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Lab Safety

Reactions: Remembering Karen Wetterhahn

August 8, 2022 | A version of this story appeared in Volume 100, Issue 27


This is an image of C&EN's June 13 magazine cover, featuring a remembrance of Karen Wetterhahn
Credit: C&EN

Letters to the editor

Karen Wetterhahn

At the time of professor Karen Wetterhahn’s death, letters to the editor by me and Robin Harris (C&EN, July 14, 1997, page 7) described safer alternatives for accurate nuclear magnetic resonance referencing, applicable to mercury and other nuclei. These obviate the utilization of esoteric or dangerous compounds and can remove the need for codissolving a separate reference standard in the solution being analyzed. In the context of the recent article commemorating professor Wetterhahn’s career (C&EN, June 13, 2022, page 28), it may be worth providing the link to these earlier letters for those concerned with this issue:

David Live
Park City, Utah

Sam Lemonick’s recent article in ACS Chemical Health and Safety remembers professor Karen Wetterhahn’s life and her many legacies to the scientific community. As Lemonick notes, she died in 1997, 10 months after an accidental exposure to dimethylmercury while preparing an 199Hg nuclear magnetic resonance standard. The subsequent forensic analysis by the team at Dartmouth College highlighted how readily a few drops of this extraordinarily toxic compound penetrated many types of laboratory gloves and has led to many changes in laboratory practices. In 2001, the International Union of Pure and Applied Chemistry recommended the adoption of a unified scale for reporting the chemical shifts of all nuclei. Under this approach, 199Hg chemical shifts can be referenced to Hg(CH3)2 (δ = 0.0) using an established frequency offset from the 1H resonance in tetramethylsilane. While this avoids the need for routine use of dimethylmercury samples, there are several types of 199Hg NMR experiments that nonetheless require the use of a concentrated sample.

To better understand how experimentalists have sought safer practices, we surveyed the 199Hg NMR literature. Our findings are posted at ChemRxiv as the manuscript undergoes review for journal publication. We found over 90 papers reporting 199Hg NMR data in the 25 years since Dr. Wetterhahn’s death. While the community has generally shifted toward several alternative and safer mercury standards, four papers published in the last decade do cite the use of neat dimethylmercury. Unfortunately, a third of the papers do not detail how their 199Hg NMR spectra were referenced. Given great advances in both our understanding of mercury chemistry and advances in NMR instrumentation, experimentalists now have access to many appropriate alternatives to dimethylmercury for even the most complex of multinuclear 199Hg NMR measurements.

Thomas V. O’Halloran (East Lansing, Michigan) and David Z. Zee (Evanston, Illinois)

I read the article on Karen Wetterhahn with a profound sense of loss and sorrow that has not fully abated after 25 years. I was one of Karen’s graduate students, and I have come to recognize that she trained her other students and me very well.

I’d like to share an anecdote about Karen’s teaching style. Karen cultivated an air of omniscience, which certainly drove her students to prepare well for discussions with her about their research. One of her favorite questions was, “Don’t you know?,” implying that the student had not done their homework. Karen had wide-ranging knowledge, but she also had human limitations. Once, I called Karen’s bluff and confessed that I didn’t know the answer to a question, so I asked her what the answer was. We both chuckled when she admitted that she didn’t know either. Nevertheless, all her students learned the importance of asking insightful questions.

This brings me to a deeply troubling point raised in the article. I don’t agree with the conclusion about how Karen was poisoned. Karen taught me that if you disagree, you better have data on your side, so here goes. The New England Journal of Medicine article estimated that Karen likely absorbed about 1,344 mg of mercury, meaning she likely absorbed 0.44 mL of dimethylmercury. To do so meant she had to have been splashed with more than that—probably closer to 1 mL since some of the compound would be lost to evaporation or remain in the glove. This is a lot more than a drop or two.

When I was in Karen’s lab, I did some experiments using coaxial nuclear magnetic resonance tubes, which allowed a small volume of an external standard between the tubes. I don’t know what Karen was using for an NMR tube, but in currently available technology, where the reference goes into the center of a larger sample tube, typical volumes for the inner reference standard for a 5 mm tube are 60 µL, while the outer sample volume is 10×. If Karen was using less than 0.1 mL of dimethylmercury, how could she have absorbed 10× what she was transferring? (Her lab notebooks might provide insight.) My supposition is that either she was splashed with more dimethylmercury than what was released from the pipette through her glove, or there was another method of ingestion, conceivably involving the deliberate actions of another individual.

Samuel Brauer
Shelton, Connecticut

Editor’s note: An investigation into Karen Wetterhahn’s death concluded, “The rapid, monophasic, first-order increase in the mercury content of hair is consistent with either one or several episodes of exposure to dimethylmercury beginning on or about August 14, 1996, and is consistent with the evidence (reports from coworkers and information from labeled vials and laboratory notebooks) that a single accidental exposure to dimethylmercury occurred on August 14. . . . Our patient’s accidental exposure may have resulted from both transdermal absorption of the liquid (given the lack of protection provided by disposable latex gloves) and inhalation of vapors (even though the work was conducted under a fume hood)” (N. Engl. J. Med. 1998, DOI: 10.1056/NEJM199806043382305). Wetterhahn did not record in her lab notebook the quantities she used or planned to use, according to John Winn, a Dartmouth professor emeritus of chemistry, who was chair of the department when Wetterhahn died.

The recent C&EN article about Karen Wetterhahn’s death due to poisoning by dimethylmercury (dmm) saddened me and prompted me to expand on that subject. Professor D. M. Ritter at the University of Washington was one of several mentors that guided me through my research career in organic chemistry. His research was mainly in organoboron chemistry, and he tasked me with preparing about half a kilogram of dmm when I was a senior undergraduate in 1954. It was explained to me that the compound was volatile and extremely toxic and that in a previous incident (which I don’t think was at UW), a person in an adjacent room had been killed when dmm was being prepared and was transmitted through the wall or ventilation system. The precaution for me was to work in an atmosphere saturated with butylmercaptan. Well you can imagine what that was like and why the person with low seniority got the job, but mission accomplished and here I am at 89 years old.

Most of my 40-year research career was spent at the Research Labs of Eastman Kodak in Rochester, New York. My first month on the job showed me that no one is infallible, as I accidentally broke a mercury thermometer, and a few drops of mercury spilled on the floor. This turned out to be an emergency situation, and the Mercury Squad was summoned immediately to clean up the spill. It had been found early on that mercury vapor caused desensitization of photographic films. As most chemistry research labs’ floors become saturated with mercury, so it had been at the old labs in Rochester. It has been found that dentists and others working for long periods with mercury amalgams where mercury spills can occur can develop symptoms of mercury poisoning. I suspect this is also true for chemists working for many years in labs where the floors have accumulated mercury droppings. Three cheers for the Mercury Squad.

Roy C. De Selms
Asheville, North Carolina

I read the tragic story of Karen Wetterhahn and her lethal poisoning by just a few drops of dimethylmercury spilled on her latex-gloved hand. I came very close to being fatally poisoned by dimethylmercury! In 1959–60, as part of my master’s research at the University of Toronto, working in the lab of professor George F Wright, my research assignment was on oxymercuration of organic compounds. For my initial task, Wright asked me to synthesize and purify 50 g of dimethylmercury for the Physics Department for studies using its brand-new NMR machine. The machine when it arrived was so massive that an outer wall of the building had to be partially demolished before the NMR machine, hoisted by crane, could be housed inside.

The warnings that professor Wright gave me about the synthesis was that dimethylmercury was very volatile and very toxic and I could lose teeth like the ones he showed me he had to have replaced. I remember methylmercuric chloride dissolved in diethyl ether, a precursor, spilled on my rubber gloves, which I quickly washed off.

I still recall the smell of the purified end product. After the synthesis and purification, I cleaned all my glassware in the lab fume hood containing a hot bath of nitric acid and sulfuric acid. My lab coat became full of holes, but I survived!

Wright’s students recall what an excellent organic chemistry teacher he was. As an example, teaching the SN2 nucleophilic inversion reaction, Wright jumped up on his desk in front of the class and proceeded to invert himself!

Norman. L. Weinberg
Buffalo, New York

I am embarrassed to admit that I pretty much missed the tragedy of Karen Wetterhahn’s untimely death from dimethylmercury poisoning. My only excuse is that I did a lot of extended business travel during that time. However, the article in C&EN did remind me that I may have escaped a poisoning by organomercury back in the early 1960s. That was probably more by sheer luck than good planning while working on a mercury-catalyzed reaction also involving liquid 100% hydrogen fluoride (HF). We knew and planned very well and extensively for issues around the hazards of 100% liquid HF but handled the organomercury catalysts—diphenylmercury and some of its analogs—sometimes rather less carefully. Luck prevailed for several reasons. The hazards of HF required that all work was done in a hood and required the use of double neoprene gloving as well as double face and eye protections and a neoprene apron. This included the handling of not only the HF but all mercury compounds evaluated as catalysts just because it was easier to work with all reaction components after donning all the personal protective equipment and the fact that the organomercury compounds chosen as catalysts were a lot less volatile than dimethylmercury. I also do not recall that there was much information available at the time about the toxicity of organomercury. Certainly no material safety data sheet, as I recall. I and my research colleague were lucky that we had prepared for a worst case and dutifully followed the protocols in place for that at a time when lab safety and materials toxicity information did not seem to be as high a priority as they have become.


The common-sense message here is don’t rely on luck for your safety, and definitely plan and be prepared for the worst case possible. Thanks for an insightful article on professor Wetterhahn as well.

James F. White
Richland, Washington

The article on Karen Wetterhahn’s tragic poisoning by dimethylmercury reminded me of my PhD project on the mercuration of benzene. Inasmuch as phenylmercuric acetate and similar salts are quite toxic, we treated our products with great caution. In the fume hood was an iron basin containing boiling nitric acid, where we could safely rinse the glassware to oxidize away any organomercurials. Although symptoms of mercury poisoning include loss of hair and depression, I decided that those were just a normal hazard of graduate study. Of more concern was our use of mercuric perchlorate, a possible explosive. My PhD adviser, Frank Westheimer, told me to test that by hitting a sample with a hammer! Actually, he was very knowledgeable about explosives, having worked with them during World War II, and he knew that Hg(ClO4)2 was far too overoxidized to have so exothermic a decomposition. So I did the experiment and survived.

Charles L. Perrin
La Jolla, California


This article was updated on Aug. 25, 2022, to correct Charles L. Perrin's name. The last name is Perrin, not Perrinbr>.


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