Defending against chemical acts of terrorism

Apr 19, 2012

Researchers may have found a way to protect us against otherwise deadly chemical attacks, such as the subway sarin incident in Tokyo that left thirteen people dead and thousands more injured or with temporary vision problems. The method is based on a new and improved version of a detoxifying enzyme produced naturally by our livers, according to the report in the April 2012 issue of Chemistry & Biology, a Cell Press publication.

"The sarin attack in Tokyo in 1995 demonstrated that both the raw materials and know-how of producing deadly nerve agents are available to people outside government or military institutions," said Moshe Goldsmith of the Weizmann Institute of Science in Israel. "We hope that our work would provide a prophylactic drug that will effectively protect the medical, police, and other teams that will have to act in a contaminated area following such an attack and would also provide these teams with a drug that could be administered on-site to intoxicated individuals to greatly improve their chances of survival."

Today, protection against nerve agents relies primarily on physical barriers such as gas masks and protective suits that can easily be breached, Goldsmith explained. Following exposure, people are treated with drugs that help with the symptoms but don't eliminate the nerve agent.

Goldsmith and the study's senior author Dan Tawfik hope to change this, relying on the principles of evolution to produce a more efficient version of an enzyme that occurs naturally in all of us. Known as paraoxonase 1 (PON1), this enzyme was originally named for its ability to assist in the breakdown of the insecticide paraoxon. It is also involved in drug metabolism and detoxification.

PON1 normally does counteract G-type nerve agents, including sarin, tabun, soman, and cyclosarin, but not well enough. Tawfik's lab specializes in a technique called "directed enzyme evolution,"in which they artificially introduce mutations into the gene encoding a target enzyme, in this case PON1. The mutated versions of the gene are then put back into bacteria, which produce the enzymes for testing. The goal was to end up with enzymes capable of detoxifying G-type nerve agents before those nerve agents could reach their target and cause harm. Those that passed the initial test went on to further rounds of evolution and testing.

After four rounds of evolution, the researchers obtained PON1 variants that worked up to 340 times better than those produced previously. Overall, the researches reported that the PON1 variants showed 40- to 3,400-fold higher efficiency than the normal enzyme in metabolizing the three most toxic G-type .

These new and improved PON1 enzymes have become promising candidates for use as preventive and postexposure treatments in the event of a terrorist attack.

"We hope that our enzymes would be able to act together with currently available drugs to improve survival rates following intoxication," Goldsmith said. More broadly, the findings show the power of laboratory evolution to completely reshape existing enzymes for a variety of uses.

Explore further: Structure of sodium channels different than previously believed

More information: Chemistry & Biology. DOI: 10.1016/j.chembiol.2012.01.017

Related Stories

Researcher working on destruction of chemical weapons

Sep 24, 2008

America's war on terror includes fighting the dark side of deadly chemical agents, and Texas A&M University chemist Dr. Frank Raushel is helping with the fight by developing an enzyme that might neutralize one such chemical ...

Recommended for you

Breakthrough points to new drugs from nature

Apr 16, 2014

Researchers at Griffith University's Eskitis Institute have developed a new technique for discovering natural compounds which could form the basis of novel therapeutic drugs.

World's first successful visualisation of key coenzyme

Apr 16, 2014

Japanese researchers have successfully developed the world's first imaging method for visualising the behaviour of nicotine-adenine dinucleotide derivative (NAD(P)H), a key coenzyme, inside cells. This feat ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Telekinetic
5 / 5 (1) Apr 19, 2012
I once thought of a similar enzyme type that would metabolize the black tar lining of a smoker's lungs, leaving it pink and healthy. It might actually work as long as it didn't migrate to the smoker's brain and start house-cleaning there- or maybe therein lies a potential way to clear out the amyloid plaques of Alzheimer's.

More news stories

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...