By Rick Weiss
Washington Post Staff Writer
Wednesday, December 14, 2005
Federal health officials yesterday launched the biggest genetic research endeavor since the landmark human genome project: an ambitious effort to categorize all of the hundreds of molecular glitches that turn normal healthy cells into cancers.
The Cancer Genome Atlas, whose total cost could reach $1 billion or more, will for the first time direct the full force of today's sophisticated genetic technologies to the thorough understanding of a single disease -- one that will eventually strike nearly half of all Americans alive.
Leaders of the National Institutes of Health, which will administer the project through grants and contracts, predicted it would revolutionize the diagnosis, treatment and prevention of cancer, which will kill 564,000 Americans this year.
"This is really the beginning of a new era," NIH Director Elias A. Zerhouni said at a news conference in Washington, flanked by researchers, doctors and patient advocates.
Although the lofty rhetoric echoed that of Richard Nixon's now-disparaged call for a war on cancer almost 35 years ago, Zerhouni and others emphasized that scientists have learned crucial lessons totally unknown at that time. Most centrally, it is now known that cancer is a genetic disease, caused by errors in a cell's DNA that can be identified and targeted with molecular medicines.
By identifying the full spectrum of genetic errors that allow cancer cells to divide recklessly, spread and take root throughout the body, doctors hope to be able to classify every cancer -- not by today's crude measures of where it forms and how fast it is growing, but according to hidden molecular hallmarks that can tell which drugs will work and which ones will not.
"The planets have aligned to tackle cancer in a comprehensive way that we've never had the tools to do before," said Francis S. Collins, director of the NIH's National Human Genome Research Institute. That institute and the National Cancer Institute will provide $100 million for a three-year pilot project to test the project's feasibility.
A genetic map of everything that makes a cancer cell cancerous could speed the development of drugs that specifically target tumor cells' Achilles' heel. It could also lead to molecular imaging tools able to detect tumors when they are young, and provide clues about how to prevent them in the first place.
"The future will look no more like the past than a butterfly resembles a caterpillar," said NCI Director Andrew von Eschenbach, adding that he sees cancer devolving soon from a killer to a "chronic, manageable condition."
The Cancer Genome Atlas is the outgrowth of a year and a half of planning by NIH advisory groups. It would build on the emerging recognition that cancer is a collection of diseases that have rampant overgrowth in common but disparate genetic roots.
Some cancers are caused by a mutation in a single gene that normally keeps a cell from making offspring. Others are caused by the mistaken duplication of a gene that promotes normal cell division, boosting its reproductive capacity to abnormal levels.
In other cases, entire pieces of chromosomes -- long, gene-bearing strands of DNA inside cells -- break off and reattach to other chromosomes, inducing spurious and unregulated growth signals.
Still other cancers result when rogue molecules attach themselves to genes whose job is to control cell division. Such "epigenetic" changes are invisible on standard tests that look for mutated genes because the genes themselves are healthy but are being manhandled by the other molecules.
The Cancer Genome Atlas faces formidable challenges, not least of which will be collecting hundreds or thousands of tumor specimens -- each of which must be properly preserved, freely donated for research by patients who have been informed of the project's goals and accompanied by detailed clinical information such as the tumor's response to various drugs.
Then will come the tedious work of analyzing all the relevant genetic traits of those cells and correlating those details to the cancer's clinical characteristics. Collins likened that undertaking to "thousands of human genome projects," a reference to the $2 billion effort, completed in 2003, to learn the order of all 3 billion letters of genetic code that go into making and maintaining a human being.
Collins emphasized that gene research costs have dropped considerably in recent years and expressed hope that an initial "back-of-the-envelope" estimate of $1.5 billion for the cancer atlas will prove high.
As the atlas gets filled, its contents are to be placed on a computer database freely accessible to researchers, doctors, patients and the public.
Not everyone supports the effort. In letters to scientific journals and in other venues, some scientists have complained that now is not the time for such an effort, given the already pinched federal research budget. Others have suggested that the approach is bound to fail on scientific grounds.
Garth Anderson, a cancer geneticist at Roswell Park Cancer Institute in Buffalo, said that because cancers are by definition genetically unstable, even a single tumor has cells with different mutations, many of which played no role in its emergence. And while a few new molecularly targeted drugs have worked against cancers where other drugs have failed, he said, even those drugs typically buy patients just a few months before the tumor finds a way around the medicine.
"If it's going to cost me $100,000 to add 45 days of life, I'd rather drop dead and give my kids the money," said Anderson, who added that he puts more faith in better tumor imaging and old-fashioned surgery.
But Bruce Stillman, president of the Cold Spring Harbor Laboratory in New York and one of several experts who advised NCI on the proposal, disagreed.
"It would be ridiculous to say at this time, 'Okay, we finished the genome. Let's not do anything with it.' To say we shouldn't be doing this is to say we're not interested in solving cancer."