One day on Twitter, some science bloggers who began life on the dark side, in the humanities, happily discovered a shared taste for classic mystery writers.  We thought we might write a series of posts, all on the same day, about the science in mystery books and so we did exactly that in December. And it was so much fun we decided to do it again.

My colleagues in crime, Jennifer Ouellette and Ann Finkbeiner, have looked to the great crime novelist, Dorothy L. Sayers, to explore other areas of science.  At her blog, The Last Word on Nothing, Ann writes about post-traumatic stress syndrome in the aftermath of World War I. And at Cocktail Party Physics, Jennifer takes another Sayer’s book as the starting point for a journey through the physics of music.

As for me, this time around, I found a combination of Agatha Christie and the terrifying toxicity of strychnine to be an irresistible combination…..

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There is altogether too much strychnine about this case – The Mysterious Affair at Styles, Agatha Christie,  1920.

In the midst of World War I – or so the story goes – a young Englishwoman received a literary challenge from her sister. Could she write a mystery novel in which the true villain was impossible to guess?

The response to that challenge was a tale of strychnine and murder that launched one of the most successful careers in crime fiction. No exaggeration whatsoever:  the book was published, after several years of publisher hunting, in 1920; its title is The Mysterious Affair at Styles; its brilliant fictional detective is called Hercule Poirot and its author (30 years old at time of publication) is named Agatha Christie.

Christie would go on to write about 65 detective novels and some 14 short story collections (not to mention the occasional play) before her death in 1976. Over the years, sales of her books reportedly have reached close to four billion. But for purposes of this poison-obsessed blog, let us stipulate her dazzling success, her famed fictional characters, and even her famously intricate plotting techniques. Let us focus instead about another celebrated Christie characteristic: she also was obsessed with poisons.

They were her weapon of choice, so much so that a University of Texas pharmacology professor even wrote a book on the subject, titled The Poisonous Pen of Agatha Christie , a survey of the 30 odd poison murders in the mystery novelist’s 66 books. The poisons spanned such a range that the professor felt compelled, as one reviewer noted,  to include a 76-page alphabetical listing of all the toxic compounds – from strychnine to arsenic to thallium to taxine – and all the related chemistry in the Christie ouevre.

I’ve been reading Christie and admiring her devious plotting since I was a teenager given to raiding my mother’s prized collection of murder mysteries.  Her work and others from  the 1920s and 1930s, a era sometimes called the golden age of detective fiction, always fascinated me. The wickedness of the poisons, the cold calculation of the poisoners in the stories, all influenced my own non-fiction book, The Poisoner’s Handbook, which takes a narrative look at forensic toxicology in that same time period. In an earlier Science of Mysteries post, I paid tribute to another brilliant crime novelist of the time, Dorothy L. Sayers and her well-researched study in arsenic, Strong Poison.

But no crime novelist wrote about poison with such knowledge and enthusiasm as Christie, who once said: “Give me a decent bottle of poison and I’ll construct the perfect crime.” In fact, at the time that Christie began work on A Mysterious Affair at Styles, she had been working as a wartime nurse, had been employed in a hospital pharmacy ( then called a dispensary), and had studied for and passed  a test to become a member of the Society of Apothecaries.

So she began her career with a subject she knew well. And the plot of this first novel involves the strychnine poisoning of Emily Inglethorp,  a wealthy and dictatorial elderly woman living at Styles, a classic English country house. The soon-to-be victim is recently remarried to a mysteriously bearded and slightly smarmy younger man. The marriage has thrown into disarray the inheritance plans of her two step-sons who both also live in the house. Residents also include the exotically beautiful wife of the older son and the love interest of the younger, a nurse who happens  to work in a hospital dispensary, and assorted other suspects.

In fact, it’s very much a first novel,  a writer finding her style. Christie would grow into an author with a smooth style,  skilled in elegant misdirection. The Mysterious Affair at Styles has the misdirection without the elegance. It’s cluttered with quarrels, accusations, footprints, spies, cheating husbands, cheating wives and other misunderstandings among the red herrings litter the landscape. But in my particular version of fandom,  all can be forgiven in admiration of the precise (and elegant) chemistry that underlies the story.

The crime comes one summer morning when the household is awakened by “the most alarming sounds” coming from Mrs. Inglethorp’s locked bedroom. When the door is broken down, the woman is found to be suffering from horrible convulsions, one of which “lifted her from the bed, until she appeared to rest upon her head and her heels, with her body arched in a most extraordinary manner.” She dies shortly later and, triggered in part by those terrifying spasms, a criminal investigation is launched.

The story is narrated by a convalescing British soldier, Arthur Hastings, also residing at Styles. He’s an iconic mystery character,  the one who fancies himself a detective but pretty much misses every clue. Hastings, however, does discover an old acquaintance in the village, a former police investigator from Belgium whom he had met while on the continent. He convinces Mrs. Inglethorp’s relatives to hire his friend – Hercule Poirot – as a private investigator.  They establish a Watson-and-Holmes relationship that continues through a numer of Christie books to follow.

The poison in question is quickly identified as strychnine, famous for inducing such horrifying convulsions. Strychnine is a naturally occurring plant poison, a crystalline alkaloid found in the Strychnos family of tropical trees  and climbing shrubs. The best known of these plants is the Strychnos Nux Vomica tree from Indonesia; the hard, disk-like seeds of the tree are sometimes referred to as vomit buttons.

But that mostly refers to the poison’s very bitter taste.  Its primary effect is as a neurotoxin, binding to motor neurons that control muscles and interfering with neurotransmitters that act to moderate and shut down electrical signals. At lethal doses,  result is a constant barrage of signalling that results in sometimes non-stop muscle contractions, creating the kind of convulsions described by Christie in her book.

At the time that Christie was writing, the chemistry and mechanism of strychnine remained something of a mystery too. The alkaloid itself would not be synthesized until 1954, work done by the American biochemist and Nobel Laureate Robert Woodward. But it was a long established poison, a recognized vermin killer in 17th century Europe. And its impact on the nervous system action was known and well-respected. In low doses, it was even prescribed as neuro-stimulant, a kind of chemical pick-me-up for people complaining of flagging energy.

To further confuse the case, then, the story’s victim, Mrs. Inglethorp, has herself just finished taking a strychnine tonic. But she had been taking it for weeks at far too trace a dose to have triggered the convulsions. The police suspect instead that her evening cup of coffee was poisoned. The coffee, of course, was left sitting on a hall table so  that almost anyone in the house could have poisoned it.

And the coffee theory set up another poisonous puzzle. Strychnine is a notably fast-acting poison; in animals, symptoms often arise within 30 minutes, according to the Merck Veterinary Manual. In humans, as soon as 15 minutes after ingestion, according to the U.S. Centers for Disease Control and Prevention (CDC). Yet Mrs. Inglethorp’s death occurred between five and six hours after she apparently drained her cup.

Strychnine itself is a tricky choice for the homicidal killer because its violent action leads so rapidly to suspicion. During the 19th century – a time when poisoners flourished, largely because forensic chemistry was still in its infancy  – a few notable cases occurred. Probably the best known is that of Thomas Neil Cream, who poisoned a series of London prostitutes with strychnine in the 1890s. Before he was hanged, Cream also took credit for the crimes of  Jack the Ripper. A widely publicized earlier case was that of William Palmer, who was executed for the strychnine murder of a friend but suspected of also killing four of his children, all of died of convulsions before their first birthdays.

These are isolated incidents, though. Killers of the day far preferred to use arsenic, antimony and other poisons that tended to mimic natural illness in their effects. Arsenic only fell fully out of favor in the early 20th century, after scientists proved repeatedly that it was readily detectable in a corpse.

In his recent book, Bitter Nemesis: The Intimate History of Strychnine, author John Buckingham suggests that Christie had, however, studied the Palmer trial for inspiration. He points out that the Palmer case included a coffee pot left out in a hallway so that many people could have put poison in it, an inquest at a village in, a doctor already up and dressed in the middle of the night, and a pharmacist who having sold strychnine to Palmer, believing it was to be used to kill a feral dog. All of those elements occur in The Mysterious Affair at Styles – although in Palmer case, Palmer himself was the overdressed doctor in the night and in the Christie telling, the suspected physician turns out to be (spoiler here) a German spy.

But his larger complaint lies with the chemistry-based solution to the mystery itself. Consider this only a partial spoiler because I’m not going to give away the killers in the case.  I am going to tell you how Christie solved the timing of Mrs. Inglethorp’s death. As Hercule Poirot investigates the killing, one of the clues he discovers is an empty box of potassium bromide powders, a compound used as a mild sedative in the early 20th century.

As Poirot discovers, potassium bromide can be used to precipitate strychnine out of a suspended solution. In other words, by mixing it into Mrs. Inglethorp’s tonic, the killer can cause all the strychnine to settle into a lethal layer at the bottom of the bottle. When she takes the last dose, late at night, long after drinking her coffee,  she receives a concentrated amount of this very dangerous poison.

Buckingham complains: “We are expected to believe that medically unqualified conspirators, whose main talent appears to be running around the village wearing false beards (yes, another spoiler) are party to an obscure piece of physical chemistry that only Christie, a qualified dispenser, and at most a handful of her readers would have known.”

He wasn’t the only person to note this weakness. Christie herself didn’t deny it but she pointed out that one of the characters in the book is, after all, works in a dispensary, is studying for the apothecary exam and leaves her notes and books all over the house. Anyone at Styles could thus have – with a little homicidal enterprise – figured out the chemical ways and means in the case.

And you have to admit that it’s a wonderfully geeky solution to a murder mystery. The book received positive reviews from publications ranging from The Pharmaceutical Journal to The New York Times, which said: “Though this may be the first published book of Miss Agatha Christie, she betrays the cunning of an old hand.” But don’t take their word for it, or Buckingham’s, or even mine. As it was published in 1920, The Mysterious Affair at Styles has outlived its US copyright protections. You can find it at Project Gutenberg and elsewhere for free. And that Miss Agatha Christie would probably have considered a crime as well.

Note: I linked to my Sayers and arsenic piece, from the first round of Science of Mysteries, in the post. If you are curious about the rest of that package, Jennifer’s posts can be found here and here. Ann’s is here.  They are brilliant, of course.

I’m a long-time fan of New York Times columnist Nicholas Kristof. To be more specific, I’m a long-time fan of his work in social justice journalism, his passionate reporting of problems of others ignore, his dedication to helping people in traumatized regions of Africa.

It’s outstanding work and, oh, how I wish he would stick to it. Because his secondary crusade of the last few years, you know, the one against evil industrial chemicals, is really starting to annoy me. This is not saying that he’s entirely wrong – there are evil industrial chemicals out there. And, in many cases, they aren’t as well researched or as well regulated  as they should be.

But if we, as journalists, are going to demand meticulous standards for the study and oversight of chemical compounds then we should try to be meticulous ourselves in making the case. And much as I would like it to be otherwise, I don’t see enough of that in Kristof’s chemical columns. They tend instead to be sloppy in their use of language, less than thorough, and chemophobic enough to undermine his legitimate points.

In the matter of chemophobia, I’d like to refer you to a piece I wrote two years ago following a Kristof column of May 2010: Here’s a short excerpt: “After proposing a link between too much chemistry and not just cancer but diabetes, obesity and autism, Kristof goes on to say “This is not to say that all chemicals are evil…”.  I still cannot read that line without rolling my eyes.

Because, how do you define a good or an evil chemical? Hydrogen (H) is an essential element of water (two hydrogen atoms, one oxygen= H2O) which comprises more than 90 percent of our own bodies and sustains most of life on earth. It’s also found in the incredibly poisonous formula of HCN (hydrogen cyanide). Oxygen in a doublet (O2) keeps us alive. In a triplet (O3) it’s known as a toxic pollutant called ozone. And while ozone is dangerous in ambient air it’s also essential in the upper atmosphere for blocking ultraviolet radiation from the sun.

Yes, there are unambiguously dangerous materials – the naturally occurring element lead (Pb) comes to mind. But mostly, it makes no sense to randomly throw the word “chemical” around as if it had any meaning in terms of human health. And when we have influential journalists using the word chemical as a synonym for spawn-of-Satan then we have journalists who’ve missed their opportunity to inform the public as to what is a legitimate risk and what is not.

Instead we – by which I actually mean Kristof  – run the risk of teaching nothing more than a generalized chemical anxiety.  To this instance, I cite another of his columns from 2010, “Do Toxins Cause Autism?”, which notes the upward trend in autism diagnoses and speculates that “one culprit may be chemicals in the environment.”  As our environment is, in fact, nothing but chemical compounds this fails what I might call the helpfulness test. Or, as the blogger Polly Palumbo of Momma Data put it, “How do you scare parents silly? Mention toxins, prenatal development and autism together.”

Which brings me to Kristof’s column of this month, which is titled “How Chemicals Change Us.” Right. But let’s not just roll our eyes. Let’s try inquiring as to what he means. So, you say, which “chemicals” do you mean precisely? He answers in the first paragraph:  “common hormone producing chemicals”? Oh, you respond, and what are those precisely? “A widely used herbicide,” he replies in the second graph, one that apparently feminizes fish and gives alligators tiny penises.  Oh, you try again, what herbicide exactly? But here, reader, you are just out of luck. Because he is just not going to tell you that. Not in that graph or anywhere in the piece.

I’m going to guess that it’s (a) the herbicide Atrazine which was linked ten years ago to “hermaphroditic, demasculinized frogs.”  But it could be (b) Roundup, instead, according to this one of many scientific studies on that subject.  Or it could be (c) another glyphosate pesticide. Glyphosate (a chemical cocktail of carbon, nitrogen, hydrogen, oxygen and phosphorus) is the central ingredient in herbicides such as Roundup. It’s also the endocrine disruptor in question,  the actual reason for concern. Or it could be (d) all of the above.  You tell me, reader, because the New York Times column doesn’t.

Kristof does cite some other endocrine disrupting compounds here such as BPA, best known for its use in plastic bottles and packaging,  and perfluorooctanoic acid (PFOA), used in everything from non-stick cookware to fire-retardant materials. But he breezes through their possible risks. Oddly, the one specific claim he makes against PFOA is an iffy study suggesting that prenatal exposure could, possibly, make girls – but not boys – overweight later in life. He ignores entirely a recent finding that the compound may be a more potent carcinogen than had been suspected.

You would think that a writer who wants to win a fight with “Big Chem” (as Kristof refers to the makers of these compounds) would choose the best ammunition at hand, wouldn’t you? Perhaps he needs a better researcher. Or perhaps, as Palumbo suggests at Momma Data, he needs a better fact-checker.  Or perhaps he needs to consider what he’s really trying to accomplish here.

Consider the conclusion to his most recent piece. He quotes a government scientist who no longer microwaves his food in plastic and avoids canned food (presumably because cans are lined with BPA although that isn’t clear here). And then he adds:”I’m taking my cue from the experts and I wish the Obama administration would as well.”

That the Obama administration would what exactly? Abandon canned food or better regulate regulate toxic chemical compounds? Are we talking household hints or policy implications?  If I didn’t believe we actually need smarter, more thoughtful regulation of toxic compounds, I wouldn’t find Kristof on chemicals so annoying. He’s wasting his opportunity and his outstanding platform on this half-researched, half-thought out muddle of a crusade.  I wish he would focus and do it right. Or not do it at all.

This is the Hour of Lead-
Remembered, if outlived,
As Freezing persons, recollect the Snow-
First – Chill – then Stupor – then the letting go –

When 19th century poet Emily Dickinson wrote those lines, she was describing the terrible paralysis of grief. A good century later, analysts for the Environmental Defense Fund, would also note that the last line “aptly describes some of the symptoms of lead intoxication.”

I’ve always suspected that they also just liked the poem and wanted to use it – certainly that’s partly my motive here. But I’ve also been thinking about one phrase in Dickinson’s verse because it seems to me, recently, that as a human society we seemed perpetually caught – by which I mean poisoned – in an endless” hour of lead.”

The chemical symbol for lead is Pb, from the Latin word “plumbum” which referred to a malleable metal. The term plumbing comes from the use of lead pipes by the Romans; a plumber fixes them, a plumb bob refers to a lead weight, a plumb line is pulled straight by such a weight. An old-fashioned term for lead poisoning is plumbism. We are surrounded by references to what is arguably the most important poison in human history.

Many scholars have argued, for instance, that the plumbum-loving Roman empire – enthusiastically using lead pipes, bottles, and wine cups, leaded cosmetics and paint – came to its end partly due to lead-poisoning of its upper classes. One U.S. Environmental Protection Agency paper on the history of lead poisoning, cites “the conspicuous pattern of mental incompetence that came to be synonymous with the Roman elite” as evidence of lead’s destructive effects.

Interestingly, the EPA paper also cites poetry to illustrate the evils of lead poisoning, a scrap of anonymous verse, attributed to a Roman hermit and translated in 1829:
The feeble offspring curse their crazy sires,
And, tainted from his birth, the youth expires.

The key points there being, of course, crazy sires and dead children. “No safe blood lead level has been identified,” notes a U.S. Centers for Disease Control and Prevention (CDC) backgrounder on exposure risks. Lead is a broad spectrum poison – it interferes with enzyme production, especially enzymes needed by red blood cells, and is known to cause lethal anemias. It targets neurons, disrupting the production of neurotransmitters such as glutamate (which plays a key role in learning by enhancing plasticity). It deposits itself into bones and stays there – the half-life of lead in human bones is up to 30 years. Muscle weakness, numbness and tingling, nausea, severe stomach pain, depression, fatigue, sleeplessness, loss of libido – all are symptoms of lead poisoning and all speak to its ability to impact every part of the body.

The Romans weren’t the only major civilization from our past to be affected by lead poisoning. Last summer, environmental scientists in Japan reported the results of an investigation into lead exposure in the Edo period, which lasted from 1603 to 1867, a time when the country was dominated by shogun leaders, and laws enforced by an aristocratic class of samurai warriors.

According to Tamiji Nakashima, an anatomist at the University of Occupational and Environmental Health in Kitakyushu, the investigators studied the remains of samurai men, their wives and children, about 70 in total. Earlier tests had found unusually high levels in the women compared to men; the last study looked at the children. The researchers tested for lead in rib bones, x-rayed the childrens’ arm and leg bones looking for signs of lead poisoning.

The Japanese scientists had already concluded that the lead levels in women were directly related to the white face paint popular in aristocratic circles, which turned out to be loaded with lead. They wondered if exposure to the same material might have harmed the children and the new results showed them precisely right; they found evidence of lead levels more than 120 times background level as well as bands of lead deposits in the bones.

Nakashima and his colleagues believe that the children were poisoned by touch, as they were fed, hugged, carried by their mothers, the lead-rich paint rubbed off on them. They also speculate that the gradual lead-poisoning – with its inevitable taint of death and disability – helped put an end to the shogunate reign in the late 19th century, setting up the transfer of power to an emperor.

It has only been in the last century, of course, that we’ve realized just how dangerous lead actually is. That knowledge has resulted from the new ability of scientists to detect it in very tiny amounts and to connect those trace exposures with health problems. In the dawn of lead awareness, governments have banned lead paint and leaded gasoline, moved to replace lead pipes in water systems, squeezed down allowable lead levels in consumer products.

Is this a smart response? Yes, obviously, if we are talking about poison unsafe at all levels. But only if said governments are actively – and honestly – trying to enforcement protective standards. For instance, as reported last year by The Washington Post, when inspections discovered massive lead contamination from pipes in Washington D.C. in 2004, the Bush administration not only issued misleading reassurances but moved to loosen protective measures designed to protect against lead poisoning.

Or consider the discovery of lead in popular lipstick brands sold in the United States. Although some of these products showed clear lead contamination in amounts above EPA safety levels – and although women inevitably swallow some lipstick – the U.S. Food and Drug Administration insists that the lipsticks are perfectly safe.  But as I noted in a recent post for the Knight Science Journalism Tracker, there remains considerable consumer doubt and fear about such findings.

Our leaded history continues to haunt us in this country. Lead-based paint remains in hundreds of residential buildings around the country, especially in poor neighborhoods, and our government seems newly reluctant to fund programs that remove such hazards. And it’s not just a paint-in-the living room problem. As USA Today reported this week, the government has been slow to alert city residents of lead-contaminated soils surrounding their homes, linked to long closed factories.

And to raise a non-urban example, considered the still unresolved petition filed with the EPA last year, trying to force the agency to regulate the use of lead shot in hunting, which advocates say is now killing more than 10 million birds and animals every year, mostly due to consumption of spent lead pellets. contaminated by lead.

“It’s long past time do something about this deadly – and preventable – epidemic of lead poisoning in the wild,” said Jeff Miller, conservation advocate for the Center for Biological Diversity. The government does ban the use of lead pellets in shooting waterfowl but conservationists say this barely touches the problem. Still, the EPA has been notably reluctant to take an this issue angrily opposed by hunting groups, who are already describing the petition as an attack on traditional hunting values.

This is not to suggest that lead problems – or even the worst lead problems – are concentrated in the United States. In 2010, more than 1,300 children were sickened in China by lead exposure from nearby smelting plants, leading to furious protests from their parents against government cover-ups. Not to mention, lead poisoning related to gold-extraction in Nigera, where  where health experts say more than 400 children have died and thousands more been sickened – as a result of lead exposure related to handling of contaminated ores.

The feet, mechanical, go round
A wooden way
Of ground, or air, or ought, Dickenson wrote in The Hour of Lead and she was writing, of course, of the clock-work motions of those caught in grief. But it strikes me that the mechanical analogy applies here too because we keep repeating these same actions that bring us into harm, as if we cannot seem to fully learn – or fully respect – what our own history should have taught us here.

We remain, thus, in our eternal hour of lead, still not fully awakened from that our lead-induced stupor, apparently, and still unable to let go.

(This is an update of one of my favorite posts, partly because lead is such an important poison, and partly because I managed to weave the poet Emily Dickinson’s wonderful poem into it!)

The primary reason, as CDC notes, is the rise of opioid pain-killers and their increasing abuse: “During the past three decades, the number of drug poisoning deaths increased sixfold from about 6,100 in 1980 to 36,500 in 2008.”

I mention this because this week (March 18-24) is National Poison Prevention Week, which began 50 years ago in 1962. (That particular year also saw the publication of Rachel Carson’s crusading novel, Silent Spring, which helped galvanize public attention concerning the risks associated with what she recognized as too casual use of industrial and agricultural chemicals.)

We should obviously add to that warning list the too casual use (and abuse) of prescription drugs. In its press release, which I’ve linked to above, the Poison Prevention Week Council notes that emerging hazards “have again ignited the need for increased awareness. In just the past year, America’s 57 poison control centers fielded 4 million calls, treating 2.4 million human poison exposures and handling 1.6 million information calls.”

As readers of this blog know, increased awareness of our chemical world is one of my ongoing crusades. And while I’m not given to public service announcements, I do like to take every opportunity to sound that trumpet. The rise in poison deaths and injuries should remind us that however well informed we may consider ourselves – there is much room to do much better.

For instance –  yes, another a pet crusade of mine – we could reduce carbon monoxide deaths if we would just take more seriously the dangers posed by that odorless, colorless and extremely poisonous gas. On the very first day of poison prevention week, I read this story from California about five people hospitalized with carbon monoxide poisoning due to a heater leak. As the story noted, there were no working carbon monoxide detectors in the house. As the CDC also notes, this gas kills hundreds of people every year and sends an average of 15,000 annually to the hospital in the U.S. alone.

But enough about me and my crusades. There’s a slew of good information this week about protecting yourself – and your pets – from every day toxic substances.

Here, for instance, is some good advice on protecting children from Health News Digest.

Here’s some ways to protect your pet, courtesy of Pet MD.

There’s a smart piece here from Consumer Reports on when to lock away household chemicals.

And an announcement here from the U.S. Environmental Protection Agency (EPA) which summarizes some of the major issues. (Both Canada and Mexico are also participating in poison prevention week.)

Pay attention to this, okay? Oh, and go get that carbon monoxide detector. You don’t want to end up in this blog, do you?

Kathleen Hobson was eight years old when her mother unknowingly dosed her with poisonous cough syrup. She’d only taken a couple spoonfuls but when investigators came round, they still found nothing left to test.  After the little girl died, her mother had set the bottle on fire and then thrown it into the trash.

Charlene Canady was just four when she died from the same medication. Her father had carefully packed the cough syrup bottle, waiting for justice to come calling.  I always imagine him silent when he handed the bottle over, grief and his daughter’s name caught like a kind of suffocation in his throat.

Both little girls lived in Tulsa, Oklahoma, both came down with nasty little colds in the fall of 1937,  and both died because they were dosed with a brand new medication, a popular, raspberry-flavored cough syrup.  In all, the syrup would kill 11 people in Oklahoma, within a few weeks. Ten in Alabama. Ten in Georgia. Twenty-three in Mississippi. Nine in South Carolina. Seven in Texas. More in California, Ohio, Illinois, Missouri, Virginia, Louisiana, and more.

More than one hundred dead nationwide, in fact, and most of them children, Charlenes and Kathleens scattered across the United States like so much storm wreckage.  “Nobody but Almighty God and I can know what I have been through these past few days,” a Louisiana doctor later wrote to the U.S. Food and Drug Administration, after six of his patients died in one week.

As FDA scientists would quickly realize, the syrup was lethal because it was sweetened by a compound known as diethylene glycol which kills by causing acute kidney damage. Both diethylene glycol and the obviously closely related compound, ethylene glycol (even more toxic) are best known today for their use as antifreeze agents and  homicidal weapons on more than one occasion.

But at the time that Elixir Sulfanilamide came to be, produced by the S.E. Massengill Company of Bristol, Tennessee, that wasn’t well understood.  There was actually no legal requirement that companies understand their products, much less safety test them.

The company chemist who designed the cough syrup by mixing a sulfa drug into the poisonous sweetener claimed to have no such knowledge. And as the company president, Samuel Massengill responded: “We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results. I do not feel that there was any responsibility on our part.”

The resulting  Elixir Sulfanilamide scandal – and it was, indeed, an incendiary, nation-rocking scandal at the time –  is mostly forgotten today. But it shouldn’t be. Those rippling deaths, the feeble government response, the indifference of the manufacturer and its big business allies –  provoked such a passionate outcry that a year later, the long-delayed  U.S. Food, Drug and Cosmetics Act was signed by President Franklin Roosevelt.

The 1938 law was first major upgrade of 1906 legislation. The earlier law established the U.S. government as a guardian of the American people’s safety, set precedents in regulating toxic chemicals in food and drugs. But that turn-of-the century law was in many ways a piece of regulatory lace, full of exceptions and exemptions.  The new law filled many of those holes, gave power to protective rules.

Now, for  the first time,  manufacturers were required to safety test their wares and could be held responsible for consumer death and injury. In the case of Elixir Sulfanilamide, the company could not be held liable for a single death. It could only be charged with mislabeling – elixirs were supposed to contain alcohol and the cough syrup contained none.

The 1938 law also required manufacturers to list ingredients on their labels in some detail – another first. One of my favorite books of the 1930s, 100,000,000 Guinea Pigs, by Arthur Kallet and F.J. Schlink, is basically a litany of the hidden dangers that preceded that rule: the toothpaste that contained so much potassium chlorate that it was possible to commit suicide by eating a single tube; the high levels of lead in hair dye,;and the use of the toxic element thallium in depilatory creams. One of the side effects of thallium poisoning is that hair falls out. Cosmetic manufacturers of the 1930s thus found it handy in hair-removal products. They expressed surprise at the small epidemic of baldness, paralysis and occasional death that resulted. But, as they reminded irate physicians, they could not be held responsible for that.

But although advocates like Kallet and Schlink spent years marshaling such evidence in an effort to persuade the government to give the FDA actual enforcement powers, they were stymied by business opposition until the Elixir Sulfanilamide scandal galvanized the country. In an essay for the Annals of Internal Medicine, toxicologist Paul M. Wax called it “one of the most consequential mass-poisonings of the twentieth century.”

And it’s that case that always comes to mind when I hear politicians trumpeting the wonders of an unregulated marketplace, as with the current Republican party mantra that we don’t need strong environmental protections or – at the most extreme vantage point – even a U.S. Environmental Protection Agency at all. Last year, along the same lines,  conservative legislators were busily trying to defund the FDA as well.

The Washington Post’s Ezra Klein points out that Americans tend to sound anti-regulation when queried. But, he adds, if you press them on which oversight they’d like to give up, the picture becomes more complicated. Klein cites a Pew Research survey done in February which found that 53 percent of respondents wanted food and food product regulation increased – only seven percent thought it should be reduced. For environmental regulation, slightly more – a full 17 percent – argued for relaxing the rules.  The survey was, actually, unable to locate a majority of American citizens seeking to be less well protected.

We hear legislators suggest that hard economic times demand the loosening of regulations. But don’t forget that our country was still mired in the long-reach of the Great Depression when that 1938 law was passed. The government recognized, even then, that protection of American citizens meant more than policing our cities and defending our borders. It meant dedicated protection of public health.

Do we sometimes wish that such protection was smarter, moved faster, was more richly knowledge-based?   Less influenced by politics, on occasion, by corporate lobbyists? Of course, we do. But I see that as a call to keep the process as politics free as possible (dreaming, I know), to  invest more in good risk research and to use that knowledge to improve protection against everything from food poisoning to chemical contamination.

We may not remember by name the Kathleen Hobsons and Charlene Canadays of our past. And as I said, the Elixir Sulfanilamide story, is mostly forgotten as well. But we should be grateful for the way it changed our lives. And we should occasionally acknowledge those lost children;  whether we recognize it or not, their ghosts still walk among us today, reminding us of what is right.

The chemical symbol for lead is Pb, from the Latin word “plumbum” which refers to a malleable metal.

And lead is that – soft, malleable, wonderfully conformable, metal of a hundred uses. Its presence – and indeed the very language of lead  – infuses our culture today.  The term plumbing dates back to the use of lead pipes by the Romans. The person who installs and repairs those pipes is called a plumber. A plumb bob refers to a lead weight, a plumb line is pulled straight by such a weight.

Then there’s the word “plumbism” which doesn’t get much use these days. But that happens to be my topic here – plumbism is the  old-fashioned term for lead poisoning, which plagued the Roman empire and continues to plague us today. Some scholars have argued that the Roman’s profligate use of  lead (pipes, bottles, and wine cups, leaded cosmetics and paint) helped put it an end to that empire. An EPA  paper on the subject points out that lead’s neurotoxic contribution is considered a key part of “the conspicuous pattern of mental incompetence that came to be synonymous with the Roman elite.”

Interestingly, Japanese scholars have made a similar case for lead poisoning as a factor in the end of the Edo period in 1867, the decline of the once-powerful  shogunate ruling class.   A recent study by  Tamiji Nakashima, an anatomist at the University of Occupational and Environmental Health in Kitakyushu, and his colleagues analyzed the bones of some 70 samurai men, their wives and children from that period. They had wondered if heavy use of lead-based white face paint had been a health factor and their investigation showed them precisely right; they found evidence of lead levels more than 120 times background level as well as bands of lead deposits in the bones.

Of course, they didn’t know what we’ve learned in the intervening years. “No safe blood lead level has been identified,” according to a current U.S. Centers for Disease Control and Prevention (CDC) backgrounder on exposure risks.

The wonderfully useful metal lead is also a wonderfully broad spectrum poison – it interferes with enzyme production, especially enzymes needed by red blood cells, and is known to cause lethal anemias. It deposits itself into bones and stays there – the half-life of lead in human bones is up to 30 years. Muscle weakness, numbness and tingling, nausea, severe stomach pain, depression, fatigue, sleeplessness, loss of libido – all are symptoms of lead poisoning and all speak to its ability to impact every part of the body.

It is also a notorious neurotoxin. We understand, as the Romans did not, that this happens in part because lead can destroy production of essential neurotransmitters  (such as glutamate which plays a key role in learning by enhancing plasticity). In this country, we’ve been cataloging lead’s ability to do harm for well over a hundred years – U.S. scientists were diagnosing lead poisoning as early as 1887 – sometimes despite the attempts of industry to deny that work. Last summer, I wrote about some of the early 20th century science, and the resulting controversy,  in a post on the troubled history of leaded gasoline.

I mentioned all these moments from history here because they add up to one clear point: we’ve known that lead was dangerous for a very long time. Eventually, in fact, the evidence was so overwhelming that the federal government banned it from paint in 1978 and started phasing it out of gasoline shortly later (although that process didn’t end in this country until the early 1990s.)

Should that have happened sooner. Yes. Did those bans remove all industrial lead contamination from the environment? No. By some estimates, U.S. use of leaded gasoline sent some 7 million tons of lead into the atmosphere, which obviously precipitated right back down to us. And programs to removed leaded paint from old buildings have been woefully underfunded, especially in the country’s poorest neighborhoods where lead-poisoning of children continues to be reported at dismaying levels.

So why, with all this painfully learned awareness in our hands, why in the name of lead-free sanity would our federal government decide to gut the meager program dedicated to helping protect those very family. Yes, the U.S. Center for Disease Control and Prevention (CDC) Healthy Homes and Lead Poisoning Prevention Program has been slashed from $29 million to $2 million for the next fiscal year.

“There’s a serious irony here,” The New York Times noted, this week, pointing out that new public health guidelines recommend reducing childhood lead exposure to even lower levels than now exist. There’s also the fact that removal of lead paint has dragged on for so long that some tenants are turning to civil lawsuits to force the issue. And the fact that a pilot study in St. Louis found that lead paint removal did, indeed, offer some real protection to families in affected neighborhoods.

In other words, in the scheme of our federal budget, this is a very small amount with a very large proven benefit. So why would our government back away from supporting it. “Poisoned Poor Kids?” wrote a columnist for the Colorado Springs Independent. “Congress Doesn’t Care.” At the OpEdNews.com, Peter Montague was even more pointed in a piece titled, “Poisoning Urban Children: White Privilege and Toxic Lead.”

In fact, there’s not a single good public health reason to support this cut – and plenty of potential very bad results to follow. I’m writing here to add my own voice to those calling for these funds to be restored. Let hese children and families least receive a slim promise that we are here to protect their well-being and that we actually do care about their futures. They deserve more than that but I’m not optimistic that they’ll get it.

But the mistakes of our poisonous past should remind us here that this is a very wrong direction. Or perhaps we should just call it plumb crazy.

As

Zimmer is one of the most acclaimed science writers working today. He’s also has a gift for making things happen. After the  meeting, he gathered together a group of especially intrigued science writers and proposed that we launch a new venture – a website dedicated to reviewing science e-books.

To a person  we loved the idea. And barely a month after our first discussion, we launched the site, Download the Universe, yesterday with a book-savvy introduction from Carl and a review by me of Theodore Gray’s gorgeous chemistry-focused e-book/app The Elements. You can read Carl’s post about it at his blog, The Loom, here.

I also want to draw your attention to the other founding editors of the project who are some of the best science writers and bloggers in the country. They include, in no particular order, David Dobbs, Jennifer Ouellette, Brian Switek, Annalee Newitz, Sean Carroll, Maia Szalavitz, Steve Silberman, Ed Yong, Maggie Koerth-Baker, Tom Levenson, Eric Michael Johnson, John Hawks, and John Timmer.

Timmer wrote today’s post on the state of the e-book and there are many more in the queue. But if you have an idea of an e-book you’d like to see reviewed, please do share it. We’re talking about the universe, after all, and there’s a lot of territory to cover.

Last week, a team of researchers from Dartmouth University released a widely publicized study with the somewhat provocative title  “Arsenic, Organic Foods and Brown Rice Syrup.”

The study was yet another general reminder that words like “organic” or “natural” are not synonymous with the word “safe.”  But more specifically it detailed unexpected amounts of poisonous arsenic compounds in everything from infant formula to snack bars, especially compounds containing rice or sweetened with brown organic rice syrup as a healthier alternative to high fructose corn syrup.

I’ll return to the question of exact amounts later; let us just note for now that all findings were in part per billions,  numbers that may raise concerns about long-term exposure but do not suggest that anyone will be dropping dead after snacking on a cereal bar.

The more interesting immediate question anyway, at least to me, was:  why were Dartmouth chemist Brian Jackson and his colleagues looking for arsenic in these supposedly healthy products at all?  I rapidly discovered though that I just hadn’t been paying attention. They were simply following up on an issue well known in health science, a body of work establishing a troubling connection between rice and arsenic in the food supply.

In fact, my use of the word “unexpected” probably is more accurate in describing dismayed public reaction to the results.  The authors of the new study emphasized that their working hypothesis, from the start, was that  brown rice syrup would introduce arsenic into these foods.

So why rice in particular?

As it turns out, the rice plant is uniquely engineered to pick up arsenic from the environment. This begins with the fact that the plant is designed to easily absorb the mineral silicon which helps give  rice grains their elegantly smooth structure. The crystalline structure of arsenic is just close enough that rice plants readily uptake arsenic as well. In fact, a toxic metal study, also from Dartmouth, described rice as “a natural arsenic accumulator.”

The efficiency of this system also means that the arsenic tends to be absorbed directly in its more toxic inorganic from rather than being converted to an organic form of arsenic. Here I mean organic not in the USDA-approved farming sense but in the chemistry sense in which organic refers to carbon-based compounds. And this is important because we metabolize organic arsenic compounds pretty neatly, reducing their toxic potential. It’s inorganic arsenic that’s most dangerous  – it tends to bond tightly into living cells where it destroys them by disrupting their metabolism. And rice, experts say, may be the largest source of inorganic arsenic in our diets.

How does rice find the arsenic? Well, as I said, arsenic is a naturally occurring

element, sprinkled through soil and rock across the planet.  I’ve put a basic arsenic map of the world here to the left to show you the general distribution and hotspots. This is geologic map, of course, and there can also be human introduction of arsenic into a region. A 2007 report, titled “U.S. Rice Serves Up Arsenic” noted that rice-growing regions in the Southeast appeared also show signs of contamination from early 20th century use of arsenic-based insecticides to control for pests like the cotton boll weevil. That study found higher levels of inorganic arsenic in Louisiana rice, for instance, than that from California’s Central Valley, which has a far greater natural distribution of arsenic.

But that map should also remind us that although rice seems to have an affinity for arsenic, we’re surrounded by and exposed to that poison on a daily basis in many different ways.  A very thorough Consumer Reports write up of this latest research points out that last fall similar concerns were raised about arsenic contamination of fruit juices.

The Dartmouth study, in fact, did not turn up an arsenic free food product. The researchers looked at 29 brands of cereal bars, 22 contained a rice product and seven did not. All the cereal bars contained some trace of arsenic. Those without rice ranged from 7 to 28 parts per billion. As you might now expect, the readings from the rice products were higher, ranging from 23 ppb to a high reading of 128 ppb. Infant formula sweetened with rice syrup hovered close to 60 ppb.

And what does all that really mean? As the authors note,  the U.S. Food and Drug Administration (FDA) does not set a safe arsenic standard for food.  (And we’re not along in that. A Canadian Broadcasting Corporation story on the Dartmouth findings also noted a lack of public health standards for arsenic food exposure in that country.) But the U.S. Environmental Protection Agency (EPA) has established a 10 part-per-billion level for drinking water.

In an interview with NPR, Jackson said the EPA standard should probably be considered in assessing risk for something like infant formula – also a liquid consumed on a daily basis. It works less well for cereal bars and occasional consumption only and by a generally much larger, less vulnerable human being. And it’s almost important to note than the  10 ppb standard signifies EPA’s effort to set standards far, far below an actual toxic effect.

In other words, these are pay attention numbers rather than immediate alarm numbers.  They should remind us that, as always, a varied diet is healthier than relying too much on any single source of food. But as Jackson also pointed out the growing body of work on arsenic contamination of food in general, should also serve as prompt to our government agencies to take some of these unexpected hazard issues out of our food supply, start working out those much needed official safety standards for arsenic in our diet, and provide us with some kind of realistic assessment that will allows to make our own decisions about such risks.

I couldn’t agree more.

Well, sure you say. Obviously. This is chocolate, after all.  Almost goes without saying. Which is why I won’t. Actually, I’m mostly trying to explain why the  most potent chemical compound  in chocolate – a plant alkaloid, slightly bitter in taste, surprisingly poisonous in some species – is called theobromine.

And while chocolate, as a whole, has a wonderfully seductive  chemistry, this poison-obsessed blog will remain, well, obsessed. Today’s obsession is inspired by  the fact that  every Valentine’s season, in addition to stories about love and lace, newspapers run cautionary candy tales. In the last few days alone, there have been headlines ranging from Chocolate Poisoning and More to  Pets and the Peril of Chocolate.

And that’s entirely due to, yes, theobromine.

So theobromine is an alkaloid, meaning it’s part of the everyday chemistry of the plant world.  Plant alkaloids are nitrogen-based, typically with with flourishes of carbon, hydrogen and occasionally other atoms such as oxygen.  The recipe (or as chemists like to say, formula) for theobromine is seven carbon atoms, eight of hydrogen, four of nitrogen and two of oxygen.

And while this may sound like a recipe for the routine, alkaloids are anything but.  The first plant alkaloid isolated (in 1804) was morphine from the flowering poppy.  Other notable examples include cocaine (1860),  nicotine (1828), caffeine (1820), strychnine (1818) and a host of pharmaceuticals including the anticancer drug Vincristine; the blood pressure medication, reserpine; and the antimalarial compound, quinine.

By this standard, theobromine discovered in cacao beans in 1841, might sound to you

like a basic wuss of the alkaloid family. It’s mostly known as a mild stimulant in humans; it contributes (along with caffeine and a few other compounds) to that famed lift that people get from eating chocolate.

There is some evidence that if people get carried away with chocolate consumption, of course, theobromine will make them a  little twitchy. According to the National Hazardous Substances Database: “It has been stated that “in large doses” theobromine may cause nausea and anorexia and that daily intake of 50-100 g cocoa (0.8-1.5 g theobromine) by humans has been associated with sweating, trembling and severe headache.”  Occasionally, people (mostly the elderly) have needed hospital treatment for a theobromine reaction.

But if one looks at LD50 values, it’s obvious that the alkaloid is far more threatening to other species. LD50 is an oral toxicity measurement; it refers to the dose that will kill 50 percent of a given population and is usually calculated in milligrams of poison per kilograms of body weight.  The theobromine LD50 is about 1000 mg/kg in humans. But for cats it’s 200 mg/kg and for dogs it’s 300 mg/kg – in other words, dangerous at a far lower dose.

This varies, of course, by animal size and shape and breed. A few years ago, in fact, National Geographic published a fascinating interactive chart so that pet owners could search out the individual risk.   The chart focuses on dogs because they are more likely than cats to eat something sweet. And it notes that theobromine is more concentrated in dark chocolates making them more dangerous than milk or “white” chocolate. The dark chocolate effects are so acute for canines, that the alkaloid has been tested with some success as a means of controlling coyote populations. (Interestingly,  rats and mice are much less affected; their theobromine LD50 is much more like that found in humans.)

The different toxicities have to do with the way different species metabolize the alkaloid; humans process it much more efficiently than canines. And in small amounts, theobromine’s effects can make it medically useful.  But even here, it shows complexity. It increases heart rate and at the same time it dilates blood vessels, acting to bring down blood pressure. It can also open up airways and is under study as a cough medication.  It stimulates urine production and is considered a diuretic. It interacts with the central nervous system, although not as effectively as caffeine.

At toxic levels – in a characteristic dog death, for instance – all of this adds up acute nausea, convulsions, internal bleeding and often lethal over-stimulation of the heart. “See a vet immediately” is the message of one cautionary post, titled Toxic Chocolate. Another column, written by a vet, suggests rather hopefully that an evening walk is far more romantic and less likely to feature pet vomit (which she describes in revoltingly foamy detail).

We had that same foamy experience in our household in December, actually, when our dog discovered our son’s holiday stash. We all survived but the humans in the house are a lot more careful about where they leave their chocolate. And this Valentine’s Day, we’re sticking to champagne. Sure, ethanol is also a poison in its own right. But that’s a different story.

I

Early this week, a British criminology professor wrote a slightly plaintive essay about the 19th century serial poisoner, Mary Ann Cotton. Why, he wondered, did no one remember the evil Mary Ann and her remarkable homicidal career: poisoning  an estimated 21 people, including her mother, children and five husbands before being hanged in 1873?

In retrospective, I worry that my first reaction to these questions is not what he wanted to elicit.  Oh, yeah, Mary Ann Cotton, I thought. Arsenic.

In the 19th century, arsenic (specifically arsenic trioxide (AsO3), also called white arsenic) was used so often that its nickname was “the inheritance powder.” That began to change in the mid-19th century after chemists – notably a determined British scientist named James Marsh – learned out to detect it in a corpse. Cotton was hanged, in fact, in part due to forensic evidence from the Marsh test.

And then my next thought was, well, yeah, but Cotton was kind of a dreary, sneaky kind of  serial killer, a carefully drab woman who liked to slip into the kitchen and mix arsenic  into porridge, soup, a cup of milk.  The author of the Cotton essay, David Wilson, attempts to give her more flamboyance, arguing she enjoyed the deaths themselves, got a charge out of watching people suffer, that “she was, in other words, a psychopath.”

No argument from me.  Cotton did kill some 21 people including her own children. Even if she didn’t get a charge out of watching, I think we could all agree that she possessed the most famous characteristic of a psychopath: “a profound absence of guilt or empathy.”  Whether she was enjoying herself or whether she just possessed a kind of gray, sneaking evil, it’s the body count that really gives her away.

But Wilson, I think, underestimates the role of arsenic here, misses the seductive lure of the poison itself. An analysis of 19th century crime statistics by the American forensic chemist, Rudolph Witthaus of Columbia University (author of the 1896 book, Medical Jurisprudence, Forensic Medicine and Toxicology) found that arsenic alone accounted for about 40 percent of poison homicides in Europe from about 1835 and 1880.

At the time,  poison was astonishingly easy to acquire – it was used in tonics,

cosmetics, to color everything from wallpaper to jewelry, as the lethal agent in fly papers and rat poisons. (Several decades after Cotton’s execution, a British insurance collector named Frederick Seddon was executed for killing a boarder in his house with arsenic obtained by soaking flypaper in water.)

It slipped easily enough into food and drink. Witthaus interviewed 822 people who had survived arsenic poisoning attempts. Only 15 had noticed the strange metallic taste in their morning cereal or evening cordial.  And equally seductive for the killer, the poisoning symptoms of arsenic were frequently misdiagnosed as natural illness – the nausea and cramping as gastroenteritis, the joint pains as rheumatism, the sore throats and labored breathing as respiratory infections.

Arsenic, Witthaus noted, of 19th century crime statistics has been “in almost every instance, the agent used by those who, having succeeded in a first attempt at secret poisoning, have seemed to develop a lust for murder and have continued to add to their victims until their very number has aroused suspicion and led to detection.” And that pattern would continue until the Marsh test was so refined, the ability to detect a bare whisper of arsenic in corpse so good, that the poison lost its homicidal charm.

A notorious  arsenic case of the 1920s – the murder of his wife by the British solicitor Herbert Rowse Armstrong – illustrated this effect perfectly. Armstrong’s wife, Katherine, died in 1921; her death certificate cited both heart and kidney disease as the cause. When suspicion led to her being exhumed in a year later, pathologists were easily able to find high levels of arsenic in her body still. In fact, arsenic, a metalloid poison, can be detected in human hair hundreds of years after death.

And one of my favorite passages from Witthaus’s book notes that the poison also acts as a preservative, keeping bodies eerily intact in appearance for some time. One body exhumed 54 weeks after burial “did not differ from a living person,” he wrote, except for the mold growing on the face. It appeared, the scientist added, that molds were unfazed by arsenic.

We do forget the Armstrongs, the Seddons, the Mary Ann Cottons. And we’ve

forgotten worse serial killers:  Belle Gunness of LaPorte, Indiana, who in the early 1900s is thought to have killed more than 40 men with chloroform, strychnine, and an axe (later feeding their parts to the hogs on her farm.); Jane Toppan, of Boston, who poisoned at least 11 of her patients in the 1890s, telling police that her ambition was “to have killed more people — helpless people — than any other man or woman who ever lived…”

It’s a choice, I think,  not to dwell  in the darkest corners of human behavior, to spend too much time the company of aberrant personalities. But if we forget the poisoner, at least we do remember the poison. In the case of arsenic, most people would know the name, recognize the danger, be alarmed to find it close by.  And that’s a memory worth keeping – just in case, you know, a modern day Mary Ann Cotton shows up at the door.