SUMMARY OF PERSIAN GULF WAR ILLNESS PILOT STUDY ON MYCOPLASMAL INFECTIONS IN VETERANS AND FAMILY MEMBERS

 SUMMARY OF PERSIAN GULF WAR ILLNESS PILOT STUDY ON

MYCOPLASMAL INFECTIONS IN VETERANS AND FAMILY MEMBERS

Garth L. Nicolson, Ph.D. and Nancy L. Nicolson, Ph.D.

The Institute for Molecular Medicine, P.O. Box 52470, Irvine, California
92619-2470

Approximately 50,000-100,000 U.S. and ~3,500 British soldiers returned from
Operation Desert Storm with unusual illnesses characterized by a variety of
chronic signs and symptoms. Our step-daughter was one of these soldiers.
Since we had some experience with a disease that caused similar complex
signs and symptoms, we proposed that the Desert Storm or Persian Gulf War
Illness (GWI) might be caused by a severe mycoplasmal infection and that it
should be treatable with appropriate antibiotics. We conducted a pilot study
of Desert Storm veterans and their families for the presence of unusual
mycoplasmal infections. This study showed that 55/73 GWI patients, including
symptomatic family members, responded to an antibiotic (doxycycline) that is
effective against a variety of mycoplasmas, and these soldiers and their
family members who were sick with the same symptoms eventually recovered
from their illness (Nicolson, G.L. and Nicolson, N.L. Doxycycline treatment
and Desert Storm J. Amer. Med. Assoc. 273: 618-619, 1995). Since this study
we have continued to gather evidence that mycoplasmal infections, and
probably other chronic infectious agents, are causing the chronic signs and
symptomsof GWI that are similar to Chronic Fatigue Syndrome (Nicolson, G.L.
and Nicolson, N.L. Chronic fatigue illness and Operation Desert Storm. J.
Occup. Environ. Med. 38: 14-16, 1996).

Mycoplasmas are microorganisms whose genetic complexity and classification
are similar to bacteria. These microorganisms are usually indolent in normal
healthy individuals and are not often associated with severe diseases. In
fact, most adults may have had mycoplasmal pneumonia or a urogenital tract
infection caused by mycoplasmas. The mycoplasmas we have found in a sizable
fraction of the Gulf War Illness patients are unlikely to be naturally
occurring and could be Biological Weapons. We have based this notion on the
observation that the mycoplasmas that we have found in clinical blood
samples from Desert Storm veterans contain unusual DNA sequences that they
probably did not obtain in the wild. For example, we have detected
mycoplasma DNA sequences from Mycoplasma fermentans (incognitus strain) and
a few soldiers with modified Mycoplasma genitalium in veterans and their
family members with GWI as well as the HIV-1 envelope or env gene. The
former type of mycoplasma was studied by Dr. Shyh Lo, formerly of Tanox
Biosystems, a spin-off biotechnology company from the Baylor College of
Medicine, but now affiliated with the Armed Forces Institute of Pathology in
Washington, DC. Two points need to be clarified regarding our identification
of HIV-1 genes and mycoplasma sequences in the soldiers and symptomatic
family members that have GWI:

1. We detected HIV-1 genes in the same nucleoprotein fractions as the
mycoplasma genes but we did not detect the complete HIV-1 virus genome. Thus
these patients do not have the complete HIV-1 virus that is associated with
AIDS. This virus must contain the entire HIV-1 genome to replicate.

2. We observed a very small subset of soldiers who had another gene
sequence, the HIV-1 polymerase gene. Thus GWI patients contain individual
genes of the HIV-1 virus genome but not the complete virus.

What this might mean:

1. Mycoplasmas possessing the HIV-1 env gene could allegedly have been
engineered to make them more invasive and pathogenic and more difficult to
find. The HIV-1 env gene encodes a surface glycoprotein, gp120, that is
involved in virus attachment and entry into cells through receptors on the
cell surface. This could result in opportunistic cell attachment and
penetration of many types of cells and most tissues.

2. It is unlikely that our experiments are incorrectly detecting these
unusual genes in biological samples. We used highly specific oligonucleotide
probes for our studies. The probes are themselves unique complimentary DNA
sequences and are analogous to probes used in studies called DNA
hybridization analyses. Such techniques are well accepted in the forensic
field. If the DNA sequence from a particular infectious agent is present, we
can specifically identify its presence. Since the DNA probe is radiolabeled,
it will interlock with a specific DNA sequence from the infectious agent to
produce a radioactive signal (if the infectious DNA sequence is present). In
our case the agent DNA is detected in cell nuclear fractions, and we detect
the radioactive signal by X-ray autoradiography using Nucleoprotein Gene
Tracking (Nicolson, N.L. and Nicolson, G.L. The isolation, purification and
analysis of specific gene-containing nucleoproteins and nucleoprotein
complexes. Methods Mol. Genetics 5: 281-298, 1994).

In our ongoing studies involving several thousand Desert Storm Veterans and
their families, we have detected a preliminary pattern that may be
associated with unit deployment. Approximately one-half of the American
soldiers involved in the deep insertions into Iraq--such as the US Army's
101st Airborne Division and 5th Special Forces Group that are suffering from
GWI and Chronic Fatigue Symptoms--were positive for mycoplasmal infections,
and most have the Mycoplasma fermentans (incognitus strain) as well as HIV-1
env gene sequences. A pilot study on the diagnosis and treatment of 30 Gulf
War Illness patients has now been published in an international
peer-reviewed medical journal (Nicolson, G.L. and Nicolson, N.L. Diagnosis
and treatment of mycoplasmal infections in Persian Gulf War Illness-CFIDS
patients. Int. J. Occup. Med. Immunol. Tox. 5: 69-78, 1996). In this study
almost all GWI patients recovered after multiple (3-7) cycles of antibiotic
therapy. Although they are probably not cured of the infection, they are
able to perform normal functions such as fulfilling normal employment
duties.

There are additional points that require some explanation:

1. One could be suffering severely from this type of mycoplasmal infection
and less sensitive tests, such as antibody tests, could be negative. Since
the mycoplasma that we have detected is present deep inside the cell, the
usual antibody tests for extracellular mycoplasmas may be relatively
useless.

2. The most sensitive type of DNA test, the polymerase chain reaction (PCR)
technique, could also prove negative in an infected individual, because the
DNA chains of the invading mycoplasma may be be tightly complexed with
nucleoproteins and might not be accessible for the PCR reaction.

3. Gulf War Illness appears to be a collection of illnesses produced as a
result of multiple chemical and biological exposures from endogenous and
exogenous sources such as Chemical/Biological Weapons (CBW).

The Iraqi Armed Forces deployed CBW to forward positions and were operating
under the concept of Integrated War Strategy, a Soviet war doctrine that
proposes use of mixtures of Chemical and Biological Weapons to confuse
diagnosis and treatment. Some soldiers from the Gulf War were probably
exposed to endogenous and exogenous chemicals, such as smoke, fuel,
insecticides, etc., and have Multiple Chemical Sensitivity Syndrome (MCS)
induced by exposure to various chemical agents, some may have been exposed
to CBW, or both.

The hypothetical dissemination and exposure to Biological and Chemical
agents could have been accomplished by the following possible means:

In our Testimony to the U.S. Congress (April 4, 1996) we listed some
possible ways that soldiers could have exposed to Chemical/Biological
Weapons in Desert Storm:

1. Bombing of targets in Iraq thought to be Chemical/Biological Weapons
facilities. This caused plumes of smoke that could have transported CBW down
wind into our lines. Improper fluids and procedures for aircraft
decontamination and failure to decontaminate other vehicles returning from
various operations could have resulted in exposure.

2. Exposure to SCUD B (SS-1) skyburst warheads equipped to deliver CBW.
There were several types of SCUD warheads used in the conflict, and there
were many eyewitness accounts of the skyburst type that are usually used for
CBW exploding over Saudi and Western Kuwait.

3. Exclusionary zones may have been created with CBW agents. Military
Intelligence units reported that some areas of Southern Iraq contained
posted zones where nothing was alive (dead animals, humans, etc.). These
could have been created by spraying CBW agents on the sand.

4. The vaccines used before Desert Storm have come into question, because
some soldiers who were not deployed came down with Gulf War Illness. (But
some soldiers who were deployed and civilians who did not receive vaccines
have also come down with Gulf War Illness). Vaccine contamination, although
uncommon, can occur, and some individuals may have obtained their infections
by this route.

We have concentrated on the chronic illnesses associated with Desert Storm,
especially those involving immediate family members who also became ill.
That some Gulf War Illness patients with immediate family members who have
become sick with similar chronic signs and symptoms indicates that these
diseases are similar and are contagious. In addition, these infectious
diseases may have been transmitted to some unborn children, and this could
explain along with chemical exposures the higher apparent rates of infantile
death and birth defects in Gulf War Illness families.

For your information, we have also been studying personnel working in the
Texas Department of Criminal Justice (TDCJ) who presented with an array of
signs and symptoms that are, as assessed by environmental physicians,
identical to Gulf War Illness. These individuals were tested (like the
Desert Storm veterans) using Nucleoprotein Gene Tracking. Preliminary
results parallel our observations in Desert Storm veterans and suggest that
these illnesses were present in the U.S. before the Gulf War. We strongly
suspect that TDCJ prisoners were illegally used in Biological Weapons
testing. Thus the modified mycoplasmas detected in Gulf War Veterans may
have their origin in the U.S. It is interesting that before Desert Storm
some Texas biotechnology companies were developing vaccines (apparently
under U.S. Army contracts) and testing them in TDCJ prisons.

If detected early, the diseases associated with invasive mycoplasmal
infections are treatable with multiple cycles of antibiotics, but the
confusing panorama of signs and symptoms, and current political policies
make it extremely difficult to help veterans and their families. We have
relayed the above information to the Israeli, Syrian, Pakistani, Iraqi,
Egyptian, Turkish and French governments and their Armed Forces, and anyone
else who has asked us for assistance. Some officials associated with the
governments above have thanked us, but have also told us that their hands
were diplomatically tied in publicly discussing this issue. The manufacture,
sale, deployment and use of Biological Weapons were theoretically rendered
illegal by the 1972 Geneva Convention. Certain governments, however, have
flaunted these international agreements and have participated in atrocious
human experimentation for decades. In the U.S. this build-up began as early
as 1980, and its expansion was proposed in a 180 page secret report by CIA
Director John Deutsch when he was an Undersecretary of Defense. The impact
of Gulf War Illness on our societies will probably take decades to assess.
Biological Weapons are uncontrollable, and if we don't quickly identify and
effectively treat these infections, they will continue to spread in the
military and civilian populations.

Garth L. Nicolson, Ph.D.

Director and Research Professor

Institute for Molecular Medicine and Office Address:

Professor of Pathology and Laboratory Medicine P.O. Box 52470, Irvine, CA
92619-2470 (US mail)

Professor of Internal Medicine or 1761 Kaiser Ave., Irvine, CA 92614
(courier)

The University of Texas Medical School at Houston Direct Phone: (714)
476-7933

Nancy L. Nicolson, Ph.D.

CEO, Institute for Molecular Medicine