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Quicksilver: The Life and Loss of Karen Wetterhahn Hello friends, and welcome to episode #8. Today we have another riveting but tragic story for you. If you haven't listened to episode 7 yet, it isn't absolutely necessary, but it would do you well to hear the stories of early nuclear pioneers like Louis Sloten, Cecil Kelly, and Harry Daghlian, and the dangers that ended their lives. I think this is going to be an intriguing episode, with a fascinating scientist that most won't be familiar with. Today is not so much in my wheelhouse - Nuclear history, toxic chemical history, safety history, and high velocity subatomic history. I'm not a scientist, and I didn't stay recently at a Holiday Inn, but I am certainly a science hobbyist, and keep up with science news daily, and the fact that the last few topics are out of my milieu, so to speak, means I've had to research them more thoroughly, fact-check my assumptions, look up terms, and generally do the due-dilligance to get things right. I may miss something here or there, but I am trying hard to get it right. Just let me know where I whiff, and I can tell the DJ to fix it in the mix. You know the podcast things. Sharing the show, telling people about it, posting about it, and leaving Apple Podcast reviews all help…a lot. I appreciate those of you who do that. Thank you! Some stories make you hold your breath. Some make you check your gloves. Today we'll do both, and hopefully, when we do - we'll be all the better for it. We begin with the story of Dr. Karen Elizabeth Wetterhahn, chemist, teacher, builder of programs, and teacher of people, and of one "tiny glistening drop" that rewrote laboratory safety across the world . It's a story I want to tell with reverence and a little warmth, because we are talking about a person who balanced world-class science with backyard pool parties and baby rabbits. We're also going to talk frankly about a super-toxic compound, because Karen would have insisted that we learn everything we can. And I know what you might think when you hear the word Karen, but let's be fair. Karen Wetterhahn was anything but, and the Karens I've known have all been lovely. Don't judge people by their name - they had no say in it. Karen Wetterhahn was born October 16, 1948, in Plattsburgh, New York. She grew into a scholar of the highest order. "She earned her bachelor's degree from St. Lawrence University in 1970 and her doctorate from Columbia University in 1975," and joined Dartmouth in 1976, publishing "more than 85 research papers" (Wikipedia). Dartmouth later remembered her as "the founding director of Dartmouth's Toxic Metals Superfund Research Program," an "expert in the mechanisms of metal toxicity," and a scholar with "expertise in biochemistry and molecular toxicology" (Dartmouth Tribute). She rose to become Dartmouth's Albert Bradley Third Century Professor in the Sciences (Dartmouth Tribute) and in 1990 helped establish the Women in Science Project, which "helped to raise the share of women science majors from 13 to 25 percent" … and has become a national model for recruiting more ladies into STEM careers. She didn't just research metals; she organized people. She "played an integral role in the administration of the sciences at Dartmouth," serving as Dean of Graduate Studies, Associate Dean of the Faculty for the Sciences, and Acting Dean of the Faculty of Arts and Sciences (Dartmouth Tribute). She "trained 14 postdoctoral research associates, 20 graduate students and over 50 undergraduate research students" (Dartmouth Tribute). And she did this while building programs that actively welcomed women into the lab. She was "co-founder of Dartmouth's Women in Science Project … and was active in the Women in Cancer Research group" (Dartmouth Tribute). Now bring in the home front—because Karen's life was never just pipettes and publications. Neighbors remembered that "we never knew she was a world-famous scientist," because, in Lyme, New Hampshire, "she was just Char and Leon's mom" (The Tennessean/AP). She loved "rock music—heavy metal was her favorite," she "tended her garden," and she hosted some great neighborhood pool parties. (The Tennessean/AP). This is the paradox and the beauty: the same person who would lecture in Norway and Hawaii would also her drag family to the golf course and cheer at Ashley's hockey game (The Tennessean/AP). A life in balance. On a summer day in 1996, the story turns. Karen was "studying the way mercury ions interact with DNA repair proteins" and also investigating cadmium (Wikipedia). She was using an incredibly dangerous substance that we really don't mess with much anymore called dimethylmercury—Hg(CH₃)₂ She did what a careful chemist does. She wore "safety glasses and latex gloves," worked "in a fume cupboard," handled "very small quantities behind the fume cupboard sash," and the sample arrived in a "sealed glass vial" cooled in ice water to reduce volatility (Bristol "Dimethylmercury"). On August 14th, she transferred liquid and, by her own later recollection, "spilled several drops of dimethylmercury from the tip of a pipette onto her latex-gloved hand" (Wikipedia; NEJM). "Not believing herself in any immediate danger, as she was taking all recommended precautions," she cleaned up before removing the gloves (Wikipedia). That detail—the glove—matters. Tests later showed dimethylmercury "can, in fact, rapidly permeate several kinds of latex gloves and enter the skin within about 15 seconds" (Wikipedia; Bristol "Dimethylmercury"). In other words, the glove was no barrier, but rather provided a false sense of security, like many other modern protective measures. The Tennessean would capture the image like this: "It was just a drop of liquid, just a tiny glistening drop. It glided over her glove like a jewel" (The Tennessean/AP). There's poetry in that line, and tragedy too. The article adds: "She washed her hands, cleaned her instruments and went home. It was just a drop of liquid, just a tiny glistening drop" (The Tennessean/AP). Dimethylmercury is slow, stealthy, and cumulative. It is the very definition of insidious and more perfidious than Agatha Harkness. It is "one of the most potent neurotoxins known," crosses the blood-brain barrier, and "is a cumulative poison, being very slowly excreted from the body, and by the time its effects are noted it is too late to do anything about it" (Bristol "Dimethylmercury"). What an awful, awful sentence. Like the Blue Flash of a supercritical reaction that we discussed in our last episode, once that Dimethylmercury hits you, it's too late…even if it takes you much slower than Gamma or neutron radiation does. For months, there were no obvious signs. Then her body started sending signals. Roughly "three months after the initial accident," there were "brief episodes of abdominal discomfort" and "significant weight loss." "The more distinctive neurological symptoms … including loss of balance and slurred speech, appeared in January 1997, five months after the accident" (Wikipedia). The NEJM case report—the clinical, careful voice of medicine—notes that she presented with "a five-day history of progressive deterioration in balance, gait, and speech," after losing "6.8 kg (15 lb) over a period of two months," with episodes of "nausea, diarrhea, and abdominal discomfort" (NEJM). How many of us would know what caused such symptoms when they didn't begin until 3 months after exposure?? Her own memory solved the riddle: "in August 1996 … she spilled several drops … onto the dorsum of her gloved hand" (NEJM). Hair analysis would later show a "dramatic jump in mercury levels 17 days after the initial accident, peaking at 39 days," then a slow decline (Wikipedia). In the hospital, the numbers were grim: "whole-blood mercury, 4000 μg per liter (normal range, 1 to 8; toxic level, >200); urinary mercury, 234 μg per liter (normal range, 1 to 5; toxic level, >50)" (NEJM). That's a lot, an awful lot of dimethyl mercury. Clinicians tried everything they reasonably could: chelation, and Vitamin E was added "as a potentially protective antioxidant" (NEJM). They even attempted exchange transfusion, and it had partial impacts, as her "mean whole-blood mercury concentration" dipped from 2230 to 1630 μg/L two hours after, only to re-equilibrate to 2070 μg/L by 16 hours (NEJM). How does that happen? I know a microgram is a tiny, tiny amount of material - 1 millionth of a gram, but that is wild to me that the mercury concentration would seemingly reduce, then come back. For reference, one sand grain weighs around 12 milligrams, or 12000 micrograms, so maybe the measurements in the 1990s weren't the most precise, or maybe mercury levels can fluctuate. Dimethyl mercury is extremely toxic, and .1 milliliters is enough to kill you, I repeat, POINT 1 milliliters. One milliliter of water weighs one gram, and is about 1 cubic centimeter, or 10 cubic millimeters in size. .1 milliliters would be 10 percent of that size, or more like 1 cubic millimeter in size. That is small, considering a flea can be about 3 milimeters in size, and a regular black garden ant - the small kind - can grow to well over 4 milimeters long…but we're not done yet, because dimethyl mercury is almost three times denser than water, so a drop of it big enough to kill you would be about a third the size of water of comparative mass. This means a drop of dimethly mercury large enough to kill you would be a good bit less than 1 cubic milimeter in size, provided my math is correct…a somewhat dodgy caveat. How big is that? The average size of a drop of water from an eyedropper is .05 mililiters, so - factoring in the density of dimethyl mercury, the amount that's needed to kill you would be smaller than the drop of water from an eyedropper. Would you even notice such a small amount hitting your glove?? I probably wouldn't. We've done some math there - hopefully, let's do some chemistry now. Dimethylmercury is a liquid "with a faint sweet smell (but don't smell it, for Heaven's sake!)," It boils at 92°C/197.6 F (density 2.96 g/cm³ ). It's "supertoxic," and it "readily crosses the blood-brain barrier," likely via "a methylmercury-cysteine complex," has "a high affinity for sulphur" and attacks "the thiol groups of enzymes," inhibiting neurotransmission (Bristol "Dimethylmercury"). Clinically, symptoms include "ataxia (lack of muscle coordination), sensory disturbance and changes in mental state," with "delayed but ultimately fatal neurotoxic effects" (Bristol "Dimethylmercury"; NEJM). The hair-mercury curve in Karen's case soared to "almost 1100 ng per milligram," then declined with a half-life of "74.6 days" (NEJM). Those kinetics tell a story of a toxin that builds silently and leaves reluctantly. Dr. Wetterhahn's brain, in particular the visual and auditory cortices and the cerebellum, was profoundly injured by the mercury exposure. The mercury content in the frontal lobe and her visual cortex averaged "3.1 μg per gram (3100 ppb)," with high levels also in the liver and kidney cortex (NEJM). Outside the lab, values and scans, family and colleagues were living a vigil. The Tennessean's account is devastating and tender. Karen—who "had never been sick, never stopped working, never complained"—now found "words … getting stuck in her throat," "her hands tingled," and her "whole body was moving in slow motion" (The Tennessean/AP). Friends rushed her to the hospital. After the diagnosis, "Karen beamed when she heard the news. Finally, something she understood. … Science would cure her," she thought (The Tennessean/AP). But dimethylmercury had other plans. "Doctors didn't know it could break down the body over the course of a few months, slowly, insidiously, irreversibly." (The Tennessean/AP). Like in the case with radiation accidents and Slotin and Daghlian, we learned a lot about dimethylmercury poisoning from Karen's case. The hospital room became a command center of love and science. "E-mails flew around campus, and around the country. Students emptied libraries of books on mercury … seizing on any sliver of information" (The Tennessean/AP). Thomas Clarkson, who had studied mercury disasters, confessed: "I felt such a sense of helplessness. 'Here was one of the world's most distinguished scientists, and I was looking at this woman dying, realizing there is nothing the scientific or medical communities can do'" (The Tennessean/AP). A colleague remembered Karen's husband seeing "tears rolling down her face." When asked if she was in pain, "The doctors said it didn't appear that her brain could even register pain" (Wikipedia). On February 6, "22 days after the first neurologic symptoms," she "became unresponsive to all visual, verbal, and light-touch stimuli" (NEJM). The newspaper captures the family's promise: in the ambulance, Karen pointed to letters"N" and "H"and "Leon nodded. He promised that, whatever the outcome, he would take her home, to New Hampshire" (The Tennessean/AP). He did. On June 8, 1997—"ten months after her initial exposure"—Karen died (Wikipedia; NEJM). Like with Daghlian and Slotin, Karen Wetterhahn's case revealed that the safety culture around "super-toxic" chemicals needed to change, and change rapidly. "The case proved that the standard precautions at the time, all of which Wetterhahn had carefully followed, were inadequate for 'hyper-toxic' chemicals like dimethylmercury" (Wikipedia). Wetterhahn was not careless; she was not dramatic; she didn't display the understandable wartime bravado of Slotin - she was doing her job soberly, with the best understanding of safety and protective gear that they had in the mid-1990s, and it just wasn't enough. She taught us that, and probably saved many lives in the process. Back in the lab, her colleagues got empirical. They "tested various safety gloves against dimethylmercury and found that the small, apolar molecule diffuses through most of them in seconds" (Wikipedia). The Bristol write-up is direct: "it is now accepted that the only safe precaution … is to wear highly resistant laminated gloves underneath a pair of long-cuffed neoprene (or other heavy duty) gloves" (Bristol "Dimethylmercury"). In short: double up, laminate first. Her accident had a broad scientific ripple. Dimethylmercury had been "the common calibration standard for 199Hg (199 Mercury)NMR spectroscopy" What is 199 Mercury NMR Spectroscopy? I totally know off the top of my head, and if you'll give me a second to Google it - I mean, uh, look it up, I'll tell you. Of course, 199Hg NMR spectroscopy is a Nuclear Magnetic Resonance technique that uses the 199Hg isotope of mercury to study the structure, dynamics, and binding of mercury-containing compounds, particularly inorganic and biological complexes. And if you don't understand that, then you probably aren't a high-level chemist, and, uh, I can't explain it to you. Nah, I'm just kidding. I don't really understand precisely how they were using that isotope of 199 Mercury in NMRs either. That's the thing about brilliant people who know their field comprehensively. The most brilliant ones can explain things so clearly that non-experts can grasp it, and I simply can't do that, because I am not anywhere close to brilliant in this field. After Karen's death, "the use of dimethylmercury for any purpose has been highly discouraged" (Wikipedia). The NEJM paper was blunt about the substance itself: "Dimethylmercury may be even more dangerous than methylmercury compounds," permitting "transdermal absorption" and providing toxic exposure via inhalation; "lethal at a dose of approximately 400 mg … a few drops" (NEJM). Their conclusion: this "case illustrates the potent toxicity of dimethylmercury and the need for additional safety precautions if it is to be used in any scientific research" (NEJM). And there was legacy in people and programs. Dartmouth established "The Karen E. Wetterhahn Graduate Fellowship in Chemistry" to encourage other women in science, "whenever possible, a woman is preferred for the award" (Wikipedia). The National Institute of Environmental Health Sciences created the "Karen Wetterhahn Memorial Award," given annually (Wikipedia). Her broader legacy, Dartmouth College notes, is in the community she built: as "founding director" of the Toxic Metals Superfund Research Program and as a dean who "helped guide the growth and development of the science division and its graduate programs" (Dartmouth Tribute). Her death "prompted consideration of using an alternative reference material for mercury NMR spectroscopy experiments" (Wikipedia). Her life prompted many to become scientists and engage in their own brave, knowledge-expanding experimentation. If after this you need a laboratory proverb to tape above your hood, try this: the only thing that should pass through your glove in fifteen seconds is regret. Everything else needs SilverShield under neoprene. As the University of Bristol writes up on Dr. Wetterhan, "Doing chemistry is safe, much safer than driving a car," but "it is only by ceaseless vigilance and attention to safety that it remains so." Pioneers like Wetterahn, Slotin, and Daghlian have made science safer by their sacrifice. (Bristol "Dimethylmercury"). Ceaseless vigilance is just another way of saying: love your people enough to over-protect your hands. There's a sentence late in the AP story that won't leave me: "In many ways, Karen Wetterhahn's death was as important as her life" (The Tennessean/AP). That shouldn't diminish her life, but it's to honor her wish. "While she could still speak, she urged doctors to learn everything they could from her accident. And they did" (The Tennessean/AP). Out of that courage came data, papers, safety circulars, and—most importantly—policies that mean other scientists go home after their experiments. Her colleagues' early ignorance of dimethylmercury's glove permeation wasn't negligence; it was a gap that Karen's tragedy closed. "Wetterhahn's accidental exposure occurred despite her having taken all measures required at that time. … her colleagues tested various safety gloves … [and] as a result, it is now recommended by OSHA to wear Silver Shield laminate gloves … while handling dimethylmercury" (Wikipedia). The NEJM article adds the sober medical coda: they could find "only three previously reported cases of poisoning with dimethylmercury, all of which were fatal" (NEJM). This is a chemical for which there is no margin. And yet, this is also a story about love—the way her husband Leon promised "New Hampshire" with two letters; the way friends filled hospital walls with photos; the way students "stayed up all night to translate obscure research papers," riding waves of "elation … then crying" (The Tennessean/AP). It's about a scientist who could still crack a line with the hospital psychologist. Asked if she was depressed, she smiled: "'Wouldn't you be?'" I appreciate the Ph.D level gallows humor there, and her bravery in the face of the unknown terrors ahead. Karen's death galvanized institutions. OSHA guidance changed. NMR standards were reconsidered (Wikipedia). Dartmouth and NIEHS named awards in her memory (Wikipedia). Her Superfund program continued, drawing "scientists from Dartmouth College and the Geisel School of Medicine," with collaborators from other institutions (Dartmouth Tribute). The woman who built bridges in life kept building them after, helping others cross safely. The AP article leaves us with her husband's ongoing ache: "He still wakes in the middle of the night and wonders if it's true. He still half expects her to come striding through the door with her laptop and her notes and her smile" (The Tennessean/AP). And then there's the photo in that article that Leon held: "Karen working in her lab, a study of intensity in her goggles and gloves, staring at her test-tubes and vials. 'She loved her work,' he says. 'It made her happy'" (The Tennessean/AP). So what do we do with this story, so sad and poignant? First, we say her name with gratitude: Dr. Karen E. Wetterhahn. Second, we adopt her final lesson like a lab oath: super-toxic chemicals demand super-protective habits. And third, we remember that safety is love in practice—because someone is waiting at home who thinks of you as more than a scientist. They think of you as Mom, or Dad, or friend, or mentor. They don't care how elegant your NMR spectrum is if the glove fails. Maybe you aren't a chemist, but you'd still be missed if you were gone, so be vigilant. Thank you, Dr. Karen Elizabeth Wetterhahn, teacher, builder, scientist, for teaching us to give careful thought to our ways. Next episode, we meet Dr. Anatoli Bugorski, the Soviet scientist who survived - somehow - a direct hit to the face from a particle beam fired by a giant particle accelerator. Tell your people about the show - give us some reviews or shares on social media, yeah, yeah. You know the drill. Until next time…keep digging! Quoted Sources * Wikipedia (Wikipedia: Karen Wetterhahn). * Dartmouth Tribute: Biographical and institutional roles, Superfund program, administrative leadership, mentoring, and program-building (Dartmouth College: A Tribute to Karen Wetterhahn). * Bristol College (Chemistry, Molecule of the Month) Narrative of the lab procedures and spill, glove permeability "within 15 seconds," physical properties, toxicology, neurotoxicity, and safety admonition ("Doing chemistry is safe … only by ceaseless vigilance …") (University of Bristol: The Karen Wetterhahn Story / Dimethylmercury). * New England Journal of Medicine(1998 Case Report) Clinical course, dates, mercury levels, chelation and exchange transfusion details, hair kinetics, half-lives, autopsy findings, and "supertoxic" dose characterization (Nierenberg et al., "Delayed Cerebellar Disease and Death after Accidental Exposure to Dimethylmercury," New England Journal of Medicine, 1998). The Tennessean / Associated Press (Sept. 20, 1997) Human-angle reporting: "tiny glistening drop," family vignettes, Leon's promise ("N" and "H"), student and colleague efforts, Clarkson's quote, OSHA note, and closing reflections (Helen O'Neill, AP, The Tennessean).
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