Radio Freethinker

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The Academic Scenic Route

Posted by Jenna Capyk on July 26, 2011

If I’ve learned anything in my four years squeezing pipets in a research lab it’s that science costs money. Lots and lots of money. Although some money is doled out for some interesting studies with questionable applications (i.e. does tequila make fish more aggressive than vodka…) a lot of money is pumped into scientific efforts aimed at coming up with new medications to treat human disease.

There are two main basic approaches you can take when doing drug discovery research: target-based or phenotypic screening. In the first, you identify a target, which can be a component of a human cell or a bacterial cell or viral component, and then you try to rationally discover compounds effecting that target. The second approach, phenotypic screening, is a more shotgun approach in which you take the process you’re looking at and throw a bunch of compounds at it (either from an estabilished library or a bunch of “natural products” from a natural source) and basically see what sticks. That is you determine what compounds effect the process you’re looking at. In the target based approach you know what physiological mechanism you’re looking to have an effect on, whereas with screening you know the effect but might have to go looking for the mechanism. Both of these approaches make sense on paper, but which one tends to have the better outcome for drug development?

A piece in Nature Reviews: Drug Discovery titled, “How were new medicines discovered?” (Swinney and Anthony, 2011) went back over the literature and examined new drugs brought to market over the last ten years. They found that for new classes of small-molecule drugs almost twice as many were derived from screening approaches than from target based approaches. Strikingly, this is during a period that drug development efforts and associated funding has been dominated by target-based research. So although most people are concentrated on target-based research, this approach is yielding fewer viable results.

These kinds of papers bring up a lot of issues for me because they hint at the (sometimes conflicting) motivations in scientific research. The public wants science it can use, in this case, functional drugs. The public funding agencies tend to want the same things as the public wants because that’s what keeps the money coming in (and not diverted exclusively to building tanks). Some scientists want functional drugs because they can/it’s good for society/they like developing stuff/etc. There are lots of scientists, however, who are essentially curious human beings and want to study interesting stuff. In an immediate sense, target-based research is better for this last scientific motivation, because it involves directly studying the target. Scientists get to approach an area of interest not only in the context of possible drugs, but in all kinds of other ways as well. This method allows for intentional investigation of the natural world in a broader context than drug discovery. Screening also lead to many basic-science discoveries, as knowing a compound that effects a process often leads scientists to find out how it effects that process and leads to understanding of the process itself. This phenotypic screening approach is, however, much more drug-centric, no matter which way you slice it.

This paper points out that what many scientists want to do isn’t actually in line with producing the outcomes that the greater public want to see. This is, in my personal opinion, the not-so-dirty dirty little secret of medical research science: its not all about improving human health, but also about general exploration of life science. As as research scientist who truly values gathering knowledge in any field, I for one hope this secret doesn’t get out too widely; I’m frankly dubious about how happy the public would be to fund basic research without an immediate societal benefit, especially if they could see the price tag…

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