One of my sons is an artist in Brooklyn. As such, an artist’s statement is de rigueur — something almost impossible to write without sounding pompous. Hopefully I’ll do as well as he did with this first post. A cousin had a hand in the recently released “Julie and Julia” which is as much about blogging as it is about cooking. It all seemed to be about ego and fame. Not so with this one (he lied) — I’m most interested in the comments the posts bring forth.
So the posts will be mostly about matters scientific — molecular biology, organic chemistry, medicine (particularly neurology), neuroscience, physical chemistry, biochemistry — particularly protein chemistry (and the math and physics required to understand it). Anything remotely political seems to incite flame wars, so contentious nonscientific topics will be pretty much avoided.
Why such a spread? Because of where I’ve been and what I’ve done. I started as pre-med in college, but an inspiring professor (Paul Schleyer) and the fact that, unlike many pre-meds, I really liked organic chemistry and found it intuitive switched into it. 2 very pleasant years in grad school coupled with incredibly lousy lab technique switched me back to medicine. This was the early 60s, when molecular biology was just beginning to bloom, so it was very easy to follow, given what I knew.
Again, another inspiring teacher (G. Milton Shy) influenced me to go into Neurology (along with nearly 10% of my class –an unheard of proportion). So I was either in training or practicing clinical neurology for 36 years. Neurology is a tough specialty — the patients are often very sick (think stroke, brain tumor, etc. etc.), and there isn’t much you can do for the really sick ones (headaches, convulsions are another matter). Yet another inspiring teacher (Michael Brooke) got me interested in muscular dystrophy, and I started and ran one of Jerry Lewis’s clinics for 15 years (thanks Jerry). Most of the muscular dystrophies are hereditary, and there’s nothing like watching kids with it deteriorate and die (while you stand helplessly by with various fancy degrees) to keep you focused on molecular biology.
In retirement, an Nature article April ’07 on the synthesis of lyconadin rekindled my interest in organic chemistry, and I began getting back into it and blogging on the late, lamented ChemBark blog of Paul Bracher. When the blog died (probably because Paul had to finish his PhD) Stuart Cantrill asked me to continue for “The Skeptical Chymist” (which I did as Retread — which I clearly am — you can find them all under “Chemiotics”). The comments on ChemBark were fast, furious and interesting. Unfortunately, those in Nature Chemistry were few and far between (but still very good).
But the stuff I want to write about doesn’t really fit neatly under chemistry (or molecular biology, or neuroscience etc. etc.). Even so it’s still related to all of them. Here’s a rather longish example — which will also show you why a typical post won’t completely fit anywhere.
Start with my senior thesis under Dr. Schleyer — it concerned hydrogen bonding of alcohols (OH groups) on the side chains attached to a benzene ring to the pi electron cloud of the benzene. The extent of hydrogen bonding was determined by the stretching frequency of the OH bond in the infrared — bonding to the pi electrons lengths and weakens the bond so there is a shift where the OH bond absorbs infrared light (e.g. a shift in the spectrum). Benzyl alcohol is a good example and one of the first things I studied.
Move on to a benzyl alcohol derivative — norepinephrine. Now remove the benzyl oxygen atom and you have dopamine. Norepinephrine and dopamine are among the compounds used in the brain to allow neurons to talk to each other (neurotransmitters). Even though nearly indistinguishable, they have wildly different actions in the brain. This all depends on the receptors for them (the proteins to which they bind). Distinguishing between them involves some rather exquisite (physical) chemistry. Thinking on how this came about leads to the molecular biology of gene duplication, mutation and natural selection — since both are descendents of what must have been the same membrane protein.
On to clinical neurology and neuropharmacology — a huge number of recreational and therapeutic drugs (cocaine, amphetamine, phenothiazines, atypical neuroleptics, tricyclic antidepressants) work in part by altering their availability of dopamine and/or norepinephrine, or by mimicking them and interacting with their protein receptors). God knows, we need better drugs than I had, so you’ll also hear about drug development etc. etc. if you read future posts.
To really understand how drugs interact with proteins, you have to understand the physical chemistry behind it — force fields, quantum mechanics, etc. etc. And to understand that, you’ve got to understand math (as opposed to knowing which handle to crank so you can pass tests). I never felt I was even close to understanding math until a few years ago, thanks to auditing some courses in the local colleges. So there will be some math and physics in the posts (probably questions for the cognoscenti reading this, should there be some) about things I don’t understand.
Interested? Stay tuned, and please comment (politely).