The Art and Science of Medicine
Volume XXVI Number 1
Photo David Kirk Photography
Vial of British Anti-Lewisite
Photo courtesy Joel Vilensky
The Strange Life of a Chemical Agent
To Joel Vilensky, one of the most fascinating things about science is the unforeseen influence one researcher can have on another. Names and ideas pop up in unexpected places, revealing astonishing chains of events and linking the most unlikely people.
That's what happened when Vilensky, professor of anatomy and cell biology at the Indiana University School of Medicine's Fort Wayne Center for Medical Education, was deeply immersed in studying the work of Derek E. Denny-Brown (1901-1981), a preeminent neurologist of the 20th century. Vilensky's past research has delved into the locomotor behaviors of primates and non-primates, so he was drawn to Denny-Brown's work, which involved creating brain lesions in monkeys and observing the resulting pathologies to better understand neurological illnesses in patients.
In the early 1990s, Vilensky learned that a warehouse in Ann Arbor, Mich., held more than 500 rolls of motion-picture film from Denny-Brown's experiments. In addition to recording the monkey studies on film, Denny-Brown shot a great deal of footage of his patients, Vilensky says.
"These were people with diseases such as Huntington's and Parkinson's, with symptoms that are now rarely seen by physicians, because of the more effective drug therapies that are used and because these patients 'disappear' into nursing homes," he says.
With the help of a grant from the National Institutes of Health, Vilensky and collaborators including Sid Gilman, chair of neurology at the University of Michigan, have been analyzing the films and publishing their findings. They have also produced two teaching videos based on the films, Introduction to Neurology and Neurological Disorders. Both videos, Vilensky says, "are unique in their depiction of patients with end-stage or uncommon neurologic disorders."
It was while he was examining Denny-Brown's writings on Wilson's disease, a condition in which patients are unable to metabolize copper, that Vilensky stumbled on a strange twist of scientific history.
Denny-Brown referred to a drug called British anti-lewisite, or BAL, originally developed as an antidote to lewisite, a chemical warfare agent. BAL also proved effective in treating the potentially fatal Wilson's disease. Vilensky recalls, "I was getting ready to present a paper at a neurology meeting, and I thought, 'What if someone asks what lewisite is?'"
In his effort to answer to that question, Vilensky unearthed a story that features not only Denny-Brown, but also a legendary Catholic priest from Notre Dame University, a former president of Harvard, and even Winston Churchill. It's a story that unfolds across several continents, through two world wars, and into the present, when many nations' efforts to develop chemical weapons have left a toxic legacy. Vilensky is currently recounting the story in a manuscript with the working title Lewisite: The Strange Life of a Chemical Warfare Agent.
Among the many things that have astounded Vilensky about the story of lewisite is the identity of its inventor, Julius Nieuwland. A priest and graduate student in chemistry at Catholic University in Washington, D.C., in the early 20th century, Nieuwland seemed an improbable architect of weapons of mass destruction.
Nieuwland's research at Catholic University inquired into the properties of acetylene, which was widely used at the time as a source of heat and light. "Nieuwland combined a lot of substances with acetylene to see what would happen and then recorded the results," says Vilensky. "One of these substances was arsenic trichloride. Nothing happened, so he added aluminum chloride as a catalyst. The mixture began to bubble, an odor developed, a black cloud of smoke rose up, and the gas put Nieuwland in the hospital for several days."
Nieuwland recovered to complete his doctoral degree, briefly noting the reaction in his thesis, and went on to a distinguished career as a chemistry professor at Notre Dame. (Although he never experimented with the poisonous gas again, he did develop the first successful formula for synthetic rubber).
By 1917, when the United States was entering World War I, Nieuwland's dangerous discovery was nearly forgotten. But as overseas allies were devastated by Germany's mustard gas attacks, the U.S. military scrambled to develop its own chemical arsenal. Catholic University and American University joined the campaign. At Catholic University the chemical warfare research unit was led by Winford Lewis, a chemistry professor. Somehow, Vilensky says, Lewis learned from Nieuwland's thesis adviser about the priest's discovery. Lewis repeated the experiment, and soon realized the military potential of the agent that would become his namesake.
Meanwhile, at American University, the research team was being led by the scientific prodigy James Conant, who would eventually become president of Harvard as well as director of the government's support for the Manhattan Project in World War II. Conant joined the research on lewisite, developing a method to reduce its volatility so that it could be considered seriously as a potential weapon. Conant also headed up the first lewisite production facility.
"In July of 1918, the United States decided that 3,000 tons of lewisite needed to be in Europe by March 1919," Vilensky says. "A site was leased in Willoughby, Ohio. Hundreds of soldiers came in to work. The pace was frantic--24 hours a day. In about six months, they went from an abandoned factory building to a chemical plant making 10 tons a day. Then, just as they were ready to make their first shipment, the war ended. So the plant was dismantled, and the lewisite was shipped to Baltimore and dumped into the sea."
Lewisite was not forgotten, however. After the war, Winford Lewis often spoke publicly about his involvement in developing the poison gas. "He defended its use," Vilensky says. "He proposed that societies capable of developing more advanced chemical weapons are more advanced evolutionarily and more deserving of victory." Father Nieuwland, too, claimed that chemical weapons were superior. In an article about the priest for Notre Dame Magazine, Vilensky quotes Nieuwland: "Today the primary aim in war is not to kill but to incapacitate," the priest said. "If a man goes to the hospital suffering from gas, he is as useless as if he were dead, and to care for him several other persons must be kept out of the battle lines. The chances are that ultimately the victim will recover."
Nieuwland died in 1936, suffering a heart attack while visiting the Catholic University laboratory where he first synthesized the chemical.
In 1940, as war again consumed Europe, James Conant was asked to direct a division of the National Defense Research Committee, which supervised production of bombs, fuels, gases, and chemical agents. As he researched this point in Conant's career, Vilensky suddenly reencountered the scientific figure who had originally inspired his curiosity: Derek Denny-Brown.
"Conant went to England, where Denny-Brown was serving in the military," Vilensky says, "and persuaded Winston Churchill to release Denny-Brown from duty to become director of Harvard's neurological unit."
Eventually, Vilensky says, the United States produced 20,000 tons of lewisite for World War II. "The government tested it on thousands of soldiers. It was secretly dropped from airplanes," he says. The conclusion of the tests was that lewisite was not well suited to the Allies' needs because it breaks down too easily when exposed to water. The United States never deployed it in battle.
"Then Conant was assigned to run the government end of the Manhattan Project," Vilensky notes. "His success in building atomic bombs was directly linked to his experiences with lewisite."
Even though the United States scrapped its lewisite project, other countries began obtaining the formula in the 1920s, and it has appeared in conflicts throughout the world.
"It's still around," Vilensky says. "Japan used it in Manchuria during World War II. Iraq probably used it in its war with Iran. The Soviet Union was once a major manufacturer of it and reportedly has dumped more than a hundred tons of it into the Arctic Ocean."
Lewisite could possibly become a tool of terrorism, but Vilensky considers it an unlikely candidate. Contact with lewisite can certainly have horrifying effects, however, including painful blistering of the skin, damage to the eyes and respiratory system, and, because of its arsenic content, death.
In addition to fears about tactical uses of lewisite, there are plenty of concerns about its environmental effects. Contaminated sites exist around the world, Vilensky says, including some in its birthplace, Washington, D.C. In the early 1990s, landscapers dug up bottles while working on the American University campus, breaking them open in the process. "They had difficulties breathing and complained of burning skin, which developed black spots," Vilensky wrote in Washingtonian magazine. "D.C. health officials investigated and determined that the workers, who were treated at a nearby hospital, most likely had been exposed to lewisite." High concentrations of arsenic have been found in the soil at other locations on the campus as well as in surrounding neighborhoods.
The development of lewisite has, however, had at least one positive consequence: BAL, the drug referred to by Denny-Brown in his writings on Wilson's disease. British biochemists at Oxford University first formulated this antidote in 1940, and it was further refined at DuPont Laboratories in the United States. Vilensky says that it is highly successful in preventing burns caused by lewisite and can also reverse its systemic effects. After World War II, BAL was found useful in reversing other kinds of heavy metal poisoning. It is still manufactured and is the recommended drug for treating lead poisoning in children.
Scientists have also tried to identify peacetime uses for lewisite itself, Vilensky has discovered. "They've used it for removing barnacles," he says. "It was also diluted and fitted into bank burglar alarms, including one in Elnora, Ind., in the 1920s."
Such applications hardly seem to outweigh the dangers that the developers of lewisite brought into the world, but Vilensky declines to judge them harshly. "When studying things like this, you have be very careful to consider the mindset of the times," Vilensky says. "It's very easy for us to criticize, but in World War I, the Germans were winning until the United States got involved. I agree with something that Conant once said--that all war is immoral, but if you're going to have war, you ought to win."
Karen Grooms is senior editor in the IU Office of Publications in Bloomington.