A Drug to Fight Chemical Weapons
WHY YOU SHOULD CARE
Because toxic nerve agents are among the most devastating weapons ever created, and this research could stop them in their tracks.
By Niamh Ni Mhaoileoin
Early on Aug. 21, 2013, rockets filled with toxic agents were fired into the suburbs of Damascus, Syria, killing 1,429 people, including at least 426 children. This attack, believed to have been perpetrated by the regime of Bashar al-Assad, occurred despite President Obama’s “red line,” proving that political threats alone cannot deter the use of chemical weapons.
The U.S. and Russia responded to that attack by convincing Assad to relinquish his chemical weapons arsenal, but researchers at the University of Tennessee in Knoxville are arguing for an entirely different approach for future crises. They want to employ advanced quantum and molecular mechanics to design an enzyme that neutralizes deadly nerve agents within the human body. The prophylactic would essentially immunize people against many of the world’s most lethal and horrific weapons.
It turns out that squid, of all things, may hold the secret to fighting sarin.
Chief among those deadly agents is sarin, the best known of the “organophosphorus nerve agents” the team hopes to disable. These chemical weapons disrupt the functioning of nerve cells so that they fire constantly, causing the heart and respiratory muscles to spasm. Inhalation of sarin can kill within minutes, which means that although antidotes exist, medical staff can rarely reach victims in time. For this reason, introducing preventative drugs is a far more effective way to save lives.
And it turns out that squid, of all things, may hold the secret to fighting sarin. The Knoxville team, led by Professor Jeremy Smith, is working with enzymes known as “bioscavengers,” which occur naturally in the bodies of would-be calamari — although no one quite knows why. The gene was originally taken from European squid, or Loligo vulgaris, many years ago, and scientists now can develop the enzyme recombitantly using bacteria. In other words, very few squid have been harmed in the course of this research.
Scientists like Smith and others have a unique opportunity to engage in this area of research because of previous breakthroughs in quantum and molecular mechanics, for which Smith’s one-time supervisor Mark Karplus was awarded the Nobel Prize in 2013.
Earlier research on chemical weapons was limited by the extreme risk involved, even in a controlled lab environment. That risk is nullified when the substances can be simulated on a computer. Enzymes are too small to see, but by using a revolutionary method known as “neutron scattering,” scientists can now determine their shapes in three dimensions and make calculations that clarify the reaction caused by the bioscavenger.
In layman’s terms, the team can computer engineer effective enzymes. So while it may be years before the enzyme is clinically tested, the computational component significantly reduces risk and increases the likelihood of success in clinical testing.
[The goal is] to engineer prophylactics effective enough that potential belligerents … no longer see any tactical gain in deploying these weapons…
Smith, the governor’s chair in molecular biophysics at the Oak Ridge National Laboratory (ORNL), explains that his team had access to a three-dimensional structure of the candidate bioscavenger, thanks to previous X-rays and neutron crystallography.
“We were able to use that structure as a starting point for our computations to figure out how the enzyme breaks sarin up chemically,” he said. Those computations confirm that the squid enzyme has the potential to “chew up” toxic agents in the bloodstream.
The team is now focused on increasing the speed, efficacy and adaptability of the enzyme. The final product would need to operate quickly enough in the system that it could completely offset exposure, respond to a variety of different nerve agents and avoid destabilizing the immune system. Smith emphasizes that similar issues must be overcome in the production of any biological drug, such as cancer-fighting antibodies, and that “none of these challenges are necessarily deal-breakers.”
The work may be in its early stages, but Smith has a clear vision for the potential of the technology. He tells OZY that his team wants “to engineer prophylactics effective enough that potential belligerents, such as future incarnations of Assad and Saddam, no longer see any tactical gain in deploying these weapons in the field.”
To accomplish that, the prophylactics would need to be cheap and readily available, so that when a vulnerable area is identified, the drug can be rapidly administered. Importantly, the enzyme would not work like a vaccine, inoculating recipients for life. Rather it would remain active in the bloodstream for a little over a week. An admittedly small window, but materials published in the aftermath of the Syrian attack show that the U.S. had extensive intelligence on the nature of the weapons and the plan to deploy them. Close cooperation between intelligence services and medical units could mean that military personnel, NGO staff and civilian populations could be shielded from imminent attacks.
The Knoxville team is currently seeking additional funding for its research, which could be mobilized by the international outrage over Assad’s use of chemical weapon. Since the Syrian war began, the U.S. Army has issued a call for research in this area.
Unfortunately, even if the research bears fruit, the institutional challenges on the ground are even greater. Smith acknowledges that war zones can “deteriorate to the point that it is impossible to get medical help in.” This is borne out in Syria, where polio was eradicated in 1999 but has re-emerged due to the impossibility of vaccinating children in the areas most affected by the conflict.
Because little can be done to intervene in conflicts that have grown too dangerous, Smith suggests that the “hope must surely be to get this drug into the zones well before that stage is reached.”
Ultimately political leaders determine the nature of warfare, but scientists can provide tools to support the process. Many are counting on ORNL’s research to help alleviate the terror and suffering caused whenever the chemical red line is crossed.
- Niamh Ni Mhaoileoin, OZY Author Contact Niamh Ni Mhaoileoin