From Vietnam to Proteins — RVW #5

July 16th, 2007

In 1968, the USA had half a million men in Vietnam.  The Army needed lots of docs to take care of them and their motto was “If you can practice medicine outside the army, you can practice it inside the army”.  There was no 4F for docs, nor were there medical excuses.  There were excuses for individuals of exceptional value, and as chemists, you should know where this arose (see the starred footnote at the end of this post if you don’t). This meant that all newly minted MDs would spend two years during or after residency training in the service.

Fortunately (for me) the Army was short of neurologists in 1968, so with just one year of residency (instead of the usual three) under my belt, I was sent to one of their best hospitals (Fitzsimons) to work under an excellent and seasoned neurologist (Col. Halbert Herman Schwamb — whose name alone scared the hell out of me).

The tour of duty in Vietnam was one year for everyone, so docs who had been there for their first of two years got their pick of where to go for their final year.  Naturally, Fitzsimons was one of their top picks, so the place was full of them.

What in the world does this have to do with molecular biology?  The army had something called the ‘body count’ which meant the number of Viet Cong (and possibly civilian) bodies they could find.  It gave a number, which was increasing with each passing month.  It showed we were winning.  However, not one of the returning two-year docs I talked to (and I talked to a lot of them) thought we were winning.  Most thought we were losing, and badly.  They were, of course, right.  The point is that what we could not measure was far more important than what we could.

Consider the following terms from molecular biology: nonsense codon, noncoding DNA, Junk DNA.  Two of them are downright pejorative.  All imply that anything in our DNA not coding for an amino acid going into a protein is unimportant.  As most of you probably know, the four bases of DNA (A, T, G, and C) are read in groups of three (these are the codons) giving 64 possibilities.  The 3/64 not coding for an amino acid are called nonsense codons.  They tell the protein making machinery (the ribosome) to stop and start on another protein.  The 3 codons are just as vital for life as the other 61, or we’d just be one big protein.  Calling them nonsense always seemed peculiar to me.

Noncoding DNA means DNA which doesn’t code for an amino acid going into a protein.  The implication is that it doesn’t code for anything else.  Of our 3.2 billion positions in DNA, perhaps 2% codes for amino acids going into proteins.  The rest has been called ‘junk DNA’ — again the implication is that it does nothing.

You have doubtless heard that we are 98.5% chimpanzee.  What this means is that our proteins are 98.5% similar (e.g. they have the same sequence of amino acids in 98.5% of positions).  Again, the proteincentric view is dominant here—proteins are all that you have to know.

Now, we all love chemistry or we wouldn’t be here reading this.  Consider Independence Hall and Monticello from the chemical point of view.  They’re both made of bricks, and a chemical analysis of them could certainly figure out that one set of bricks came from South Jersey and the other came from the Virginia piedmont.  However, the most sophisticated chemical analysis can not tell us why the two buildings look so different.

Why not?  Chemistry can’t deal with the way the bricks are put together.  You can do a lot with bricks if you stack them just right (and the chemical nature of the bricks doesn’t matter very much for this).

However, for at least 30 years, minor differences in proteins were thought to determine the differences between a man and chimp.  In fact, it was seriously stated at one point, that chemically man and chimp weren’t different enough (as far as their proteins were concerned) to be considered separate species.

Well, we are, and the determining difference lies in the 98% of the DNA which does NOT code for protein.  In some way (which we are just beginning to find out) it determines which protein is made where, how much of it is made, and when it is made.  Molecular biology is definitely still in the hunter gatherer stage at this point.

That’s enough for now.  The details are emerging and including things like epigenetics, microRNAs, RNA interference, and even in bacteria metabolite control of mRNA translation into protein (look up the work of Breaker at Yale if you’re interested).

**The answer is Henry Mosely who died at age 27 in the battle of Gallipoli in 1915.  Moseley used X-ray diffraction to show that each element has an atomic number. With this tool he was able to fill the six remaining gaps in the periodic table (at the time) and to put some order into the rare earths.  After that, the British (and everyone else) decided that brains like that shouldn’t be used as cannon fodder.

At my father’s recent 79th Rutgers reunion ( yes his 79th ! ) I met an 87 year old graduate.  I asked him where he served in the war (because just about every male in his generation did).  He said that he didn’t.  I asked him how come. The answer — “I was making penicillin for Merck.”

Retread

Previous Comments

  1. Naive Says:
    July 17th, 2007 at 3:36 am Blame the current researhers. Nonsense, Junk etc were sensible when these were introduced, but no longer. Anyway I am sure, as the field become more mature, these labelling will be changed.
  2. Captain Catalysis Says:
    July 17th, 2007 at 8:45 am In his autobiography, Richard Feynman recounts how, after having worked on the atomic bomb, he still had to convince the army he was insane to get out of being drafted for the occupation of Germany.

    “Surely, You’re Joking” is a must read, on the off chance that anyone here hasn’t already read it.

  3. Milkshake Says:
    July 17th, 2007 at 1:25 pm You have completely misread the story (and did Feynman too). I am convinced that the psychiatrists on the committee were trying to help him and that’s why things developed the way they did. The only misunderstanding was on Feynman side.

    I lived under communism and know how things work if you cannot say things openly. I think the first young psychiatrist was quite amazed whom he got to the interview (many draftees were just average dudes, not too interesting to talk to) so he took extra time. He probably thought F. was way too excentric and brilliant and for that he would not work well in the army, and that F. has done already enough for the country and that it would be a great waste if he was sent to patrol the streets somwhere in Wurtzburg. And F. played unwittingly along, by being hostile to him. So the psychiatris asked all the specific loaded questions to get answers that made F look like a paranoid delusional hallucinating nut. The senior psychiatrist cought immediately what’s going on and re-confirmed the “diagnosis”.

    Imagine you are a self-respecting psychiatrist or physician and they make you sit whole day and interview bunch of draftees and work like a rubber stamp for a dumb prickly collonel who likes to decide for you who is healthy enough to serve in the army. And then you get Feynman. What would you do.

  4. Wavefunction Says:
    July 17th, 2007 at 3:22 pm I don’t think the misunderstanding was on anyone’s side as such. What I got from the story was just that nobody was really too serious about actually recruiting Feynman. And Feynman also had a habit of slightly exaggerating his adventures and in fact creating them in the first place (not of falsifying them but adding just that extra garnish to make them tastier). That’s why the story sounds the way it does. I think we will need to hear the psychiatrists’ side of the story to get the whole picture (which we almost certainly never will). But I did like the part where he declared to Hans Bethe that they failed him because he was crazy. Whatever the truth, the whole farce was characteristically Feynman and very entertaining.

    On another note, at one point, they actually thought of assigning military rank to the scientists on the Manhattan Project…can you imagine “Colonel Oppenheimer”, “Major Fermi” and “Captain Feynman”. Whew. Thankfully this idea did not stand for any decent time because of vehement opposition from the scientists.

    As an aside, John Sheehan’s story of penicillin, “The Enchanted Ring” makes fascinating reading.

  5. Captain Catalysis Says:
    July 17th, 2007 at 3:47 pm I thought of that possibility, especially when the senior doc is hiding the smile behind his hands, but it shouldn’t have even gotten that far. They deferred scientists all through the war, why suddenly stop for the occupation? In a sense, they already “served” for the length of the war.

    “Imagine you are a self-respecting psychiatrist”

    You lost me there.

  6. Kyle Finchsigmate Says:
    July 17th, 2007 at 4:45 pm I’m not really seeing how introns relate to Vietnam.
  7. the dude Says:
    July 17th, 2007 at 10:14 pm Kyle Finchsigmate Says:
    July 17th, 2007 at 4:45 pm
    I’m not really seeing how introns relate to Vietnam.

    “…there may not be a literal connection”

    “No, Walter, there isn’t any connection.”

  8. Tim Says:
    July 17th, 2007 at 10:35 pm Kyle Finchsigmate Says:
    July 17th, 2007 at 4:45 pm
    I’m not really seeing how introns relate to Vietnam.

    The point is that what we could not measure was far more important than what we could.

    In case you really didn’t see the connection. I know I didn’t – I had to go back and reread until I got to that line.

  9. Milkshake Says:
    July 18th, 2007 at 12:07 am To the Vietnam connection (a highly relevant piece):

    https://www.cia.gov/library/center-for-the-study-of-intelligence/csi-publications/csi-studies/studies/vol50no4/a-review-of-who-the-hell-are-we-fighting-the-story-of-sam-adams-and-the-vietnam-intelligence-wars.html

    It is not true that “what we could not measure was far more important than what we could.” The reality is that the available but diagreabole data was doctored to fit the political agenda.
    The actual Vietcong numbers were about 3 times higher than what CIA was officially reporting. Since the prezidents and congresmen were bulshiting the public in order to sell their Vietnam policy, CIA was giving them the info designed to not to clash with the official proclamations that US is winning. The voices of few good analysts that disagreed were mufled.

    So it is not like by looking in the wrong directions the politicians and military has fooled themself. It is more like if one starts with plotting the graph in order to determine the data points he needs to “measure” to please his boss.

  10. Boing Says:
    July 18th, 2007 at 10:26 am I am not sure I understand the connections in this post.
  11. eugene Says:
    July 18th, 2007 at 11:44 am “I am not sure I understand the connections in this post.”

    Okay, once again, here is the connection:

    “The point is that what we could not measure was far more important than what we could.”

    If that is not enough for you, I’ll give a short crash course in prose written by humans in a few short paragraphs:

    You see, even if the connection is tenuous to the central issue, it can still be made since our language and our perception of ideas conveyed by language is based on metaphorical understanding. Success is correlated with ‘rising’ or ‘up’ such as “She’s moving up in the world” and “time” becomes an animate concept that is in forward motion as in “Look at how time flies”.

    The basic connections inherent in language reveal a deeper structure or interconnections present in the brain that makes memorization easier if there is a mnemonic, or gives rise to a picture or memory unassociated with a word uttered in an unrelated context. The best prose follows this dictum. Poetry, a very popular human art-form, is very metaphor rich and evokes much imagery. Likewise, a short story about DNA/RNA will have more resonance if a connection is made, however tenuous it may be, to what is now a pop culture event.

    Reading about the author’s time in Vietnam naturally makes us imagine his/her time there and the everyday life for a split second. Many are mystified by the connection to DNA/RNA until they get to the sentence I pointed out, and may be upset that it is so tenuous, but will nevertheless have a better association for the basic scientific idea if it is connected to the human experience (of making tenuous connections throughout our lives). The Vietnam picture with a soldier standing before a burning hut also plays a role in all of that.

    I hope this has been helpful. It took me two years of higher level theory courses, that I mostly forgot, to write all that.

  12. SSBiochem Says:
    July 18th, 2007 at 12:16 pm A sentence starting with the words “The point is…” would have been very useful placed at the end of the post.

    Given the photo and the first paragraph, my first thought was that the post was headed towards providing the details of using 70’s style molecular biology to ID charred corpses. Given that, I didn’t actually mind it’s lack free form writing style.

  13. Retread Says:
    July 18th, 2007 at 2:04 pm I didn’t think I was being that subtle. I guess I was influenced by Hofstadter, whose absolutely brilliant “Godel, Escher, Bach” I am re-reading. Hofstadter always introduces concepts in logic, math, computer science, etc. etc. by illustrating them. Only then does he formally discuss them. It’s quite effective in his hands (but not mine apparently).

    The protein-centric Zeitgeist definitely needs some work. The following sentence appeared in a book review in the 31 May ‘07 Nature (p. 533) “we share more than 98% of our genes with chimpanzees” — this by someone said to be a professor of evolutionary biology in England. True if the only function of our genes is to code (and make) proteins. I don’t know if book reviews in Nature undergo peer review.

  14. Kyle Finchsigmate Says:
    July 18th, 2007 at 3:38 pm Ah, I see. Tenuous may be a good way to put it. Very tenuous may even be better.
  15. ZAL Says:
    July 18th, 2007 at 3:53 pm For sure I am not more brilliant than anybody else reading this blog, but I think I got the connections of the post quite easily, and more, I would say this was one of the best posts I’ve ever read in this blog (or in the chemical blog-o-sphere for that matters). In all my biology and biochemistry classes, first at the high school and then in the university, coding for proteins has always been presented as the major, if not the only, function of the DNA; learning that things could indeed be different was surprising and prompted me to read more on this subject, so thanks Retread for this stimulating contribution!
    BTW, Retread, I recall that more or less the same reflection about “…what we could not measure was far more important than what we could.” was made by S. Karnow in his “Vietnam: a History” (maybe not with the very same words). Have you read that book too or you came to same conclusion based only on your experience?
  16. SSBiochem Says:
    July 18th, 2007 at 4:16 pm The entire sentence from the cited review is: “The usual answer, that we share more than 98% of our genes with chimpanzees, is becoming hackneyed.” This is in repsonse to a self posed question about evolutionary biologists can do a better job of explaining Darwin. My take is that the reviewer agrees with you.
  17. Kyle Finchsigmate Says:
    July 18th, 2007 at 4:28 pm Perhaps I shouldn’t have gotten us off track with the observation. It’s a good post, but I typically don’t read blog entries as closely as I would a textbook and, perhaps, should have before commenting. *shrug*
  18. Wavefunction Says:
    July 18th, 2007 at 4:49 pm Steven Pinker in How The Mind Works says that our solipsism is prevelant to a wide extent in most of the phrases we as humans use, such as “higher” and “lower” organisms. One of the great enabling functions of science is to first let us know how much we don’t know, and then to let us know that we are not special. Ironically this should humanise us, but it does not. Evangelical opponents of abortion forget that killing flies kills 100,000 cells in just their brain, but killing a first trimester foetus kills only 150. Scratching their nose results in genocide everytime they do it.
  19. Shrug Says:
    July 18th, 2007 at 11:41 pm RU rah rah! RU rah rah! Hoo-rah, hoo-rah, Rutgers rah! Upstream, red team! Red team, upstream! Rah, rah, Rutgers rah!

  20. Retread Says:
    July 19th, 2007 at 11:22 am ZAL — thanks for the compliment. “…what we could not measure was far more important than what we could.” was a conclusion I (and many others) reached on our own. Karnow’s book came out in ‘83, long after I finished my two years in the Army.

    This brings up a philosophic point — there are things that are talked about as if we CAN measure (or calculate) them, but we can’t. The wave function of the universe is one, and the potential energy surface for anything but the simplest chemical reaction is another. Physical biochemists talk about these surfaces in the context of protein folding, but I think they are whistling in the dark (hopefully a correspondent will prove me wrong). In a 100 amino acid protein, the surface lies in a space of over 6,000 dimensions (figuring at least 10 atoms/amino acid — except glycine of course)

    Shrug — Yess ! ! ! Although I went to Princeton, I’ve gone to far more Rutgers reunions (with my father) than Princeton, and a good friend in grad school at Harvard was Joe Landesberg — RU ‘60 and currently the chemistry chair at Adelphi.

  21. W Says:
    July 19th, 2007 at 2:33 pm Eugene, your Harvord Tenure will not help you to become a better person, as you said. We all know that, and we do not appreciate you just for this fact.
  22. Shrug Says:
    July 19th, 2007 at 5:16 pm Heh heh… My undergrad research advisor (Lionel Goodman) was also the undergrad research advisor for Kevin Lehmann, who was at Princeton and is now at UVA.

    Not too many RU chemists are accepted in the CCB department at Harvard these days, for one reason or another (in fact, only one prospective student from Rutgers visited during my grad school tenure — he went to Berkeley) which is wildly unfortunate.

    Also, are you allowed to be a Princeton grad but bleed scarlet? That’s so confusing to me… I mean, what are your feelings about the cannon?!

  23. Retread Says:
    December 10th, 2007 at 11:43 am In the 6 Dec ‘07 Nature p. 788, a letter criticizing a review of a book by Pinker, notes that although we differ from mice by having only 300 genes not found in them, the genes themselves are different.

    Both the reviewer (Churchland) and the letter writer — from the Department of Psychology at Harvard miss the point that it ain’t the bricks it’s the plan, noted in this post. The zeitgeist that all the genome does is code for protein is widespread.

    It also ignores the explosion of work on genes for microRNAs (which aren’t proteins). For some current thinking on the subject see — Trends Genet. vol. 23 pp. 243 – 249 ‘07 — “350 microRNA genes are thought to regulate over 25% of all genes in mammalian cells. “

  24. Darksyde Says:
    December 13th, 2007 at 12:15 am Mice and rats are super close, genetically speaking. Yet, somehow, rats lack gall bladders.
  25. Retread Says:
    December 13th, 2007 at 7:19 am The letter mentioned in #23 also shows how inhabitants of two of the more rarified groves of Academe can be functional illiterates on the topics about which they expound and nonetheless get their musings into Nature.


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