Fundamental biological research is a non-negotiable, essential first step for any kind of medical research. It seems quite obvious right? Without understanding how something works in the first place, how can we hope to influence it? While it is true that many remarkable scientific discoveries historically could be attributed to “lucky accidents” or outright mistakes, this is neither sustainable nor a sound strategy for systematic, comprehensive biomedical research. Yet our misguided, and, frankly, irrational attempts at “getting lucky” and accidentally (more like magically) stumbling upon the cure for dementia or cancer is wasting millions, perhaps billions of federal dollars every year without fail. Of course we would all be thrilled if this worked out and the infamous penicillin discovery story was the way we did science. But unfortunately that is not even remotely close to the truth. The inconvenient but undeniable reality is that comprehensive, systematic and most importantly, reproducible research that gives us the cure for dementias and cancers is achievable only through the “unsexy”, tedious, slow and expensive but reliable and rigorous systematic research. This slow and difficult process mandatorily starts with step 1: basic, fundamental research into the biochemical structure and properties of the given system: from fundamental classes of biomolecules aka building blocks of life, to complex multicellular organisms, to biochemical mechanisms of the base processes that constitute this infinitely complex (seriously, so complex that most of the mediocre scientists have given up on trying to make sense of it) yet satisfyingly consistent and predictable phenomena that we consider “carbon-based life”. That is, predictable if you know its structure, atomic/molecular composition and properties. Indeed, isn’t it comforting to remember that by merely comprehending the simple principles of Mendelian inheritance, old man Gregor (who by the way was actually an ordained monk) could reliably and consistently predict the colour of the flowers, the shape of the seeds and many other characteristics of the humble peas, thus giving us the astonishingly complex yet stoically beautiful and elegant  field of genetics. 

The message couldn’t get any simpler: when you have adequate understanding of the properties of a given system and the principles that govern its’ behaviour, only then you can hope to control or modify them. But you can’t skip the Step 1, there is no way around it, no shortcuts, no “getting lucky”, no easy fixes. High quality, rigorous, reproducible research is a titanic effort, it is painfully slow, difficult, and requires an army of dedicated, highly trained and researchers and many lifetimes of relentless effort to answer the infinite questions about biological systems and the wider physical universe. 

This is not to be confused with the dogmatic reluctance to accept actual innovation and paradigm shifts (when warranted) that plague some of our unhelpfully stubborn colleagues that still “don’t believe epigenetics is real”. But there is a fundamental difference between stubbornly holding on to outdated and flawed theories due to lack of knowledge and comprehension, and asking chatGPT what we should treat epilepsy with. I confess, it is tempting and, alas, in the current academic environment, even beneficial (at least career-wise) to go for the safe, unimaginative, embarrassingly derivative and utterly useless iteration of an originally flawed design that was never going to work in the first place – even if it was a clever design at the time, because the “at the time” was 150 years ago when we didn’t know the first thing about biological organisms, and treated infections by “bloodletting” and prayer, so any idea that didn’t involve spirits and holy water could be very nearly thought of as a “good attempt”. I admit, in principle, there can be some value to derivative, incremental research, but this should BY NO MEANS be our primary strategy to achieve breakthroughs that we so desperately need. Need I quote Einstein’s definition of insanity: doing the same thing over and over but expecting different outcomes! Indeed, this is the formula that a concerning number of researchers adopt and stick to for a range of reasons. Some are too limited in their comprehension and imagination; some are too lazy or too incompetent; others, while having the knowledge, comprehension and conviction, may lack resources or are simply limited by the technology of their time; and, alas, some of us have forgotten what scientific research is all about and are trying to make a quick buck at the expense of the patients and any prospects for actual scientific advancement. The latter, I submit, have no business pretending to be a scientist, and should consider other career paths. Eventually, we are all guilty of one or the other of these failings, none of us are free of faults. 

But let me ask you this. If the future and very possibly the survival of the human race holds on our ability to come through and actually do the job right, isn’t it more strategically sound to at least attempt to do the tedious rational thing, with sound experimental design, statistically valid sample size and solid analysis methodology,  which at least stands a chance to produce some real results, hopefully in time to save our shebs, than keep taking shots in the darkness and hoping for a lucky break? Hell, if we had unlimited resources we could do both – and settle for a really expensive lesson in distinguishing between possibility and probability (you know, for those who are still statistically innumerate), but unfortunately we are limited in resources, namely, time. 

Only very recently in the chaotic years of covid19 we had a reassuring example where doing things the difficult but correct way actually worked. When faced with a global emergency that threatened us as a species, did we (by “we” I mean rational people, guided by competent science, not Trump-loving imbeciles drinking bleach) say, “oh, lets treat this virus with vitamin C and see if that does anything? No, we systematically characterised the coronavirus, all aspects of it, sequenced its genome, then comprehensively analysed it, figured out the best way to combat it, then devised a strategy for producing not one, not two, but three adequately working vaccines (and a couple of bonus 50:50 knock-offs, I guess A for effort to Russia and China) in record time and saved the day. So it is, in fact, possible (at least for coronavirus research, but I’ll go out on a limb and generalise to at least include the whole field of infectious disease) to not skip any steps, do the job properly and get results, but only when we put the planet on a timeout, have literally unlimited funding and have our existence threatened. Still, I consider this a positive outcome of the existential crisis – at least it is possible and we saw the evidence, no two ways about it. 

So, is it too much to ask of the honourable senior “authorities in the field” to reconsider their current strategy of “one potato two potato”, perhaps familiarise themselves with the last couple decades of research and leave their weaponised incompetence for times when they need to convert a word doc to PDF – all in the name of a brighter, less disease-ridden future… 

It’s not like we have a plan B!!!