The Solace of Molecular Biology

Neurology is fascinating because it deals with illnesses affecting what makes us human. Unfortunately for nearly all of my medical career in neurology ’62 – ’00 neurologic therapy was lousy and death was no stranger. In a coverage group with 4 other neurologists taking weekend call (we covered our own practices during the week) about 1/4 of the patients seen on call weekend #1 had died by on call weekend #2 five weeks later.

Most of the deaths were in the elderly with strokes, tumors, cancer etc, but not all. I also ran a muscular dystrophy clinic and one of the hardest cases I saw was an infant with Werdnig Hoffman disease — similar to what Steven Hawking has, but much, much faster — she died at 1 year. Initially, I found the suffering of such patients and their families impossible to accept or understand, particularly when they affected the young, or even young adults in the graduate student age.

As noted earlier, I started med school in ’62, a time when the genetic code was first being cracked, and with the background then that many of you have presently understanding molecular biology as it was being unravelled wasn’t difficult. Usually when you know something you tend to regard it as simple or unimpressive. Not so the cell and life. The more you know, the more impressive it becomes.

Think of the 3.2 gigaBases of DNA in each cell. At 3 or so Angstroms aromatic ring thickness — this comes out to a meter or so stretched out — but it isn’t, rather compressed so it fits into a nucleus 5 – 10 millionths of a meter in diameter. Then since DNA is a helix with one complete turn every 10 bases, the genome in each cell contains 320,000,000 twists which must be unwound to copy it into RNA. The machinery which copies it into messenger RNA (RNA polymerase II) is huge — but the fun doesn’t stop there — in the eukaryotic cell to turn on a gene at the right time something called the mediator complex must bind to another site in the DNA and the RNA polymerase — the whole mess contains over 100 proteins and has a molecular mass of over 2 megaDaltons (with our friend carbon containing only 12 Daltons). This monster must somehow find and unwind just the right stretch of DNA in the extremely cramped confines of the nucleus. That’s just transcription of DNA into RNA. Translation of the messenger RNA (mRNA) into protein involves another monster — the ribosome. Most of our mRNA must be processed lopping out irrelevant pieces before it gets out to the cytoplasm — this calls for the spliceosome — a complex of over 100 proteins plus some RNAs — a completely different molecular machine with a mass in the megaDaltons. There’s tons more that we know now, equally complex.

So what.

Gradually I came to realize that what needs explaining is not the poor child dying of Werdnig Hoffman disease but that we exist at all and for fairly prolonged periods of time and in relatively good shape (like my father who was actively engaged in the law and a mortgage operation until 6 months before his death at age100). Such is the solace of molecular biology. It ain’t much, but it’s all I’ve got (the religious have a lot more). You guys have the chemical background and the intellectual horsepower to understand molecular biology — and even perhaps to extend it.

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Comments

  • RDG  On September 23, 2009 at 2:47 pm

    “You guys have the chemical background and the intellectual horsepower to understand molecular biology”

    Intellectual horsepower? More like ideology.

    The ideologies are based on information theory, selectivity, and specificity. Read this garbage on the central dogma of molecular biology and try not to laugh at loud:

    http://www.oup.com/us/catalog/general/subject/LifeSciences/MolecularCellBiology/?view=usa&ci=9780195140576

    “In The Touchstone of Life , world-renowned biophysicist Werner Loewenstein seeks answers to these ancient riddles by applying information theory to recent discoveries in molecular biology

    If selectivity and specificity had any value, MBA’s wouldn’t be cutting the chemists and molecular biologists loose in favour of low cost BRIC.

    Now the new religion is chemical biology…thats where the lastest high priests (physicists turned computer science opportunitists) claim authority on determining models based on “analyzing” ad-hoc datasets. This is their crazy idea of legitimate science.

    Its all a racket driven by Wallstreet driven power mongerering and not actual science. Robert Laughlin has it right, you can’t get funds to do real experiments in biology because the all encompassing “evolution did it” nonsense is immediately thrown in your face from the grand masters of money creation.

    We don’t need any financial regulation because that would violate the ideologists central dogmas biology. Evolution thrives on predation, tinkering, blah blah blah.

    So spare me your naive belief real progress is being made.

  • luysii  On September 24, 2009 at 11:14 am

    RDG — perhaps I should have said “better understand” (which is certainly true) rather than “understand”. I watched molecular biology change from insisting that humans and chimps are really the same species because our proteins are nearly identical — at that time it was thought that all the genome did was specify the amino acid sequences of proteins. Certainly the discovery of the fact that genes occur in pieces (e.,g they are a mosaic of introns and exons) helps us better understand what’s going on inside the cell. Ditto for microRNAs. I’m far from convinced that we even know all the metabolic and genomic players at this point. Riboswitches come to mind. The next post will concern a newly discovered (e.g. reported this month) chemical link between amino acids in proteins.

    On a more philosophic level, I don’t think our brains are going to be strong enough to understand what’s going on inside our cells. We think linearly, and the cell is full of feedback. Please see my posts of 12 March ’08 “The Decline of the Master Gland and the Rise of Feedback” and 20 March ’08 “The vanishing Simplicity of Chemical Pathways in the Cell” which is in the Chemiotics section of the Nature Chemistry blog “The Skeptical Chymist” for some elaboration.

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