Protection against nerve gas is a main part of the defense system in many
countries, as the toxic substances are a threat to both military and civilian
populations. However, existing drug solutions have limited efficiency. Now a
multidisciplinary team at the Weizmann Institute of Science in Rehovot has
succeeded in developing an enzyme that breaks down such organophosphorus nerve
agents before damage to nerves and muscles is caused.
Their results have
been published in
Nature Chemical Biology. Recent experiments performed in an
American military lab have shown that injecting a relatively small amount of
this enzyme into animals provides protection against certain types of nerve
agents, for which current treatments show limited efficacy.
RELATED:
Health Ministry to supervise IDF medical experimentation Nerve agents
disrupt the chemical messages sent between nerve and muscle cells, causing loss
of muscle control and ultimately leading to death by suffocation, and interfere
with the activity of acetylcholinesterase – the enzyme responsible for the
breakdown of the chemical messenger called acetylcholine. Acetylcholine
continues to exert its effect, causing constant contraction of the body’s
muscles.
There are several drugs used to treat nerve agent poisoning;
although they are somewhat effective when exposed to small doses of nerve agent,
they don’t provide protection against high-dose exposure; they aren’t effective
against all types of nerve agents, or they cause serious side effects. They also
cannot prevent or repair cerebral and motor nerve damage.
An ideal
solution to the problem is using enzymes – proteins that speed up chemical
reactions – to capture and break down the nerve agent before it has the chance
to bind to the acetylcholinesterase. The main obstacle is that nerve agents are
manmade, and evolution has not developed natural enzymes able to do this.
Scientists worldwide have succeeded in identifying enzymes able to break down
similar materials, but these are not highly efficient.
Large amounts of
the enzyme are therefore required in order to break down the nerve agent,
rendering their use impractical.
Prof. Dan Tawfik of the institute’s
biological chemistry department and colleagues developed a method to
artificially induce “natural selection” of enzymes in a test tube, enabling them
to engineer tailor-made enzymes. It’s based on introducing many mutations and
scanning the variety of mutated versions created to identify the most efficient.
These improved enzymes then undergo further rounds of mutations and selection
for higher efficiency. Tawfik chose a natural body enzyme called PON1 that has
been extensively studied in his lab and whose main role is to break down the
products of oxidized fats that accumulate on blood vessel walls, thus preventing
atherosclerosis. But PON1 has also been found to degrade compounds in the family
of nerve agents.
By using “directed evolution,” scientists hope they will
be able to evolve this random “moonlighting” activity into PON1’s main “day
job,” which would be carried out more quickly and efficiently than before. After
several rounds of scanning, the scientists succeeded in identifying active
mutant enzymes able to quickly break down the nerve agents soman and cyclosarin.
Tests have shown that when these enzymes were given before exposure, they gave
animals almost complete protection against these two types of nerve
agents.
Remembering Ilan RamonEvery February, a US-Israel conference on
space is held here in memory of Ilan Ramon, the first Israeli astronaut, who
tragically died with his six colleagues in the 2003 failed US National
Aeronautics and Space Admission flight Columbia.
At the latest meeting, a
joint NASA-Israeli project to send a remote sensing mission to Venus was
discussed. Dr. Jacob Cohen, the NASA AMES Research Center deputy chief of
mission design, said during a visit to BGU that NASA was very interested in
international collaborations. The late Israeli fighter pilot was a native of
Beersheba.
Cohen and Prof. Dan Blumberg, head of BGU's Earth and
Planetary Image Facility and a researcher with a long-time record of
collaboration with NASA, are leading an Israeli-USA team that includes NASA,
BGU, Houston’s Lunar and Planetary Science Institute, Israel Aerospace
Industries and Northrop Grumman. A decision on whether to launch a radar mission
to Venus is expected within a few months.
“The winning proposal will have
three years and over $400 million to design and implement a science-led mission,
with the goal of answering questions about the evolution of Venus,” said
Blumberg. “We are using existing technologies... that include a very
sophisticated radar system which is significantly lighter than any similar
system in the world. The weight makes a huge difference when you’re trying to
reach Venus,” he continued. Blumberg is sure that the fact that the Israeli-USA
program is based on existing technologies currently in use in the Israeli
satellite TecSAR gives this group a unique advantage.
Cohen said the team
decided to use radar remote sensing to overcome the difficulties in sending a
lander to Venus, where high temperatures and massive cloud cover have limited
optical imaging of the surface, and the current proposal uses much higher
resolution and better technology than all earlier missions.
“Venus has
clouds, so you can't see what’s happening on the surface, and it is too hot, so
long wavelengths are the solution,” he said.