Scenes from Sequestration Nation

Is the sequestration leading to a 'dark age' of science in the US?

Full-text access for registered users only. Existing users login here.
New to GenomeWeb? Register here quickly for free access.

This reply is lifted verbatim

This reply is lifted verbatim from my commentary on LinkedIn on this article. The referrer, Bernard Siegel, a respected advocate for stem cell research, is mentioned by name.

It is a fact of life that public support of scientific research depends strongly on advocates such as yourself and politicians such as Mr. Reid and President Obama. It is equally a fact of life that the direction and objectives of that research are defined by the source of that support – the halls of congress and the oval office. Virtually from its inception and certainly from the explosive growth initiated under President Nixon, the mandate of the NIH has been directed to an investigation of disease – a statement not to be equated to an understanding of biology. More recently, the NIH has moved even further toward active participation in drug development and a great deal of its energies and funds are already “targeting cures.” In doing so, its range of scientific support has actually diminished. When, for example, the NIH budget was doubled under President Bush (the latter), the number of supported projects only increased 30%. Given that many of those 30% were awarded to existing grant holders, the two-fold budget increase actually opened few new avenues of research (The NIH has long since abandoned serious support for efforts such as those cited in the dramatic Huffington Post article). The real question though is, does this “directed,” “applied,” or “translational” approach to research work? Convincing evidence says, “NO.”

“Translational” research must pass several stink tests: 1. Data must be reproducible, 2. underlying principles must be valid, and 3. the outcomes must be viable products or services. Publications as diverse as the Wall Street Journal, Boston Globe, Nature and Science have reported on the sorry state of data reproducibility. As early as 2010 the WSJ reported pharma industry findings from both Bayer and Amgen that 66-89% of university reports (our best universities published in our most prestigious journals) on drug target identification could not be repeated. Universities in Texas now also report that published results can be reproduced only half the time. Other voices such as those of John Ioannidis provide even more sobering conclusions: “Hypothesis-driven” research results are likely to be false at rates as high as 80%. Bernard, to me this says that if we pre-specify an outcome – i.e. a known “right” answer exists – we WILL see that outcome. Stink test one appears to have failed – data are not reproducible. Are the underlying principles valid?

Recent findings (dating from mid-2012) indicate that, at least for genomics-driven identification of disease-related mutants, the answer is again, “NO.” A report largely out of the Broad Institute demonstrates that upwards of 98% of gene mutants identified as cancer-related are wrong, not for the reasons cited above but because the identification is not consistent with underlying principles. Perhaps even more fundamental, this month’s Science recaps reports that our personal genome varies from tissue to tissue and as a function of age. These findings, among other considerations, raise the question of, “What’s normal?” when we search for mutations. Stink test two also appears to fail. Have viable products or services been created?

In the only arena for which data exist the answer is also, “NO.” Development of new drugs has been almost wholly given over to a model highly dependent on gene-mutant identification of drug targets. As a result, pharma R&D effectiveness has fallen to a few percent of its value decades ago. Based on the information already provided here, that outcome is readily understood – the targets pursued were phantoms. Realize that the price tag is enormous – hundreds of billions of dollars and countless missed opportunities spent while chasing ghosts. This same errant path is now dominant in both privately and publicly supported efforts in pursuit of personalized medicine and new diagnostics.

The NIH response to these fundamental problems has been muted, to say the least. Reports in last week’s Nature speak to a profound disconnect. There are no apparent plans on the drawing board to address reproducibility per se and the lack of scientific validity is not addressed at all. I would urge advocates such as you and champions such as Mr. Reid and President Obama to tie a more disciplined and accountable behavior to any increase or renewal of NIH funding. And reissue a warning: defining an outcome virtually insures that you’ll get that outcome – and it will be wrong.

What a ridiculaous, drama

What a ridiculaous, drama queen thing to say.

I think an important point to

I think an important point to stress is that basic research is an extremely difficult enterprise. Consequently, it should not be surprising that it is high risk and a high error rate. However, many discoveries will nevertheless be reproduced and validated. This is how knowledge is advanced and Science is the best tool we have for understanding how things work. Instead of emphasizing the failure rate we should talk about the success rate. From the discovery of insulin as a treatment for IDDM, to the discovery of blood stem cells and their use in BMT, to the discovery of cell signaling mechanisms leading to drugs like Gleevec, to the human genome project and personalized medicine (and many many many more discoveries), the practice of medicine has truly been revolutionized during our lifetime. Without strong and unequivocal support for basic research, none of this would of happened. I am afraid we are indeed heading to a dark age where discovery, new knowledge, constant innovation and advancing technology are no longer priorities for western civilization.

One of the dangerous

One of the dangerous consequences of the sequestration situation is that there is a much more dramatic decline in the purchases of goods and services from vendors from academic laboratories that are grant funded. Even a 5% cut in grant funding means that much less money is available for the purchase of consumables, equipment and outside services that are necessary to support academic research programs. This is because the salary component of grants are usually fixed costs and can represent 75% or more of the total grant expenditures (i.e. a 5% cut for an academic lab could mean closer to a 20% cut in their outside spending). This is ultimately very problematic for academic research too, because if vendors of scientific products and services become unsustainable as businesses, they can no longer produce innovative and quality products and services that are necessary to advance biomedical research. The situation for North American and European companies is even further compounded by the growing trend of pharmaceutical research to be outsourced to Asia.

In response to Ray Perkins' points, I am inclined to agree that there has been an over-emphasis on supporting genomics research with the notion that the identification of mutations in genes will permit much improved diagnoses and treatments of diseases. The vast majority of diseases, outside of cancer, arise more from environmental factors than underlying genetics. As a consequence, other often more promising and translational directions have withered from lack of grant support long before sequestration became a reality.

If only unsuccessful authors

If only unsuccessful authors of NIH proposal are interviewed, it seems like this article could have been written any year during the last 15 years with exactly the same tone.

Where are the numbers of where the money is actually being spent? Does the 100M brain mapping pull from other programs? Isn't the 29B funding the most important research, based on oversight from a panel of experts? How was the money distributed in 2012 compared to 1992? I agree science is relatively underfunded - in a big way. But by the articles own numbers, a year-to-year flat funding is not bad in a time austerity and political gridlock.

It's ironic that this article (like others) 'defend' science by simply stirring emotions and instilling fear with little data. I would think that the main audience of GenomeWeb would be expecting a much higher standard of reporting such that it wouldn't bear repeating the emotions of the lay press.