J. Craig Venter on EST Development
  J. Craig Venter     Biography    
Recorded: 02 Mar 2006

I think the first thing in the early field was getting the first neurotransmitter receptor from the human brain. That actually led to the development of the EST method along with doing the test sequencing for chromosomes. So we were doing test sequencing from human Chromosome 4, looking for the Huntington’s disease gene, and human Chromosome 19, looking for the Myotonic Dystrophy gene. We found that when we actually had the first random chromosome sequences, it was impossible to interpret the data. In fact, the only way we could interpret the human genome sequence was to have a cDNA sequence. So that’s where I got the idea to develop what I called Express Sequence Tags; we just randomly isolated cDNAs from the Human Brain Digital Library and sequenced those. And we discovered overnight hundreds and hundreds of genes. Then it turned into thousands and then tens of thousands.

So we published this in 1991, and it’s been a paper that’s been very heavily cited and used and extended. There is now something like well over twenty million ESTs in GenBank. In fact, people are using the technique more today than they were in the early ‘90s, because with eukaryotic genomes, it’s the way to get at genes very rapidly, very inexpensively, and this was key in interpreting the human genome by everybody.

I actually thought of the method on a long flight back from Tokyo. So I had nothing to do for twelve hours, but I had just finished doing a tour of Japan. These people were very interested in Japan about all our genome data and the work that we were doing. And in Japan people like Kenichi Matsubara and Okayama had developed some wonderful methods for making really good cDNA libraries from tissues. So we had lots of discussions in Japan about cDNA approaches and how Japanese scientists were going to concentrate on cDNAs, full-length cDNAs, not sequencing the human genome.

So after a week of these discussions, so I had nothing to do. I finished my book on the way to Japan, so on the way back I had nothing to do for twelve hours, so I just thought about all the conversations I had and how we were having trouble to interpret the human genome even when we had the sequence. So the random methods when we were shotgun sequencing pieces of the human genome, we sequenced a thousand pieces of DNA and we’d get maybe a half of one gene. So I just got the idea on the plane to try that same approach and see what would happen if I sequenced a thousand cDNA clones.

When I got back to my lab I tried to convince people to try this idea. Nobody wanted to do it. So Dick McCombie was a postdoc in the lab at the time. He was doing one of the projects, the first test sequencing from, I think he was doing Chromosome 4 on the Huntington’s disease gene, looking for that. And he didn’t want to be getting diverted, and thought it was a bad technique to try and it wouldn’t work. But a young postdoc who started one week before in my lab, Mark Adams, got excited about the idea. So even though I had the money, I didn’t have to get any money from anybody, I still had to convince my own team to try the experiment. And it wasn’t easy. All of them argued very strongly against it except for Mark. I think he was young, you know, vigorous scientist and he got excited about it and he immediately tried it and we got fantastic data from the first time. He helped build it into a real method, you know combining—we had to do a lot of computer work and informatics. Develop ways to really sequence these things and improve it. And we took a long time to publish the first paper because we were trying all these different ideas. But he was essential to helping to get it going.

We just had a lot of new ideas all emanating from the EST method. It was all random processing. In fact we’ve had now four major breakthroughs of whole new fields that have started because we are using the random method, using computing to help interpret data. So it started with ESTs. The EST method led to the first genome in history from a living species, not a virus. That was influenza in 1995. And then the next big breakthrough was applying this on orders of magnitude larger scale, first with Drosophila and then with human and now with basically every lab has used my techniques. But the new areas we applied to the environment and now it’s totally changing environmental research. It’s the same random method. We’re characterizing whole environments, not just single genomes. So there’s four major areas that totally emanated from the idea that I got on the airplane coming back from Japan.

J. Craig Venter, biologist and genomic research pioneer, was born in Salt Lake City, Utah in 1946. Following military service in Vietnam, he studied biochemistry as an undergraduate at the University of California, San Diego, where he also received a Ph.D. in Physiology and Pharmacology in 1975. He joined the faculty of the Medical School of State University of New York at Buffalo in 1976, joining its affiliated Roswell Park Cancer Institute in 1982 as Professor and Associate Chief Cancer Research Scientist. Beginning in 1982, and for the next decade, Dr. Venter headed various sections of NIH's National Institute of Neurological Disorders and Stroke.

In 1992 he founded The Institute for Genomic Research (known as TIGR,) where he and colleagues became the first to successfully sequence the genome of an entire organism. Dr. Venter's Celera Genomics, founded in 1998, used a strategy known as the whole genome shotgun approach to compete with the publicly-funded Human Genome Project, which served to accelerate the mapping of the whole human genome by 2000. Dr. Venter's current venture, the J. Craig Venter Institute, was formed in 2006, from the merger of several predecessor enterprises. A leader in genomic research, the J. Craig Venter Institute announced in January 2008, the largest synthetically derived DNA structure, advancing it towards its goal of creating a living cell based on an entirely synthetic genome. In September 2007, the J. Craig Venter Institute announced the sequencing of Dr. Venter's genome, the first sequencing of an individual's genome.

Among Dr. Venter's numerous awards and honors are the American Academy of Microbiology Fellow (1997), the American Chemical Society, Division of Biochemical Technology David Perlman Memorial Lectureship Award (2000), and the U.S. State Department, Secretary's Open Forum Public Service Award (2001). Dr. Venter is a member of the American Society of Human Genetics, the American Association for the Advancement of Science, the American Society of Microbiology, and the American Academy of Arts and Sciences.