HER-2
The Making of Herceptin, A Revolutionary Treatment for Breast Cancer
By Robert Bazell
Random House, 256 pages, $24.95

The New York Times Book Review
September 20, 1998

By Robin Marantz Henig

This is a troubling and fascinating book. Populated with single-minded scientists, clueless biotech company executives, and women stricken with a particularly vicious form of breast cancer — the kind that rages through a body so fiercely that it can erupt along the fault lines of a mastectomy incision before the scar even has a chance to heal – "Her-2" tells the story of how an entirely new kind of cancer therapy was shepherded to the marketplace. In the hands of veteran science journalist Robert Bazell of NBC News, that story is told, like a good TV script, clearly, simply, and dramatically.

Herceptin, the first gene-based medication for cancer, was created by Axel Ullrich of Genentech (an early entrant into the now-burgeoning field of biotech companies) and Dennis Slamon of UCLA from a new kind of scientific logic: designing a molecule that would target the gene responsible for excessive cell growth. In this case, the gene in question leads to the overproduction of a protein known as Her-2/neu, which is found in the tumors of one-quarter to one-third of breast cancer patients and accounts for their special ferocity. When the Her-2/neu compound links up with the Her-2/neu gene, it interferes with this protein-producing capability, and stops cell growth in its tracks.

Ullrich drops out of the picture early on, resigning from Genentech to teach in his native Germany, and it is Slamon who emerges as the unsung and embittered hero of the Herceptin story. A tall, intense scientist from an impoverished Appalachian background, Slamon is a man consumed by a "murderous resolve" to cure cancer in a way that "will earn him a place in the textbooks." He is, writes the author, thwarted at every turn: by executives at Genentech who basically ignored the drug for more than three years; by established academic scientists who thought his ideas about inhibiting cell growth were far-fetched; by oncologists who ultimately designed a clinical trial to test Her-2/neu’s efficacy that was so misguided that one official of Genentech, which was footing the bill, admitted that it was like sending an explorer "on a mission to Antarctica without a coat."

According to Bazell, the only people who understood and adequately supported Slamon’s vision were the folks at Revlon, who ended up donating $13 million to the Revlon/UCLA Women’s Cancer Center under Slamon’s directorship. Indeed, Revlon executives were the first people Slamon thanked when he presented the results of the Herceptin drug trial at a highly-publicized meeting of the American Society of Clinical Oncology meeting last May.

Since that announcement, Herceptin has been approved by the Food and Drug Administration for treatment of advanced breast cancer. No doubt it will also be used for women with much earlier stages of breast cancer, where it can possibly do even more good. But while the drug, because it is not a traditional anti-cancer agent, leads to none of the nausea, hair loss, or other side effects that frighten women away from chemotherapy, it does have some serious drawbacks of its own. Herceptin seems to be associated with a higher-than-expected rate of progressive weakening of the heart muscle, and with a high rate of metastases of stray breast cancer cells to the one spot in the body that Herceptin cannot penetrate – the brain.

The human faces of the women waiting in the wings for Herceptin to come to market, and of those who joined the early clinical trials to help bring it there, are what give "Her-2" its particular sting. So many of them are young, with growing children, filled with spirit and feistiness – but nothing in their generally lucky lives quite prepares them for this final horrific battle. It is a battle many of them will lose, like Marti Nelson and Ricki Dienst, who had the misfortune of developing fulminant breast cancer in the late 1980s, after her-2/neu was discovered but before it was generally available. Not until two days after Dienst died, in August 1995, did Genentech announce plans to distribute Herceptin to morbidly ill women through what is called a "compassionate-access program" – too late for these two young women, but in time for more than 300 others.

Bazell is tackling a huge assignment in a relatively short book: the science of oncogenes and cancer immunology, the politics of drug development, the mismanagement of Genentech, the psychology of placebo control trials, and many other complicated issues. He sometimes seems to be rushing through it all, maybe to get the book out at the most propitious time. (Herceptin is expected to reach the marketplace this fall, just as "Her-2" hits the shelves and Bazell takes off on a nine-city media tour.) But better that he be overambitious and pique the reader’s interest than that he shy away from some rather bold pronouncements just because he cannot take the time to flesh them out. The final impression left by "Her-2," complete with its tantalizing suggestions of richer stories still untold, is that maybe we really are on the threshold of a new way of understanding and treating one of our most dreaded diseases.

bio/resume/latest book/other books/essays/magazines/home page