J. Craig Venter on Automated Sequencing
  J. Craig Venter     Biography    
Recorded: 02 Mar 2006

Well, the automated sequencing technology was very early and very primitive. There wasn’t good software. We had to actually read some of the data manually. The protocols that everybody was using, nobody else could get them to work, except my lab had great success in it because we are very quantitative about what we were doing and measuring the DNA and the concentrations. There was a secondary binding site for one of the primers, that if you didn’t have the stoichiometry just right, you just got noise. So other labs when they tried the machine, they just got random noise and said it didn’t work. So for three years, my lab was the only one that had any success. That’s because we measured things carefully and we got great data. But people are very reluctant. The labs like Bart Barrell, who were some of the best sequencers using manual techniques – they had it down to an art form, they just got beautiful data – they were very reluctant to change. So I was new to DNA sequencing. I only sequenced one gene. It was very slow. It was very painful. So I was looking for a better method. So, you know, often it’s the people that are coming in new to an area that make some advances because they are willing to try something new.

There was only one person working with me. It was Jeanine Gocayne, who was a lab technician. She and I worked every day on trying to run the automated sequencers. I did it myself because I figured that was the only way to really learn it and see how to improve it. So I spent a lot of time myself running the machine with Jeanine; working out the bugs, how to fix it, how to improve it. I think that’s why we had such good results. So, I don’t remember the exact name, but it was published in PNAS in the fall of 1987. It described sequencing, I think, two neurotransmitter receptors, one from rat heart and one from rat brain. But they were the first genes sequenced with the automated sequencing. We had to compare the automated sequencing to manual sequencing. It was a landmark paper because it’s the first thing that actually showed that you can get real data off the machine. So after that paper was published, people from all over the world came to my lab to try and learn how to use this new technique to try it in their labs.

Well, they believed that some people could get it to work. It was still in 1987, no other labs could get the machine to work because they didn’t have the stoichiometry right of the primer. So Lee Hood’s lab—I had now a famous meeting with Jim Watson describing the techniques and he had just come from Lee Hood’s lab. He said that Lee Hood was still using manual sequencing. But he didn’t believe in his own machine, they said. But we believed in the new techniques. I know whenever you take on a new technique, it doesn’t just instantly happen. I mean so many people were very naïve. They bought a box, plugged it in and expected to get the human genome coming out of it. So any time we take on a new complicated technique, I know it takes three to six months of really dedicated effort on somebody’s part to learn it. In this case it was my effort and Jeanine Gocayne’s.

Well, I’ve always believed in using new tools and techniques. In fact, I had just recently moved to NIH and the advantages, we had unlimited budgets. But there was very limited space so you had to use your imagination of how to use automation or how to use high throughput techniques to do things that other labs, you know, could hire a hundred people for, we had to use our brains to use new approaches. So that was part of the motivation. But it was just exciting to use a new technique after a decade of hard work to get one gene, one protein. All of a sudden in a few months having two complete gene sequences and the ability to start moving forward, it was very exciting.

So I was in the neurology institute of NIH and they were very happy because I was making breakthroughs on genes from the human brain. But as the discussion came, you know, the genome doesn’t have a chromosome for the brain. When you characterize genes, they come from all over. So they were nervous about the neurology institute funding the genome effort. So they wanted me to ask Watson to see if he would help contribute funding. Initially he was very excited. In fact, he asked how much money I needed to get going. I said, I think it was either four or five million dollars and he immediately he promised that money and then went to Congress the next day and said that we had the best lab in the world, and he needed more money in his budget to fund this to get it going. But it took some turns from there. I think, had he been left up to his own instincts the genome project would have been done much sooner, because I think he had great instincts and he saw what we were doing would lead to big success and he wanted to fund it. But other people talked him out of it.

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.