The Futile Cycle

Chad Orzel at Uncertain Principles and Janet Stemwedel at Adventures in Ethics and Science are both having a go at describing the difference between chemistry and physics. Chad thinks it’s a matter of scales and subject (i.e. what’s being studied), while Janet thinks it’s more of a difference of methodology.

At some point, though, there’s not going to be a clear distinction between chemistry and physics. The difference between “chemical physics” and “physical chemistry” is largely a matter of the speaker’s biases and personal identification. People who think they’re physicists will talk about “chemical physics”, while people who want to be chemists will talk about “physical chemistry”; in the end, they’re all talking about the same thing.

Take low-energy nuclear physics. I definitely covered some basic nuclear physics in my inorganic chemistry and physical chemistry classes, such as the ideas of nuclear orbitals, nuclear decay, and so on, and chemists use nuclear physics for lots of things, with NMR being one of the most common ones. As another example, there was a chemist in my undergrad department who studied Bose-Einstein condensates, which definitely overlaps with Chad’s atomic and molecular physics. Thermodynamics too, is in physics and chemistry, especially statistical mechanics. What about protein folding and protein structure determination — Linus Pauling won the Nobel prize in chemistry, but does that make him a chemist for sure? Can’t he also be a physicist?

The distinction between chemistry and physics isn’t just the toolbox people use, or what they study. Obviously, some things are chemistry (like organic synthesis) and some things are physics (like the Theory of Relativity), but people can be studying the same thing from radically different directions, and methodologies can be swapped back and forth between fields. Physicists often do programming, but they’re not doing computer science (usually). I think the difference is in what questions they’re trying to answer: chemists want to know how to manipulate and make things, and physicists want to know how things interact. There is a lot of overlap still, of course, and there all I can say is “physichemistry.”

As for me, I’d like to go into computational, quantitative chemical biophysics. How’s that for interdisciplinary research?

Today was the first working day of my first lab rotation.

A bit about the rotation system. Biology graduate schools tend to have a system in which, for the first year or so, graduate students formally try out a couple (usually three) different labs, doing miniprojects and getting a feel for the work and the people in each lab. It’s a great system, because it helps prevent gross personality mismatches between advisors, labs, and new graduate students (and having a good match with an advisor and his/her lab is probably the most important determinant of happiness in graduate school). In fact, I thought rotations were so obviously good that all fields did them, but surprisingly, they seem to be a relatively uncommon phenomenon. I know chemistry doesn’t do them, and apparently engineering doesn’t either. I assume physics doesn’t? Very strange. My professor was an engineering professor, and he hadn’t even heard of the rotation system. For me, I just can’t fathom joining a lab without rotations. With the advisor being such a make-or-break part of graduate school, rotations seem like such a essential part of the experience.

Anyway, this was my first time doing work in yeast, and really the first time in a while that I’ve done biology labwork (before, I did a lot of synthetic organic chemistry). And as I relearn things like sterile techniques, it reminds me of when I first learned about how to do chemistry without contamination from water or oxygen. It was essentially beginner’s jitters.

When I first started working in an organic chemistry lab, I was ultra-paranoid about having water ruin my reaction, or oxygen silently poisoning my transition metal catalysts. I concentrated very hard every time I had to transfer material from one flask to another (in a syringe, or with a metal-tube syphon), carefully checking and rechecking to make sure unreactive argon or nitrogen gas was protecting my chemicals from oxygen and water. But after some time, it just became second nature. I wasn’t as paranoid, because I became relatively confident about my experimental technique. I wasn’t less careful, but it didn’t require my consciously going through a mental checklist of what to do next (”flush the needle, take up the compound, suck in some argon, remove, stick the needle in before air gets through, stick the needle in!”). I just did it. I knew what would and would not contaminate my chemicals, and I didn’t have to worry as much.

But now I’m back with the beginner’s jitters, the paranoia of having my sterile solutions get contaminated by random bacteria or yeast getting blown around in the air. Every time I have to pipette something from one container to another, I get flustered and worried (”Did I hold the container open too long? Make sure I’m not touching anything. Close the cap, close the cap!”). But it’ll soon pass and become second nature, I expect, just as the dry and airless techniques I learned in chemistry soon became second nature.

But for the time being, I have beginner’s jitters, and a strange interesting feeling.

I sometimes jokingly refer to the study of metabolic pathways as “old school” biochemistry, from the era of Hans Krebs, Melvin Calvin, and Konrad Bloch. More often than not, when you hear “biochemistry” uttered by a molecular or cellular biologist these days, they’re referring to measurements of how much proteins stick to each other, not studies of the biosynthesis of a sugar or other molecule. Really, it’s kind of a divide between biologists and chemists. When organic chemists talk about biochemistry, they still pretty much have old school biochemistry in mind, whereas biologists don’t seem to think of that too often.

Still, “old school” biochemistry is still kicking, and its study still generates great life-saving cures, like the Statins, which inhibit HMG-CoA reductase. Metabolic diseases are still some of the highest causes of death in the world, so the study of all these pathways by med students is still of great use. As an aside, Harvard, of all places, doesn’t really seem to have a biochemistry course (the closest is the “Chemistry 27″ course on topics in bio-organic chemistry). Guess they figure the students can always look it up and learn it later if they need it.

One thing I really like about medicines targeting metabolic pathways is that sometimes (and this is just sometimes), there’s something just refreshingly intuitive about the approach to those diseases. Too much cholesterol? You can keep it from being made (e.g. via statins) or you can get rid of the excess (via bile acid sequestrants, like cholestyramine). The latter method is quite interesting; though statins get all the press, bile acid sequestrants apparently also work quite well (but they’re not as easy to take as popping a statin pill). These are essentially resins that a patient swallows, which then absorb bile in the intestine. Thing is, bile is made from cholesterol, so if you remove a lot of bile, the body tries to make more from the cholesterol, thus draining the amount of cholesterol in the system. Pretty harmless.

Another really interesting application of “old school” biochemistry in medicine cropped up in the science news recently, with a 25-year study that was published in the NEJM today. See, the urea cycle processes the nitrogen in the body, breaking down proteins and removing the nitrogen parts as urea, which goes into urine. Some people, however, are born with defects in the urea cycle, which can lead to having too much nitrogen in the blood in the form of ammonia. Ever smelled ammonia? Yeah, don’t want too much of that in the blood. People fall into comas because of it.

So, what to do? How about supercharging another pathway in the body that gets rid of nitrogen atoms? One way is to hike up the synthesis of hippuric acid, which is the form in which the body gets rid of benzoic acid. Hippuric acid is just benzoic acid with a glycine molecule attached; glycine is an amino acid with one nitrogen atom in it. So, just add a bunch of benzoic acid (or sodium benzoate, which is equiavalent), and when the body tries to get rid of that, glycine will hitch a ride! It works quite well, according to the study. The other way to help is to form phenylacetylglutamine, which is phenylacetic acid stuck to a glutamine molecule (which is another amino acid). Glutamine has 2 nitrogen atoms per molecule. Even better! So just hike up the phenylacetic acid in the body, and in the race to get rid of that excess, the body will get rid of a bunch of glutamine with it. Put the two ways together, and you get a great way to reduce the ammonia levels in the blood. Pretty neat, I say!

Frank Westheimer died this past Saturday at the age of 95. He was a great biochemist, one of the old-school giants, back in the day when the foundations of biochemistry were being laid by physical chemists and physicists. Apparently even until the last few years, he was still walking around the halls of the Harvard chemistry buildings. I remember passing his door often on my way to lab. It was simple and modest – just a tiny name-plate on a non-descript wooden door.

He was the leader in studying enzymes, which catalyze reactions that ordinarily wouldn’t proceed very quickly. One of the things that he showed in the early 1950s was that biology tends to be “handed” (or “enantioselective”, to use jargon), an implication that is almost taken for granted now in chemistry, but was unexpected at the time.

Chemical molecules can often come in mirror images that are different, like hands. Have you ever tried to use a right-handed pair of scissors in your left hand? Painful. Can’t put a right-handed glove on the left hand, either.

In the same way, many biological molecules are left or right-handed, which means that they only interact with their corresponding left or right-handed molecule. Carvone, a molecule which can be left or right handed, tastes like caraway seeds in one mirror image, while it tastes like spearmint in the other. Handedness is especially important in drug design, where sometimes one handed-ness of a molecule can do what you want, while the other one won’t, or can even be toxic.

His classic papers detailing this discovery are online at JBC:
Fisher et al., (1953) “The Enzymatic Transfer of Hydrogen. I. The Reaction Catalyzed by Alcohol Dehydrogenase,” J Biol Chem. 202, 687-697.
Loewus et al., (1953) “The Enzymatic Transfer of Hydrogen. II. The Reaction Catalyzed by Lactic Dehydrogenase,” J Biol Chem. 202, 699-704.

This was written before, but I found it today. From Org Prep Daily:

On cannot be careful enough when working with methyl triflate. The vapor inhalation can cause lethal lung edema, skin absorption will cause painful blisters and the long-term effect is genotoxicity and cancer. Be careful when opening the MeOTf ampule, work with the stuff only in the hood. Evaporating some concentrated ammonia can be used to decontaminate the rotavap after the methylation step. Leave the MeOTf syringe to dry up in the back of the hood. Use double gloves. Do not try to clean a MeOTf spill - evacuate.

Along with another good post from Org Prep Daily on what to do when you spill corrosive things on you: pour ethanolamine on it.

Lately, experimental high-energy particle physics (HEPP) is getting harder to do, mostly because it becomes more and more expensive to run the particle accelerators that are the workhorse of HEPP. For the Stanford Linear Accelerator Center (SLAC), however, they’re figuring out something else to do with their expensive accelerator: the Linac Coherent Light Source.

Essentially, they’re going to use the linear accelerator to jiggle electrons and coax them into emitting X-rays. What for? To create a giant, short-pulsed X-ray laser! Why?

Well, X-rays are currently used to study the atomic structures of a lot of different molecules, from synthetic materials to proteins and protein clusters. Right now, because of the damage caused by X-rays to the imaging substrate, we need crystals of the material in order to get a proper image. With the fast X-ray pulsed laser, though, we can get a snapshot of the molecule with the laser in a very short time, getting a picture of our target before it decomposes.

In addition, the pulse laser means we can see the structure of things in short time points, which means we can take snapshots of chemical reactions in progress! By combining this technology with the crossed molecular beam methods developed at Harvard by Dudley Herschbach could revolutionize chemistry, biology, and physics!