To The Classroom!

A recent post at Chemiotics sparked some old, dimly remembered memories from my grad school days as a gen. chem. TA leading weekly discussion sections.

Now, general chemistry is, from what I can figure, is a slightly different beast than organic chemistry.  At the universities I attended, the class was also a requirement for physical science and engineering majors, and could make up a substantial fraction of the class given the strength of the engineering programs at my alma maters.  Organic chemistry tended to draw from a smaller student pool - outside of the legion of premeds, it was populated by those with chemistry & biological science majors, as well as the expected chemical/materials engineering students. 

Back to general chemistry - this situation leads to walking an incredibly tricky path so as to keep the material interesting, relevant, and not too off-putting to anyone in the audience.  In short, no one is entirely happy with things, but one might consider that a sign that everyone is getting what they need in the final accounting, although not necessarily what they'd prefer. I'll be a bit obnoxious as usual here and suggest that gen. chem. can be an opportunity to demonstrate chemistry's status as the central science to a diverse audience, if done well. 

Back to the premed issue, though - I think what perturbed many of us is the attitude that arises in a class with a significant premed population.  I won't belabor this point with various horror stories (as we all have them), but, for example, the majority of the "point lawyering" I experienced was from premedical students.  In all of those cases I can still remember/wrote down for the record, none of them involved an actual grade breakpoint (e.g., they were nowhere near the boundary that would have resulted in a different overall final grade).

Of course, perhaps what we need is a different model for medical education.   Or maybe not.  Perhaps what we need is to be reminded of the difference between education and training.  Learning about something that may not be transparently applicable to your post-university career plans is not the end of the world.  A radical idea, I know. 

Obligatory mention - congratulations to the new Nobel laureates! 

P.S. - If anyone wants to share their horror stories teaching undergraduates, please share in the comments.  Read more!

Generality and Contingency.

There's an interesting post over at In the Pipeline regarding the nature of how enzymes work, and it has inspired excellent comments (as is par for the course at ItP).  One notion comes up that if so-called generalized mechanisms can't be devised, it's a failure of sorts for chemists.

My question - the photosynthetic reaction center is an enzyme (oxidoreductase).  Dinky soluble proteins that do isomerizations are enzymes.  Metalloproteins that rip apart chemical bonds are enzymes.  Some proteins float around in the cytoplasm.  Others are embedded are in a membrane of some sort or another.  Others exist at a membrane/solution interface.  Others are extruded from the cell to go do their thing in the cell's environment.  So, how general can a mechanism be for an enzyme? 

One of the things that is often brought up is that there's an element of historical contingency to consider when examining the history of life on this planet.   While we obviously can't just throw up our hands in defeat to try and understand the mechanistic details of biological chemistry, neither can we truck along without acknowledging that context and history are important aspects of the grander scheme.

If that is still not comforting, perhaps one can find some solace in Kornberg's reminder to trust in the universality of biochemistry.  Consider it a tradeoff - while your one enzyme might not shed light on all enzymes, it can shed light on the same enzyme (or similar ones) across many organisms, from the modestly-scaled unicellular beasties to the gargantuan eukaryotes that now populate the Earth.  Read more!

Danger!

Chiming in late on the Toxic Carnival, but I can't help but mention one of the most historically significant chemical threats to life on this planet.

My chosen chemical is arguably responsible for one of the greatest environmental catastrophes in history, whose effect was global in its reach and certainly changed the biological face of the planet.  Said chemical is still produced in vast amounts to this very day, and no one seems inclined to do anything about it.

The culprit, of course, is dioxygen (O₂).

Billions of years ago (a bit over 2 billion of them, in fact), the Earth's atmosphere became significantly more oxygenated due to the increasing extent of oxygenic photosynthesis. I can't even begin to fathom how many otherwise innocent anaerobic bacterial species must have been driven to extinction. Of course, it was perhaps just a matter of time once oxygenic photosynthesis evolved from its anoxygenic roots. 

The worst part is that oxygen still wreaks havoc among organisms to this very day.  Exposure to higher-than-normal partial pressures of oxygen can be toxic, and - in fact - many animals have elaborate mechanisms of oxygen transport that serve to protect the organism from unfettered oxidative damage, including specific "oxygen chaperones" (in essentially all vertebrates, this role is filled by hemoglobin).   Of course, anaerobic organisms are still susceptible to the threat of dioxygen in their environment to this very day.  The reasons for this can range from insufficient amounts of enzymes capable of metabolizing reactive oxygen species (catalase, peroxidase, and others) to oxygen poisoning their (frequently novel) catalysts  - err, metalloenzymes - that are specific for anaerobic metabolism. 

At a more molecular level, dioxygen is critical for the function of cytochromes P450, which has been termed "nature's blowtorch."  That doesn't sound very soothing, now does it?  One of the oxygen atoms is doubly reduced and scoots off as water, leaving behind a vicious biological oxidant which will insert the remaining oxygen atom even into fairly unreactive C-H bonds.  Reactive oxygen species such as superoxide and peroxide are produced as a result of oxidative phosphorylation, due to incomplete reduction of dioxygen by the cytochrome c oxidase complex.

When you take a deep oxygen-rich breath one of these days, think of the poor anaerobes who can't. You should feel a twinge of guilt. Read more!

Black boxes and rigor.

There was a thought-provoking post over at the Curious Wavefunction regarding a Nature op/ed piece on the increasing "black boxification" of modern biological research.  While it is both concerning and makes for an easy bit of mockery, I have to sometimes wonder where one can draw a line.  For example, it's been fairly typical (in my experience) for some specific physical/spectroscopic method to be introduced in a manner consistent with one's expected minimum physical chemistry background.  It's not uncommon for there to be a step or two which is essentially "and we take this result from classical mechanics/electrodynamics" or "this is actually a result of a certain mathematical theorem/relation" in such an introduction.   Some might claim that there's a huge difference between not knowing a technique relies upon a particular mechanism versus (for example) not having worked out a laborious series expansion for a particular term that yields the desired form in that case.  But I would view it as a caution - what happens if you stumble across a case where, in fact, you need to go back and rederive the expression for a term since some parameter or limiting case has changed?  Naturally, you find that if you end up relying upon that method in your research to any significant extent, you are going to dig in deeper.  You will figure out what the limiting cases are, and where any approximations are likely to break down. 

Of course, here I'm reminded that there is a difference between being able to contend with the formalisms of an argument and being able to develop a more physically rooted intuition for said argument.  I suspect many of us have encountered the "it's not rigorous enough" student somewhere along the line - they're the ones who find the experimental nature of scientific research a bit troubling and are worried that we're not careful enough with our mathematics.  We don't want to go in that direction either, of course.  Well, those of us who are scientists and not just frustrated mathematicians, at least.  I'd like to think that there can be a fruitful synergy between the two - when one is able to invoke physical intuition is a good time to develop one's mathematical skills and understanding, and then later on apply that mathematical expertise to a new problem where intuition is lacking at the start. 

I have more stuff to blather about, as it distracts me from extremely unfortunate technical difficulties in my own research.  Stay tuned. Read more!

Cultural Differences

There was an interesting post over at In The Pipeline last week about the differences between chemists and biologists, in particular the nature of how chemists and biologists conduct research presentations in mixed company. As the vast majority of my experience is in academic environments, I will not claim that any of the following observations necessarily extends beyond the weed-ridden walls of academe.

1.) Biochemists do aspire to make details of individual preparations something that can be avoided. Certainly, for those of us who are not working with wretchedly ill-behaved proteins (at least on occasion), we can basically just describe the protocol in broad terms (overexpression, cell lysis, clarifying the lysate, and the chromatographic methods/other procedures). I've done that without specifying buffer compositions in exacting detail before. Also, we are trying to make things as routine and unexciting as possible - preparing protein constructs with cleavable affinity tags; expressing eukaryotic in bacterial cell strains that compensate in various ways for not having all of the innate eukaryotic metabolic machinery; using multi-well plates for spectrophotometric assays of various sorts. We would like for things to be boringly reliable, rest assured.

2.) One fundamental problem with presenting material to mixed audiences is that your own people are in attendance waiting to pick your stuff apart. Not necessarily in a malicious manner, of course - well, at least not always. In short, you might decide to go light on the detailed mechanistic enzymology (say, for sake of example, you are an enzymologist) in your latest talk, but what then happens in the Q&A session? Your fellow enzymologists pepper you with a dozen intricate mechanistically oriented questions in no time at all. Six months later, you present again in front of this mixed audience. You have included adequate enzymological detail in your talk and slides. The cell biologists and analytical chemists yawn, and the synthetic chemists wonder why you're boring them with this information. And now you'll never break the chain.

3.) Biology fundamentally means working with living organisms. I sometimes have the impression that chemists who haven't ever done any substantive biochemistry or biology research don't fully appreciate this distinction in the visceral way that those of us who have fallen to the Dark Side do. If it takes a week for something to grow up, then that is what we do. We can't just toss it on a hot plate to speed things up. Conversely, not everything can be stashed in a freezer to wait until tomorrow (although when it can, we do appreciate it). There's also the price of doing interesting biology/biochemistry, where the efforts to make things boringly reliable in point 1 are nowhere near being implemented.

There's certainly more I could eventually think of, but these were the major points I wished to mention. I, personally, do my level best to make my points as understandable and transparent as possible when giving a talk. Of course, given that some of my ideas involve slaughter by spin Hamiltonian, it can be easier said than done...... Read more!

Sunday Contemplations

It's been a lively time on the chemical interwebs.

The entire chiral space dinosaur story is kind of getting tedious at this point. While the allegations of plagiarism certainly needs to be investigated, adjudicated, and resolved, I was most intrigued by the post here at the Curious Wavefunction. I find it convenient that he brings up the famed geologist Charles Lyell - there is a personally beloved example of what might be termed geological/geochemical contingency that I perpetually bring up at these moments.

Xanthine oxidase. You may or may not remember this enzyme from undergraduate biochemistry (well, for those of you took such a class). I mention it since it is a fairly well-known example of an enzyme which uses molybdenum as a cofactor. There are a number of molybdenum-utilizing enzymes that organisms use. However, it has been observed that certain organisms prefer to use tungsten. These are usually so-called "extremophiles" (deep-sea hydrothermal vents, in particular), where tungsten is more abundant than molybdenum, as well as needing to do chemistry at higher temperatures and under far more anoxic conditions. Perhaps it is not as dramatic as the sorts of substitutions that have been bandied about by some (hello, #arseniclife!), I will admit. But it bears consideration - how might multiple perturbations along these lines shape and remodel biochemistry?

(For anyone who wants more info on the above, I'd suggest first checking out the work of Michael Adams at the University of Georgia. If you are just curious about a point I bring up, let me know so I can reference you properly.)

The other interesting point that was brought up, IMO, was the idea of convergent evolution. This relates broadly to the idea that there are going to be certain physical "boundary conditions" one has to consider. My latest book of interest on this is Living at Micro Scale - the Unexpected Physics of Being Small by David Dusenbery. Here, the focus is on microorganisms and - to recall Edward Purcell - life at low Reynolds numbers.

I don't have anything interesting to note about DHFR since I neither deal with drug discovery nor with the biochemistry of DHFRs. Although I wonder - what if that paper hadn't shown up in J. Med. Chem.? What if it had ended up in a more general-audience biochemistry journal? Would there have been the same response? Would anyone have even noticed it on the chemistry blogosphere? I wonder.

Anyway, I'm going to contemplate lipid bilayers, detergents, and how they are clearly conspiring to make my life difficult. Read more!

Break On Through To the Other Side

I was reminded to share this page in light of some recent conversations elsewhere. I would also encourage interested readers to check out the rest of Prof. Sethna's web site - there's a whole lot of great material on numerous interesting topics in physics and "complex systems," as well as what seems to be a nice, modern introduction to statistical mechanics for a wider audience than for whom most texts are intended. (I've only skimmed over it here and there so far - your mileage may vary.) Disclaimer - I am not affiliated with the lab. In fact, my only affiliation with Cornell is that I once dated a girl who lived in Ithaca, and her father worked at the university. Heh.

I will say that many physicists I've known - at least publicly - aren't convinced that they are after finding 3 laws to explain 99% of the behavior in the known universe. Most have far less ambitious goals (like being able to explain superconductivity for non-BCS systems), although I suppose this is their PR problem - they clearly need more Philip Andersons and Robert Laughlins to champion what most physicists are actually interested in, and not just what the very prolific high energy theorists and astrophysicists are putting on the book shelves. Of course, it's not to say that there can't be some excellent synergy going on - there's plenty of fundamental physics going on at neutron sources worldwide, and many groups are interested in using the tools of AMO physics as increasingly powerful probes of fundamental physics.

We can all recount anecdotes from our personal experiences - I met a bio grad student who clearly thought of their project in terms of cartoon diagrams without a number or semi-quantitative thought in mind, the theoretical physicist who thought that explaining his ideas to the experimentalists (or anyone who wasn't actually a frustrated mathematician) was the role of the phenomenology folks, and the chemists who complain about lack of rigor yet still seem desperate to explain everything in terms a first-year chemistry student would recognize. What we should focus on is trying to understand what is useful in such diverse approaches and work from there.

Biophysical chemists such as myself do not suffer from such faults, as we have all of their strengths and none of their weaknesses. We're also very modest. :) Read more!