Ten years after the first survey of the human genome, the project's payoff is getting mixed reviews. Francis Collins, former head of the National Human Genome Research Institute, praises the wealth of genetic data produced. J. Craig Venter, who led the private sequencing push, and Robert Weinberg, who discovered the first human cancer-causing gene, said information gained from genomic research doesn't justify the cost. Their views were published last week in editorials in the journal Nature.
Genome projects, mostly designed to generate data, are taking funds from those that are designed to test ideas about the cause of cancer and its treatment, Weinberg said. It's unclear whether the onslaught of genetic data has helped illuminate the biology underlying cancers or just added more complexity, Weinberg said.
"There has not been an adequate critical examination of how useful some of these massive data-generating projects and technologies are," Weinberg said. "The question is how much bang we've gotten for the buck, and from certain perspectives it's been modest."
Citing advances in molecular and cellular biology, immunology and neurobiology, Weinberg argued in his editorial that hypothesis-driven science — the process of coming up with a theory and testing it experimnetally ---- has served scientists well over the past half-century.
Genomic data has yet to yield "major breakthroughs" in our understanding of how a tumor develops or how many mutations are needed to cause one, said Weinberg, co-founder of the Whitehead Institute for Biomedical Research in Cambridge, Mass.
"These projects consume an enormous amount of resources and researchers' energy," said Weinberg.
"The repercussions of major agencies shifting their funding allocations will be felt for a generation."
The National Human Genome Research Institute in Bethesda, Md., receives about $500 million in annual funding, according to public records.
For companies like San Diego-based Illumina and Life Technologies in Carlsbad, deciphering a person's full genetic code takes about a day and costs $4,500 to $10,000.
Venter said he is impressed by the rapid improvements in sequencing tools, though feels that the technology is outpacing scientists' ability to interpret the data for the benefit of patients, he said.
"Spending lots of money to generate huge data sets without any real effort to getting to new knowledge or understanding has been a huge frustration," Venter said.
"It's now easy with the new technology to generate a lot of different data, but there are very few groups or scientists generating knowledge out of this data. We're at a frighteningly unsophisticated level of genome interpretation."
As the current head of the National Institutes of Health, Francis Collins, who stood alongside then-president Bill Clinton in 2000 to announce the first draft of the human genome, is in a position to influence funding. In his editorial, he praises ambitious ventures like the Cancer Genome Atlas, which is analyzing tumors and blood samples from 20 types of cancer.
"As the cost falls and evidence grows, there will be increasing merit in obtaining complete-genome sequences for each of us," he wrote.
Todd Golub, director of the cancer research program at the Broad Institute of MIT and Harvard in Cambridge, Mass., disagrees with Weinberg. "This large-scale, data-harvesting approach to biological research has significant advantages over conventional, experimental methods," he said in a separate Nature editorial.
Genome-based screening technologies are "providing a powerful new source of leads" about how cancer develops, he wrote.
He offered the example of Novartis's Gleevec, now the standard treatment for chronic myeloid leukemia. The key discovery about what drives this form of cancer came from comparing the genomes of tumor cells to normal cells, he said.
Another genome-driven triumph, according to Golub, was the discovery of a new class of drugs for treating skin cancer. In 2002, DNA sequencing revealed that melanoma patients have frequent mutations in the BRAF gene. It was a "smoking gun," but prior to that discovery, there had been no reason to suspect it, Golub said. Now Basel, Switzerland-based Roche and Berkeley-based Plexxikon have developed a BRAF-inhibiting drug that is in the last stage of testing needed for U.S. approval.
These successes "didn't come from our deep dissection of cancer biology pathways," Golub said. "They came from unbiased surveys of the cancer genome. If you let the genetics speak for themselves, that gives you a very direct path to drug discovery."
Of course many challenges lie ahead. Eventually genomic analysis will reveal the complete set of genetic abnormalities involved in cancer.
"That's a great place to start, but to really have impact, we need to be able to manipulate those abnormal mechanisms," Golub said. "At the moment, the conventional drug-discovery approach is not fully up to the task."
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