Type A problems

Here is something I have been ruminating over for quite some time. It relates to the pitfalls of interdisciplinary research. I will talk about collaborations with biologically minded colleagues, but you might probably find analogies in other cross-settings that involve chemistry.

If you look at the diagram below, you will see squares that correspond to four intersections between “type-A” and “type-B” chemistry and biology. I will define what I mean. Inevitably, exciting advances in synthesis are associated with interesting molecular structures (I refer to synthetically oriented students). If you think about synthesis, there is no doubt that these individuals are likely to be more excited about molecules that are complex and structurally intricate. Those who study method development are more likely to be interested in reactions that enable construction of relatively sophisticated structures. Let’s call this “type A” chemistry. Biologists would have their own “type A” problems and these might correspond to some exciting new proteins or a cellular pathways. The caveat is that biologists can address many of their “type A” challenges using molecules that are completely uninteresting to our students (they are in the “type B” category). For instance, thinking about a simple amide structure will not keep synthetic chemists up at night, although there is plethora of biological probes that are built around this trivial bond (and no other chemistry is involved in their syntheses, just “Acylate your amines, baby!”). There is a good explanation for this phenomenon from the standpoint of a biologist, who is the end user of chemical synthesis here: there is little reason to employ something elaborate if simple molecules do the trick. There are many landmark advances of this kind, yet our synthetic students have way more “firepower” as a result of their training. Consequently, they have no inclination to view these advances as interesting.

Conversely, there might be some complex and structurally interesting chemistry (“type A” chemistry) out there being applied to biological problems that are not exciting to biologists (“type B” biology). Typically, these proof of concept studies serve to highlight the perceived value of synthesis, yet they do not advance biology far enough.

I am not going to talk about the marriage of “type B” chemistry and “type B” biology because it is not interesting.

So herein we have a problem: an ideal scenario would combine exciting chemistry with exciting biology, but the corresponding examples are exceptionally rare. I am not sure what to do about this. I think that each of the three crossings I described has its reason to exist, but synthetically trained students surely prefer to be in the top left corner.

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2 thoughts on “Type A problems

  1. I think the most exciting biology is currently doing well without pure synthesis at all (take for instance CRISPR, siRNA or iPSC). It’s probably because of the gap in understanding of fundamental principles of organization of the living matter. Once (OK, if) we’ll be good enough to rationally design biologically functional molecules de novo (and not to mimic nature’s tools or randomly playing around by trial-and-error), the chemistry should regain its momentum.
    The other thought, is that probably there’s a good reason why nature picked chemically ‘non-interesting’ amide and phosphodiester bonds instead of C-C or whatever you can imaging for connecting its building blocks.

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