Big Science, Big Egos, Big Money

Mapping the human genome was a fight to the finish.

January/February 2003

Reading time min

Big Science, Big Egos, Big Money

Richard Downs

A hundred years from now, historians may look back upon the last half of the 20th century as the beginning of a golden age of biology, when scientists invented the tools that would make life forms engineerable and programmable. Of course, the golden age of physics resulted in the nuclear bomb, so we can’t count on the future bringing only miracle cures and rounds of golf at age 150. Still, no matter how long we live, biomedicine and biotechnology will be a major force in our lives.

Some might date this new age from the discovery of the structure of DNA in 1953, while others could argue that it really got going 20 years later when Stanford scientists made the genes of one organism work in another. Nearly all would agree that the climax of Act One was the sequencing of all 3 billion DNA “letters” in the human genetic blueprint, an international effort that has been called “biology’s moon shot” because of the huge amounts of money and brainpower different groups have expended.

In The Gene Masters: How a New Breed of Scientific Entrepreneurs Raced for the Biggest Prize in Biology (Times Books, 2002, $26), Ingrid Wickelgren masterfully weaves together what can be a confusing tangle of ideas and personalities to tell how the breakthrough was accomplished. It is a story of technological ingenuity, brilliant insight, scientific infighting, patent disputes and fierce competition between public science and private enterprise.

In 1985, when a Department of Energy biologist named Charles DeLisi proposed a massive project to map the entire human genome, most scientists were aghast. To them, $10 million was a good-sized grant; the idea of pulling billions out of other research to fund this project was threatening. When the DOE took up DeLisi’s idea and solicited Congress for $3 billion, researchers at the National Institutes of Health saw a hostile takeover of their turf. The NIH quickly set up its own genome sequencing program, partly in response to the DOE and partly because it had become clear that funding would be newly allocated.

Stories about big government programs risk sinking to their axles in a bog of bureaucratic detail. Wickelgren, ’88, a science writer based in New Jersey, keeps things moving by bringing to life the characters involved. She reminds us that science is driven by brilliant individuals who are passionate about finding the truth—and finding it better and faster than others. The study of nature can be just as red in tooth and claw as nature itself, and Wickelgren concentrates on the two people who embodied the rivalry: Francis Collins, head of the NIH effort, and J. Craig Venter, who started his own company, Celera Genomics.

Wickelgren introduces Collins as a well-liked professor who has risen quickly by finding the genes for cystic fibrosis and other disorders—a task she likens to finding a grain of rice somewhere along the equator. Collins envisions using proven sequencing techniques on a massive scale to produce a complete sequence by 2005. Keenly aware of ethical obligations, he wants access to the final sequence to be free.

Enter Venter, equally brilliant but apt to be impatient and iconoclastic. As a medical corpsman in Vietnam, he impressed others with his intelligence and gained a fervor for living life fully. Returning home, he tore through college and a doctoral program in six years. Venter sees the Human Genome Project as needlessly slow and expensive. He first proposes going straight for the genes and bypassing the vast majority of “junk” DNA. Later, he favors a “shotgun” method for mapping all the DNA by ripping it to shreds, sequencing the shreds, and using a computer to put it together again.

Collins and his colleagues resent Venter disrupting their well-laid plans with unproven methods—all the more because he plans to use private funds and, for a time, to make the sequence available only to paying customers. The conflict is settled only when President Clinton steps in.

For much of this drama, Venter—whose shotgun method pares years off the process—appears to play the bon vivant to Collins’s stick-in-the-mud, but ultimately Venter seems more conflicted. Having angered government and academic scientists with his pay-to-play proposal, he later confounds his business partners by pushing for free public release of the sequence.

Venter’s deepest motivations seem obscure even to himself, but a startling declaration he made last year may offer a clue. Although an elaborate procedure had been set up to keep the source of his team’s final genome anonymous, Venter announced that the full sequence, the basis for future gene research around the world, was mostly his own genome. Like the Stone Age painters who outlined their own hands on cave walls, he seemed to be saying, “I was here. Remember me.”

Christopher Vaughan is a science writer in Menlo Park.

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