Archive for July, 2007

The wrap up is on its way. In the meantime, Retread has come to the rescue with the next installment of his Rip Van Winkle series. Enjoy.

I think Jones’ book is terrific. It’s just a leisurely discourse on organic chemistry, with plenty of examples, hints, exhortations, warnings, opinions etc. etc. It’s always friendly and never turgid or pompous. I’ve now (20 July) made it halfway through, doing most of the problems (as suggested by Paul and Excimer).

A series of comments on the first half would be rather disjointed, so I’ll put just one in now and then. Here’s today’s: I wrote my Junior paper on the Grignard reagent, and it seemed obvious that no one knew what was going on back then. From the discussion on p. 236, it seems like not much has changed. Any comments?

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There wasn’t much response to the request for examples of chemical serendipity in the last post, so here are two from medicine to get the discussion going.

Interns don’t get much sleep. On a three-month surgery rotation, it was 36 hours on/12 off, but to get a weekend off, call was bunched so that in one 7-day stretch, it was 5 nights on/2 nights off, making 24 of 168 hours off call. Most nights we got 3-4 hours of crummy sleep. According to legend, Mary Walker was one such intern who in 1934, fell asleep during a lecture on myasthenia gravis (a disease characterized by muscle weakness, which can affect the ability to breathe, hence the “gravis”) for which there was no known treatment. She woke up after the lecture, walked up to the great man and asked how to treat myasthenia. The great man, irritated, said — “It’s just like curare poisoning”, so she went off to the library, looked up curare poisoning, found the treatment (physostigmine), administered it to a myasthenic and became famous.

Few of the drugs first used to treat neurological disease were discovered rationally. The first drug for epilepsy (bromide ion) was thought to work by decreasing libido, as epileptics were thought to be sexually overwrought. Things improved in the 30s with the discovery that seizures could be induced by electric shocks administered to the brain. Zillions of hapless rabbits were shocked while pumped full of various drugs. If the drug increased the current required for seizures, it was a potential anticonvulsant. This is exactly how Dilantin was discovered. Cruel, but at least rational.

Science marches on, and it was soon discovered that drugs getting into the brain (which is mostly fat) had to be soluble in lipids (which meant they weren’t too soluble in water). So potential drugs were first put into amphipathic (soluble in water and lipids) solvents, like soap. Soap is basically a bunch of long chain (12-18 carbons) carboxylic acids. One such solvent was 2-propylpentanoic acid (valproic acid).  Many drugs put into it seemed to work pretty well. Fortunately, someone had the brains to do a control, and found that the actual anticonvulsant was valproic acid (and a very useful one it was — although like everything else in medicine, not without side effects). A case of not throwing out the bathwater. Anything similar in chemistry?

Retread

I’m still writing that introspective post, so enjoy this one instead.

When I think back on why I became a chemist, I always point to my 10th-grade chemistry class. Our teacher, Dr. Liebermann, was absolutely fabulous. He developed an engaging, rigorous two-year AP Chemistry course with great lecture notes and a detailed laboratory component. The focus was on really understanding the general principles at play, and the massive lab reports and essay questions on tests forced us to understand what was going on. A month into his class, I was certain that I would become a chemist.

But that decision probably had deeper roots. I knew that I wanted to go into math or science in 7th grade, when I had the legendary Vern Williams for math. Before that, in elementary school, I religiously watched Mr. Wizard’s World and would mess around with those experiments in our kitchen. Finally, this periodic table has dominated the landscape of my (old) bedroom since 3rd or 4th grade:

With pictures and small blurbs about each of the elements, it’s still the best periodic table poster I’ve come across. My father brought it back from a trip to England, and I think the Royal Society still sells it. The yellowed pieces of packing tape are a testiment to the sentimental value I hold for the poster. I had to piece it back together after my sister ripped it in a violent rage circa 1992.

Whenever I go back home to Virginia and see the poster, I always chuckle at how funny it is that the periodic table was the last thing I saw at night for nine straight years, and sure enough, now I’m a chemist.

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

Monday: Rip Van Winkle post #5

Wednesday: An introspective essay that will set the record for longest and boringest post of all time.

Friday, maybe Thursday: An investigative report.

Next Monday: The worst contest in the history of the chemical blogosphere. The winner will get to name Ed the Dog’s new girlfriend.

After That: Detailed analysis of the news out of Princeton. I’m hoping that I won’t have to write this post because you all will have covered the issue inside and out by then. It only took 48 comments to get on the right track, but pertinent data is missing (edit to add: and some of the info people have posted is wrong). Finally, the analysis so far has been severely lacking. Some key points have been brought up, so keep working on it…

Blah blah blah.

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YouTube works. Google Video does not. Hmmm. I can live with that.

Edit:  Umm…hopefully this fixes the broken RSS feed?

It’s time for a little experiment. Allow me to apologize in advance for being so cryptic in this post, but I want to observe how the discussion here proceeds without any interference from me.

In the last several weeks, a number of people have brought to my attention a fascinating story relating to careers in academia. Not since the SSS have I heard people voice such strong opinions on a subject that falls squarely in the arena of scientific culture and politics. I believe the story merits discussion and analysis, just because it is so atypical of “standard operating procedure.” Who knows? Maybe the SOP is changing?

Anyway, since this story seems to be well known to the community already, I thought that you all could have first crack at it without hearing my opinion first. I’m sitting this thread out…at least, to begin with. To start the discussion, I’ll throw out a single word and the guidance that it is a story that has not even been tangentially discussed on this blog before today. Keep the discussion civil, but feel free to voice your opinion. Be sure to use proper grammar, especially if you have no idea what’s going on and are just leaving some random insult directed at me.

Now, the word: Princeton.

I just finished watching The Universe: Spaceship Earth on The History Channel. As someone intimately involved in origin-of-life research, I’d give it a B for accuracy. As an unabashed fan of TV documentaries, I’d give it a C+ for entertainment value. Fortunately, an episode of Ice Road Truckers came on immediately afterward to cleanse the palate.

The first twenty minutes of Spaceship Earth were a pretty solid introduction to the formation of the solar system and planetary accretion. The only gripe I had was that the producers seemed to heavily favor the water-from-comets theory over the water-from-volcanic-outgassing theory, where the debate in the community isn’t nearly so one-sided.

The program soon moved into the development of life, and that’s where the wheels came off. They used the origin of life as a tease, like, “we’re going to tell you how life originated after you watch these fabulous commercials.”

“This will be interesting,” I thought, “Here’s comes the chemistry; I wonder what they’ll focus on. Prebiotic soup? RNA world?”

Nope. Boy, was I disappointed. After a two-minute segue that implied the Earth was seeded by life from an asteroid (the panspermia theory), the discussion quickly moved to photosynthetic bacteria (which now magically existed). What a cop out. I suppose we chemists have made little progress in solving the problem, but the producers really provided a disservice to their viewers by resorting to using panspermia as a bridge from physics to biology.

As if the handwaving wasn’t bad enough, obvious errors soon followed. At one point, a professor being interviewed said that the first bacteria had a lot of gases like H₂S and CH₄ to use and a little CO₂. Hmmm. If 96% of the atmosphere is a little, then I guess he’s right.

The discussion quickly moved into thermophilic and extremophilic bacteria being potential models for early life, then into some simple evolution. The last 10-15 minutes of the hour-long program focused on the boring and played-out story of how the global climate is changing and that humans are probably to blame.

Overall, I guess it was OK. They could have included some interesting OoL chemistry, but until we have a more compelling and complete story, I suppose producers are going to be reluctant to talk about it. Bottom line: If you’re looking for something good on TV, watch Ice Road Truckers, Copa America action, U-20 World Cup action, or le Tour instead of a Spaceship Earth re-run.

Some people are real attention whores, like this girl who hijacked her chemistry class at Carleton University to sing her stupid original song about the elements.  It is really, really poor.  I especially despise how she annoyingly interrupts her terrible singing with pointless commentary.  I can’t believe she earned ”an extra mark” for this piece of garbage:

Of course, for a top-notch elements song, look no farther than Harvard’s Tom Lehrer: