already encompass everything we know about conservation. So we need a fundamental shift. We have to find a different energy source. My goal as a biologist is to see what biology can contribute to ending fossil fuel dependence. If we can find only 10 percent of the solution, that is enough to power every car currently in the world.

Milken: What is the greatest obstacle to the promises of genetic knowledge?

Venter: The great obstacle is the miserable state of scientific education, particularly in the United States. As I've described, the issues involved in unraveling the mysteries of biology are very complex. If the science is not understood, then we will get the kind of bad decisions for our species we've seen at the national level in the U.S., for example, on stem cell research.