Scientific Research and Basic Research: What is “Worthwhile”?

At the end of my last blog, you might notice I promised 3 more articles on the topic of “tinkering with nature”, dealing with DNA, protein, and carbohydrate manipulation respectively. So here is an article that has pretty much no relation to any of those things. Those three posts will materialise, fear not (because I’m sure you were deeply worried…). However, I wanted to take this chance to post about something that required less research in these times of Phd-thesis-writing caught my eye recently.

Chemists amongst us may have heard of the molecule maitotoxin. Not because it is a highly potent poison (it is), but because it has a fiendishly complex structure and represents, in terms of actually synthesising it, pretty much the toughest challenge out there. It’s a challenge that has in recent times been taken by the synthetic chemistry group of K.C.Nicolau in Texas. After 8 years and rather more workers, they nearly made it. But something has stopped them. What, I hear you ask? Is it simply too hard? Was there a large chemical explosion? Did they actually make it, then succumb to violent maitotoxin poisoning? (Oh the irony). Nope, none of these (well, option 1 presumably can’t be discounted, though to the best of my knowledge the latter two probably can). Something rather more pragmatic – funding cuts.

For the record, the original article I found this in is here: https://www.chemistryworld.com/research/chemistrys-toughest-total-synthesis-challenge-put-on-hold-by-lack-of-funds/8152.article. It’s well worth a read. This said, I don’t know if everyone can access it, hence partly why I summarise the scenario above. Here’s a picture of maitotoxin. It might not mean so much to everyone, but…it’s very big and looks complex.

maitotoxin

This, for me, is a slightly sad situation. Presumably, if your research project has its funding cut, someone thinks it it’s not worthwhile. (Someone, in this case, is the NIH). It leads onto a more fundamental topic. Maitotoxin synthesis is a clear example of so-called “basic research”; science for the sake of advancing scientific understanding, with no immediately apparent commercial or socio-economic benefits, motivated more by simple curiosity. (Sure, they might say that its analogues might help understand alzheimers or something, but let’s be honest, that’s not why they’re making it, and even if that were the case, it’d be a seriously expensive and laborious way of doing so). The other generalised field is “applied science”; science that more directly addresses problems in today’s society. Cancer research, for example. Whether it is just my perception or otherwise, it seems that one’s chances of finding funding are increasingly slim in fields of basic research, but not in applied research, perhaps reflecting a shift in emphasis towards the latter as we are confronted by problems such as famine (à GM crops research), new viruses and epidemics (Zika, Ebola), and Donald Trump. Some funding proposals now require a section detailing, essentially, the relevance and benefit of the research to society. So what I want to address are really two points: 1) why should we continue to fund basic research, and 2) are there other factors that might influence the (perceived) worth of research?

You may notice that there is not a question on “why should we continue to fund applied scientific research?”. That isn’t because I don’t think it should be funded; quite the opposite. Rather, it isn’t such a necessary question. Applied science has application in a “real-world” sense, kind of by definition; it frequently has evident potential commercial benefit. If one were to ask various people whether applied science should be funded (let’s say, development of potential cancer imaging technologies, drug development, etc.), there probably wouldn’t be much of a debate. Most people can often relate, on at least some level, to the problems that applied scientific research pertains to address, and thus can see the worth in pursuing solutions to problems.

But try asking people why we should continue supporting the synthesis of maitotoxin, or indeed of a range of other molecules with no immediately relevant (in a real-world practical sense) purpose. If you were to restrict your audience solely to academics, you still wouldn’t have much problem. But academia can be very much the proverbial ivory tower (more on this later…). Strangely enough, if you were to expand your audience to society in general, you might find that a number of people don’t quite see the need to make large, complex and very poisonous molecules in the same way that they see the point in researching methods to treat Alzheimer’s disease. This can be extended more generally to basic research as a whole; it is undoubtedly harder to grasp the “point” of it, given its lack of obvious potential socio-economic benefit/impact. One can always pull out the mantra that basic research informs applied research. This is undoubtedly true, but perhaps not all of the time, and even if it is, it can be rather hard to spot. I’ve read enough obscure scientific papers to be able to say that.

So why should we support basic research? (I should perhaps point out – this genuinely isn’t a personal plea to fund the remainder of my PhD, although I wouldn’t refuse any offers…).  Many academics who pursue this type of work do so fuelled by nothing more than innate curiosity, and the sheer satisfaction and pleasure of new scientific understanding. Yet this perhaps isn’t going to convince the masses that we should support it, although a thirst for greater understanding can surely be no bad thing (see below). The sceptic’ response to the maitotoxin scenario might be something along the lines of, “yes, that’s all very well, but what’s it actually going to solve in the real world?”. To those carrying out the research, by definition this is completely beside the point, but it is understandable that this is more of a concern for, say, funding bodies, and particularly the government, with a particular socio-economic agenda.

Yet whilst its motivations may sometimes lie very far from practical application, the point is that its results may not. There’s a great quote by an eminent Cambridge professor, Steve Ley, in the article I linked to earlier, where he points out that it’s not just the making of a huge molecule like maitotoxin that is of value, it’s what you learn on the journey. Many of the molecules synthetic chemists make are almost definitely totally useless in a practical, real-world sense. But every so often, on the way to making such a molecule in a fundamental research project, someone unearths a new technique. After a bit of evolution and a few (or, more than a few) years, this technique, say, becomes a linchpin of a method of making loads of important drug molecules. Suddenly, the lines between fundamental and applied research are blurred. What started as synthesis for the sake of synthesis has morphed into drug development.

journey
The journey of knowledge and surprise

 

It’s impossible to predict the future (sadly, sometimes – it’d make my PhD so much easier). Some of the greatest examples of discoveries in basic research, that seemed totally lacking in application at the time, now are anything but. X-rays, for example, and indeed radioactivity, were very scientifically interesting at the time of their discovery but lacking in any obvious practical purpose. I don’t think I need to go into the huge range of applications they now have – medical imaging being a particularly prominent one. So, if you’re the most staunch supporter of only applied science, believing that all our funding should be directed towards science that has tangible benefits to society and that apparent science for science’s sake shouldn’t be supported, have a think about exactly what constitutes applied science. Unless you are a seer, it’s not as straightforward as it seems. Science that is purely motivated by curiosity often ends up having applications its developers could never have foreseen.

radioactivity
The discovery of radioactivity. It looked just like this…

There’s a very good reason, incidentally, that I picked the maitotoxin example to start this off. It’s pretty much the biggest challenge in its field, and represents a perfect example of ambitious research in at least an academic sense. Myself and my PhD supervisor may not see eye to eye on a number of things, but one thing I will remember him saying is that he likes to “go after the big questions”. On the flip side, I recently went to a lecture on a topic that was – even in the niche field of academic chemistry – so niche that I simply failed to see how any discovery in that area could ever be of serious impact in any sense, academic or applied. To me, it came across as lacking in ambition, being happy just to meander on by, with a pleasing lack of competition from anyone else of course. Maybe I was far mistaken. But if there really is scientific research out there that is, irrespective of its field, lacking ambition, just plodding along – and I’m quite sure there is – it’s surely that sort of research that might be being over-supported.

Ambitious science, that really strives to push our understanding further, represents the hard option, with a greater chance of abject failure, but any success is going to be higher in impact, however that impact manifests itself. Perhaps funding bodies, including the government, shouldn’t be judging science on how relevant it is in a “real-world” sense, on its socio-economic benefits. Rather, ask a different question: is this research really striving to be ambitious, to push the boundaries in its overall field? Science can be of value whatever its area, even if that value might not manifest itself in immediately apparent ways. Whether or not you think the synthesis of maitotoxin could ever have any relevance or not, one thing it cannot be accused of is being low-impact, or lacking in ambition, and for that alone it deserves support. I, for one, would far rather see that funded than see some low-level, unambitious research in a more obviously applied field supported instead.

So what is worthwhile science? For me, judging that by application is a mistake, simply because it can’t be done in a non-retrospective sense. Judging it by impact and ambition perhaps makes more sense. But in my mind there’s a further factor too, and that is communication. As some of you might know, I’m fairly passionate about science being more widely communicated, and feel that far too much of it is contained in academic journals restricted to a small audience through access rights and, frankly, writing style. Some members of our lab recently published an article on a new method to improve wheat growth that made it as far as the Daily Mail (http://www.dailymail.co.uk/sciencetech/article-4035332/Crop-spray-makes-wheat-20-larger-s-GM-free-Molecule-plant-helps-soak-fuel-photosynthesis.html), Guardian, Telegraph etc. This is genuinely great, not just because it’s a former colleagues who is the joint first author on the paper! But I often feel that for every academic article of this kind, there are 10 more that simply remain confined to the academic world, never making it further. That’s a great shame. Sure, ambitious science is worthwhile. But if it’s communicated outside of the academia ivory tower, in my mind that makes it – or, the results – even moreso.

I’ll close with a final thought. If, instead of being about crop growth, that article had been about the total synthesis of maitotoxin – every bit as big a challenge – would it make it to the newspapers? I’d go out there and say almost certainly not. Science magazines, maybe. Perhaps this also contributes to a lack of understanding and support for basic research. Sure, by definition (lacking obvious application at present), it is harder to communicate, but perhaps a bit more effort might help to encourage a minute increase in public enthusiasm for it, amongst those so inclined, and thus maybe a bit more understanding of why we might support it.

 

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