Additional indications of decline.

Along with many others, I too had my obligatory weekly dose of rage the other day when I read Is Algebra Necessary? by Andrew Hacker. 

Now, I'm not going to pretend that there isn't room for improvement in the U.S. educational system.   But I think calling to teach "citizen statistics" without teaching algebra is rather silly.  I can't imagine trying to teach statistics without some significant exposure to algebra.  (Truth be told, calculus is also immensely helpful in learning/understanding statistics as well, but I won't even try and deal with that at the moment.)   Ultimately, I think the point that many others have made regarding education versus training is germane here.   They are not the same, and if we deem algebra unnnecessary, soon enough we will be dropping literature classes for courses in how to compose PowerPoint presentations and reading Twitter updates.

In other news, I've been busy.  Will attempt to get back to semi-regular blogging in the near future, I hope. Read more!

The Eternal Struggles

I managed to wrap up some experiments for a paper (sent back the revised version just the other day), While doing all of that over the last two weeks and change, I was stimulated to contemplate some long-standing issues off and on.  I figured they might be of mild interest.

The first - I'd like insight and numbers.

There's a fairly famous quote attributed to the late theoretical chemist Charles Coulson on obtaining insight versus just numbers.  My question - why can't we have both?  My  purely anecdotal experiences have suggested that chemists tend to be really ambivalent on this topic - on the one hand, we tend to be annoyed if we can't intuit everything from just a glance at the periodic table and a smattering of semiclassical physics (as I once vaguely alluded to recently), but on the other hand, we're quite quick to complain about things not being rigorous and how it's all just a model.  Other fields tend to be a bit less gripey about this sort of thing in my experience - they've either learned to deal with the indeterminacy or uncertainty, and/or come to grips with the ups and downs of toy models. 

The second - the perpetual translation that goes on in the head of anyone working at an interface.

A long time ago, I had gotten myself into a little back-and-forth because, in short, I was reading with my physics filter on when I should have been reading it with my chemistry filter.  This is hardly new, and it's certainly happened since then, for that matter.  It usually manifests in turns of phrase or underlying assumptions that - for example - aren't anything unusual in one setting but might be a bit odd or worse in another setting.  I'm not sure how to resolve this recurring situation, except to try and be more careful.   Suggestions would be welcomed.     

The third - is biochemistry really just "applied organic chemistry," as I was once informed as an undergraduate and have heard off and on since then?

Please.  One is only fooling the innocent undergraduates with that pompous bit of nonsense.  There's a reason it's called biochemistry - one needs to appreciate and understand how to navigate through the entirety of chemistry.  Once one casts aside the self-completing fantasies of some deluded chemists, it's rather straightforward to see interesting chemistry of all stripes manifest in biological systems.  There are incredible metalloenzymes that can fix nitrogen (nitrogenase), we have a chromophore bound to a membrane protein which experiences a photochemically induced conformational change (bacteriorhodopsin), and of course there's all of the multiple feedback and regulatory pathways that all seem to tie into one another in ever-increasingly labyrinthe but beautiful ways that seem to be well-attacked (to some extent, at least) with the mathematical formalisms of physical chemistry.  And all of that is just the tip of the iceberg.  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!

Quantum biology - A Rose By Any Other Name?

I believe I may have off-handedly mentioned some of this work somewhere in a blog comment semi-recently, but I suppose some further thoughts would not be out of place at this time.  I bring it up because of this preprint and this article about said preprint.

Clearly, on one level, quantum mechanics - via chemistry - underlies biology.  This is, I suspect, a fairly unoffensive statement.  Chemical reactions are quantitatively studied in a quantum mechanical framework, and I don't see biochemical reactions being much different. 

On another level, direct appeal to quantum mechanical behavior to explain biology can seem kind of silly.  Biology is slow, wet, messy, and takes place at a whole bunch of time and length scales.  I imagine many of us recall the exercise - likely done in an introductory general chemistry course, at least in my experience - where one calculates the de Broglie wavelength for an electron and then, say, a baseball. 

Of course, when one looks at table 1 in the preprint, a light goes on.  Long-range electron transfer in proteins?  The role of tunneling in enzyme catalysis?  Vision - which involves the photochemistry of a protein-immobilized chromophore?  Photosynthesis?  A proposed radical spin mechanism for avian magnetoreception? 

This all reeks of physical(ly predisposed) chemists trying to get their dirty mitts onto a whole lot of funding.  Not that there's anything wrong with that, mind you - I'm presently trying to work "quantum biology" into my CV/resume as we speak. 

But for sake of argument, let's take a look at the Fenna-Matthews-Olsen (FMO) protein from a green sulfur bacterium where quantum effects were observed via 2D electronic spectroscopy.

Yep, definitely a protein.  But what's all of that inside the protein?

Why, it looks like the protein is the wrapping for a photochemically delicious filling of chlorophyll molecules!  I could envision that this is the sort of environment which would be conducive for maintaining some sort of quantum mechanical excitation. 

But what about - for instance - microtubules, which some have suggested play a role in consciousness via quantum mechanical effects?  Why, there's even GTP (GDP) known to associate with tubulin in the structure!  Let's take a look -

Hmmm.  Let's focus on the GTP and GDP, so how about….

Well, that was kind of anticlimactic.  That's it?  That is somehow supposed to sustain and nurture our very consciousness from the harsh decoherent world out there?  I find myself skeptical. 

I suppose that is as good a place to end as any.  I may or may not have more to say in the future after I've had a chance to properly consume and digest the preprint.  While I do find the idea of nature exploiting exciton transport, radical spin pair chemistry, proton tunneling, and so on incredibly exciting - I don't think taking that and wantonly speculating is the best route.   

FYI - This was also mostly a chance to play around some more with UCSF Chimera.  Just started using it a bit earlier this year, so if anyone has any tips or list of useful tricks, please share!  The structures were generated with this program using PDB ID 3ENI (FMO protein) and 1JFF (tubulin).  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!

Trifling Observations

The major issue with working at interfaces is that when you need to return to a place of stability, said place of stability often needs quite a bit of attention. You've left it abandoned and unattended, and it will suck up all of your effort until you've returned it to a state of steady reliability. Of course, one never lingers for long, as there either is a new avenue to wander down in one's research or to bring a different project off the back burner.

This tangentially ties into some discussion last month (at a couple of blogs, by my recollection) about how the academic sector does not adequately prepare one for positions in the private sector, at least insofar in chemistry. While numerous wry remarks can be made about the state of the chemistry job market in response to this, it relates - broadly - to the breadth of modern chemistry. Even if you were to organize a curriculum solely for aspiring chemists (here in the US, aspiring engineers and biologists & medical students make up a non-trivial fraction of the general and organic chemistry student populace), you still have to figure out how to make a course palatable for those who may end up working in any number of fields and subspecialties, and will likely end up switching and moving about in any case. The idea (naive as it might be) is that one develops the foundation to pursue anything from synthetic organic chemistry to ultrafast chemical dynamics to chemical biology. Or even all three, if you're feeling adventurous.

Anyway. 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!