Nuisance or Nobel?

Bryn Mawr's Center for Science in Society hosted a discussion of gender and science earlier today. Al Albano showed a short clip from Nova on Naomi Halas, who got her Ph.D. in physics at Bryn Mawr. Have things changed? Are women generally seen as potential Nobel laurates, or nuisances? Certainly they are better than in Goeppert Mayers's day!

Maria Goeppert Mayer is one of the few women to have won the Nobel prize in physics or chemistry (trivia question - who are the others?). She was cited for her work on the structure of the nucleus. Though she received her Ph.D. from the University of Goettingen in 1930 and worked on the Manhattan Project during World War II, her first full time paid position was at the University of Californai at San Diego in 1960! She had often worked at the same institution as her husband (a chemist), and hiring rules at the time forbade spouses from having faculty positions at the same place. At the beginning of her career, many places considered her a "nuisance". Her early work in chemical physics was with Herzfeld on the colors of organic molecules (see my earlier post on Cheetos, flamingos and quantum chemistry).

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Winning the prize wasn't half as exciting as doing the work itself.

Maria Goeppert Mayer
Nobel Prize winner in physics (1963)

Hazy days

In my part of the country, it's seriously allergy time. My car is covered in a green haze, and my eyes and nose are running like they're in the Penn relays. The ads promise me "Claritin clear" days if only I would take 10 mg of loratadine. One ad features an allergy sufferer who takes only the brand-name version (Claritin) to be sure that he gets exactly what his doctor used to prescribe. Viewers are cautioned that some other allergy medications might make you drowsy and shows a box with the word diphenhydramine circled in red. It all vaguely implies that if you don't take Claritin itself, you might get something that will put you to sleep. If you know your chemistry, you might realize that diphenhydramine is actually the generic name for Benadryl (which can in fact make you drowsy). If you take Benadryl, generic or otherwise, you could drift off to sleep in the middle of that critical meeting. But if Claritin doesn't make you sleepy, neither will any generic brand of it. Bottom line: if it says loratadine on the box - it's the same stuff your doctor used to prescribe as Claritin. No need to buy the brand name box.

Both loratadine and diphenhydramine are H1 blockers. They bind to a particular type of histamine receptor, and sit there. An overabundance of histamine, released in response to an allergen leads to the woes of pollen season. If the histamine can't get into the receptors, it can't make you miserable. Interestingly, histamine production also plays a role in acid reflux. Several good heartburn drugs (Zantac and Tagamet) are H2 blockers.

One purple pill is much like another

One purple pill is much like another, perhaps even more than you might think. You can't open a magazine these days without seeing an ad for "the purple pill", Nexium. The original purple pill, Prilosec, was the number one selling prescription drug in 2001. A proton pump inhibitor, it stopped the production of acid in the stomach at a different step than earlier heartburn drugs such as Zantac. Patent protection for Prilosec expired that year, and Nexium was introduced with much fanfare. The FDA approval was based on the argument that Nexium was more effective than Prilosec. Now for the chemistry trivia: Nexium is exactly the same molecule as Prilosec.

To understand the relationship between Nexium and Prilosec, you need to know that many organic molecules come in mirror-pairs. The molecules have exactly the same structure, but are mirror images of each other. Your hands are a good example of this kind of mirror pairing, and in fact the chemical term describing this phenomenon, chirality, comes from the Greek for hand.

Many biological systems show a preference for one mirror image over the other. For example, all the proteins in your body are made up of amino acids which exist in these mirror pairs. Naturally occurring proteins all use only one of the two mirror images, called the L form. Perhaps the most striking example is that of spearmint and caraway oils. Rye bread and spearmint gum taste very different, but the molecules responsible for the taste are identical except that they are mirror images of one another.

Back to Nexium and Prilosec. The active compound in Prilosec is omeprazol, which comes in two forms, R-omeprazol and S-omeprazol. The R and the S come from the Latin for right and left - just like the hands - and indicate that this is a pair of identical mirror images. Both R-omeprazol and S-omeprazol are effective in reducing heartburn, but S-omeprazol is about 4 times as effective as the R form. Prilosec contains a 50/50 mixture of the R and S forms, Nexium is pure S. So 20 mg of Prilosec is equivalent to 12.5 mg of Nexium (10 mg of S + 10 mg of R/4). The prescribing literature on Nexium obscures this fact, giving a new name to S-omeprazol: esomeprazol. Get it? "es"omeprazole.....

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If you want to learn more about chirality, check out Prof. Jean-Claude Bradley's organic chemistry lecture. Lecture 16 introduces chirality. The lecture is available as a podcast or streaming video.

Got a headache?

Several painkillers in the class of COX-2 inhibitors have been pulled from the market lately (Vioxx), and now there are questions about the cardiovascular safety of some of the NSAIDS (non-steroidal anti-inflammatories), a class believed to be generally cardioprotective, if hard on the stomach. Millions of people take baby aspirin to stave off heart attacks.

Acetylsalicylic acid (aspirin) is the oldest member of the NSAIDS. It has been used for over 100 years for pain, fever and inflammation. Until 1915 aspirin was only available by prescription. Bayer Aspirin was the first drug ever to be marketed in tablet form. It was first marketed in 1899 as a powder, but by 1900 aspirin was being compressed into a water-soluble tablet. This new method eliminated the need to package individual doses in paper bags and thus cut costs by half. Aspirin is consumed in a variety of ways. The French prefer suppositiories to pills, the Italians take fizzy forms akin to Alka-Seltzer and the British seem to like aspirin powders that can be dissolved in water.

What came between slipsticks and calculators?

"The Curta is a precision calculating machine for all arithmetical operations. Curta adds, subtracts, multiplies, divides, square and cube roots... and every other computation arising in science and commerce... Available on a trial basis. Price $125."

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From an advertisement in the back pages of Scientific American in the 1960s. The cost is nearly $700 in 2002 dollars -- about the same price as Mathematica. Curtas sell on e-Bay for thousands of dollars these days.

I found one of these while cleaning out a drawer in an old piece of furniture inherited from my husband's family. Its purpose was a mystery, until an article in Scientific American on the history of these calculating machines. What did we do before calculators and symbolic algebra code? There was paper and pencil, log tables, slide rules (based on logarithmic principles and called a slipstick by the geeks of the time!) and calculating machines based on rotating drums. The most sophisticated of these mechanical computers was the Curta. Developed by Curt Herzstark while he was imprisoned in Buchenwald by the Nazis, this small drum shaped calculator was capable of 11 digit accuracy. For comparison, a slide rule has only 3 digit accuracy and a TI-83 graphing calculator has 14 digit accuracy (even though it only displays 10!).

The physical chemistry of the flu

Fifteen different types of hemagglutinin, a protein embedded in the surface of the influenza virus, have been identified in influenza viruses, tagged as H1, H2 and H3, etc. H1, H2 and H3 have all been found in human viruses, the others are principally found in avian reservoirs. The binding of hemagglutinin, to glycoproteins on a cell's surface prompts the cell to engulf the virus, thus allowing the virus to hijack cellular mechanisms for its own reproduction. Chemical and biological studies suggest that hemagglutinin binds in a helical form, while it is generally in a random coil configuration in solution. Thermodynamics and statistical mechanics can be used to study the shift. pH appear to be a critical factor in the helix-coil equilibrium for this protein.

Hemagglutinin is often used as the immunizing agent in flu vaccines. The 1957 flu virus that was inadvertently included in a set of controls recently sent to 5000 labs around the world was type H2N2 (N refers to the type of neuroamidase - another protein found on the surface of the virus). The avian influenza circulating in Asia recently is type H5. While occasionally humans have contracted this form of the virus, it has not spread person to person, however the lack of general human immunity to H5 worries public health officials. The hemagglutinin found in the influenza virus from the 1918 pandemic is similar to avian forms of the protein. Over 12,000 people died from contracting the 1918 virus in Philadelphia alone in a one month period. World War I was raging in Europe, but the total US combat deaths in that war, staggering as they were at the time (53,513) were dwarfed by the number of Americans who died in the 1918 epidemic: 850,000.

Microscopic terrorists hijacking our cells should worry us at least as much as human terrorists - and indeed homeland security considers a flu pandemic to be a potential catastrophe.

Building better ice cream and popcorn - who says physical chemistry is useless?

Physical chemistry, which I teach, has a certain reputation among chemistry majors: as difficult, dull, mathematically intensive, time consuming. There is even a bumper sticker that says "Honk if you passed p-chem!" When you are looking at the Maxwell relations in thermodynamics, it seems hard to imagine that p-chem has any impact on your daily life at all. But in reality, researchers at Purdue University are hot on the trail of better microwave popcorn and using physical chemistry to do it. [See Role of the Pericarp Cellulose Matrix as a Moisture Barrier in Microwaveable Popcorn; Agung S. Tandjung, Srinivas Janaswamy, Rengaswami Chandrasekaran, Adam Aboubacar, and Bruce R. Hamaker; Biomacromolecules].

Unpopped kernels in your popcorn are a pain, particularly when your kids pick them out and leave them in the living room! It turns out that unpopped kernels are even more of a problem in microwaved popcorn (is there any other kind anymore?). The key to getting popcorn to pop is is the structure of the outer hull (the pericarp), which is made of a biological polymer (which is why this was published in the journal Biomacromolecules). Pericarps in which the cellulose polymers exhibit a strongly crystalline structure pop better. The researchers used differential scanning calorimetry and x-ray crystallography to study the pericarp.

Prefer ice cream with your movie? Erich Windhab, at the ETH in Zurich (where Einstein once worked), used physical chemistry and physics to figure out how to make a smoother, richer ice cream - with fewer calories. You can now buy ice cream made with this process (Edy's Grand Light where I live). [See the article by Robert Kunzig in the June 2004 issue of Discover]

Extract DNA in your kitchen

When my kids think of DNA, they think of the classic picture of the double helix. But what does DNA really look like? A lot depends on how you look at it, and since most of us don't have a good scanning tunnelling microscope at home, we can't get pictures that look like this one from Lawrence Berkeley Labs.

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With a bit of patience, you can extract DNA in your kitchen, and see what the long polymer strands look like in the aggregate! The Genetic Science Learning Center at the University of Utah has developed a protocol for extracting DNA from split peas. Last summer my kids and several of their friends spent a morning in our kitchen pureeing peas and extracting the DNA. The white threads at the top of each test tube are the DNA. A great rainy day project - even if you don't have kids.

Cranky Numbers: From the 3rd grade to Fermat's Last Theorem

What's the connection between 3rd grade math and Fermat's Last Theorem? My 3rd grader comes home with problems that ask him how many ways he can write a number, such as 4, prompting him to list such expressions as: 1+3, 2 x 2, and 8÷2. If you restrict the list to sums of non-negative integers, the list is short and finite: 0+4, 1+3, 2+2, 1+1+2, 1+1+1+1. The number of sums in the list is called the partition number; the fourth partition number is thus 5. A patient 3rd grader (if such existed) could find the partition number of any integer. Partition numbers are handy if you are a 3rd grade teacher making up problems to occupy your students or a particle physicist.

If you looked at a list of partition numbers (the first 20 are: 1 2 3 5 7 11 15 22 30 42 56 77 101 135 176 231 297 385 490 627 more), you might notice that starting with the 4th partition number (5) every 5th number is divisible evenly by 5. Beginning with the 5th number (7), every 7th number divided evenly by 7. Perhaps not surprisingly, every 11th number after 11 is also divisible evenly by 11. The pattern ends there, but not the mystery. Indian mathematician Srinivasa Ramanujan recognized the patterns almost 100 years ago, but it took almost 40 years before Freeman Dyson explained them by inventing a function which he called the rank. Dyson's rank only explained the 5 and 7 patterns, roughly another 40 years would pass (is there a pattern here?) before the invention of the crank would account for the 11's.

As it turns out, there are more sequences buried in the list of partition numbers, you just have to know where to find them (a pattern based on those divisible by 13 begins with the 111,247th partition number). It also helps to have some of the techniques in number theory developed by Andrew Wiles to prove Fermat's Last Theorem. A proof that such patterns will exist for any prime number larger than 3 was published this year by Karl Mahlburg, a graduate student in math at the University of Wisconsin.

What do flamingos, Cheetos and Quantum Chemistry have in common?

The vibrant colors of flamingos and Cheetos Cheez Whiz™ are both the result of related carotenoid dyes. Carotenoids (named for the vegetable in which they were first found!) are based on a linear conjugated diene skeleton, and provide nature with many colorful accents. Canthaxanthin, for example, is fed to captive flamingos to produce their characteristic pink color (a similar pigment found in brine shrimp does the same favor for wild flamingos). Astaxanthin is responsible for the characterstic color of lobsters. Canaries, whose signature color is a greenish yellow, can be turned red if they are fed paprika during their molt. The new feathers will grow in orange-red.

If you're tired of only changing the color of your hair, you can try for a pumpkin look for fall. The compound that gives this class of vegetable pigments its name - β-carotene - when consumed in large quantities by humans, will turn them orange. [Really, but don't try this at home! It was observed clinically in Britain during WW II when food shortages led some people to include large amounts of carrots in their diets.]

If you thought the bright color of Cheez-Whiz and Cheetos was artificial -- it's not. Bixin or annatto, a natural pigment used for centuries, is the source of that unforgettable orange. Researchers have recently elucidated the biochemical pathway for the synthesis of bixin and are pursuing genetic engineering approaches to its bulk synthesis in tomatoes [Florence Bouvier in Science, 300:2089-2091, June 27, 2003].

What does this all have to do with quantum chemistry? A very simple quantum mechanical model, the particle in a one-dimensional box, can be used to predict the color of conjugated dyes.

UPDATE: Bixin isn't used to color Cheetos, but is used in Cheez Whiz.