image: Jennifer Heemstra (left) works in her laboratory with postdoctoral researcher Joseph Ibukun.
Credit: Sean Garcia, Washington University in St. Louis
Mustard gas, also known as sulfur mustard, is one of the most harmful chemical warfare agents, causing blistering of the skin and mucous membranes on contact. Chemists at Washington University in St. Louis have been awarded a $1 million contract with the Defense Threat Reduction Agency (DTRA) to develop a new way to detect the presence of this chemical weapon on the battlefield.
As with many chemical threats, quick identification of sulfur mustard is key to minimizing its damage, according to Jennifer Heemstra, the Charles Allen Thomas Professor of Chemistry in Arts & Sciences and principal investigator of the new DTRA grant.
“It’s important to be able to detect sulfur mustard, because once people are exposed, there is no antidote,” Heemstra said. “Detection is key to preventing exposure, and currently there aren’t good technologies to do that rapidly in the field.”
Mustard gas was used during combat in World War I, World War II and the Iran-Iraq conflict in the 1980s. Exposure to mustard gas does not often cause death, but it can cause temporary or permanent eye injury, second- and third-degree burns and other serious problems with breathing.
Even after a war is over, service members, contractors and civilians who demolish or handle explosive ordinance can be exposed to mustard agents. Current methods for detecting sulfur mustard require expensive instrumentation and specialized sample preparation, making them impractical for the type of real-time detection that is needed in the field.
Under the new grant, Heemstra and her collaborators, including M.G. Finn at Georgia Institute of Technology, will develop a new, streamlined way to detect an entire class of chemical compounds called vesicants, a group that includes sulfur mustard.
“We will initially focus on model compounds that act like mustards, but that can be handled safely in the laboratory. This will allow us to test different molecular sensor designs, with the Heemstra lab and ours working together on complementary approaches,” Finn said. Other key project team members include Joseph Ibukun, a postdoctoral research associate at WashU; Seth Taylor, a postdoctoral research associate at Georgia Tech; and Makenzie Walk, a graduate student at WashU.
The scientists will use nucleic acid molecular recognition to generate biomolecules that first bind to specific vesicants and then initiate a cascade of reactions that will generate a highly visible fluorescent signal.
“Often sensors have a simple, linear output — as in, the one molecule you detect produces one molecule of signal on the other end,” Heemstra said. “Here we are planning to generate an amplified output, so that for every molecule of toxin, you’re generating several signal molecules so that you can detect them with the naked eye.”
Her collaborators at Georgia Tech have specialized experience in producing amplified signals using dendrimers — synthetic molecules with a highly ordered, branch-like structure.
“For this kind of branched chain molecule, you generate more and more branches with every generation,” Heemstra said. “After one reaction with a toxin molecule, we hypothesize that we can trigger a cascading reaction that will then release dye molecules at the end of each of the branch points.”
Countering weapons of mass destruction is important for military personnel, but this research can lead to outcomes that are important for civilians as well.
Heemstra points to the example of another chemical weapon, sarin, which was used during the Iran-Iraq conflict. In military conflict, it is used at high doses and can cause death in minutes. But certain organophosphate pesticides can have a similar structure and biological mechanism as sarin, just with lower toxicity. Over time, people exposed to such pesticides can suffer from chronic organophosphate poisoning.
“Milder versions of the types of toxins that are used in warfighting and as chemical weapons show up in everyday life,” Heemstra said. “When they’re not handled properly, they can be a real threat to society and to human health.”
About the Defense Threat Reduction Agency: DTRA is a defense agency that provides cross-cutting solutions to enable the Department of Defense, the U.S. government and international partners to deter strategic attack against the United States and its allies; prevent, reduce and counter weapons of mass destruction and emerging threats; and prevail against weapons of mass destruction-armed adversaries in crisis and conflict. In fiscal year 2024, WashU received more than $15 million in contract awards with the Department of Defense.