This article has been corrected from an earlier version, which incorrectly reported the manufacturer of a Gaucher's disease drug.
COLD SPRING HARBOR, NY, May 29 -- NHGRI director Francis Collins called for academic scientists to focus on chemical genomics, in discussing the future priorities for genome research at the 68th Cold Spring Harbor Symposium on quantitative biology today. "The time may be right for a chemical genomics initiative to get underway," Collins said.
This initiative would be of a much larger scope than current nonprofit efforts to characterize the interaction of small molecules and gene-based drug targets, he said. While most current efforts to study small molecules and the genome are taking place behind the walls of big pharma and big biotech, Collins said it is time for academic labs to go further downstream, and focus on developing high-throughput screening and other assays to validate small molecule targets.
"Am I talking about turning academic labs into drug developers?" he asked the audience, which was probably wondering as much. "No." This effort, Collins said, would not be limited to the small number of targets in the so-called druggable genome, such as kinases and GPCRs, but would cast a wide net to examine the interaction of hundreds of thousands of small molecules with other regions of the genome. In this way, it would not be hamstrung by the drug-discovery imperatives that big pharma researchers must abide.
Additionally, Collins said, academic efforts in chemical genomics could focus on study of targets for treatment of rare diseases. While pharma, other than the occasional exception such as Genzyme with Gaucher's disease, has traditionally turned its guns on common diseases, a biotech or phama company might be more likely to develop a potential treatment for a rare disease when academics have completed "the first few steps" of discovery and validation, according to Collins.
This chemical genomics initiative would involve a large computational aspect, in which researchers would compile a mega-database of as many as half a million small molecules, and would make that database freely accessible the way GenBank is.
The actual machinery for conducting the wet lab work, Collins acknowledged, is quite expensive, but the problem could be adressed similar to that of sequencing and functional genomics, with facilities concentrated in core labs at large research centers.
This chemical genomics initiative is part of the vision for the future of genomics research that Collins and his NHGRI colleagues outlined in an April 24 Nature paper. They sketched out the vision as a Frank Lloyd Wright-style house, with the Human Genome Project as the foundation, and three horizontal levels, transected by vertical chimneys. The horizontal levels include Genomics to Biology, Genomics to Health, and Genomics to Society. The chimneys that slice through this infrastructure and jut out the top include technology development, resources, computational biology, training, education, and ethical, legal, and social issues. In his talk, Collins also mentioned the International HapMap project, in which researchers from the US, China, Japan, Canada, and the UK are looking to define common haplotypes for the human species based on 270 DNA samples from four populations: European, Japanese, Chinese, and West African (Yoruban.)
An audience member questioned Collins as to why only one African population is being included in the project, given the enormous diversity of peoples within that continent. "We need to start somewhere," Collins answered. The HapMap project aims to find haplotypes that would be common to the entire human race, "and it may be sufficient that the haplotypes generated from these groups will be usable anywhere," he said. Collins also noted that there is a pilot project underway to collect DNA samples from populations in East Africa, South Africa, and elsewhere in case the populations currently under study by the HapMap project do not sufficiently characterize those of the entire species.
Commenting on another controversial topic -- the question of how applicable the fruits of the human genome project are to the health challenges of the developing world -- Collins emphasized that these applications must be explored in the next phase of human genome research. He did not provide any details of this type of study, but, in a comment that approached the boundaries of his usually mild-mannered, apolitical persona, he added, "we should not only think of ourselves as soldiers to the world, but also as physicians and scientists to the world." (Several researchers clapped.) After Collins' talk, a crowd of hungry disciples from academia and big pharma alike gathered around him to discuss his proposal on chemical genomics.