Behind the Science: Craig Venter vs The World

FRIDAY, 25 JANUARY 2013

Badass scientists around the world look to one man for inspiration. In fact, the scientific community has seen few recent controversies to rival that created by one John Craig Venter. It’s a common story in science, really — sick of the limitations of publiclyfunded research, Venter left a position at the National Institutes of Health (NIH) to find his own capital and gain freedom to pursue things his way. But when Venter became president of Celera Genomics back in 1998, his aim was not just to go about quietly conducting his own avenue of research. Instead, he challenged the Human Genome Project to a race to complete the first genome mapping.

The Human Genome Project aimed to identify our genes and determine the sequence of the base pairs that form our DNA, which contains all the genetic instructions to make us who we are. Often labelled an egomaniac, Venter infuriated many by suggesting that the $3-billion Human Genome Project — backed by the US Department of Energy and the National Institutes of Health (NIH) — turn its attention to sequencing the simpler mouse genome. He was confident that his “whole-genome shotgun sequencing” approach would reduce costs and accelerate the pace of discovery, while scientists involved in the Human Genome Project believed this would lead to more inaccuracies compared to their “clone-by-clone” method.

Unlike the clone-by-clone method, whole-genome shotgunning breaks up DNA and relies on computer software to work out where each piece should go. Without creating a map for each bundle of DNA before sequencing it, scientists were worried that the software would get confused and be unable to establish where the DNA fragments belonged. James Watson, co-discoverer of DNA and head of the NIH branch of the Human Genome Project for some time, was of the opinion that Venter’s shotgun sequencing “could be run by monkeys” and didn’t consider it science. Another concern was what Venter would do with a monopoly over the important information from the sequenced genome once finished. It was certainly a ballsy move on Venter’s part to take on such an endeavour and to make such outrageous claims in the process. Where exactly did he get the guts to be so brash and so bold?
Venter was born in 1946 in Salt Lake City, Utah, and grew up in a working class suburb near San Francisco, California. He was reportedly a poor student, preferring to spend his time on the beach. In order to avoid being drafted into the Vietnam War, Venter instead enlisted in the Navy, but ended up there anyway after being court-martialled for disobeying a superior officer who happened also to be his girlfriend at the time. In a move that was good for neither him nor likely his relationship, Venter’s six month stint working in a hospital in Da Nang meant witnessing thousands of soldiers dying, a rocket blasting through his sleeping quarters, and his attempted suicide by swimming out to sea. Returning to the States, Venter married and attended community college, before studying biochemistry and subsequently physiology and pharmacology to graduate with a PhD in 1975 from the University of California, San Diego. In his Mercedes-driving, bell-bottom-wearing years that followed as a faculty member at the State University of New York, he divorced his wife and was remarried to one of his students.

Venter joined the NIH in 1984 where he presented his idea to use whole-genome shotgunning to accelerate the sequencing of the human genome. But his idea was rejected by the NIH, so he went about finding venture capital to try it out himself. The bacterium Haemophilus influenzae was his first project and a promising start, becoming the first organism to have its genome mapped back in 1995. So began the drama for which Venter is now renowned. He was made president of the new company Celera and boldly pledged to finish mapping the human genome in three years, four years ahead of the projected finish date of the Human Genome Project. Watson’s response, as former head of the NIH branch of the Human Genome Project, was to proclaim “He’s Hitler”. And indeed, Venter was an easy enemy: egomaniacal, seemingly capitalistic, and apparently unconcerned over the quality of his data (though shotgun sequencing has since become standard practice). A close, bitter race ensued and the Human Genome Project stepped up its efforts, resulting in a tie announced in 2000. In the end Venter’s pledge was broken, Celera’s stock plummeted, and he was driven out of the company. Disheartened, he told a journalist “My greatest success is that I managed to get hated by both worlds.”

For some, this defeat would be enough. He had money from Celera, he had made his mark on genomics, and he’d had more than fifteen minutes of fame (or infamy). But after licking his wounds, Venter re-emerged and with his considerable earnings founded the J. Craig Venter Institute in Maryland. The controversial figure continued his work in genomics with a number of projects. In his Global Ocean Sampling Expedition, Venter climbed aboard his transformed luxury yacht, the Sorcerer II, and proceeded to circumnavigate the globe, picking up microbial species along the way to be shipped back and sequenced. In 2007 Venter published the results of the exploration in PLoS Biology, which highlighted the tremendous amount of genetic diversity in the marine microbial community. Even this expedition raised doubts, with some questioning the merit of blindly sequencing the genomes of unidentified microbial species and without having a specific scientific question in mind. Venter hopes that eventually his trip will be looked upon as a Darwin-style adventure (a trip to the Galapagos Islands led Darwin to form his revolutionary theory of evolution), potentially by publishing his sequences in a freely-accessible public database.

In other synthetic biology projects, Venter is dedicated to developing new sources of fuel. He first seeks to find a ‘minimal genome’ that will provide a base for inserting engineered genes to perform a desired task – in this case, making cellulosic ethanol to be used as fuel. Of course, this engineered genome is no use without a cell in which to perform its functions. In a Science publication in May 2010, Venter’s team reported being the first to create synthetic life when they inserted man-made DNA into cells that were capable of self-replicating. After ten years of work for twenty scientists at an expenditure of approximately US$40 million, Venter can check this off his to-do list. The DNA was complete with “watermarks” written into it and included an encrypted alphabet and punctuation along with an email address to contact for anyone capable of cracking the code. The creation of synthetic life and its ramifications are, in true Venter fashion, controversial to say the least.

The life and achievements of J. Craig Venter, still on-going, are indeed remarkable. From challenging the US government in a race to map the human genome to creating synthetic life, Venter is a man who dares do the unthinkable. His ego may have created a few enemies for him along the way and he seems to take considerable pleasure in creating controversy, but he’s somehow made science a more human endeavour. Scientists see internal disagreements all the time in the literature, lab meetings, and in comments we get back from the reviewers of our manuscripts. The public often has a very different view of them, as a cooperating entity whose sole directive is to make discoveries to better the human condition. But with Venter, they see the claws come out and drama unfold with all the ugly human ego and selfishness science can often entail in reality. Maybe he is just what we need to shake up the public’s perception of scientists, and perhaps even of ourselves.

Jordan Ramsey is a 2nd year PhD student in the Department of Chemical Engineering and Biotechnology