Monday, September 18, 2017

Teaching Biology Evidence: Old or New?

I've been toying over a week with writing something based on an interesting Twitter discussion started by Dr. Laura Williams (@MicroWavesSci) of Providence College pondering the best way to approach teaching molecular genetics (really, science in general) at the undergraduate level.  In particular, Professor Williams wondered about the dangers of branding various key experiments with the names of the experimenters, such as Hershey-Chase or Meselson-Stahl.  The risk she points out is that this can devolve into an exercise in memorizing names and dates without assimilating concepts, or conversely that some students will find the names more of a hindrance than a help.  I'm going to play a bit with this, but I do emphasize that for her this is reality and for me it is a hobby (or perhaps a retirement fantasy, if I should ever actually retire).  Or in other words, for the academic this is her industry but for this industrial scientist it is academic.
Science is taught many ways and that is certainly reflected in my memories of my classroom experiences.  Particularly in introductory courses, there is a tension between teaching the broad body of knowledge that science has exposed (and which forms a foundation for later classes) and ensuring that students understand why this knowledge is held to be sound.  Otherwise, there is a danger, manifest in too much public discourse, of knowledge arrived at by scientific inquiry being treated as just another body of received wisdom guarded by a jealous priesthood.  Additionally, as in our back-and-forth tweeting, there is a value in placing scientific discovery withing historical and cultural contexts.  This is both to see how society impacts science -- perhaps Linus Pauling would have solved the double helix first if he had not been prohibited to travel outside the U.S., due to his political activities -- and how science is used and misused by society -- with eugenics forever casting a shadow over biology.

I should confess that my personal learning style favors a historical approach, though I remember only a few bits of learning that relied heavily on it.  I actually don't easily memorize random names and dates, but my brain often finds weaving timelines as a useful means of organizing information.  But I completely understand that there are many others, and Dr. Williams identified herself as one, for whom this really becomes an impediment.  There's also the danger or learning somewhat potted history: in his excellent book Life's Greatest Secret, Matthew Cobb calls out the multitude of textbooks and teachers (including one of my best) who have taught that the Hershey-Chase experiment nailed down DNA as the hereditary material.  No, it was really no better than Avery's works in terms of protein contamination, and neither Hershey nor Chase ever claimed otherwise.  Nor, to my disappointment, did it actually use a kitchen blender but a instrument designed for lab use.    And nearly all historical treatments suffer from the fact that a few leaders end up with outsize credit for what are really team efforts.  Watson & Crick is perhaps the most notorious, but not necessarily for entirely the correct reasons.  Rosalind Franklin's crystallography was key (though Photo 51 was actually taken by Raymond Gosling under Franklin's tutelage), but there were many key suggestions by others in their orbit that led to the successful modeling.

Another aspect of the historical approach that can have value -- but perhaps can overtake other things -- is to see the reflections of some of the personalities of the experimenters in their experiments.  Both Oswald Avery and Erwin Chargaff were extremely meticulous analytical biochemists, which was what their famous experiments demanded.  Conversely, it was a willingness to take leaps of logic that assisted Watson and Crick in imagining the double helix.  Marshall Nirenberg's dogged pursuit of the genetic code was driven in no small part by a bit of a chip on his shoulder, feeling excluded by some of the chummy groups like the RNA Tie Club.  Fred Sanger had to push forward with protein sequencing when it wasn't even clear that proteins had a sequence. Or Matt Meselson, who has an impish sense of humor, hoping that his centrifugation would upend the double helix model (at least that's what he claims in conversation with graduate students, though perhaps he was pulling our leg).

A student at Harvard delivered a glorious anachronism that I've usually just laughed at, but in turning over this issue of teaching science as history I've seen it in a different light.  The late, great Bill Gelbart (I think -- it could have been Matt Meselson who was the other lecturer -- a killer lineup!) had just reviewed Seymour Benzer's exquisite phage experiments.  Benzer had developed the system to a very fine precision, so precise that he knew he should be able to see recombination distances much smaller than the smallest he could detect.  Therefore, he concluded, there was an atomic unit of genetic recombination -- which we now know as a nucleotide.  A student raised his hand and asked "why didn't he just sequence it?"

Of course, it was good for a laugh then and I still chuckle, but at some level there is a truth there to be grappled with.  These experiments existed in a certain time-and-place, and it is difficult to get students to mentally go to that place, as the popular media is full of stories of DNA.  I remember even as an undergraduate being mystified why anyone could think DNA was too simple to be a genetic store, as I was steeped in binary thinking from my many years of programming.  I even rationalized that Jaccard looms and Hollerith punchcards and Morse code predated Avery and colleagues, so why was it  so difficult.  Alas, I didn't know about Phoebus Levine's experiments "proving" that DNA was  composed of tetranucleotides with the four bases in equal measure, a spectacular wrong turn.  Unfortunately, the generally excellent historical approach Dr. S. gave us first years at Delaware missed that key detour.

But what if we think about, and perhaps teach, how we would do things today.  Avery's experiments, as detailed by Cobb, are a masterpiece of progressive refinement on par with Albert Michelson's refinement of the speed of light (as detailed by Maclean).  Benzer's phage experiments are so spectacular, or the "uncles and aunts" experiment of Crick and Sydney Brenner to demonstrate the genetic code was probably a multiple of three.  Or the cracking of the genetic code by Ochoa, Nirenberg, Matthei, Leder, Khorana and others.  

But if next week I want to prove DNA is the transforming material, then I can just order a gene from IDT or Twist.  By looking at DNA sequences for a few organisms, I believe the three-periodicity would be apparent even to aliens with no prior knowledge.  Perhaps in some alternate universe protein sequencing and One required graduate course had centrifugation experiments explored ad nauseum; I might try to show semiconservative replication of DNA by some other method (BrDU labeling?) -- I might make an exception for Meselson-Stahl, but please don't ever bring up linking numbers!  Think of any classic experiment, and there is probably a simpler, faster and probably better way to prove the same point today.

Teaching many of these old experiments and methods is often justified for teaching scientific thinking or reinforces concepts.  I suspect they often do, and as someone with an interest in the history of science I'd be aghast if they were all thrown overboard.  But it does, in my opinion as a dilettante, make sense to regularly ask which are worth teaching.  For example, my Quora feed periodically suggests that genetic recombinational mapping problems are still popular in homework assignments.  In real life, how relevant is this now? The core concepts are certainly the same for mapping with arrays or whole genome sequencing, yet the execution would seem quite different.  Or perhaps some of that time would be better spent emphasizing the sorts of forward genetic approaches such as Cas9 or genome-wide transposon libraries, since that sort of thinking has become dominant.

This sort of discussion makes sense in any of the sciences, but is particularly challenging in biology.  I am fond of pointing out in this space and elsewhere that we really aren't settled on what subject material to cover in introductory biology.  Non-relativistic physics was basically wrapped with a bow before the 1900s and freshman chemistry strays little past the World War II years, but we're still finding fundamental concepts in biology even today.  A fact I am sure is taken very seriously by a multitude of educators who, unlike me, endeavor to educate a new set of fresh faces every new school year.

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