The Wellcome Trust is to fund 67% of a two year, $45m (£30m), international project to define some 300,000 DNA sequence variations in the human genome. The remaining funds come from a consortium of ten of the world's leading pharmaceutical companies, who have also agreed to put the newly discovered information directly into a public database. What is behind this unprecedented collaboration?
The Human Genome Project, which is sequencing the entire human genome, is due to finish ahead of schedule by 2003. This recently announced consortium is concerned with the next step: defining the normal DNA sequence variations (DNA polymorphisms) between individuals. For technical reasons the project is concentrating on single nucleotide polymorphisms (SNPs), namely variation at single 'letters' of the DNA code. SNPs are thought to comprise some 90% of the meaningful human genetic diversity, with any two people differing in their DNA sequence at roughly every 1000 nucleotide bases and we each have a genome of some 3 billion base pairs. The expectation is that a proportion of these SNPs will alter the structure or amount of the protein encoded by the gene in which the SNP(s) occurs. This alteration may change the way the protein functions in the cell. This in turn could underlie the difference in people's susceptibility to common diseases, such as asthma or coronary heart disease, which arise from a complex interaction between environmental and genetic influences.
Armed with information on SNPs within and around many of the 100,000 or so human genes, it should be much easier to search for genes that are associated with particular disease susceptibilities or reactions to drugs - areas of great importance to pharmaceutical companies. However, it should be noted that SNP maps alone don't get you very far. This research needs the co-operation of representative populations of people in which their development, health and wellbeing are meticulously documented over time. And this is not all. The nature of their particular physical and social environment needs to be known, since environmental changes, in diet for example, can lower or raise the threshold for the expression of a genetic susceptibility. An SNP that is disease-related in one environment could be completely neutral in another, so comprehensive longitudinal population studies that take account of both genetic and environmental variables will be needed to really understand the role of genetic influences in common disease and the utility, if any, of predictive genetic profiling.
The pharmaceutical companies know that an SNP map is just one component, but a necessary one. They don't wish to pay SNP map access fees to genetic biotech companies, so it makes sense to join forces with the Wellcome Trust to commission the major human genome laboratories, such as the Sanger Centre in Cambridge, to produce a public SNP database. Will they be so public spirited, when it comes to the linking of clinical outcomes to specific genetic variations? Indeed the whole way in which pharmaceutical companies form commercial alliances with patient groups or populations for their genetic research needs wider debate.