A long time ago, I was an undergraduate.  I had good grades, and everyone I knew with good grades was desperate to get into Med School.  Not me.  I don’t like how hospitals smell, I don’t like to prod people’s orifices, and mostly, I don’t like the guesswork necessary in the practice of medicine.  I don’t mean to belittle the profession in any way--I have great admiration for medics, but there is so much we don’t know about the inner working of the cell that a molecular understanding of disease mechanisms...and what to do about them...necessarily lags behind.  Let’s face it, medicine is as much art as science, and therein lies the beauty of it.  That said, it still drives me nuts when I ask my medic what his hypothesis is and he looks at me like I’ve got two heads.  Not to mention the look you get if you ask about the detection limit of some test they’ve run, or the false positive/negative rates.  No, medicine is fundamentally about caring for people, and that’s how it should be.

 

    But my career path took another route.  I am more interested in what makes a cancer cell a cancer cell than a trial and error approach to making it go away.  The idea of dosing people with toxic chemical and radiation seems barbaric to me.  Granted, it’s the best we have for now, and it even works, but the toll it takes on patients is high.  There has to be a better way.  I’m convinced that  once we really understand what’s gone wrong in different types of uncontrolled cell growth, we’ll be able to devise a strategy to address it.  Granted, that kind of precise, targeted fix doesn’t come along every day and we seldom blunder into it by accident, but history has shown over and over again that the key to cheap, effective medicine is to invest in fundamental knowledge in the broadest sense.   In my view, targeted research initiatives are an oxymoron...true discovery, finding something new and unexpected, simply cannot be predicted.   True, the gathering of information (like sequencing genomes) proceeds on a predictable schedule, and as such is attractive to the accountants who hold the purse strings, but it is vitally important not to confuse the gathering of information with the garnering of  knowledge.  Information doesn’t just spontaneously organize itself into understanding, it takes old fashioned hypothesis driven research for that. And this, my friends, is where the fun really begins.  

 

    Don’t get me wrong, I’m not opposed a priori to large scale science, but bang for the knowledge buck, it is an expensive way to go.  Yeah, you can map all the genetic interactions of every gene, but if you don’t care which are truly informative vs those that result from non-specific synthetic death (sick+sick=dead), then all that is produced is a large number of potentially interesting leads, with many many duds thrown in (I know, I’ve chased some of them).  It takes a hypothesis driven approach to figure out what’s really interesting, and in my hands anyway, that’s far more difficult work.  Having the list doesn’t really help the little guy out  much either (which is often an argument for spending mega bucks on these omics projects), since the chance of any given interaction turning out to be biologically relevant to your favorite process is much smaller than one would like.  So you have to do all the hard work of teasing it out, and if it’s a dud, you’ve wasted your time and if it’s biologically relevant, the real deal, you’ve already been scooped.  It’s a lose-lose scenario.   By the same token, the idea that determining random protein structures will be fundamentally useful to the scientific community is just silly.  As is mapping random phosphorylation sites--it takes a monstrous effort to show that any of those are relevant to anything, and too often just leaves blood, sweat and tears on the floor.  Don’t go there unless you have to.  

 

    Now if all of this were cheap, and we  had lots of extra money to spend, then I’d be all for it.  But in these days of limited research dollars, I’m much more in favor of funding more small projects testing hypotheses.  After all, discovery, the real thing, can come from anywhere so it makes sense to fund the broadest research possible, rather like diversification of a financial portfolio.  Science is just not predictable, and that is why it’s so hard and at the same time, so much fun.  Who would  have foreseen, at the outset, that those scientists extracting proteins that degraded DNA from weird bacteria would uncover restriction endonucleases and revolutionize modern biology?  Never mind the sheer silliness of catalytic RNA.  Who would have thought that a phage of E coli, called Mu, which replicates its DNA by jumping its genome around, would encode a transposase that would be a model for HIV integrase?  We can go back further.  Before antibiotics, tuberculosis (consumption) was a multi-systemic disease, and the only treatment was to send the patient off for fresh air, good food and hope they recovered.  Months and months of expensive care.  And mostly people succumbed anyway.  With the discovery of antibiotics, armed with a good knowledge of the causative agent of TB, a cheap and effective treatment was suddenly available!  Not that we’ve really solved the problem, bacteria are sophisticated adversaries and it didn’t take long for drug resistance to evolve, but nonetheless, we’re still ahead of the game.  We just can’t rest on our collective laurels.  We need more creative solutions, and that means more hypotheses to test...  Even in times of fiscal restraint, research is a wise investment.  We train new generations of creative thinkers, keep working towards better solutions to medical problems, but it’s important that we don’t get too impressed with our technology at the expense of asking good scientific questions.  Yes, you can determine the structure of hundreds, nay thousands of proteins, but is that money well spent if there’s no one to ask what they do?  Food for thought anyway.