Decoding Life:
The Next Phase of Discovery

Thursday, November 15th, 2007

The repertoire of biology is vast. What’s exciting now is that we have an idea of what’s there and we have the tools to answer key questions.
Dr. Craig

J. Craig Venter

Founder and President , J. Craig Venter Institute
J. Craig Venter, Ph.D., is regarded as one of leading scientists of the 21st century for his invaluable contributions in genomic research and is one of the most frequently cited scientists. He is of the and the J. Craig Venter Science Foundation, not-for-profit, research and support organizations dedicated to human genomic research, to exploration of social and ethical issues in genomics, and to seeking alternative energy solutions through microbial sources. In addition Dr. Venter is the founder and chairman of The Institute for Genomic Research (TIGR).

Dr. Venter began his formal education after a tour of duty as a Navy Corpsman, in Danang, Vietnam from 1967 to 1968. After earning a bachelor’s degree in biochemistry and a Ph.D. in Physiology and Pharmacology, both from the University of California at San Diego and both in three years, he was appointed professor at the State University of New York at Buffalo and the Roswell Park Cancer Institute. In 1984, he moved to the National Institutes of Health campus where he developed expressed sequence tags or EST’s, a revolutionary new strategy for gene discovery. In 1992, he founded The Institute for Genomic Research (TIGR). There he and his team decoded the genome of the first free-living organism, the bacterium Haemophilus influenzae, using his new whole genome shotgun technique. TIGR has sequenced more than 50 genomes to date using Dr. Venter’s techniques.

In 1998, Dr. Venter founded Celera Genomics to sequence the human genome using the whole genome shotgun technique, new mathematical algorithms, and new automated DNA sequencing machines. The successful completion of this research culminated with the publication of the human genome in February 2001 in the journal, Science. In addition to the human genome, Dr. Venter and his team at Celera sequenced the fruit fly, mouse, and rat genomes. Dr. Venter and his team at the Venter Institute continue to blaze new trails in genomics research and have recently published several important papers outlining advances such as: environmental genomics through the characterization of more than one million new genes found from shotgun sequencing of the Sargasso Sea; synthetic biology with publication of the synthetic PhiX 174 research; and the sequence and analysis of the dog genome.

Dr. Venter is the author of more than 200 research articles and is the recipient of numerous honorary degrees, public honors, and scientific awards. These include: Financial Times’ Man of the Year Award, TIME Magazine’s Man of the Year (runner-up), 2002 Gairdner Foundation International Award, and the 2001 Paul Ehrlich and Ludwig Darmstaedter Prize. Dr. Venter is a member of numerous prestigious scientific organizations including the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Society for Microbiology. Dr. Venter was also one of the first 38 people to be selected by Desmond Tutu as part of his “Hands that Shape Humanity” world exhibition.

In the world of scientific discovery, Dr. Craig Venter has always been a lightning rod. The man whose philosophy is best summed up by his personal motto--Speed Matters, Discovery Can't Wait--challenged the publicly funded scientific effort by saying that he could complete the sequence of the human genome both more quickly and at less cost. The proverbial race was on. All of a sudden, science was running at a faster pace--in Venter time. And he won! Now that the human genome--the blueprint of humanity--has been unraveled, researchers are embarking on the next and arguably more complex phase of discovery--the world of proteins. Dr. Venter has left Celera Genomics to return to basic science.

Medical Update editor Patrick Perry spoke with Dr. Venter in his office at The Institute for Genomic Research in Maryland.
PP: Could you elaborate on the function of proteins, and why they are so important in drug discovery and treatment?
CV: Our cells and all our biological activity occur at the level of proteins and protein products. We don't see DNA or RNA. Humans are made of protein and protein metabolites. All the molecules of life come from protein activity. For example, lipid comes from the action of specific enzymes making fat and cell lipids. Without being able to understand all our proteins, we can't understand how our cells work and how they misfire, producing cancer and other diseases.
In the genetic code, if there are 26-30,000 genes, there are probably 300,000 proteins.
PP: Are proteins more complex and difficult to study than genes?
CV: Proteins are definitely more complex. The genetic code is linear. It is something that can be determined once in one small center. To study proteins, it is going to take hundreds of centers on a massive scale to understand all the protein interactions.
PP: Can you offer an example of how we can use proteins to detect and treat disease?
CV: Here is a very simple one. What is insulin used for? It is used to treat people who have diabetes. Insulin actually binds to the insulin receptor, which is also a protein. All the biology in your cells happens at the level of protein--every single action happens at that level. Every process that you can think of--from insulin used for diabetes to erythropoetin, a protein being used to increase red blood cells--happens at that level.
PP: Will we also begin using these proteins in diagnostics?
CV: We are right now. The prostate specific antigen (PSA) is a protein that is measured in the blood to detect prostate cancer. When I left Celera, we were dealing with protein diagnostics--for pancreatic, lung, and breast cancers. Diagnostics are just ways to produce new protein markers as a means for early detection of cancer.
PP: When will we have a firm grip on the workings of proteins in health and disease?
CV: It is going to take most of the present century to understand all the different protein interactions in the hundred trillion different cells. Stop and think what a big number 100 trillion is.
PP: I have read where many say that we will have this information in five to ten years.
CV: That is the standard reaction for everything that is new.
PP: What is protein folding, and by understanding this, will we better understand how proteins work in health and disease?
CV: Proteins are three-dimensional molecules. Right now, we can only get those three-dimensional molecules by x-ray crystallography of one protein at a time. If we can actually understand from the amino acid sequence of the protein the rules of protein folding, we can then predict the structures of the proteins, just from seeing the linear amino acid sequence. Like anything else that works in three dimensions, you unravel it and it doesn't look so impressive in a single dimension.
PP: Why do you take exception to the term "proteomics"?
CV: There isn't such a thing as "proteomics." People have been very misleading even using that term. There is no single collection of proteins. In your hundred trillion cells, you have 100 trillion different, constantly changing environments of new proteins being synthesized, others being shut down, in a constant regulatory phenomenon. What we need to understand is which proteins are there and how they are being regulated. There was a recent study published in Science by Svante Paabo in Germany, showing the only difference in protein expression between humans and chimpanzees was in the human brain. All the other cells were the same.
Chimpanzees, as is true for most mammals, have a great deal of higher intelligence. Anyone who has dogs certainly knows that animals have a lot of emotion and intelligence. Chimpanzees obviously have more, and we will be able to track the exact evolutionary events that occurred between chimpanzees and humans. We will know those events precisely before this century is over.
PP: When we spoke with you two years ago, you said that sequencing the human genome would bring us only to the doorstep of a new understanding of biology and medicine as we know it. What has occurred in the last two years?
CV: Unfortunately, not very much. We now know that human biology is far more complicated than we imagined, looking for a simple linear relationship out of the genetic code. As a society, we think as genetic determinists. Everybody talks about the genes that they received from their mother and father for this trait or that trait, when in fact those have very little impact on life outcomes.
Our biology is very complicated, dealing with hundreds of thousands of independent factors. And it is going to take a very long time to sort it all out at the pace things are moving.
PP: You have mapped the human genome. But are our genes our fate, our destiny?
CV: Genes are absolutely not our fate. They can give us useful information about increased risk for disease, but in most cases they will not determine the actual cause of the disease, or the actual incidence of somebody getting it. Most biology will come from the complex interactions from all the proteins and cells working with environmental factors, not driven directly by the genetic code. Knowing you have a 30 percent increased risk of getting colon cancer does not tell you very much about colon cancer. It certainly doesn't tell you whether you will get it or not, but it can tell you that because you have an increased risk, you might be able to prevent yourself dying from colon cancer by having a checkup each year to detect its presence.
PP: One of your new institutes will be looking at the issues surrounding genetic discovery. With all this capability, do we run the risk of genetic discrimination in the future, and what are your thoughts about this whole issue?
CV: It is a tremendous risk, because we as a species want to discriminate against one another. The most important legislation that Congress can pass is the nondiscrimination bill that keeps people from using the genetic code as a factor in employment or insurance companies using it as a factor in individual insurance decisions. It makes sense to use it for populations. It doesn't make sense to use it against individuals.
I think it is critical that Congress pass this legislation, or the major benefits to society from the discoveries that my colleagues and I have made won't reach their potential. The TIGR Center for the Advancement of Genomics is going to work on key ethical and social issues related to my sequencing of the human genome.
PP: Can you refer readers to a source for information on genetics and proteins?
CV: The TIGR.org Web site to the section called GNN (Genome News Network) has some information. People just need to use common sense and not think that they are just the sum total of their genes, or they would be robots and not individuals with free will.