Riding the Dna Trail

By J. MADELEINE NASH/BETHESDA

Dr. Francis Collins may not have been ready for Saturday Night Live, much less prime time, but the University of Michigan students screamed with laughter all the same. As the last class of the semester was ending, the 43- year-old geneticist slipped an acoustic guitar from its battered case and in a reedy tenor began warbling lyrics of his own invention to the tune of one of Frank Sinatra's enduring hits. "So start today," Collins crooned into a microphone. "Love DNA, and do it ouuuuurrr way." The star of this spoof stood 6 ft. 4 in. tall. He wore cowboy boots beneath his white lab coat and slung a stethoscope round his neck like a wayward tie. And as his last note faded, the delighted audience gave him a standing ovation.

What the students could not have known was how bittersweet this moment seemed to Collins. It marked the end of a remarkably rewarding and productive period of his life and the beginning of an expedition into an exciting but uncertain future. Last year, after months of deliberation, Collins left his faculty post at the University of Michigan Medical School to lead the Human Genome Project, an audacious effort to decipher the complete genetic script contained in human cells. Collins considered it the most important under taking in the history of biological research. He was moving from classroom gigs to the big show.

Is Collins up to the role? If not, it is hard to imagine who would be. He is a natural performer whose stage presence and easy eloquence make him a persuasive spokesman for the multibillion-dollar genome project on Capitol Hill. He is a workaholic who logs 100-hour weeks and flies more miles in a month than most people do in a lifetime. He is an empathetic clinician who agonizes when delivering a devastating diagnosis.

Above all, he is a relentless hunter of disease genes. Finding a gene embedded in long, nearly featureless spirals of DNA, he likes to observe, is harder than locating the proverbial needle in a haystack. "At least a needle looks different from a haystack," he says, "but a gene is just another piece of DNA." His love for lab work won't let Collins become merely a bureaucrat. He has already established his own research center at the National Institutes of Health so he and colleagues can continue their search for errant genes.

When people describe Collins, they do so in oddly contradictory terms. Thus he is said to be one of the most compassionate people in the world, and also one of the most aggressive. He is a skeptical prove-it-to-me scientist but is also capable of deep religious faith. He is as intent on the impression he is making as any politician up for re-election. Yet he appears to be utterly unpretentious, preferring to dress casually in jeans and, when he rides his Honda Nighthawk 750 motorcycle, a black leather jacket. (On one of his motorcycle helmets he sticks decals that keep a running tally of every gene he and his collaborators have tracked down, including the ones responsible for cystic fibrosis and Huntington's disease.)

The youngest of four brothers, Collins grew up on a small farm in Virginia's Shenandoah Valley. His father, in addition to raising cows and sheep, was a serious musician who collected folk songs and taught at a nearby women's college. His mother, who educated him at home until he was nine, wrote plays, which were performed at a small theater the couple started in an oak grove on their farm. "When Francis was seven," his father recalls, "he wrote a full script for The Wizard of Oz and directed its performance." He played bluegrass and Bach on the pump organ and guitar, and he would spend hours pondering the consequences of dividing numbers by zero.

By the time Collins graduated from high school, at 16, he was determined to become a chemist. Biology, curiously, did not interest him at all. "Somehow," he muses, "I had the notion that life was chaotic and that whatever principles governed it were unpredictable." This prejudice stayed with him through his undergraduate years at the University of Virginia, where he excelled in the hard sciences and avoided biology as if it were basket weaving. But as a Yale Ph.D. candidate in physical chemistry, he took biochemistry, encountering for the first time DNA and RNA, the molecules that carry the code of life. "I was," he says, "completely blown away."

Increasingly restless, Collins began to wonder whether he should devote his days to arcane research that had little immediate impact on other people. So while completing his doctoral dissertation in physical chemistry, Collins enrolled in medical school at the University of North Carolina. A three-week course hooked him on medical genetics, a specialty that let him be both humanitarian and researcher.

By 1984, when Collins signed on as a junior faculty member at Michigan, he had been married for 15 years to his high school sweetheart and had two daughters, ages 14 and 10. Just as important to him, he had become a devout Christian, focusing on what had previously seemed an irrelevant corner of life. While living in the campus town of Ann Arbor, Collins and his wife helped start a Baptist church. The congregation -- and his marriage -- has since dissolved, but his faith, which he describes as basically nondenominational, endures.

The search for spiritual fulfillment has led Collins in unexpected directions. Twice, in the company of his daughter Margaret, a medical student, he has traveled to Nigeria to treat patients in a small missionary hospital. The first time, he and his colleagues were closing in on the cystic-fibrosis gene, and yet at that critical moment Collins risked leaving his laboratory. Once in Nigeria, he agonized over whether his presence there made any difference at all. Then a farmer appeared, suffering signs of imminent heart failure. Collins dared a procedure he had never tried before, plunging a needle deep into the man's chest to draw off the fluid that was apparently pressing on the heart. "Dr. Collins," the patient said later after recovering, "I know you're wondering why you are here. I believe you were sent here just for me, because without you I would have died."

Medicine, science and religion -- in Francis Collins these disparate worlds daily connect and sometimes collide. Personally Collins is distressed by abortion, a common outcome of prenatal screening for genetic defects. Yet as a geneticist he honors a code of professional ethics that demands he hide from patients his own feelings of right and wrong. As the discoveries of disease genes move from the lethal maladies of early childhood to the lingering ailments of advanced adulthood, Collins confesses an increasing level of personal discomfort. In talks he gives on Huntington's disease, he invariably shows a slide of the folk singer Woody Guthrie, "one of my heroes." He goes on to explain that Guthrie died of Huntington's, but he leaves unspoken the terrible questions: Was Guthrie's life not worth living? If he had been aborted, wouldn't it have been everyone's loss?

Even as Collins leads the genetic revolution, he refuses to downplay its dangers. He is worried that private genetic information will be too readily available to insurance companies and employers. He worries about telling patients they have the gene for Alzheimer's but then offering them no cure. He worries about the "slippery slope" that could lead couples to abort fetuses with merely undesirable characteristics -- obesity, for example, or the wrong sex. "The use of this technology for sex selection," Collins exclaims, "insults the reasons I went into genetics in the first place. Sex is not a disease but a trait!"

Counterbalancing Collins' deep concerns, however, is his passionate conviction that the new genetic discoveries bode more good than ill and that a reasonable society will curb abuses. "These are exciting times," he declares, "and the consequences for clinical medicine will be dramatic." Now that he has taken on the genome project, Collins can do more than imagine those consequences. He has an unparalleled opportunity to help shape them.