Too Slow for Cancer
Bless that reporter who cut to the chase at the press conference last month announcing the new project to map the genes of individual cancers. The Cancer Genome Atlas, said National Institutes of Health officials, will blow open the instruction book on cancer. But if this venture is so revolutionary, the reporter asked, why is its pace so agonizingly slow? For the 40 percent of Americans who will face cancer, and for nearly everybody who's been convinced we are at the dawn of a new age of gene-targeted therapies, his question couldn't be more right on.
The Atlas should be the hottest thing in genome exploration since the map of the normal human genome was completed in 2003. But insecurity about a slow-growing NIH budget and a cultural bias against big science projects have frozen a bold-footed move into a tentative tiptoe: A three-year pilot studying only two to three as-yet-to-be-determined cancers (wait until that selection process starts!) will cost the National Cancer Institute $17 million of its annual $5 billion budget and the National Human Genome Research Institute an additional $17 million. Only if the pilot reaches unnamed milestones will the Atlas be stretched into a decade-long, billion-dollar study of 50 cancers--out of over 200.
Cancer is a disease of our genes. Chemical glitches develop across our DNA strands and transform normal cells into a mass of perpetually growing ones, poised to march through the body in a deadly takeover. But these glitches have turned out to be unexpectedly numerous, complex, and variable, even across some cancers with the same look. That explains why one tumor responds to treatment and another of the same type doesn't. Or why one cancer pokes along for years and another kills in a flash. But the explanation remains hidden within the many cancer genomes and their mysterious behavior.
Because of this knowledge gap, cancer treatments are mostly scattershot with lots of collateral damage--and are often fruitless. Francis Collins, who leads the NHGRI, bemoans the darkness that envelops cancer and limits its research. He compares it to searching for keys on a dark street where there's only one lamppost. You search where there's light, and it's sheer luck if you find them. For cancer, he says, we need "a thousand lampposts to shed light on the darkness of our ignorance." The Atlas is just that. We have the means, we have the brainpower, and we have ever better and cheaper technology to get there.
And we have witnessed the power of knowing about even one or two toxic genes in a cancer cell. The designer drug Gleevec puts one form of leukemia into remission by targeting a DNA error once thought to be a result of the cancer, not its cause. The new drugs Tarceva and Iressa block the handi-work of another gene gone bad and can extend a one-year survival with lung cancer to two--but only in the 10 percent of patients with the gene. A small victory perhaps, considering we have an incomplete blueprint of what's really happening in those cells. But a victory nonetheless for the 10 percent of patients whose survival increases 100 percent. As NIH Director Elias Zerhouni says, cancer research is hamstrung from moving on a broader front because of limited genomic insight.
Undertow. Of course, there are technical issues related to sequencing thousands of tumors or sifting out the gene happenings that cause cancer from those that result from it. They are the very problems that must be solved. But we must also overcome the undertow in the medical research community (which I also witnessed as a former NIH director) that resists large, centrally directed science projects because they drain money from the smaller efforts of independent researchers following their dreams--as if they are at odds.
Talk about deja vu. In the late 1980s, that same mind-set incited bitter battles at NIH over its participation in the Human Genome Project. It was the Department of Energy, and its big science expertise, that ensured the project's future by steaming ahead until the NIH belatedly joined in. Now, with an annual budget of almost $30 billion, three times what it was back then, money as a reason to go slow on deciphering cancer genomes will be hard for the public to understand. The real issue, however, is NIH' s stated goal to eliminate suffering and death due to cancer by 2015. If the Atlas, long on time and short on money, remains underpowered, there is little chance this goal will be reached. How about four years, 20 cancers, and a billion dollars--as a start, not a pilot?
This story appears in the January 9, 2006 print edition of U.S. News & World Report.