For educational purposes
Dr. Furlong's Research
Sensitivity to Organophosphates
Due to Enzyme Paraoxonase
By LAURIE GARRETT
Excerpts from NEWSDAY Article
The ability to withstand exposure to the nerve gas sarin is genetically
controlled, with Caucasians most resistant to the dangerous chemical
and Asians most susceptible, according to a report released Friday.
The discovery of a genetic basis to sarin vulnerability may have
powerful implications for investigation of complaints of medical
problems among Persian Gulf War veterans.
Last month, the Department of Defense admitted that 20,000 Gulf
War military personnel may have been exposed to toxic levels
of saran when an Iraqi stockpile was bombed by U.S. forces.
And some may be suffering symptoms related to sarin exposure.
"We think that research into possible health effects of organophosphorus
[sarin type] compounds is important and we welcome responsible
research," said an official statement released by the Department
of Defense on Thursday.
"We agree that the question of individual genetic differences may
be important in understanding the susceptibility of certain individuals
to [organophosphorus] exposure. The DOD is currently negotiating
a study that addresses these concerns."
Chemist Clement Furlong and his University of Washington
colleagues have for several years studied a class of chemicals
called organophosphates, all of which
exert their lethal effects
by blocking a crucial neurotransmitter called
Most organophosphates are used as pesticides, but a few - like sarin -
have been developed as nerve gas weapons. The United States,
for example, has stockpiles - all of which are scheduled for
destruction by 2000 - of 25,000 tons of such nerve agents.
In the blood of all human beings is an enzyme called
or PON1, which normally plays a poorly understood role in
Furlong's group demonstrated years ago that PON1 also
breaks down or destroys the super-lethal component
organophosphates, a chemical called
Furlong has injected rabbits and other test animals with the
PON1 enzyme and shown that subsequent exposure to usually
lethal organophosphate pesticides is harmless.
In other words, PON1
the animals against the
lethal effects of pesticides by
In Friday's issue of the British publication
Furlong's group shows that PON1 has the same effect on sarin,
which is not surprising because the chemical is a classic
But what is startling is discovery that some people
make a form
of PONI that doesn't work against sarin.
The trait - called type R - is genetic. People who inherit type R
genes from both of their parents, rendering them homozygous
for the trait, are extremely vulnerable to the toxic effects of sarin.
People who make normal PON1 - this is regulated by type Q genes -
are better able to resist the lethal chemical. If one is heterozygous,
having inherited Q from one parent and R from the other,
susceptibility to sarin is midway between the two extremes.
A separate, as yet unidentified, gene regulates how much
PON1 is made.
Even if a person is homozygous for the beneficial
type Q gene,
it will do no good if the amount of PON1
is low [as in when it
is depleted by repeated exposure] when sarin [or a related
organophosphate pesticide] enters the body.
"Now what I think is real important to do would be to look at
people in Japan who were exposed to sarin in that [1993 Tokyo
subway] attack," Furlong said, "to test their PON1 enzymes -
the genetic forms in those who got sick vs. those who didn't."
Gene tests show Asians are most likely to carry the
type - R genes. Twenty-five
percent of Asians
for sarin susceptibility.
About 16 percent of Latinos are
homozygous type R while only
10 percent of Caucasians are
so vulnerable. Researchers
not yet tested Africans or African-Americans.
A Department of Defense spokesman said last week that no racial
breakdown of Gulf War veterans who claim war-related illnesses,
compared with the overall demographics of the 700,000 U.S. troops
who served in the war, has been done.
But the Furlong study suggests two crucial points: People are not
equally susceptible to the nerve gas, and Pentagon assumptions
about "significant exposures" - assumptions used in the past to
dismiss the possibility that chemical weapons were at the root
of so-called Gulf War syndrome - may fail to consider elements
of the population that are particularly genetically vulnerable to
sarin and other nerve gases.
Five soldiers could, for example, have been exposed to the same sarin
dose, at the same time and only one go on to develop paraoxon-caused
Marie and her classmates were exposed to a wide array of
organophosphate pesticides while attending SBU -- all of
which had the potential to:
cholinesterase, and thereby precipitate a full-blown
an individual to any additional organophosphate
*and destroy or disrupt
the individual 's defensive
*but also -- to
deplete and disrupt the
metabolism and leave an individual
vulnerable to disease
Marie is a European Caucasian -- blonde-haired, blue-eyed,
light-skinned, lean, tall, and athletic.
Her ancestry -- which is British, Irish, Germanic, and Nordic --
dates back to the May Flower (and beyond) and includes:
explorers, scholars, journalists, educators, musicians, merchants,
revolutionaries, legislators, statesmen ... and even a President.
Her genetic PON1 status is unknown as the genetic test is
yet available to the public -- but other factors appear to make
it unlikely that Marie carries the homozygous gene for the
type R paraoxonase trait.
estimated one out of
ten SBU students
or visitors to the campus do carry this racial/genetic
Research has shown that
infants are born with almost
no resistance to these organophosphate pesticides.
The young age of most students -- in and of itself -- increases
their vulnerability and the likelihood of low
Lowering the activity of
paraoxonase in the blood is associated
with increased risk of cardiovascular
disease, according to new
research. Please see Dr. Michael Aviram's
Should Dr. Michael Aviram's
research concern the SBU
A disconcerting number of people have suffered from
cardiovascular disease while on the SBU
football player suffered back spasms and
seizures and died of a heart
attack while playing on the
(diazinon crystal-covered) Plaster Field;
student playing tag football died of a brain aneurysm
cardiovascular disease; a sac-like widening of a blood
vessel) on the SBU playing field;
freshman football player had a heart attack
field several days before the semester began,
*and while visiting his son, a father (an SBU alumnus)
went to take a nap in a SBU dorm room and
died of a heart
When exposed to organophosphate compounds, those
individuals with depleted or low levels of paraoxonase
whether the result of repeated previous exposures, physical
injury and stress, natural predisposition and racial/genetic
variation, or youth -- are at much greater risk of disease,
serious injury, or
Please protect yourselves
For more information on the pentagon-sponsored
on the enzyme paraoxonase and the exposure of Gulf War
Veterans to sarin and organophosphate pesticides.
~How Can I