A day in pchem lecture: NMR, lululemon yoga pants and tattoos

By lululemon athletica
(Flickr: Yoga Journal Conference)
 [CC BY 2.0], via Wikimedia Commons

It's the end of term, two more 90 minute lectures left in my introductory quantum chemistry and spectroscopy course.  We've done the basics of wave functions and expectation values, we've looked at linear variation theory and written code to do Hückel MO calculations, we've covered rotational and vibrational and rotational-vibrational spectroscopy.  So what to do with these last few days?  The quantum mechanics of NMR.

I kicked off today's lecture by looking at magnetic field strengths, what's the earth's magnetic field (5 μT) or of a refrigerator magnet (5 mT), compared to the superconducting magnets used in NMR, which are on the order of 10T. (1T is one tesla.)  This led to a quick review of the risks in MRI, which aren't about the energy of the radiation used (which is billions of times lower than X-rays), but more about the interactions of the high magnetic fields, the radiofrequencies and metals.

A hand shot up and student who is an EMT describes a patient whose tattoo started burning during an MRI.  I pointed out this is a known phenomenon, and while most inks don't pose an issue, it should discourage you from DIY tattooing.  Then a student asked, "Is it true you can't wear lululemon pants when you have an MRI?"

I admitted this was out of my zone, but promised to follow up.

I can now report that yes, wearing lululemon pants — or any clothing with metallic microfibers, such as those great antimicrobial t-shirts — in an MRI can lead to serious burns, particularly in patients that have been sedated or are otherwise unconscious and unable to signal their discomfort.  Even non-ferromagnetic materials presents problems in the MRI as eddy currents can develop around them, creating little induction heaters.  Loops of all sorts, even skin to skin contact between a patient's own body parts can lead to heating and subsequent burns.  And tattoos with large loops in them?  They can heat as well.

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Other things I learned this afternoon.  You can levitate a frog with a 16T field (thank you Wikipedia), and neutron stars have magnetic fields on the megaTesla scale.

Marketing molecular fear

"A woman can recite the most complicated recipe, but how many can name the ingredients in a headache tablet?  If you don't want drugs you know nothing about, take Bufferin...."

This short commercial by actress Joan Fontaine aired in the mid-1960s, an era when Tylenol (acetaminophen) was just gaining market share in the US as a painkiller for adults.  I'm fascinated with the way in which it foreshadows the modern trope of avoiding chemicals you can't pronounce, already marketing the molecular fear that now fuels the largely unregulated, 12 billion dollar a year vitamin and nutritional supplement market in the US.  Rachel Carson's Silent Spring had appeared in 1962, starting a shift towards seeing chemical as a synonym for poison.

Much like the material put out fifty years later by Jospeh Mercola, Dr. Oz and The Food Babe, this ad tacitly assumes people are incapable of understanding science and must rely on experts of some sort.  Who you should not trust.  And women, no matter how competent within their limited domestic sphere, are even less capable.

Chemophobia: The Boy with a Thorn in His Joints

I'm at ScienceOnline2013 where Carmen Drahl and Dr. Rubidium just finished running a terrific session on chemophobia: how can we bridge the gap between "better living through chemistry" and ads for "chemical-free sleep aids." The thrust of the session was not how to convince people chemistry and chemicals are good, but more about how to inject nuance into the public conversation. Chemicals have risks and benefits — and of course, are unavoidable. But we current view chemical as synonymous with toxic, hazardous, unnatural or just plain bad.

What are the roots of this cultural shift? Can understanding these help scientists and writers communicate more clearly and in the end help people not only understand what is in their "stuff" — chemicals, it's all chemicals — but give them tools to work with and make decisions about the materials that make up the world — chemicals. As @docfreeride (ethicist Janet Stemmwedel) noted at another session yesterday, we can agree on facts, and still make different decisions based on them.

Today's New York Times has a perfect example of the various ways chemophobia presents in the Magazine: The Boy with a Thorn in His Joints. The piece chronicles Susannah Meadow's search for an effective treatment for her son's rheumatoid arthritis. She agonizes about the decision to give him methotrexate (which in high doses is used in anticancer treatment) and turns to alternative treatments, in particular four-marvels powder. There are intense arguments with the pediatricians and with her husband over the issue. I was struck by two things in this piece. First, the language Meadows uses to limn the controversy, and second her ignorance, not so much of the chemistry that is in your face (methotrexate), but of the ways in which chemistry is couched in alternative cultural schemes(four-marvels powder).

It makes me wonder how chemophobia is linked to the language we use to talk about it. It can be nearly impossible for an non-chemist to figure out what methotrexate is (beyond "a chemical"). The very name sounds harsh. Four-marvels powder is easy to parse: a powder with four effects. Its name rings with hope.

I also wonder if we worry more about stuff we are familiar with, we've heard more talk on the street about their risks. So we obsess about vaccines, because we hear and read about the side-effects of vaccines, but how many people know anyone who has died of measles? (One of my sister's friends died of measles when I was a child, before there was a vaccine.) So we get in the Times' piece "I was desperate to find a way...without the drugs." pushed up against "[My husband] has always been more comfortable with pharmaceuticals, more trusting in general."

Of course, four-marvel powder is a pharmaceutical, it's just from a different pharmacopoeia — the traditional Chinese — than the one Meadows or her husband is familiar with. Meadows can read the package insert with information on the side-effects of methotrexate, she may be unaware of the routine advice given in Chinese medicine programs (and yes, there are formal academic programs in Chinese medicine, e.g. at Nanyang Technical University) about four-marvels powder (it should never be given to pregnant women, for example, which might make you hesitate before giving it long term to infants or young children).

The session at SciOnline2013 brainstormed about effective ways to help people develop a better sense of nuance around what is a chemical and what are the risks of this particular chemical? What strategies do you think would be most effective?

Warning, Dr. Smith! Warning!

An SF fan from the moment I discovered Heinlein's Have Spacesuit -Will Travel in the minuscule public library in the small (population 2500) Midwest town I grew up in, it's probably not a surprise that I would have been an avid watcher of SF on TV. When I get various 'urgent warnings' in my inbox, I often hear the Lost in Space robot's voice in my head, "Warning, Dr. Smith! Warning!"

A few days ago, this warning about the dangers of taking business cards from strangers appeared. Take one of these drug laden cards in your bare hands and soon you will be easy prey for swindlers and worse. Is such a thing possible? Can you be drugged against your will by briefly touching a drug?

In principle, yes. Unbroken skin, though a good way of keeping your insides in, is not an absolute barrier to molecules entering the body. Some molecules — such as DMSO — are better at getting in than others.

When I teach mathematical modeling, one topic we look at is ways to model diffusion. An application that many of my students find interesting are passive drug delivery systems that capitalize on diffusion. In other words - patches. To me this warning sounds like a folkloric riff on drug patches. In fact, delivery through a patch is a pretty complex system, it's not just a matter of soaking the equivalent of a gauze pad in a drug and taping it to your arm.

The drug cocktail purported to be on the business cards is burundanga - a mixture of two plant alkaloids, atropine and scopolamine. Both can be administered through the skin, when I had surgery a couple of years ago, the anesthesiologist use a scopolamine patch to manage my post-op nausea. But he didn't hand me a "don't throw up" card to hang onto for a few minutes in pre-op - that patch he applied behind my ear was a marvel of pharmaceutical engineering!

Burundanga has been used criminally but by slipping into a victim's food or drink. Incidental contact with atropine or scopolamine won't incapacitate you — though the prescribing information for the scopolamine patch points out that you should avoid touching the patch and then your eyes - resulting in dilated pupils and blurry vision.

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Scopolamine was used as an amnesia inducing agent during labor and delivery in the 60's. I suspect Betty Draper's halucinations during labor and delivery on Mad Men (The Fog, Season 3, episode 5).

Image is of belladona, from which atropine and scopolamine can be extracted.

Word Wraps: From the ACS meeting

I am at the ACS meeting in Washington DC, here as "press" rather than chemist. It's a very different way to see the meeting. I went to a press briefing this morning - on the first phases of development of aresol vaccines for measles (Robert Sievers). The press center is tucked away next to the registration, and has everything a writer might want: food, wireless access and a steady stream of caffeine and conversation.

The briefings are being streamed live on the web and journalists watching can send their questions in to be asked. Miss something the first time round? Watch the replay here.

Listening as a scientist to a talk, and as a writer to the briefing turn out to be slightly different experiences. Both require critical listening, but listening as a writer prompts me to think far more about the words the science is coming wrapped in. The shorthand scientists use sounds almost staccato in this context. "Measles naive" instead of "never exposed to the measles virus" or "no evidence of viremia" instead of "no measurable virus in the bloodstream".

We try to be both precise and concise, but I wonder how often the combination in giving a talk, or even reading a paper in the literature leads to attentional processing deficits? An interesting experiment in attentional processing is to present subjects with a rapidly changing sequences of letter, interspersed with numbers. If two numbers are placed too close together, subjects can "miss" the second letter while their brain is busy processing the first. Pack too much into a sentence, and your "subjects" might miss bits.

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My Thesis column in Nature Chemistry this month, Stretching Toplogy, takes a slightly different tack in thinking about the ways words wrap around science.

A rose by any other name is poison ivy

In 1865 John Maisch published a short paper "On the Active Principle of Rhus Toxicodendron". For the unsensitized, rhus toxicodendron is the botanical name for poison ivy. Maisch isolated a fraction he considered to be the "active principle" responsible for the misery that is poison ivy and dubbed it toxicodendric acid. Are you itchy yet? (I am and Maisch surely was, he and various visitors to his lab suffered with outbreaks of poison ivy.)

By 1897 Franz Pfaff of Harvard had weighed in. Toxicodendric acid extracted from poison ivy turned out to be acetic acid - yes, vinegar, by another name, CH₃COOH. He showed the itch was in the oil.

The Grecian Bends: Ladies' Corsets and Henry's Law

In an earlier post I suggested there was a connection between ladies' corsets and Henry's Law. A general statement of Henry's Law is that the solubility of a gas in a liquid depends on the pressure of the gas above the liquid. An everyday example is soda. A can of soda is pressurized by exposing it to carbon dioxide having equivalent of about 2.5 times atmospheric pressure at room temperature. When you quickly lower the pressure of carbon dioxide over the liquid, say by opening the can, the solubility decreases and the gas adjusts by rapidly coming out of solution. Fizzing results (and eventually the soda goes flat).

When a diver dives the pressure of the gases breathed increases, and the amount dissolved in the blood increases. Diving to just 50 feet increases the total pressure to roughly that of the carbonated soda! Rapidly ascending reduces the pressure, just like opening the can of soda, and the gas rapidly comes out of solution - the diver's blood can "fizz". Bubbles in the blood and body tissues are clearly not a great thing, and the physiological effects range from the relatively minor (bubbles in the skin layers) and joint pain, to potentially lethal embolisms in the brain and lungs.

This phenomenon was first observed by Robert Boyle in 1670 who noted the formation of bubbles in the eyes of a snake that had been placed in a high pressure environment, then rapidly decompressed. "I once observed a viper furiously tortured in our exhausted receiver… that had manifestly a conspicuous bubble moving to and fro in the waterish humour of one of its eyes." Before the effects was widely understood, many construction workers suffered from "caisson workers' disease" while working in pressurized environments (caissons) under rivers.

Dive tables - a schedule for ascending from a dive that reduces the chance of decompression sickness - were first created for use by British Navy divers in the early 20th century. How do whales and dolphins cope without dive tables? Half-mile deep, hour long dives are not uncommon - and a rapid ascent from depth could cause a massive case of the bends. They may not be immune - recently researchers have found evidence for chronic decompression injuries in sperm whales. The whale bone in the photo above shows evidence of dysbaric osteonecrosis (bone death caused by rapid decompression).

What does this all have to do with ladies' corsets? In the 1870s tight corsets and big bustles were all the rage. The posture forced upon women wearing these fashionable undergarments was called the Grecian Bend. As decompression injuries caused a similar posture, workers on the Brooklyn Bridge christened the syndrome "the Grecian bends", soon shortened to "the bends".

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The photograph of the whale bone is by Tom Kleindinst, Woods Hole Oceanographic Institution and is used with permission.

The image of the Grecian Bends is from the Library of Congress

Repackaging Vitamins: Niacin

Vitamins are small molecules (where small is relative to proteins!) that a living organism cannot synthesize, but are nevertheless required. The word vitamin was coined by a Polish biochemist, Kazimierz Funk by sandwiching together "vital" and "amine". Not all vitamins turned out to be amines (molecules with an NH₂ group in them), however the name stuck.

One such non-amine "vital amine" has the structure shown below. It's a carboxylic acid (the COOH group). Originally designated as vitamin PP, it is now better known as the third of the B vitamin complex or B₃. PP stood for pellagra preventing factor. Pellagra is a nutritional deficiency, once common in Italy, that results in rough skin - pella is Italian for skin.

The original common chemical name for B₃ was nicotinic acid. (The synthetic form can be made by oxidizing nicotine with nitric acid.) In the late 1930s, niacin (NIcotinic ACid vitamIN) was adopted as the preferred name, to avoid confusion with nicotine. (I'm unclear why this was undesirable; smoking was pervasive.)

Repackaging scientific terms to make them less frightening for the general public is not just a historical phenomenon. Much more recently the application of NMR (nuclear magnet resonance) to medical imaging saw its "nuclear" dropped (thus forestalling any potential association with nuclear radiation) to become MRI (magnetic resonance imaging). It should be made clear, that like nicotinic acid, which contains no nicotine, NMR does not require nuclear radiation.

Elemental Tales: Reduced Iron

In the 1970's I was a TV news junky. Dinner was typically late - my dad commuted an hour plus from LA in those days - and my mother would kick me and my homework off the table a bit before 6. I'd duck into the den to get the update on the war (Vietnam, not Iraq!) that my friends' older brothers were fighting. Even then, I was clearly not the advertisers' target demographic. The ads ran the gamut from DentuGrip to Phillip's Milk of Magnesia. And of course, Geritol - exhausted wives re-energized by curing their "iron poor blood" with Geritol, much to their husbands' delight ("My wife. I think I'll keep her!")

More than one in ten adult women (12-49) in the US do suffer from "iron poor blood" or more technically iron deficiency anemia, and world-wide it is the most common nutritional deficiency. (By some estimates two-thirds of pregnant women in developing countries are anemic, primarily due to lack of iron in their diets.)

The body does an impressive job of holding onto the iron it needs not only for synthesizing the oxygen carrying protein hemoglobin, but for enzymes used in other key processes. Total body stores of iron run from about 2 to 4 grams, about two-thirds circulating around in hemoglobin, and twenty percent held in reserve in the bone marrow. The daily loss ranges from 1 milligram to about 1.5 mg in women of child-bearing age. Which begs the question, why is the FDA's recommended dietary allowance of iron 20 mg?

The answer has much to do with the ability of the body to extract iron from various sources. The best form of iron, in terms of its bioavailability, is heme-iron, or iron bound to the plate-like heme structure found in hemoglobin. Non-heme iron, found in plants like the iconic iron source spinach, is tougher for the body to extract and use - estimates are only 10 to 15% of the iron can be absorbed. So to get that 1 mg a day, you need to consume about 10 mg a day. If spinach is not your cup of tea, try dark chocolate; there's 2.3 mg of iron in a 100 gram bar, about the same as in the identically sized serving of spinach.

Lots of Americans get their iron from fortified cereals. Read your box of Total. You'll find that a cup gives you 18 mg of iron. Check the ingredients and you'll notice that it's added in the form of reduced iron. Reduced iron is not iron on a diet, but iron is the pure metallic form. That's right, there's tiny iron filings in your cereal. If you're feeling experimental, toss a couple of cups with milk into the blender, then run a magnet through it. You'll pick up the filings on the magnet. The acid in your stomach turns the metal into an ionic form (Fe²⁺).

Better yet, cook in cast iron. Scramble your eggs in a cast iron frying pan and you can triple the iron content (from 1.5 mg to almost 5 mg). Cook something acidic, like spaghetti sauce and you can up the iron content by a factor of ten.

Husbands of tired wives might thus consider a nice box of dark chocolate covered apricots rather than replacing the window shades with ads for Geritol...it might cure more ills than just iron deficiency. I would not advise a cast iron frying pan with a bow!

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Dried apricots have twice the iron content of spinach and are much tastier when drenched in chocolate.

The heme figure is taken from here.

Silver linings

Yesterday I had a round of minor surgery. When all was said and done, the surgical site was cauterized with what a nineteenth century physician would have called "lunar caustic" -- silver nitrate to a modern chemist or physician. I have to admit my first geeky thought was, "how does that work?"

Silver nitrate has been used for a long time as a cauterizing agent. In 1826 John Higginbottom, a British physician wrote An essay on the application of the lunar caustic in the cure of certain wounds and ulcers. My physician used a solution of AgNO₃, Higginbottom almost certainly used a solid mixture of silver nitrate and silver chloride, but other than that the basic treatment protocol hasn't changed in almost 200 years. Higginbottom notes that the application "smarts" and I would guess that it must have. I felt it, even with a good local anesthetic. The good 19th physician also prescribed adjuvant therapy ("I took away ten ounces of blood and administered purgative medicine") which my physician sensibly eschews!

So why is the stuff called lunar caustic? The caustic part is obvious, silver nitrate is an effective oxidizing agent for organic molecules, including biomolecules. Alchemists associated silver with the moon, its Latin name, argentum derives from "white, shining".

Urrrrrr - it itches!

The spring was cold and so the itch to get outdoors once the warm weather arrived was hard to resist. As moms will tell you, scratching just makes the itching worse, and scratching even metaphorical itches can raise welts. Ask anyone who has heeded the siren call of summer and ended up with hives, or worse yet, encountered a patch of poison ivy.

My niece and I took a tour last week of the Mutter Museum in Philadelphia which has a great collection of wax models of dermatological pathology, used for teaching students in the days before slides and PowerPoint, including hives or urticaria. The name comes from the Latin for nettle, and the resulting skin wheals certainly bear some resemblance to nettle stings (as my youngest can attest after a close encounter with that plant). Histamine leaking from mast cells in the skin is responsible for hives' principal misery - itching.

True misery is reserved for those who have contacted Toxicodendron radicans - poison ivy - or a relative. These plants produce urushiol, which binds tightly to proteins in the skin. Molecules like this are called haptens, which comes from the Greek "to fasten". Antibodies don't recognize the small molecule until it fastens onto its target. Then the body reacts, in this case triggering the characteristic linear rash, and keeps reacting until the invader detaches from its binding site.

Despite the similarity in names between urticaria and urushiol, they come from different roots. Urushiol was first isolated from the Japanese lacquer tree - the urushi - by a Japanese chemist, Miyama.

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Other haptens can react with the same sites as urushiol, including substances found in mango skin and fresh cashew nuts, with similar unfortunate consequences.

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Urushiol isn't just a weekend gardener's nuisance, but can cause serious problems for fire fighters in working brush fires in areas such as the California hills, where poison sumac, another urushiol producing plant, thrives. The chemistry gives some clues to helping prevent and treat urushiol reactions. Application of an organic derivative of an absorbent mineral (bentonite) can soak up and trap any oil before it reaches the skin and binds- this is the principal behind the commercial product Ivy Block. Alternatively, something that binds strongly to the urushiol target but is not itself a hapten could act as a preventative. D-Limonene, found in citrus skins, has been floated as a possibility, but I couldn't find any evidence that it works!

Once the stuff has bound, you just have to wait it out. It takes a couple of weeks for the bulk of the urushiol-protein complexes to break down. In the meantime, steroids can reduce the inflammatory reaction and histamine blockers, H1 (like Benadryl) or H2 (Tagamet or Zantac) can provide some relief from the itch.

Half-awake, half-life

I had a moderate allergic reaction to peanuts last night. I took diphenhydramine (Benadryl) and the hives had subsided by this morning. Lecturing on perturbation theory was more challenging. I felt like I was walking in a fog. Which got me to wondering, just what was the half-life of Benadryl? Benadryl has a relatively long half-life, between 8 and 10 hours. A typical 50 mg dose leads to a peak blood level of around 80 nanograms/ml. Most people feel drowsy at blood levels around 30 nanograms/ml. Assuming first order kinetics apply to the breakdown/elimination of Benadryl, a 30 nanogram/ml is not unlikely 10 to 15 hours later. Which would certainly explain my fogged state this morning! But not so foggy as to be unable to work the kinetics....