/ 31 October 2007

The bogeyman of modern science

For a room in which one of the most astonishing experiments in modern science is being conducted, the laboratory in the J Craig Venter Institute in Rockville, Maryland, is understated. It is divided into wooden workstations reminiscent of a school science lab. There are stacks of glass test tubes and pipettes, and one wall is lined with air-controlled boxes containing Petri dishes. The mere sight of them sparks memories of interminable, soporific biology lessons.

But there is nothing soporific about what is going on inside these Petri dishes. If all goes according to plan — and the full expectation is that it will — their surface will bloom imminently with an array of small white spots that will herald a giant leap in scientific and human potential. Each spot will contain up to 10million bacterial cells, and in each cell there will be a chromosome that has been painstakingly stitched together by humans from lab-made chemicals. In short, those Petri dishes will contain the first artificial life form ever created.

Casting a paternal eye over the proceedings is Craig Venter — the scientist variously described as a rebel, maverick, outsider and the Bono of genetics. But he prefers to play down the significance of this milestone in science history. “We’re not creating life, we are creating new life forms from existing ones.”

This distinction may strike many as semantic. For if Venter’s experiment works, his team of 20 scientists will have artificially created chromosomes that will display all of the characteristics of life — notably the ability to divide and multiply, and to control the bacterial cells into which they have been transplanted.

It is this kind of jaw-dropping event for which Venter has been lambasted by his critics and venerated by admirers. “Hubris!” cry the first, “genius!” exclaim the latter. But both sides agree on one thing: the extraordinary sweep and scale of his ambitions.

In addition to being poised to declare the creation of artificial life forms, he is also unveiling two other major projects. The first is his autobiography, A Life Decoded, the product of five years’ toil without the aid of ghost writers. It gives his account of the race to decipher the human genome — the code of 3,1billion letters that forms the instruction manual that is the basis of all human life.

On one level the book is a description of code-breaking as mind-bogglingly complex as the cracking of ancient Egyptian hieroglyphs, and no less significant. On another level it reads like a foray into the grubbier side of human nature: how highly educated and gifted people can turn on each other out of envy and fear.

It was this grubby side — the exposed and often vicious spats between Venter’s privately funded attempt to sequence the human genome and a team of government-backed scientists in the United States, Britain and elsewhere — that brought Venter to prominence as the bogeyman of modern science. He was pilloried as the unacceptable face of science-for-profit, the man who wanted to turn the essentials of human existence into patents to enrich himself. The dispute raged for more than three years and only ended in a shaky truce mediated by Bill Clinton. The irony was that, despite all the histrionics, both Venter’s and the public team’s efforts were at best compromises and at worst woefully incomplete.

We are now much closer to the endgame, thanks to the second major work Venter is publishing. It is his own genome, the first individual genetic code to be deciphered. This book runs to six billion letters, strung across the two sets of chromosomes Venter inherited from his mother and father.

Our understanding of how gene sequences translate into life experiences is still primitive, but Venter’s genetic code reveals truths that would wreak havoc with a lesser soul. Top of the list is the news that he has a genetically heightened risk of early heart disease — a poignant subject as his father died from the condition aged 59, a year younger than Venter is now. In response to the discovery, Venter has self-prescribed a preventive health regime: he exercises, watches his diet and has started taking fat-lowering statins.

His genetic book also warns him of an enhanced risk of dementia (“ouch, indeed” is his reaction) as well as of a condition that can cause blindness. Even the prospect of losing his mind and his sight does not unhinge him: “The fact that I have a risk, genetically, for Alzheimer’s and blindness is not great news. But the reality is that any one of us will have dozens of these risks, and what we have to learn is how to deal with them.”

Disappointingly, he only has an average genetic disposition for risk-taking. Disappointing because if Venter is nothing else he is a taker of risks. He is a keen sailor who combines his passion for the sea with his scientific obsession wherever possible. He once sailed into gales in the Bermuda triangle atop 15m waves; not only did he live to tell the tale, he insists he enjoyed the “exhilarating” experience.

“I think I’m a survivor,” he tells me. “I could have suffered at least 100 professional deaths. I could come up with a list of the 100 times I’ve come closest to death, from having pneumonia as a child to car crashes.”

Several of the entries on that list would undoubtedly fall within the year he spent as a navy corpsman in Vietnam. He survived constant shelling and bombing, and an attack from a deadly sea snake that now hangs skinned on his office wall. Several hundred others did not survive and died in front of him.

One soldier in particular changed the course of his life. The teenager seemed normal and healthy when he was brought in, though he was unconscious. He soon went into cardiac arrest; Venter tried for more than an hour to save him. The post-mortem showed the soldier had a bullet hole in his head with a tiny entry wound. That got Venter thinking about the nature of survival.

“We have a hundred trillion cells and you would have naively thought you’d have to kill a lot of them to kill somebody; you just have to destroy a tiny fraction and all hundred trillion are lost.”

It is no exaggeration to say that without that encounter with the dying soldier, Venter would not be exploring the fundamentals of natural and artificial genes. After Vietnam he studied medicine and then biochemistry, and slipped into research. His first project was a study of how adrenaline affects cells, and from there he dug ever deeper into the essential building blocks of life.

What gained him the tag of bad boy of genomics was his aggressive attempt to beat some of the world’s best scientists at their own game. He latched on to a 15year, $5billion project to sequence the human genome and outraged his colleagues by saying he could do a better job in a sliver of the time and at a fraction of the cost.

His cocky bid turned him from an obscure researcher into a household name. But it also earned him the opprobrium of powerful individuals, institutions and the media.

The full story is more complex. Venter made efforts early on in his exploration of gene sequencing to remain in the publicly funded system, but his plans were rebuffed by funding boards that lacked the imagination to keep up with his admittedly grandiose vision. His proposal to sequence the genetic code of the first living organism, Haemophilus influenzae, was turned down in 1995 by the US National Institutes of Health on the grounds that it was unworkable. Within weeks of receiving the rejection letter he had pulled it off.

Venter also insists that he wasn’t into genome research for the money, “I was interested in money only to have the freedom to do my research.” That can’t be the whole picture, I say to him. A man who contemplates buying a $15million yacht, as he did at the height of his biotech wealth, cannot be disinterested in money.

“My actions are not those of someone who wants to do everything for money,” he replies. “On paper I was the first biotech billionaire, but I did it the hard way. I earned it and then I lost it all. If I was truly after money I would have approached everything differently and I would probably have a billion dollars now.”

It is true he lost much of his fortune after he was sacked from his then company, Celera, shortly after the human genome race ended. And it is abundantly clear in conversation with him that he is jet-propelled by the thrill of discovery and the challenge of tackling the impossible.

Venter next plans to sequence up to 10 000 individuals. That would amass a database of genetic information big enough, he believes, to answer some fundamental questions about life, such as that age-old nature versus nurture debate.

He is also planning to sequence the genetic code of all ocean organisms. The project has already found microorganisms in the Sargasso Sea that capture energy from the sun in a process utterly distinct from photosynthesis. Those findings, he hopes, may unlock the door to a new source of energy and provide the key to the planet’s survival. He is racing against the clock, this time with global warming as competition.

All that, even before he gets to announce the creation of artificial life. Given the spanking he received when he last engaged in controversial research, you could forgive him for holding back this time. — Â