Archive for June, 2007

More than a few of the posts I’ve made in the recent past are kind of depressing. Things like scientific misconduct, atrocious teaching, over-hyping mundane results, and slimy departmental politics are an unfortunate part of the chemical landscape and merit commentary. On the other hand, I don’t want to leave anyone with the impression that I think the world of chemistry is bankrupt of joy. To the contrary, there are lots of things that keep me excited about our field. Here are just a few of them:

1. Chemistry works. There is an incredible amount of reliable, fundamental work in our field. The thrill of a reaction that you’ve only seen on paper actually working in the lab never gets old.

2. Chemistry has substantially improved life. Chemicals are everywhere doing all sorts of useful stuff. From materials to detergents to lubricants to drugs, chemical technology has solved an astounding number of problems for humanity.

3. Chemistry is not too complicated. There is so much craziness in biology—so many variables, so many things to go wrong—that a lot of the time you end up having to play a numbers game to understand if what you’re doing has any significance. Chemical experiments, on the other hand, are much easier to characterize and follow. There is something satisfying about being able to keep tabs on what’s going on.

4. Chemistry has got to be the basis for figuring out a number of important unsolved problems. The greatest historical question of all time is how life originated on Earth four billion years ago. That is all but certainly a chemical problem. The greatest technological problem of our time is finding an environmentally-friendly solution to our energy needs. This is all but certainly a chemical problem. Don’t let anyone tell you that all the interesting chemistry has been done already.

5. The vast majority of chemists behave ethically. Fortunately, the fraction of posts on this blog about scientific misconduct dwarfs the fraction of crooked chemists in our field.

6. There are good teachers among us. I’ve lamented how many professors and grad students don’t take their teaching responsibilities seriously, but on the flip side, there are a number of fantastic teachers in our field. This goes beyond basic instruction in the classroom to include those who take time on the research side to develop their students into good scientists.

7. The chemical world is largely a meritocracy. Yes, there are people at the top who pull strings with editors to get their “bad” science into good journals, but if you do “good” science, it will get published and catch on. At the end of the day, there is no substitute for good ideas, reproducible results, and talent.

8 through 10 (and beyond). The Simple Pleasures. See here.

I’m sure I’m missing some good reasons chemistry rocks, but that’s not the point. The point is that despite the occasional sour taste of some of the posts here, the above list trumps everything. I’ll keep a link to this post on my desktop for the next time I lose the will to live.

I recently came across this screenshot I took of an episode of Deep Space Nine (part of the Star Trek franchise):

That molecule is a key component of Ketracel-White, the sole source of nutrition for a species of warrior slaves. When the wormhole to their home-world was blocked by a minefield, the employers of the warriors needed to find a way to synthesize it.

Sadly, that’s where the chemistry ended. I think it’s the only time I saw a chemical structure in the whole series, which was otherwise littered with fantastic challenges in biology, physics, and engineering. Of course, it’s not just Star Trek that slights our field. Maybe it’s just that engineering problems are more entertaining. I saw Apollo 13 when flipping through channels Saturday night and couldn’t stop watching it. NASA is just full of these cool stories, including my favorite: the one about flight controller John “SCE-to-AUX” Aaron saving Apollo 12’s mission when the rocket was hit by lightning during launch. There’s audio here of the communication loops, where you can listen to how Aaron saved millions of dollars and enabled a cool science mission to proceed by knowing the vehicle’s instrumentation inside and out.

Anyway, in hopes that someone in Hollywood is reading this blog, here are my best ideas for how chemistry could be worked into a hit project:

1. Book, with possible movie deal (depending on sales): A postdoc in a total synthesis lab discovers a cure for cancer, but fearing that his advisor will take the credit, doesn’t tell anyone so he can publish it as an assistant professor. Unfortunately, he doesn’t manage to get a single job offer due to his poor record of publication. He eventually pursues a career in drug discovery and dies of melanoma at the age of 33.

2. Tweener Movie: A girl genius (played by Hilary Duff) extracts a natural product from a pretty flower and discovers that it cures AIDS. When the government forces her to marry the smartest man in the country (played by me), she steals the identity of a grad student and chooses a life of misery over a life of misery.

3. Action Movie: A nerdy agoraphobe (played by Ethan Hawke, or possibly, me) solves the world’s energy crisis by using his basement lab to synthesize a donor-acceptor dyad that undergoes photoinduced electron transfer when irradiated with sunlight. The petroleum industry puts a price on his head and chases him through the corridors of the US Patent and Trademark Office in an ultimately successful attempt to eliminate all knowledge of the molecule. The movie ends with the nerd’s lab notebook disappearing into a boiling vat of crude oil being stirred by the Secretary General of OPEC.

4. TV Sitcom: In every episode, a country bumpkin uses his barn-based laboratory to cook up a new way to get high. He often runs afoul of the law, but fortunately, the local sheriff is a bumbling idiot who doesn’t understand how to interpret a simple first-order NMR spectrum or solve the Schroedinger Equation.

5. Theater: A diabolical foreign dictator assembles a team of scientists to build a chemical weapon that recognizes DNA sequences only present in the ethnic race of their enemy. The weapon works, at first, before something goes horribly wrong: every living creature on Earth dies except for me and Hilary Duff.

Anyone wishing to produce any of these ideas should feel free to contact me for the associated scripts and musical scores.

In his third post, Retread looks at some of the physics and math needed and used by chemists. 

Now that the answer book to Jones has arrived (23 May) I’m going to start over from the beginning, this time doing all the problems.  Mathematicians are fond of saying that it isn’t a spectator sport, and that problems must be done to really grasp the material.  I’m not so sure that is true for chemistry, but I’ll take excimer’s advice.

I’d gone through the first 300 or so pages of Jones and it’s apparent the two textbooks are wildly different in the way they approach the beginner.

English & Cassidy start out with hydrocarbon structures.  Molecular orbitals make their appearance on p. 63 (remember the book only has 442 pages of text). They are introduced as follows: “A somewhat more easily visualized physical picture of a double bond is given by a relatively recent theoretical development known as the molecular orbital theory.”  Recall that there are only six three dimensional drawings in the first 100 pages of E&C.  Four of them involve orbitals.

Jones drenches the reader in atomic and molecular orbitals using all the graphics at his disposal.  One needs to step back in time to realize the mathematical armor the high school graduate possessed in ‘56 entering college.  Outside a few of the great academic high schools in the USA (Central High in Philly, Bronx High School of Science) calculus was simply not taught in US public high schools.  The thinking was that is was so hard that it would destroy the brain of anyone under 18.  There was a giant dose of anxiety on taking it for the first time.  Just about all the undergraduates in the math courses I audited had a year or two of calculus in high school and some were exposed to it in the 8th grade.

So junior chem majors back then didn’t have the apparatus to tackle the Schrodinger equation etc.  Formal quantum mechanics wasn’t taught to us back then.  Even though the department had Walter Kauzmann, who wrote the influential “Quantum Chemistry” in ‘57, and who taught physical chemistry (which we all took), quantum mechanics wasn’t really discussed in the course.

The department did introduce us to quantum mechanical thought.  As juniors we were required to read a book “The Logic of Modern Physics” by P. W. Bridgman, written in 1927 in the early heyday of quantum mechanics.  I found it extremely irritating.  It argued that all we could know was numbers on a dial reporting the results of a measurement.  The notion of particle trajectory was to be abandoned, etc. etc. Jones skirts the issue on p. 10 where he talks about the node in the 2S orbital, a place where an electron is NEVER found.  An electron following a trajectory as we know it macroscopically could never pass through the node.  If you like thinking about such things, I recommend just about anything a physicist named Mark P. Silverman writes.  In particular, Ch. 5 “And Yet It Moves: Exotic Atoms and the Invariance of Charge” in his book “A Universe of Atoms, An Atom in the Universe” deals with the issue of the ‘motion’ of an electron in an atom.

I have a friend, a retired philosophy prof from Columbia, who dismisses all biology and chemistry as ‘anecdotal’.  The only thing he regards as solid is Godel’s proof.  I told him he better hope he’s wrong if he ever gets sick.  In a similar vein, Bridgman is as wrong as he can be when it comes to chemistry.  Why?  Because the theory behind chemistry may have its origin in numbers on a dial, but it gives rise to gazillions of successful predictions about reactions, structure and spectra.  Theory is immaterial, but it guides chemists (it’s the old Cartesian dichotomy between flesh and spirit).   Following chemistry in a peripheral fashion during my years in medicine by reading what appeared in Nature and Science (on a superficial level), it seemed that the work in gas phase kinetics was just confirming (always good) what we ‘knew’ back from ‘58 - ‘62.  The one surprise was the reversal (p. 245) of the acidity of primary, secondary and tertiary alcohols in the gas phase.

I’m sure you’ve all been there with some degree of regularity: You’re searching the literature for information related to a research project when the search engine spits out a paper with a really bizarre title.  Intrigued, you take a quick look at the abstract to see how that title could possibly describe an actual scientific study.

A search on ion gradients this weekend led me to an old study published in the journal Anesthesiology titled, “The Effects of Aspirated and Swallowed Water in Drowning: Sea-water and Fresh-water Experiments on Rats and Dogs.”

Check out the abstract:

Experiments involving lethal and nonlethal drowning were performed in rats and dogs to investigate the effects of aspirated and swallowed water on blood composition, scrum potassium increase owing to hemolysis, damage to pulmonary tissue, and whether blood composition continues to change after cardiac arrest. The ratios between aspirated and swallowed water amounted to 1:1 in fresh-water and 1:3 in sea-water drowning. The immediate effects on blood composition were mainly caused by aspirated water, whereas later effects probably were considerably influenced by swallowed water. A maximum of 33 per cent of the potassium increase in lethal drowning was due to hemolysis. Sea water produced more damage to pulmonary tissue than fresh water. After cardiac arrest, blood composition did not continue to change for at least three minutes.
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Source: Anesthesiology. 32(1):51-59, January 1970.

This paper stood out for two reasons.  First, I imagine that the experiments for this project must not have been very fun to do.  After the first two or three times, drowning dogs becomes boring.  Second, since I was using the Science Citation Index, it was distressing to see that in the 37 years since the publication of this paper, it has received zero citations. Nil. Nada. Zilch. Not a single freaking citation. I bet those rats and dogs are really happy about the contribution they made to science.

So what, Paul? You’re not one of those PETA whiners, are you?

No, far from it. I am an unabashed supporter of animal testing and find many types of animals to be delicious. Still, this particular study makes me wince. A pile of dead animals and no citations to show for it? I know citations aren’t the only way to measure the value of a scientific paper, so I hope someone learned something from this study.

If not, c’est la vie, I suppose.  You can’t win ‘em all.

The copyright for the above image is owned by Flickr user “soylentgreen23″. The image is used here under a Creative Commons-Attribution license. We do not wish to imply that the cuddly specimen of Canis lupus in the picture is being drowned or otherwise mistreated. — Management

• The ACS announced this week that Gabor Somorjai is the 2008 Priestley Medalist. The award is well deserved, but I was kind of surprised to see two surface scientists get it back-to-back. Since this year’s Nobel Committee for Chemistry seems stacked towards the physical side of the field, will 2007 be the year the surface crowd hits paydirt?
• .
• The Class of 2007 graduated from Harvard this week and left its report card for each “concentration” (that’s Hahvahd speak for “major”). The CCB department had a poor showing: Chemistry placed in the bottom half of the table with 3.69/5.00 (20th of 31) and Biochemical Sciences fared even worse (3.27, 27th). Earth and Planetary Sciences (5.00) earned a spot in the Champions’ League by topping the table, while Biology (3.06) finished dead last and faces relegation.
• .
• Dr. Free-Ride (who was extensively quoted in a recent issue of C&EN) at Adventures in Ethics and Science has an interesting pair of posts about the consequences of graduate students’ blowing the whistle on fraudulent research. Post #1 is based on a news story in Science about probable scientific misconduct by a geneticist at Wisconsin. Post #2 is Dr. Free-Ride’s analysis of the current system. Both posts are good reads—read post #2 even if you don’t give a lick about scientific misconduct.

In the second part of his series, Retread lays out his first impressions of Jones vis-à-vis his previous orgo text in grad school, English & Cassidy.

The book for my first Organic Chemistry course (’58 - ‘59) was English and Cassidy, 2nd edition, ‘56.  Jones is the 2004 edition.

                               English & Cassidy                Jones

Pages (text only)                442                          1323
Page size  (inches)            9 x 6                         10 x 8
Text width                          4.5                           5.25
Text height                         7.0                           8.50

The most striking difference is the graphics.  There were only six 3-dimensional representations in the first 100 pages of Cassidy, while Jones has TNTC (too numerous to count).  It is hard to find a page in Jones without one.

The tone is completely different.  Jones is chatty and conversational.  “Remarks for the Student” in E&C begins as follows:   ”It is usually taken for granted that the student who  takes up the study of organic chemistry has a thorough knowledge of first-year college chemistry.”  Not too warm and fuzzy.

One of the very best things about Jones, is that he tells you what is hard, and what you must learn. “The (R, S) convention looks a bit complicated.  It is easier than it appears right now, but it just must be learned and cannot be reasoned out.”   Repeat this advice 50,000 times and you’re through med school.  There is no reason the appendix is on the right, the heart is on the left, speech is usually in the left hemisphere  etc. etc.  Jones also tells you what looks  hard but really isn’t — drawing cyclohexane in the chair form for instance.

Another very good thing about Jones (which may seem rather trivial) is that when he points you back, he gives you a page number to go to.  On retirement from medicine, I indulged a lifelong taste for math by auditing some math courses (number theory, abstract algebra,  algebraic geometry) at the local colleges.   Math books almost never repeat anything.  You are referred back to theorem 10.3 (and have to hunt for it).   There are hundreds of theorems, corollaries etc. in the average upper level math book.  It gets irritating unless you have a completely flawless memory.

Also, math books don’t usually tell you what’s really important, and what will be used later.  Not all results are equally crucial for the argument.  On reading it for the first time, you can’t tell the wheat from the chaff.  Jones is excellent at this.

In one sense, the two books can’t be compared, just as stereos back then and now can’t be.  I worked all summer as a supermarket checker at $1/hour before entering college in ‘56 and bought an RCA Victor record player to take with me for $140.  The richest man in the world back then could not buy sound of today’s quality no matter what he was prepared to spend.

However today’s convenience store worker would have to work considerably more hours to buy Jones (167.74) and the answer book (80.59) than I would have had to for English & Cassidy back then.  I asked the student checking me out how anyone could afford books like
these.  He said that often students bought a single textbook and shared it.  Shades of the 19th century Ghetto.  My grandfather told me how there were people who could only read Hebrew upside down, or at a 45 degree angle, because 4 - 6 students would sit around the  same table and study the same page at the same time.

One final point.  Despite the dryness, formality, lack of graphics etc. etc. not much harm was done.  I liked the book back then as did most of us.  This includes Jones himself (Yale ‘59), who almost certainly used the book, as English and Cassidy were Yale professors and the first edition came out in ‘49.

Money makes the world go ’round, and the research world is no different.  Chemical and pharmaceutical companies exist to make a profit, so they will explore lines of investigation not because they are interesting, but because they are rewarding.  This purpose does not make these companies inherently evil—they simply value profit above everything else.  We have to accept this fact and make sure that we pass laws to protect the public from harmful and unethical business practices.  Part of the reason these laws are effective is that they provide a financial disincentive for undesired behavior.

In the academic world, our thirst for knowledge should be greater than that for cash, but we have all seen examples of departments choosing to tenure professors who rake in money over those who are excellent educators. Of course, who can blame them?  Schools need money to exist and funding is easy to measure, whereas scholarship, mentorship, and teaching ability are not.

Despite the fact that they are difficult to quantify, these “intangibles” can still be examined in financial terms.  Students pay tuition, so when you accept a teaching position, you owe it to them to do a good job.  What counts as a “good job” will always be a subject of debate, but knowingly slacking off in your teaching duties is despicable behavior.  When a grad-student TA proudly decides that teaching is not something to be taken seriously, he is cheating his students and their families out of their hard-earned money.  Of course, there are many other reasons to take teaching seriously, but I think the monetary aspect is lost on many of the proudest slackers.

In the lab, we must remember that we are the stewards of the taxpayers’ money.  Whether you are paid by a fellowship or off of a grant, you owe the public a good job in return for your stipend.  This includes maintaining a respectable work schedule and upholding the ethical standards of our profession.  Fortunately, most of us enjoy our work and are proud to defend our profession against those who would damage its reputation for personal gain, financial or otherwise.  Researchers who engage in scientific misconduct show a callous lack of respect for science and profound disregard for the sanctity of taxpayer money.  Those who commit fraud—and those who are grossly negligent in their responsibility to police the activities of their employees—should be charged criminally, punished by the government, and dismissed from their institutions.

Beyond the truly loathsome individuals among us who lie about or misrepresent their results, I also get upset with researchers who win grants for one set of ideas, then spend the money on projects that are not just tangential, but completely different.  To me, this smacks of obtaining funding under false pretenses, and I consider it to be dishonest behavior.  If someone offers you money to work in an area, either use it to do what you said you would do or decline the offer.  At the very least, you should contact the funding agency to disclose your intentions and make sure they are acceptable.  A famous professor here has been chided by students and colleagues alike for returning unused portions of his grant money back to the funding agencies upon completion of a project.  While this practice is viewed by many as an incredible waste of an opportunity, there is definitely something gallant about his honesty and sense of responsibility to the public.  For the record, I would have no problems with his using the remaining balance to improve his students’ efficiency by purchasing new equipment—it would probably be better for his lab to use the money instead of it getting distributed to someone else.  Still, I respect his choice.  Government funding should not be viewed as an entitlement to the scientific community. We must earn our keep and prove that it is in society’s best interest to continue to fund our work. We live in a democracy—a government of the people—and correspondingly, we owe it to everyone to spend their money in a responsible manner.

I try to be on my best financial behavior when in lab.  While in many labs at Harvard it seems like we have a limitless supply of grant money, it irks me to see people waste it.  I try not to waste time on the NMR instruments.  I try not to leave the HPLC pumps running longer than necessary.  I shut off UV lamps.  I shut off lights. I always search for the best prices on chemicals and supplies.  (With the ease-of-use of the Available Chemicals Database, there is really no excuse not to.)  Occasionally, I undertake projects like rounding up empty nitrogen cylinders in our lab and returning them (they cost us $3/month, each, to rent).  Does any of this make a difference?  I hope so.  Is it a big one?  Probably not.

Despite my best intentions, there are still times when I cheat.  I use solvents to clean stains from personal belongings.  I use bits of dry ice to blow up microcentrifuge tubes.  When pulling spotters, I warp a few Pasteur pipettes with the Bunsen burner because it is fun.  I rationalize these perks by thinking about how much money I’ve spent on office supplies for research and how many articles of clothing I’ve lost in the name of science, but I realize that these considerations don’t make my indiscretions right.  Still, my violations equate to jaywalking where the crimes described above amount to first-degree murder.

At the end of the day, my guiding principle is simple: If reports of my behavior were to become public, would I be embarrassed?  If someone were to step forward and describe my actions that day, in explicit detail, would I be proud of myself?  Could I defend my conduct without feeling dirty or guilty doing so?  Thinking back over my days in chemistry, I can’t think of any event of which I would truly be ashamed.  Don’t get me wrong: I’ve made mistakes—tons of them—but they were all honest mistakes.

Sadly, I think we all know of individuals in our field who could not make the same claim.

Don’t become one of them.