Researchers' Deaths Inspire Actions To Improve Safety

'GREAT SHOCK': The June 1997 death of Karen Wetterhahn from an accident that had occurred months earlier stunned the scientific community.

Like any profession, life science research has dangers, but fortunately, deaths are rare. The Occupational Safety and Health Administration (OSHA) reported only six fatalities in biological and life sciences, and 17 fatalities in all natural sciences, for 1994, the most recent year for which data are available. So when Dartmouth College chemist Karen Wetterhahn died in June from spilling dimethylmercury on her glove months earlier, the scientific community was stunned. "It was a great shock that such a thing could happen," says Thomas Clarkson, chairman of the department of environmental medicine at the University of Rochester. "Chemists synthesize new compounds all the time. I remember the days when chemists tasted their compounds to help identify them!"

Deaths associated with scientific research often stimulate actions to improve safety in research methods. Such was the sad case of Wetterhahn. On September 15, OSHA reduced both the number of violations it had determined last spring that Dartmouth had committed and the associated penalties because the college had taken such swift action to improve conditions as well as alert the scientific community to the danger of mercury compounds. Deaths of scientists working outside the laboratory have also inspired efforts to improve safety. What these seemingly diverse cases share is that the researchers were experienced and prepared, and doing what they loved best when they were injured or died.

Wetterhahn, the Albert Bradley Third Century Professor in the Sciences, died on June 8, 1997, at age 48. The trouble began on Aug. 14, 1996. Wetterhahn, an expert in heavy metal poisoning, was preparing dimethylmercury to use as a standard in nuclear magnetic resonance (NMR) spectroscopy against which she would compare mercury ions that interact with DNA repair proteins. Use of dimethylmercury is rare; only three previous cases of poisoning are known (see story on page 4).

Michael Blayney, director of environmental health and science at Dartmouth, reconstructed the events from lab notebooks and Wetterhahn's account. "She used tiny amounts in a fume hood; wore thin, disposable latex gloves; [and] had eye protection, and she was doing work that involved two or three simple steps," he recalls. But those precautions weren't enough. "At the time of her admission to the hospital, she recounted on two separate occasions her recollection of spilling a tiny amount of the chemical on the dorsum of her left hand near the junction of her forefinger and thumb. She also recounted cleaning the spilled material up-which, presumably, included removing her gloves and washing her hands."

In January, Wetterhahn experienced tingly fingers and toes, slurred speech, and balance problems, then constricted vision and hearing loss. When she was diagnosed on January 28 with mercury poisoning, her blood mercury exceeded the toxic level 80-fold. Three weeks later, she lapsed into a coma, in which she remained until her death in June.

In the brief time that she was conscious, Wetterhahn knew precisely what was happening. "Before she went into a coma, she said she wanted everything possible to be done to get the news out to other scientists working with mercury," reports her physician, David Nierenberg, Edward Tulloh Krumm Professor of Clinical Sciences at Dartmouth. "She was concerned that people immediately increase efforts to use better and safer handling techniques, and that physicians learn to pick up the signs earlier. She was so sick, yet concerned above all about her colleagues."

WARNING: Michael Blayney, director of environmental health and science at Dartmouth, coauthored a Chemical & Engineering News article to get the word out about Karen Wetterhahn's accident.

ASTONISHING FINDING: Rochester's Thomas Clarkson analyzed samples from Karen Wetterhahn's body and were amazed at the toxicity of dimethylmercury.

But Wetterhahn hardly had to implore Nierenberg, Blayney, and John Winn, chairman of chemistry, to act-they did so immediately. They contacted the American Chemical Society, which published their warning as soon as possible (M. Blayney, J. Winn, D.W. Nierenberg, Chemical and Engineering News, 75:7, 1997). An independent laboratory tested all the gloves in Wetterhahn's lab, finding that dimethylmercury penetrates latex and polyvinylchloride (PVC) almost too fast to be measured. A drop could transfer from glove to, and through, skin in 15 seconds. And although symptoms don't appear for months, the compound rapidly crosses the blood-brain barrier and begins its destruction, so that chelation therapy to trap and remove mercury is futile.

When Clarkson's lab analyzed samples from Wetterhahn's body, the researchers were shocked anew at the toxicity of dimethylmercury, which they had to use to calibrate their instruments. "It came in a glass vial, as a liquid. Our senior analytical technician transferred it to another vial," says Clarkson. "He was using a disposable pipette tip and put it in the wastepaper basket. Within an hour, we picked up dimethylmercury on the mass spectrometer in a different part of the room. The tiniest amount can evaporate." In a letter in the June 16 Chemical and Engineering News (T.Y. Toribara, T.W. Clarkson, D.W. Nierenberg, 75:6, 1997), Clarkson and colleagues implored manufacturers of the compound to improve packaging-glass vials can break.

Today at Dartmouth, many safety improvements are a testament to Wetterhahn's memory. Workshops instruct scientists in selecting appropriate gloves. The latex gloves that are fine for most biomedical research are not sufficient for extremely toxic chemicals; use of such substances requires laminate gloves worn under long-cuffed neoprene gloves. Brightly colored stickers on gloves are now color-coded to posters that match glove type to task. A new chemical safety committee has been formed and a chemical hygiene officer hired. And in many research laboratories at Dartmouth and here, less-toxic mercury salts are replacing dimethylmercury as an NMR standard. Concludes Blayney, "If we knew what we know today on Aug. 14, 1996, if Karen knew, we wouldn't be having this conversation."

Mercury comes in three forms-elemental (metallic), inorganic, and organic. The Washington D.C.-based Agency for Toxic Substances and Disease Registry lists elemental mercury as the third most hazardous substance, following lead and arsenic. Organic mercury is even more dangerous than the elemental form, says David Nierenberg, Edward Tulloh Krumm Professor of Clinical Sciences at Dartmouth College, where a chemistry professor recently died of dimethylmercury poisoning. The most commonly used organic mercury compound is methylmercury. "We know about this group of organic mercury compounds because of epidemics that caused sickness and poisoning in Japan, where people ate contaminated fish," says Nierenberg. "And in 1972 in Iraq, grain was treated with methylmercury as a fungicide. It should have been planted, but instead it was milled and used to make bread. The people ate it, and there were thousands of exposures and 100 deaths." The World Health Organization warned of the danger of methylmercury and halted its use in fungicide right after the 1971 Iraqi outbreak, according to Thomas Clarkson, chairman of environmental medicine at the University of Rochester in New York. Use of the dimethyl form of mercury continued, however, in about 100 laboratories worldwide, as a nuclear magnetic resonance standard. Dartmouth chemist Karen Wetterhahn was preparing such a standard when a drop fell onto her latex glove. Once in the body, dimethylmercury is broken down to the monomethyl form, crosses the blood-brain barrier, then bonds to sulfur-containing amino acids, which kills nerve cells. Methylmercury is deadly in weeks; dimethylmercury, in months. Wetterhahn's tragedy was only the fourth known dimethylmercury poisoning. The other victims were laboratory workers in England who originally synthesized the compound in 1865 (F. Dewhurst, Chemistry in Britain, 25:702, 1989); two secretaries in Canada who inhaled fumes from a leaking vial in a warehouse (Anonymous, Canadian Journal of Public Health, 43:1580, 1943), and a chemist working without adequate protection in Czechoslovakia (J. Pazderova, Int. Arch. Arbeitsmed., 33:323-8, 1974; cited in L. Magos, Metal Ions in Biological Systems, 34:321-70, 1997).

It is a long way from a New England chemistry lab to a South American volcano, but for Stanley Williams, the lesson was the same: Research is unpredictable. Ironically, Williams, a professor of volcanology at Arizona State University in Tempe, had started his career in measuring sulfur dioxide emissions from volcanoes at Dartmouth in 1972.

In January 1993, Williams was testing a prototype gas monitor at the Galeras volcano in Colombia when an eruption occurred. "It fooled us. We thought the volcano was quiet when it was really clogged up. It was 'breathing' the same amount of gas as before, but it was not able to let the gas escape," Williams remembers. His six colleagues, including scientists from the United Kingdom, Russia, and Colombia, perished instantly. Williams sustained a fractured skull, broken jaw, severe burns on his back, and two broken legs. It took two years for his strength to begin to return.

But Williams accepts what happened to him as part of scientific exploration, and the accident hasn't dampened his enthusiasm for field work. "When you really do science, you can make fatal errors," he says. "People need to go to volcanoes to make observations and collect data. I try to be more cautious, but the tragedy has not prevented me from going back into volcanic craters."

Thanks to Williams's work on volcanic gases, researchers are now better able to recognize an impending eruption-a fact film producers noted. "I was pursued endlessly by Hollywood, but I avoided all that stuff. If I had the $155 million they used to make Dante's Peak, I could radically improve volcanology. I could focus attention on a few volcanoes and learn how to lower hazards," comments Williams, who has done educational television programs.

When Francis Barany a professor of microbiology at Cornell University Medical College, read of Williams's accident, he wrote to him, welcoming him jokingly into the "American Society for Burnt Scientists." Unlike Williams, Barany's too-close encounter with a Yellowstone Park hot spring in 1991 cured him of wanting to obtain his own thermostable enzymes for use in gene amplification research. "While collecting my 13th sample, the ground simply gave way, and my left leg sank into the hot mud. It was 158°F and blistered the skin right off. I jumped out and hopped onto land, screaming," he recalls.

SURVIVOR: Francis Barany, second from right, poses with the people who saved his life, from left, Gerry Gavalcin, Carl Batt, and Rachel Conescu. The photo was taken by an anonymous tourist about one hour before his 1991 accident.

Barany and three others with him had a permit to collect microorganisms from the park's hot springs. But he acknowledges now that they used homemade collection contraptions and leaned too close over the edges. "I'm not going near another hot spring. Now I just collaborate with others who feel sorry for me so they send me their strains, or get professionals to collect, who charge about $100 a sample. Let someone be the hot dog." Barany's story had a happy ending-he recovered and married the woman who hauled him out of the hot spring.

'FOLLOWING HIS CURIOSITY': Rochester's Wolf Vishniac, shown during a 1972 research mission in the Antarctic, fell to his death in Antarctica's Asgard Mountains in 1973.
	GRIM DISCOVERY: Zeddie Bowen found colleague Wolf Vishniak's body 500 feet beneath an ice field between two mountains.

Sometimes natural conditions prove treacherous, even to the best-prepared researchers. Such was the case for Wolf Vishniac, a professor of biology at the University of Rochester, New York. On Dec. 10, 1973, he embarked on a 12-hour hike in the barren Asgard Mountains in Antarctica to retrieve slides of nutrients on which microorganisms might have been growing. The experiment was in preparation for a similar one to be conducted on the Viking mission to Mars. Vishniac's colleague, Zeddie Bowen, remained at the campsite to await a supply plane.

The men had made the trek before. "We went off alone on several occasions, always in good weather and with an expected route and timetable. The route was not dangerous. When he didn't return on time, I went looking for him, expecting, at worst, a broken ankle," says Bowen, vice president and provost at the University of Richmond in Virginia. Instead, Bowen found Vishniac's body, 500 feet beneath an ice field between two mountains. "What I really expected was to find him distracted by some fascinating new discovery or observation. Unfortunately, he had followed a different route and fell to his death. He was following his curiosity."

In retrospect, there isn't anything the duo could have done to prevent the tragedy, Bowen notes. "We were very cautious and respectful of the dangers of the environment, but never expected to be seriously injured. Our only real danger was falling, and but for one step, Wolf might still be alive. That kind of step could occur in any field experience in rough terrain," he adds. The risk, he says, is not sufficient reason not to do the research. Bowen hasn't returned to Antarctica, because he hadn't gone on the 1973 trip for research reasons. "Friendship, curiosity, and an adventurous spirit led me to join him."

In the cases of Wetterhahn's mercury poisoning, the eruption of the Galeras volcano, and Wolf Vishniac's disappearance, witnesses and evidence reconstructed the accidents. Some deaths of scientists are never explained. This was the case for another ice mishap that occurred in northwestern Alaska. On Oct. 11, 1990, John Bevins and George Menkens, research wildlife biologists with the United States Fish and Wildlife Service in Anchorage, disappeared while radiotracking polar bears, leaving no radio call or emergency locator beacon. Although the researchers had not been on many missions to this very remote locale, the pilot, Clifford Minch, was very experienced.

"The disappearance of the survey aircraft was followed by the most comprehensive and exhaustive aerial search in civilian history," recalls Steve Amstrup, a research wildlife biologist with the U.S. Geological Service in Anchorage and a close friend of Bevins's. "We had up to six chartered aircraft and three Coast Guard C-130 search-and-rescue aircraft flying search grids covering over 300,000 square nautical miles of habitat." But after two weeks, the effort was called off, and the wreckage was never found.

Amstrup took some consolation in knowing that Bevins and Menkens were in that place where few humans venture by choice. "Both were enthusiastic and loved their work, and they were aware of the risks it entailed. It truly can be said that they died doing research that they enjoyed and to which they were devoted." The same could certainly be said for Karen Wetterhahn, the volcanologists in Colombia, and Wolf Vishniac.

Ricki Lewis, a freelance science writer based in Scotia, N.Y., is the author of several biology textbooks. She can be reached online at 76715.3517@compuserve.com.