Risky Business, or Is It?
[dropcap]B[/dropcap]iologist Marston Bates once described research as “the process of going up alleys to see if they are blind.” Bates was referring to the inherent uncertainty in predicting and managing the scientific process. Research funding, particularly for fundamental science, can be a seemingly risky investment because of the uncertainty of a study’s impact. However, it is imperative that fundamental science is not viewed as a luxury, but as a necessary investment that has the potential to yield significant returns.
Fundamental research often yields unexpected benefits. Historically, many unintended technological breakthroughs have resulted from fundamental discoveries. In fact, many readers may have found Knowing Neurons through one such innovation, Google. The universal search engine started out as a National Science Foundation research grant for digital libraries. Yet because the applications of fundamental research are frequently delayed from the time of initial discovery, discoveries and their importance are often overlooked.
For example, Veteran’s Affairs funded John Eng to study the poisonous venom of the Gila monster lizard which led to the isolation of Exendin-4 compound. Exendin-4 stimulates pancreatic insulin-producing cells, in turn increasing insulin production and allowing for blood sugar maintenance. Useful for diabetics with poor blood sugar regulation, Exendin-4 lowers blood sugar levels only when blood sugar is excessively high. More than a decade after Eng’s initial discovery, Exendin-4 became the main, active ingredient in Byetta, a now prominent diabetes medication.
The discovery of Thermus aquaticus bacteria in Yellowstone’s thermal hot springs is another example of a surprisingly useful fundamental research discovery. Although Thomas Brock’s National Science Foundation-funded research originally sought to understand how microbes survived in the extremely hot environments of Yellowstone’s hot springs, his work resulted in the isolation of the enzyme, Taq polymerase. Kary Mullis later revolutionized molecular biology by utilizing the Taq polymerase enzyme, the heat-resistant agent necessary for rapidly copying DNA through polymerase chain reaction (PCR). An indispensable tool, PCR is critical for wide ranging applications from the analysis of trace evidence (e.g., a sample from a crime scene or archaeological site) to testing for a disease or identifying a gene.
“In fact, seemingly obscure fundamental research has a history of disparagement.”
My National Institutes of Health-funded research also exemplifies how unanticipated and potentially high impact findings can result from investigating fundamental biological questions. Initially, the laboratory intended to evaluate how a rat’s brain activity evoked by tactile (or touch) stimulation was affected by blocking blood flow to the primary somatosensory cortex, a brain region processing tactile sensation. The blood flow blockage in the rat’s cortex induces brain damage and models a common kind of stroke. During our studies, we found that whisker (tactile) stimulation delivered soon after a blood flow blockage augmented blood flow return through neighboring blood vessels, which in turn protected the brain from stroke damage.
Even during the blockage of a major blood vessel, blood flows freely through its neighbors, partially compensating for the shortage of blood flow in the region. Therapeutics can effectively target neighboring blood vessels and increase their ability to compensate for blood flow deficits, protecting the brain by providing brain cells with necessary nutrients from the blood. The amount of protection depends on when the blood returns and the severity of the original blood flow blockage. Although the studies’ original questions addressed how the brain responded to tactile stimulation during blood flow shortage, the research resulted in a new and potentially transformative direction for applied research by indicating that tactile stimulation may be a therapeutic that reverses blood flow deficiencies.
Studies about lizards, hot springs, whiskers, and other esoteric subjects can be easily dismissed as frivolous investments, especially because their success requires long-term funding. In fact, seemingly obscure fundamental research has a history of disparagement. During the 1970s and ’80s, Senator William Proxmire commonly mocked federally-funded studies like these as wasteful federal spending by awarding them his tongue-in-cheek Golden Fleece Award. In rebuttal to Senator Proxmire, Representative Jim Cooper later sought to reverse the perception of obscure research by creating the Golden Goose Award to highlight fundamental studies that unexpectedly yielded significant human benefits. The teams of John Eng and Thomas Brock received Golden Goose Awards because their works exemplified the high potential impact of fundamental science while also demonstrating the nonlinearity of the scientific process: small investments can have huge returns.
Although Representative Cooper and many other policymakers appreciate the tremendous potential of science, fundamental research continues to be criticized as its funding is at stake. For fundamental science to be increasingly valued and prioritized in public spending, awareness of the complexities and long-term nature of the scientific process is needed through more efforts to reach the public, such as the Golden Goose Award.
Dialog between scientists and the community, including policymakers, is critical for future investment in fundamental science and ultimately the dividends it yields. Seemingly impractical experiments may also be the most transformative and provide the foundation for future innovations. Look beyond expected returns; don’t discount weird science.
Image by Jooyeun Lee
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References:
Brock, T.D. (1997). The value of basic research: The discovery of Thermus aquaticus and Other Extreme Thermophiles. Genetics, 146: 1207:1210.
Herper, M. (2003). Amylin’s Gila Monster Of A Diabetes Drug. Forbes.
Lay, C., Davis, M., Chen-Bee, C., and Frostig, R.D. (2011). Mild sensory stimulation reestablishes cortical function during the acute phase of ischemia. Journal of Neuroscience, 31(32):11495–11504.
Shuaib, A., Butcher, K., Mohammad, A.A., Saqqur, M., and Liebeskind, D.S. (2011). Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target. The Lancet Neurology 10, 909-921.
