Hunting Big Game: Cancer Genes


The Story of the Men and Women Unlocking the Secrets of Our Deadliest Illness

By Michael Waldholz

Simon & Schuster 318pp $24

Despite its title, this book isn't about curing cancer. It is true, as author and Wall Street Journal reporter Michael Waldholz writes, that remarkable recent discoveries about the genetic roots of tumors and malignancies have finally put researchers "on the trail of crucial clues that may make it possible to conquer cancer." But the path from gene discovery to breakthrough treatment is so tortuous and uncertain that conquest remains a distant hope. In fact, a key theme in the book is just how painfully useless the new knowledge can be. Recent discoveries mean "we can identify people at risk before their cancer arises," Johns Hopkins University geneticist Neil Holtzman laments at one point. "But we can do damn little for them."

The hyped title is just one of several flaws in an otherwise engrossing book that chronicles the explosion of discoveries about the genetic causes of cancer. Perhaps the most egregious mistake comes during Waldholz' account of the search for the breast-cancer gene. "One in eight American women will develop breast cancer," he warns, "making it the second-largest annual cause of death among American women after lung cancer." He's wrong on both counts. National Cancer Institute statistics show that even by age 65, 1 in 17 women (a much less scary number) will develop breast cancer. Only those who manage to live past age 85 have a risk of 1 in 8. Moreover, breast cancer may be the second-leading cause of cancer deaths each year, but the 44,000 breast-cancer deaths each year pale before the 250,000 women who die of heart disease.

The flaws in Curing Cancer are especially unfortunate, because Waldholz is mining a rich lode. As he points out, "many...scientists have come to believe there is no more dramatic, exciting, or important story in medicine than the hunt for the human genes...that underlie cancer." What's more, this search is also "a compelling human saga involving a handful of dedicated scientists." In captivating detail, Waldholz tells how sleuths nabbed the faulty genes that lead to melanoma, colon cancer, breast cancer, and other tumors--and describes what the discoveries mean for some of the families that inherited these curses.

Many of these stories have already been extensively reported. But Waldholz makes important contributions. One is to illuminate the key roles played by previously obscure scientists. For instance, famous Johns Hopkins gene-hunter Bert Vogelstein would not have been able to collar important colon cancer genes without Jane Green, a geneticist in St. John's, Newfoundland. Green traced families who inherited the disease. Their DNA was vital to finding the gene. "Jane and the others deserve as much credit as we get," Vogelstein tells Waldholz.

Of course, the fiercely competitive Vogelstein always made sure he also got plenty of credit for himself. Indeed, Waldholz' stories remind us how science is just as much a race for fame, prestige, and research grants as it is for knowledge. At one point in the battle to nab a gene implicated in colon and other cancers, for instance, Vogelstein learned that Richard Kolodner of Boston's Dana Farber Cancer Institute and Richard Fishel of the University of Vermont had the gene in hand. To prove that mutations in the gene actually caused cancer, however, Kolodner and Fishel needed to test people who had inherited the disease. But Vogelstein was already working with Green and other scientists who were studying all the known families. Recalls Fishel: "Bert had 'em all locked up."

Then, after Kolodner and Fishel did manage to beat Vogelstein to the punch by submitting a scientific paper to a journal, Vogelstein tried to persuade them to publish their paper together with his in the same issue. Kolodner declined. Then, Vogelstein persuaded the journal editor to release his paper to the press at the same time as Kolodner's, even though Vogelstein's was scheduled to run two weeks later. The result: The more famous Vogelstein grabbed the lion's share of the headlines.

That's only one of Curing Cancer's eyebrow-raising yarns. The book describes collaborators who won't share techniques, rivals who spy on each other at meetings, and scientists who seem to think of cancer-stricken families as faceless sources of DNA rather than real people. But I wish Waldholz had tried to explore both the ethics of such behavior and whether it's really the best use of taxpayer dollars to fund many labs doing the same work as they race to snare the same genetic prizes.

Still, Waldholz doesn't shy away from all the ethical questions. He asks, for instance, what the discovery of the breast-cancer gene means for today's medicine. Executives at Myriad Genetics Inc., the Salt Lake City biotech company that discovered the gene, argue that a diagnostic test they are now selling is useful. Women who inherit the deadly mutated version of the gene can stave off breast and ovarian cancer by having those organs removed, Myriad officials argue. Yet such radical surgery may not always be necessary: Not all women with the gene get breast cancer, and only 40% to 45% get ovarian cancer. Moreover, Waldholz points out, there's no guarantee that surgery will keep cancer from developing. "It's a terrible spot, to be have a high probability of developing disease, and not be given any other medical advice," says University of California at San Diego geneticist Michael Kaback.

It's an agonizing dilemma. And like others posed by the gene hunters' successes, it will be resolved only when scientists finally catch up to the title of Waldholz' book, turning today's gene discoveries into tomorrow's cures.

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