The

OF BIOTECHInterview with J. Craig Venter, PhD J. Craig Venter, PhD

The

OF BIOTECHInterview with J. Craig Venter, PhD

16 imagine Sept/Oct 2010

LANDMARKS & DISCOVERIES A Brief Biography of J. Craig Venter

At the NIH, the establishment scientists weren’t advancing genomic research as rapidly as you thought they might. You saw a way to move ahead. Can you talk about your decision to go your own way?I could see that the procedures and the directions being taken weren’t really mov-ing us forward. I think lots of scientists have been in that kind of position. What was different in my case was that I was offered so many millions of dollars to start my own research institute, so I had the ability to actually do it. It was a very, very tough decision, probably one of the toughest of my career, to leave the NIH and try it completely on my own. But I’ve never regretted that decision.

What was it like to be in the center of things at The Institute for Genomic Research, when scientists really began to see the potential of genomics?

When we sequenced the first genome, in 1995, it was the first time the world saw a complete genetic description of a self-replicating species, the bacterium Haemophilus influenza. It was pretty heady stuff , to be the fi rst one in the world to see that, and then to publish it. And the tools we used—applying a radically different approach to decoding a DNA sequence and developing new computer algorithms—have become the standard for decoding genomes. Th ey changed the entire fi eld. Th ey were exciting times, to be sure.

Did you ever have a moment when you said, “Whoa, I’m really onto something here”?When our computational assembly of the first genome worked, we understood that it was a matter of perfecting the tools, not a matter of whether they would work. I was sure then that it would work for all genomes, including the human genome, although I think I was the only one at that time who was.

OF BIOTECH

U.S. Navy Corpsman, Vietnam

BS in Biochemistry, UCSD

PhD in Physiology and Pharmacology, UCSD

Appointed professorat SUNY

Researcher, National Institutes of Health

Working at the National Institutes of Health in the 1980s, Dr. Craig Venter developed a revolutionary strategy for rapid gene discovery. Over the next 20 years, he would leapfrog ahead of mainstream science, achieving a staggering array of scientifi c breakthroughs. The big goal, as Venter says, is “to understand life at its most elemental levels and at its broadest levels of diversity, and to use this knowledge to benefi t the planet.” Here, Venter talks about what it’s like to be at the forefront of the genomic revolution, and the applications—and implications—of his work.

by Amy Entwisle

as you thought they might. You saw a way to move ahead. Can you talk about your decision to go your own way?I could see that the procedures and the directions being taken weren’t really mov-ing us forward. I think lots of scientists

Working at the National Institutes of Health in the 1980s, Dr. Craig Venter developed a revolutionary strategy for rapid gene discovery. Over the next 20 years, he would leapfrog ahead of mainstream science, achieving a staggering array of scientifi c breakthroughs. The big goal, as Venter says, is “to understand life at its most elemental levels and at its broadest levels of diversity, and to use this knowledge to benefi t the planet.” Here, Venter talks about what it’s like to be at the forefront of the genomic revolution, and the applications—and implications—of his work.

by Amy Entwisle

At the NIH, the establishment scientists weren’t advancing genomic research as rapidly as you thought they might.

Working at the National Institutes of Health in the 1980s, Dr. Craig Venter developed a revolutionary strategy for rapid gene discovery. Over the next 20 years, he would leapfrog ahead of mainstream science, achieving a staggering array of scientifi c breakthroughs. The big goal, as Venter says, is “to understand life at its most elemental levels and at its broadest levels of diversity, and to use this knowledge to benefi t the planet.” Here, Venter talks about what it’s like to be at the forefront of the genomic revolution, and the applications—and implications—of his work.

by Amy Entwisle

1967-68 1972 1975 1975 1984

A Brief Biography of J. Craig VenterU.S. Navy Corpsman, Vietnam

www.cty.jhu.edu/imagine imagine 17

Founded the Institute for Genomic Research (TIGR)

Decoded fi rst free-living bacterial genome, Haemophilus infl uenza

Founded Celera Genomics

Sequenced human genome

Published assembly of human genome

Began three-year, round-the-world expedition on his sloop, Sorcerer II, to collect, sequence, and analyze the DNA of the oceans’ microorganisms

1992 1995 1998 2000 2001 2003

You sailed the world collecting microorganisms in order to study their genetic structures—an unusual combination of old-fashioned exploration and cutting-edge technology. How did you decide to take this approach?Aft er I fi nished sequencing the human genome, I was looking for the biggest problem to tackle, and it was clearly the envi-ronment. I had always dreamed of sailing around the world, so it was a nice way to combine the two things that I loved the most—sailing and making scientifi c discoveries. Making them about the environment from the deck of a sailboat was like a science-fi ction dream.

Did you and your team learn anything from your ocean sampling that surprised you?What surprised us was the extent of diversity that we found. Th ere have been about 41 million genes discovered by all of science to date. About 40 million of those came from the deck of my sailboat. Most of what we know about the gene repertoire came from this sailing expedition.

What are some applications we might expect to see from your discoveries?We’re trying to come up with alternatives to oil, using geneti-cally engineered algae to turn sunlight and carbon dioxide into fuel. We’re also looking at new approaches to medicine. Understanding the function of genes in key cellular pro-cesses has become an important basis for creating new drugs and therapies. Th is information could tell us how and why certain diseases affl ict certain people. It could also tell us why certain medications are safe and eff ective for some people, but cause adverse reactions or are ineff ective for other people with the same diagnosis.

We have a new vaccine program with the goal of very rapidly making new vaccines for emerging infections, such as the H1N1 fl u. And we’re going to try to invent vaccines for viruses that evolve rapidly, such as HIV, where the virus evolves so quickly that the vaccines made today can’t keep up. New approaches to vaccines are probably going to be one of the earliest applications people will see.

Decoded fi rst free-living bacterial genome,Haemophilus infl uenza

Founded Celera Genomics

1998Began three-year, round-the-world expedition

Dr. Venter at work onboard Sorcerer II

The JCVI Synthetic Biology Team

Founded the Institute for Genomic Research (TIGR)

1992

18 imagine Sept/Oct 2010

What problem hasn’t been solved that you really want to see solved?Using modifi ed microorganisms to produce billions of gallons of fuel or billions of tons of food to help feed the world. Th at would be a scale we’ve never worked on before in the history of science. Just seeing the positive applications of the technology take their place in the world—that’s what I want to see.

What’s the biggest limitation you face in your work?I think we’re limited primarily by our imaginations and by the resources to do all the work. My teams are pretty small relative to the challenge. At the Venter Institute, there are three to four hundred of us trying to make these breakthroughs.

We’re at a point where emerging technology is outpacing our ability to understand the implications of the technology. Do you ever worry about the bioethical implications your work raises?I believe that the ethical and societal implications of our work are as

important as the scientifi c research. Th at’s why, in 1995, we started with a bioethical review before we began experimenting.

In July of this year, the Presidential Commission for the Study of Bioethical Issues met for the fi rst time and included leaders in synthetic biology and experts in ethics, policy, regulation, and government. Th e meetings were free and open to the public. As this fi eld develops, continued intensive review and dialogue with all areas of society—from Congress to bioethicists to laypeople—are necessary to safeguard people and the planet. We’re going to try to continue to set good examples as we go forward.

What do you think is important for young people to know about genomics, especially kids who might be entering this fi eld in ten years?If you’re going to pursue biotechnology, you need to be very profi cient in computer sciences and bioinformatics, since all science is heavily depen-dent on computing. And keep in mind that there are going to be those who are afraid of the technology and afraid to move forward. But make no mistake, this is the future. We’re biological creatures, and what we can do with our biology is going to shape our future. i

 TO PRODUCE their synthetic self-replicating bacteria cell, Venter’s team had to learn how to sequence, synthesize, and

transplant genomes.In traditional genetic engineering, scientists

splice short synthetic DNA sequences into existing natural sequences. Venter, on the other hand, recreated life by building on billions of years of biological evolution. To do so, the team created a digital computer fi le of the genome of Mycoplasma mycoides—a natural bacterium that infects goats. They edited it, adding new code that included the team members’ names and three quotations (one by James Joyce), essentially a watermark identifying it as man-made. A com-mercial lab then used that fi le to create chemical “strips” of DNA, which were reassembled and

grown in yeast cells. After isolating the synthetic genome from the yeast cells, the team trans-planted it into another bacterial cell, Mycoplasma capricolum, replacing that bacterium’s own DNA.

“It’s like a Lego that you take apart and have to fi gure out how to reassemble to get back to what you started with,” says Venter. “The cell instantly reads the new genetic instructions and starts making a whole new set of proteins. Within a short time, all the characteristics of the fi rst species disappear and a new species emerges that controls that cell going forward.”

So why is this important? It is a proof of principle that genomes

can be designed in a computer, chemically made in a laboratory, and transplanted into a recipient cell to produce a new, self-replicating

cell—controlled only by the synthetic genome. Says Venter, “It shows how dynamic life forms are, that they change from second to second and that life is basically the result of an informa-tion process, a software process. Our genetic code is our software.”

Venter’s Synthetic Cell

Co-Founded Synthetic Genomics, Inc

Founded the J. Craig Venter Institute

Published complete sequence of his own genome

Manufactured entire genome of bacterium, Mycoplasma genitalium

Awarded National Medal of Science

Created fi rst self-replicating synthetic bacterial cell from Mycoplasma mycoides

2005 2006 2007 2008 2008 2010

www.cty.jhu.edu/imagine imagine 19