A Toxic Tale Of Serendipity
May25

A Toxic Tale Of Serendipity

This post is from guest blogger Lila Guterman, senior editor for C&EN's Journal News & Community group, and was written for the "Our Favorite Toxic Chemicals" blog carnival. I have long had a fondness for weird, complex, toxic natural products. (Witness three recent stories I assigned and edited.) So when ScienceGeist announced the “Our Favorite Toxic Chemicals” blog carnival, I knew I’d have to participate. It would give me the chance to tell the story of homobatrachotoxin. The story begins in 1963, with a young NIH chemist, John W. Daly, taking a trip to Colombia at the request of his boss to investigate the chemistry of frog secretions. His discoveries would launch his career as a chemical ecologist and pharmacologist, and would spur an outpouring of research into the toxin he discovered, batrachotoxin. He published the chemical structure, the biological effects, and a partial synthesis, in 1971. Batrachotoxin and its natural analogs, homobatrachotoxin and batrachotoxinin A, are among the most toxic natural substances known. Just 200 ng kill a mouse in 8 minutes; the lethal dose for people is thought to be around 100 µg. Daly and colleagues found that batrachotoxin binds to sodium channels, opening them. Researchers now use batrachotoxin to study how these channels interact with anesthetics, anticonvulsants, and antiarrhythmia agents. These alkaloid toxins are secreted by certain species of Colombian poison-dart frogs – so called because Indians in Western Colombia used their secretions to poison the tips of blow darts. The most poisonous frog, the bright yellow Phyllobates terribilis, secretes batrachotoxin at levels high enough to kill several people. Daly developed an unorthodox method for deciding whether to collect a frog in the wild – one he was lucky, or prudent, enough not to try on Phyllobates terribilis: “It involved touching the frog, then sampling it on the tongue. If you got a burning sensation, then you knew this was a frog you ought to collect,” he told the NIH Record, in 2002. In his work with South and Central American frogs, Daly and his collaborators ended up isolating more than 500 new natural products. A series of chance occurrences led Daly to perhaps the most intriguing discovery of his career: that homobatrachotoxin is also secreted by a songbird that lives halfway around the world. In 1989, John P. Dumbacher, then a graduate student in ornithology, was studying birds of paradise in New Guinea. His nets sometimes caught other birds, including a songbird called the hooded pitohui (Pitohui dichrous). “These are large birds that can cut your hands, and as I struggled to free them, they bit and scratched my hands,” he told COSMOS Magazine this year. “These little scratches really stung, so I just put my fingers in...

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Water and oxygen, my favorite toxic chemicals
May24

Water and oxygen, my favorite toxic chemicals

(Russ's post on osmium earlier this week and mine today are both for the "Our favorite toxic chemicals" carnival hosted by Sciencegeist. Go see the collected posts from Monday, Tuesday, and Wednesday. On Twitter, watch #ToxicCarnival.) In 2005, a California State University, Chico, student died after being forced to drink gallons of water during a fraternity hazing ritual. Four of his fraternity brothers pleaded guilty to charges ranging from involuntary manslaughter to hazing. In 2007, a woman participating in a radio contest to win a Nintendo Wii died after drinking nearly 2 gallons of water without urinating. A jury later awarded $16 million to her family. Water, H2O. Oxygen, O2. Without either one, we die. But also: With too much H2O, we die. With too much O2, we die.  The dose makes the poison. H2O is essentially the solvent in which all cellular substances are dissolved. Overall, the human body is about 60% H2O, although the amount varies depending on the body part: bone is 22%, brain is 70%, and blood is 83%. H2O is polar, with the oxygen carrying a slight negative and the hydrogens carrying a slight positive charge. That means that H2O tends to form strong interactions with other polar molecules but rebuff nonpolar ones, which is why dispersed oil droplets will gather together in a cup of H2O. At the cellular level, those polar and nonpolar interactions play an important role in things such as membrane formation, protein folding, and protein-protein or protein-substrate binding. But as the news reports above demonstrate, H2O can also kill, and not just by drowning. Drink more H2O than your kidneys can handle and the fluid builds up in your blood, diluting the sodium concentration--a condition called hyponatremia. H2O then moves into cells to equalize the sodium concentration between the two environments. The influx of H2O causes cells to swell. Some parts of your body have room for that, but your brain does not. "Rapid and severe hyponatremia causes entry of water into brain cells leading to brain swelling, which manifests as seizures, coma, respiratory arrest, brain stem herniation and death," M. Amin Arnaout, chief of nephrology at Massachusetts General Hospital and Harvard Medical School, told Scientific American. For its part, O2 is a key player in cellular energy cycles. We breathe in O2, which red blood cells deliver throughout our bodies. Mitochondria in other cells turn that O2, sugar, and adenosine diphosphate into H2O, CO2, and adenosine triphosphate (ATP). ATP then serves as the energy source for a multitude of other cellular activities involved in being alive. One molecule of glucose produces 36-38 molecules of ATP. But human bodies evolved to breathe in O2 as about 20% of...

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Our Favorite Toxic Chemical: Nitrate
May24

Our Favorite Toxic Chemical: Nitrate

Today's post is from guest blogger Melissae Fellet, a science writer based in Santa Cruz, California, and was written for the “Our Favorite Toxic Chemicals” blog carnival hosted by Sciencegeist. Feeding my vegetable garden so it will feed me I’m eager to grow some of my own food this summer, so I planted a vegetable garden in pots on my porch. Since my previous gardening experience consists of ignoring my plants, learning some gardening tips was a must. Like humans, plants need food, too. Those nutrients come from boosts of nitrogen, phosphorus and potassium-containing fertilizer. But plants need help getting their roots on some nutritious nitrogen when that fertilizer contains kelp, alfalfa, crushed bones, chicken poop and ground feathers, like the organic stuff I put in my garden. Some of those ingredients contain nitrogen as ammonia, which plants can absorb directly. Proteins are another source of nitrogen. Bacteria in the soil separate proteins into amino acids. Other microbes chomp the nitrogen off the amino acids as ammonia. And super-specialized bacteria eat ammonia and release the nitrogen as nitrate (NO3-). Nitrate is great plant food, too, because it zips through the soil straight to a plant’s roots. This biological nitrogen transformation is slow, so farmers may feed their plants a nitrate-containing fertilizer to speed growth. That’s a touchy subject in the agricultural areas near my home in California. About 10 percent of 2500 public water wells tested in the Tulare Valley and Salinas Valley exceed the state limits of 45 mg nitrate per liter of water, according to a report prepared for the state water department last March. The majority of the nitrate in groundwater -- about 96% -- washes off cropland, the report found. Nitrate takes time to trickle from a field into the groundwater, so most of that contamination is due to decades of past farming in the area. But if the nutrient pollution trend continues, 80% of the people living in those valleys could be drinking nitrate-laden water by 2050. Nitrate becomes harmful when our bodies convert it to its chemical cousin, nitrite (NO2-). Nitrite transforms the iron in our blood so that it can no longer carry oxygen. Enough altered iron -- 10 percent of the hemoglobin in your blood -- causes breathing troubles especially in infants and pregnant women. Higher concentrations can lead to suffocation. Still, it takes a lot of nitrate to harm a person. According to data from the World Health Organization [PDF], an average three-month old baby boy might have to drink about four liters of water contaminated with nitrate at twice the state limit to induce toxicity. An adult might drink up...

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Tetrodotoxin: Why Toxic Is Complicated
May22

Tetrodotoxin: Why Toxic Is Complicated

(This post was written for the "Our Favorite Toxic Chemicals" blog carnival hosted by Sciencegeist.) It was a meal Captain James Cook would just as soon have forgotten. The fish, an unfamiliar species, seemed harmless enough. But after just a small taste of its liver, he and two shipmates regretted it. "We were seized with an extraordinary weakness in all our limbs attended with a numness [sic]...We each of us took a Vomet and after that a Sweat which gave great relief. One of the pigs which had eat the entrails was found dead... When the Natives came on board and saw the fish hanging up, they immidiately [sic] gave us to understand it was by no means to be eat." Cook had a rather more dramatic introduction to the lethal chemical tetrodotoxin than I did. I learned about it from a lecture in a windowless room. (Yes, I've linked to the original slides, still online after eight years.) That presentation had plenty to make my ears perk up. Highly poisonous. No antidote. Still kills today, because pufferfish, one of the web of creatures that makes tetrodotoxin, gets carved into a delicacy called fugu, and sometimes those knives miss a little bit of the animal's toxic innards. We weren't learning about tetrodotoxin because of its deadliness. Tetrodotoxin, to the organic chemist, is a case study. The lab where I earned my Ph.D. is in the business of making the toughest molecules it can. The lessons teams learned by forging tetrodotoxin from scratch, the idea goes, will be useful in other endeavors. Chemists for decades have argued about whether this is an appropriate way to train students, but suffice to say it's still the way that most medicinal chemists in pharma get their start. Tetrodotoxin is different things to different people. To biochemists and neurobiologists, tetrodotoxin, or TTX for short, is a tool for unraveling how pain works. Researchers today know that TTX binds to sodium channel proteins involved with pain pathways in the nervous system. To those who study the cultures of Haiti, tetrodotoxin evokes something else entirely-- the zombie of Haitian tradition. In the 1980s, ethnobotanist Wade Davis fingered tetrodotoxin as a key ingredient in a powder witch doctors use in voodoo zombie-making rituals. His doctoral thesis, as well as his bestselling book the "The Serpent and the Rainbow", about the topic eventually became the basis for a movie of the same name. Davis's results came under fire from the medical and scientific community. Another team's measurements of tetrodotoxin levels in the powder detected amounts too low to have any relevant effects, though Davis and another set of...

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My favorite toxic chemical is: Osmium (and its tetroxide)
May21

My favorite toxic chemical is: Osmium (and its tetroxide)

Osmium is the densest of all natural elements and certainly one of the rarest, with worldwide production of about 545 kilograms annually. It’s incredibly expensive stuff, and yet, look at all the varied uses!  Osmium is used by itself or as an alloy for fingerprint detection and in fountain pen tips, pacemakers, light filaments, and jewelry. And it's reacted with oxygen to form osmium tetroxide. The word osmium actually comes from the Greek word "osme," or odor, for the unique acrid odor given off by OsO4. Osmium tetroxide is incredibly toxic and has an OSHA permissible exposure limit (PEL) of 0.002 mg/m3. For comparison, elemental mercury vapor has a PEL of 0.1 mg/m3.  Osmium tetroxide might even be considered a perfect component of a terrorist "dirty bomb," but it’s simply too expensive to buy enough to make that practical. A primary use for OsO4 is for tissue fixation in electron microscopy. Hundreds of hospitals use it in their clinical labs, and when the solution is spent, it needs to be disposed safely. My experience with OsO4 stems primarily from efforts to recycle the spent compound.  Ironically, despite its obvious toxicity, OsO4 isn’t regulated as hazardous waste. While it is certainly toxic to humans, it breaks down fairly readily in the environment, (apparently) isn’t toxic to aquatic or marine life, and isn’t mobile enough to be considered a threat to drinking water.  That means that theoretically one could take this non-regulated waste and sell it for a handsome sum to a refiner who could recover and resell the metal. However, here is a lesson in making sure you know the hazardous waste regulations thoroughly! It turns out that one of the several buffers that labs use with OsO4 is cacodylic acid, which has the formula (CH3)2As(O)OH. Therein lies the rub. While EPA decided that osmium isn’t hazardous to the environment, arsenic is. So, any refiner recovering osmium from the spent solution also containing that particular buffer must have a full-blown EPA hazardous waste treatment, storage, and disposal facility permit! Use a different buffer and you’re fine. It only took me stops at five hospitals to find out the popularity of the cacodylic acid buffer, thus ruining my plans for an early retirement. For more on osmium, check out this essay on the metal from C&EN's 80th anniversary special issue on the periodic table and this video from the Periodic Table of...

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