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Future Shock or Future Letdown?
In the November 17 edition in the Science and Technology section, Wade wrote: "The company's demise suggests that the medical promise of the human genome may take much longer to be fulfilled than its sponsors had hoped." But there may be more to the story. "The discovery that major diseases do not have any simple genetic pattern of causation has dealt a serious setback to the gene-hunting field as a whole," he added.
Signs of the deflation of the field of "gene hunting" over the past 10 years since the Human Genome Project was completed and the second phase of the HGP was announced as focusing on the "conquest" of disease are:
- Discovery that genes are not found in continuous sequences or segments or even on the same chromosome.
- Realization no DNA can be considered "junk DNA" and even "non-coding" loci have at least place-holder functions and hence their values are not neutral.
- Greater respect for the role of environment in inheritance, including the nano-environments within the cell where DNA is stored and replicates.
- Jumping the gun on numerous claims concerning genome-wide association studies in scientific journals like Nature and Science, and subsequent retractions by editors and authors.
- Ever increasing sample sizes with ever increasing lack of robustness for the data and clarity for conclusions.
- A push for extending genetic surveys to rare and under-represented populations, with few surprises in the analysis of the implications for medical research or consequent benefit for public health.
- Diminishing returns on research investment (ROI) on nearly every front.
- Not a single viable gene therapy product ever introduced.
- Realization that only very rare genes are discoverable and selection usually takes care of them and extinguishes them over time; hence the bulk of medical research funds goes toward the rarest of cases and not widespread disease such as cancer or diabetes.
Harvard biology professor Richard Lewontin maintained as long ago as the 1960s, and continued to warn even on the eve of the completion of HGP I in 2000, that gene hunting was essentially a scientific fetish with little true power or efficacy. In 1992, he wrote "The Dream of the Human Genome" as a review article in response to The Code of Codes: Scientific and Social Issues in the Human Genome Project, edited by Daniel J. Kevles and Leroy Hood, and seven other recently published books on the subject of genetics and medicine. The essay was reprinted in Lewontin's own book It Ain't Necessarily So (second edition, New York Review, 2001).
I think it is time to elevate gene hunting to the danger of something beyond a harmless fetish for the members of a narrow profession or scientific sect. Its waste and failures have taken on the proportions of a national form of folly and collective denial. While huge expense and sensational efforts continue to be thrown away on the molecular biology revolution, the need to renovate our neglected infrastructure and reform political mechanisms goes unanswered. Resources that might be better allocated keep dwindling. The supposedly most advanced society in history turns a blind eye on such relatively easy measures of public health as universal health care and uncontaminated chemical-free food and water supplies. While geneticists continue to cackle about inch-sized strides in their progress toward scaling the distant peaks of genetic medicine we are slipping into the abyss of logical disconnects.
Comments
The area of personalized genomics for health intervention has not really panned out. For example, the BRCA 1 and BRCA2 genes were hailed with great fanfare a few years ago as causal agents of breast cancer. But the true percentage of BRCA 1 and 2 mutations contributing to breast cancer are between 5 and 10%, leaving an astounding 90-95% of breast cancer due to other environmental factors. It is those factors that bear looking into, not the "faulty" genes. The available personalized SNP (single nucleotide polymorphism) panels that are available today for use without a physicians input, are leading people into unproven territory as the true associations between these SNPs and the disease they purport to contribute , is not supported by science.