A Dramatic Dispatch From The Gene FrontJohn Carey
Gene Therapy and the Retooling of Human Life
By Jeff Lyon and Peter Gorner
Norton 636pp $27.50
Ever since a historic experiment in 1989, when researchers at the National Institutes of Health slipped new genes into a cancer victim, gene therapy has been not just an exciting and controversial science but a media phenomenon as well. And over the past year or so, books on this brave new world have started emerging. So far the best of the bunch is Altered Fates by Jeff Lyon and Peter Gorner, two Pulitzer Prize-winning reporters at the Chicago Tribune.
The tale that fills the first half of their tome may be familiar by now: how the irrepressible NIH scientist William French Anderson, with a supporting cast of colleagues and often-bitter rivals, turned into reality a once-scorned dream of using genes to treat people. What makes Lyon's and Gorner's account compelling is their wealth of riveting detail--and their knack for capturing the human dramas that occur as researchers and their patients venture into the unknown.
During a climactic 1990 experiment, Lyon and Gorner manage to chronicle the minute-to-minute saga as Anderson's team tries to cure Ashanthi DeSilva, a 3-year-old girl suffering from adenosine deaminase (ADA) deficiency, a severe inherited-immune deficiency. We learn how Anderson, so nervous that he has barely eaten or slept for several days, is at Ashanthi's side in the small room in NIH's blood unit while some of her white blood cells are being removed. But his attention is riveted by a video monitor playing the movie Dumbo. "It's a great movie," he says. And after the gene-altered cells are returned to Ashanthi's veins, the big-eyed child asks her father for a promised treat of M&Ms. Like a "man possessed," Raja DeSilva races to the cafeteria, a "strange, grinning dark-complected man frantically draining the vending machine of bag after bag of M&Ms."
The authors also prove adept at capturing the Machiavellian maneuverings, strong personalities, ego clashes, and stumbling steps forward that mark the real world of science. In 1988, for example, Anderson realized his immune-deficiency experiment wouldn't get the go-ahead from the key NIH oversight committee, in part because of concerns about the quality of the underlying science. So he and colleague R. Michael Blaese took a calculated detour. They roped in powerful NIH surgeon Steven Rosenberg, who was conducting clinical trials on melanoma patients. Instead of actually doing gene therapy, Anderson and Blaese proposed using genes as "markers" to track melanoma's progress in Rosenberg's patients. That wouldn't have any effect on the disease, but it could show that the gene-transfer process was safe, paving the way for the ADA experiment.
But even Rosenberg's clout failed to win the day in a pivotal June, 1988, meeting. So Anderson resorted to a last-ditch plan to shame the skeptics. "Since we began this discussion 146 minutes ago, 146 patients have died of cancer," he told the committee. The guilt trip worked.
The alliance with Rosenberg proved short-lived, however. After the marker-gene experiment went off without a hitch, Rosenberg launched his own bid to be the first to put a therapeutic gene--one that fights cancer--into a person. Anderson's team was stunned by what one member calls the "brutal competition" that resulted. When Anderson won, the authors report, Rosenberg was crushed: He "could not bring himself even to look at Anderson."
It's not yet clear whether it was an important victory for medicine. Both DeSilva and another girl with the same disease have responded well after gene therapy, developing stronger immune systems. But they are also taking a drug that may be responsible for much of the effect. Moreover, Anderson couldn't devise a way to correct forever their genetic defect. Instead, the girls need periodic infusions of gene-altered blood cells. As Lyon and Gorner conclude: "French Anderson...had ridden to glory, not on the flowing steed he had once imagined, but aboard a patchwork mount, its parts concocted to please everyone, its legs hobbled so as never to reach its destination, and its body oxbowed from the weight of the three collaborators Anderson had found it expedient to hitch up with."
Lyon and Gorner probably should have stopped there, after 294 pages of one of the best yarns in science. But they decided to add an additional 273 pages to the book, promising to "explore the ways in which gene therapy is refashioning the practice of medicine" and how it "may ultimately extend the human life span and perhaps even influence the course of human evolution."
They don't really deliver. Instead, they offer what might be dubbed the "Greatest Hits of Genetics," as the authors rehash major recent accomplishments and controversies. Although competently told, these stories aren't nearly as fresh or as vibrant as the Anderson saga. More troubling, Lyon and Gorner occasionally lose their customary critical judgment. They fail, for instance, to be properly skeptical of such claims as the anti-aging effects of human-growth hormone or the discovery of an "alcoholism gene." You can learn a lot browsing through this second part of the book. But for something special, stick to the story of French Anderson and his dream of gene therapy.