103d Congress, 2d Session - COMMITTEE PRINT - S. Prt. 103-97 IS MILITARY RESEARCH HAZARDOUS TO VETERANS' HEALTH? LESSONS SPANNING HALF A CENTURY A STAFF REPORT PREPARED FOR THE COMMITTEE ON VETERANS' AFFAIRS UNITED STATES SENATE DECEMBER 8, 1994 JOHN D. ROCKEFELLER IV, West Virginia, Chairman DENNIS DeCONCINI, Arizona FRANK H. MURKOWSKI, Alaska GEORGE J. MITCHELL, Maine STROM THURMOND, South Carolina BOB GRAHAM, Florida ALAN K. SIMPSON, Wyoming DANIEL K. AKAKA, Hawaii ARLEN SPECTER, Pennsylvania THOMAS A. DASCHLE, South Dakota JAMES M. JEFFORDS, Vermont BEN NIGHTHORSE CAMPBELL, Colorado Jim Gottlieb, Chief Counsel/Staff Director John H. Moseman, Minority Staff Director/Chief Counsel Diana M. Zuckerman, Professional Staff Member Patricia Olson, Congressional Science Fellow
During the last few years, the public has become aware of several examples where U.S. Government researchers intentionally exposed Americans to potentially dangerous substances without their knowledge or consent. The Senate Committee on Veterans' Affairs, which I have been privileged to chair from 1993-94, has conducted a comprehensive analysis of the extent to which veterans participated in such research while they were serving in the U.S. military. This resulted in two hearings, on May 6, 1994, and August 5, 1994.
This report, written by the majority staff of the Committee, is the result of that comprehensive investigation, and is intended to provide information for future deliberations by the Congress. The findings and conclusions contained in this report are those of the majority staff and do not necessarily reflect the views of the members of the Committee on Veterans' Affairs.
This report would not have been possible without the dedication and expertise of Dr. Patricia Olson, who, as a Congressional Science Fellow, worked tirelessly on this investigation and report, and the keen intelligence, energy, and commitment of Dr. Diana Zuckerman, who directed this effort.
John D. Rockefeller IV, Chairman
Appendix -- Survey of 150 Persian Gulf War Veterans
The goals of many of the military experiments and exposures were very appropriate. For example, some experiments were intended to provide important information about how to protect U.S. troops from nuclear, biological, and chemical weapons or other dangerous substances during wartime. In the Persian Gulf War, U.S. troops were intentionally exposed to an investigational vaccine that was intended to protect them against biological warfare, and they were given pyridostigmine bromide pills in an experimental protocol intended to protect them against chemical warfare.
However, some of the studies that have been conducted had more questionable motives. For example, the Department of Defense (DOD) conducted numerous "man-break" tests, exposing soldiers to chemical weapons in order to determine the exposure level that would cause a casualty, i.e., "break a man." (Note 3) Similarly, hundreds of soldiers were subjected to hallucinogens in experimental programs conducted by the DOD in participation with, or sponsored by, the CIA. (Note 4), (Note 5) These servicemembers often unwittingly participated as human subjects in tests for drugs intended for mind-control or behavior modification, often without their knowledge or consent. Although the ultimate goal of those experiments was to provide information that would help U.S. military and intelligence efforts, most Americans would agree that the use of soldiers as unwitting guinea pigs in experiments that were designed to harm them, at least temporarily, is not ethical.
Whether the goals of these experiments and exposures were worthy or not, these experiences put hundred of thousands of U.S. servicemembers at risk, and may have caused lasting harm to many individuals.
Every year, thousands of experiments utilizing human subjects are still being conducted by, or on behalf of, the DOD. Many of these ongoing experiments have very appropriate goals, such as obtaining information for preventing, diagnosing, and treating various diseases and disabilities acquired during military service. Although military personnel are the logical choice as human subjects for such research, it is questionable whether the military hierarchy allows for individuals in subordinate positions of power to refuse to participate in military experiments. It is also questionable whether those who participated as human subjects in military research were given adequate information to fully understand the potential benefits and risks of the experiments. Moreover, the evidence suggests that they have not been adequately monitored for adverse health effects after the experimental protocols end.
Veterans who become ill or disabled due to military service are eligible to receive priority access to medical care at VA medical facilities and to receive monthly compensation checks. In order to qualify, they must demonstrate that their illness or disability was associated with their military service. Veterans who did not know that they were exposed to dangerous substances while they were in the military, therefore, would not apply for or receive the medical care or compensation that they are entitled to. Moreover, even if they know about the exposure, it would be difficult or impossible to prove if the military has not kept adequate records. It is therefore crucial that the VA learn as much as possible about the potential exposures, and that the DOD assume responsibility for providing such information to veterans and to the VA.
The person involved should have the legal capacity to give consent;
should be so situated as to be able to exercise free power of choice,
without the intervention of any element of force, fraud, deceit,
duress, overreaching, or other ulterior form of constraint or
coercion; and should have sufficient knowledge and comprehension of
the elements of the subject matter involved as to enable him to make
an understanding and enlightened decision. This latter element
requires that before the acceptance of an affirmative decision by the
experimental subject, there should be made known to him the nature,
duration, and purpose of the experiment; the method and means by which
it is to be conducted; all inconveniences and hazards reasonable to be
expected; and the effects upon his health and person which may
possibly come from his participation in the
experiments. (Note 6)
There is no provision in the Nuremberg Code that allows a country to waive
informed consent for military personnel or veterans who serve as human
subjects in experiments during wartime or in experiments that are conducted
because of threat of war. However, the DOD has recently argued that wartime
experimental requirements differ from peacetime requirements for informed
consent. According to the Pentagon, "In all peacetime applications, we
believe strongly in informed consent and its ethical foundations.....But
military combat is different." (Note 7) The DOD argued that
informed consent should be waived for investigational drugs that could
possibly save a soldier's life, avoid endangerment of the other personnel
in his unit, and accomplish the combat mission.
More than a decade after the development of the Nuremberg Code, the
World Medical Association prepared recommendations as a guide to doctors
using human subjects in biomedical research. As a result, in 1964 the
Eighteenth World Medical Assembly met in Helsinki, Finland, and adopted
recommendations to be used as an ethical code by all medical doctors
conducting biomedical research with human subjects. This code, referred to
as the Declaration of Helsinki, was revised in 1975, 1983, and
1989. (Note 8) It differs from the Nuremberg Code in certain
important respects. The Declaration of Helsinki distinguishes between
clinical (therapeutic) and nonclinical (nontherapeutic) biomedical
research, and addresses "proxy consent" for human subjects who are legally
incompetent, such as children or adults with severe physical or mental
disabilities. (Note 9) Proxy consent for legally competent
military personnel who participate in military research is not considered
appropriate under the Nuremberg Code or the Declaration of Helsinki.
On June 18, 1991, the Federal Government announced that 16 U.S.
governmental agencies would abide by a set of regulations, referred to as
the "Common Rule," designed to protect human subjects who participate in
federally funded research. (Note 10) The provisions of the
"Common Rule," first promulgated for the Department of Health and Human
Services (DHHS) in 1974, described how federally funded research involving
human subjects shall be conducted. However, local Institutional Review
Boards (IRB's) may revise or exclude some or all consent elements if the
research exposes subjects to no more than "minimal risk," meaning "that the
probability and magnitude of harm or discomfort anticipated in the research
are not greater in and of themselves than those ordinarily encountered in
daily life or during the performance of routine physical or psychological
examinations or tests." (Note 11) IRB's vary greatly in their
interpretation of the risks of daily life.
There are three provisions governing research funded by DHHS that are
intended to protect vulnerable populations, such as pregnant women and
fetuses, prisoners, and children. (Note 12) There are no special
Federal regulations to protect military personnel when they participate as
human subjects in federally funded research, despite logical questions
about whether military personnel can truly "volunteer" in response to a
request from a superior officer.
Current law prevents the Department of Defense from using Federal funds
for research involving the use of human experimental subjects, unless the
subject gives informed consent in advance. This law applies regardless of
whether the research is intended to benefit the
subject. (Note 13)
Based on findings from the National Academy of Sciences, the Department
of Veterans Affairs recently published a final rule to compensate veterans
for disabilities or deaths resulting from the long-term effects of
inservice exposure to mustard gas and other agents which blister the skin
(these are called vesicants). (Note 17) The final rule expands
coverage to veterans exposed to mustard gas under battlefield conditions in
World War I (WWI), those present at the German air raid on the harbor of
Bari, Italy (WWII), and those engaged in manufacturing and handling
vesicant agents during their military service. Thus, for the first time, VA
will compensate certain veterans for illnesses which may have been caused
by their exposure to vesicants over half a century ago.
Unlike most of the studies discussed in this report, Operation Whitecoat
was truly voluntary. Leaders of the Seventh-Day Adventist Church described
these human subjects as "conscientious participants," rather than
"conscientious objectors," because they were willing to risk their lives by
participating in research rather than by fighting a
war. (Note 20), (Note 21)
In 1968, approximately 6,400 sheep died following the intentional
release of a deadly nerve gas from a plane. According to a veterinarian who
evaluated the sick and dying sheep, there was little doubt that the sheep
had been poisoned with nerve gas. (Note 24) The sheep and other
animals in the area had depressed cholinesterase levels, suggesting
organophosphate nerve poisoning. Initially, the Department of Defense
denied any responsibility for the accident, stating that the sheep died
from organophosphate pesticides sprayed on a nearby alfalfa field. However,
the nerve agent VX was identified when the poisoned sheep were autopsied,
which made it clear that the deaths were not caused by
pesticides. (Note 25) Eventually, the Department of Defense
reimbursed the ranchers for their animals.
It is unknown how many people in the surrounding vicinity were also
exposed to potentially harmful agents used in open-air tests at Dugway. In
1969, concerns were expressed at a congressional hearing about the possible
public health implications of the VEE virus tested at
Dugway. (Note 26)
Due to previous problems with dangerous organisms and chemicals, Dugway
has developed an active program of "simulant" testing. According to the
Department of Defense, simulants are harmless organisms or chemicals which
do not cause disease. However, during 45 years of open-air testing, the
Army has stopped using a variety simulants when they realized they were not
as safe as previously believed. (Note 27)
Data obtained on some military personnel who were exposed to radioactive
fallout were collected after these men were unintentionally exposed.
However, some atomic veterans believe they were used as guinea pigs to
determine the effects of radiation from various distances, including those
at ground zero, on human subjects. Their suspicions are supported by a 1951
document from the Joint Panel on the Medical Aspects of Atomic Warfare,
Research and Development Board, Department of Defense, which identified
general criteria for bomb test-related "experiments" and identified 29
"specific problems" as "legitimate basis for biomedical
participation." (Note 30)
The National Research Council's Committee on the Biological Effects of
Ionizing Radiation (BEIR) have prepared a series of reports to advise the
U.S. Government on the health consequences of radiation
exposure. (Note 31) The first of these reports was not published
until the late 1980's, decades after military personnel were first exposed
to ionizing radiation. For the last 13 years, the VA has provided free
medical care to atomic veterans who have disorders they believe to be
caused by ionizing radiation, even if there is no conclusive evidence of
the cause. (Note 32) In addition, the VA provides monthly
compensation to veterans who were exposed to ionizing radiation during
military service, who have illnesses that are believed to be associated
with their exposure. The lists of compensable diseases have been revised as
more research information has become available. For example, on October 11,
1994, the VA announced that tumors of the brain and central nervous system
would be considered for disability compensation for veterans exposed to
ionizing radiation. (Note 33)
To assist in identifying those people who may have been harmed by secret
experiments utilizing ionizing radiation, the Clinton administration
solicited complaints from possible victims by installing several telephone
hotlines. As of September 1994, 86 percent of the 21,996 callers to the
radiation hotline were veterans who believed they had participated in
various radiation "experiments." (Note 35)
A VA advisory committee has concluded that activities other than atomic
weapons tests and occupation force activities resulted in the exposure of
veterans to ionizing radiation during their military service prior to
1970. (Note 36) The committee concluded that the records for many
individuals who were exposed to such activities are inadequate or
inaccessible. Additionally, the committee concluded that information
pertinent to military exposures is not always adequate to evaluate the
health risks.
One test subject was Lloyd B. Gamble, who enlisted in the U.S. Air Force
in 1950. In 1957, he volunteered for a special program to test new military
protective clothing. He was offered various incentives to participate in
the program, including a liberal leave policy, family visitations, and
superior living and recreational facilities. However, the greatest
incentive to Mr. Gamble was the official recognition he would receive as a
career-oriented noncommissioned officer, through letters of commendation
and certification of participation in the program. During the 3 weeks of
testing new clothing, he was given two or three water-size glasses of a
liquid containing LSD to drink. Thereafter, Mr. Gamble developed erratic
behavior and even attempted suicide. He did not learn that he had received
LSD as a human subject until 18 years later, as a result of congressional
hearings in 1975. (Note 39) Even then, the Department of the Army
initially denied that he had participated in the experiments, although an
official DOD publicity photograph showed him as one of the valiant
servicemen volunteering for "a program that was in the highest national
security interest." (Note 40)
According to Sidney Gottlieb, a medical doctor and former CIA agent,
MKULTRA was established to investigate whether and how an individual's
behavior could be modified by covert means. (Note 41) According
to Dr. Gottlieb, the CIA believed that both the Soviet Union and Communist
China might be using techniques of altering human behavior which were not
understood by the United States. Dr. Gottlieb testified that "it was felt
to be mandatory and of the utmost urgency for our intelligence organization
to establish what was possible in this field on a high priority basis."
Although many human subjects were not informed or protected, Dr. Gottlieb
defended those actions by stating, "...harsh as it may seem in retrospect,
it was felt that in an issue where national survival might be concerned,
such a procedure and such a risk was a reasonable one to
take." (Note 42)
FDA also regulates medical products that are proven safe and effective
for some uses or with specific doses, but not for other uses or other
doses. If the product is only sold at certain doses and not others, its use
at the non-approved dose would be considered investigational. If the
product is legally available for sale at the same dosage, physicians can
legally prescribe it; however, manufacturers can not advertise it for that
purpose. Such "off label" use is also considered investigational. So, for
example, a drug may be proven safe and effective to treat one kind of
cancer, but be considered investigational to treat a different disease.
Under current law, an unapproved vaccine or investigational use of a
drug could only be administered by the DOD under an Investigational New
Drug (IND) procedure. (Note 43) Under an IND, any individual who
is given the investigational product must give informed consent, i.e., must
be told of the potential risks and benefits of the product, orally and in
writing, and choose freely whether or not to participate. In addition, the
IND requires that the medical product be distributed under carefully
controlled conditions where safety and effectiveness can be evaluated.
When the Department of Defense began preparations for Desert Shield and
Desert Storm in 1990, officials were extremely concerned that Iraq would
use chemical and biological weapons against the United States. Despite
years of study and billions of dollars, the DOD lacked drugs and vaccines
that were proven safe and effective to safeguard against anticipated
chemical nerve agents and biological toxins. Therefore, DOD officials
wanted to use a medication (pyridostigmine bromide) and vaccine (botulinum
toxoid) that they believed might protect against chemical nerve agents and
botulism. Because the safety and effectiveness of pyridostigmine bromide
and botulinum toxoid had not been proven for their intended use, these
products were considered investigational drugs.
Pyridostigmine bromide is a chemical which enhances the effectiveness of
two drugs, atropine and 2-PAM, which are proven effective for the treatment
of nerve agent poisoning. (Note 44) Pyridostigmine is also a
nerve agent itself. Nerve agents exert their biological effects by binding
to, and inhibiting, the enzyme acetylcholinesterase (AChE) which normally
shuts off the neurotransmitter, acetylcholine (ACh). When levels of ACh
increase, nerve impulses and organ activity increase. When nerve and organ
stimulation are excessive, death can result.
There are two major categories of nerve agents, carbamates and
organophosphate (OP) compounds. (Note 45) German scientists
developed many of the OP compounds for warfare agents and pesticides in the
1930's and 1940's. Examples of warfare agents include tabun, sarin, soman,
and VX. Many organophosphates permanently inhibit AChE. This permanent
effect, which can only be reversed when new enzymes are synthesized, makes
OP warfare agents extremely lethal.
Pyridostigmine bromide is a carbamate, rather than an OP
compound. (Note 46) Although it is a nerve agent, pyridostigmine
has a reversible effect which can protect the AChE from permanently binding
to OP compounds. When appropriate doses are selected, pyridostigmine
theoretically should not cause nerve agent poisoning and should help
protect against some lethal chemical warfare.
Efficacy. Pyridostigmine only works when taken in combination with other
drugs and only if taken before exposure to nerve gas. (Note 47)
Two antidotes to nerve agents, atropine and pyridine-2-aldoxime
methochloride (2-PAM), are reportedly enhanced if pyridostigmine has
already been given. Atropine and 2-PAM were included in the nerve agent
antidote kits (Mark I) which were issued to U.S. troops in the Persian
Gulf.
In research studies, animals given pyridostigmine, atropine, and 2-PAM
were more likely to survive exposure to one chemical nerve agent, soman,
than those given only atropine and 2-PAM. However, pyridostigmine is unable
to enter and protect the brain, so that animals exposed to soman can still
suffer from convulsions despite the pyridostigmine
pretreatment. (Note 48) To protect against brain damage from
ongoing seizure activity, valium may also be required following exposure to
a warfare nerve agent. Similarly, pyridostigmine may offer little
protection against the damage caused by nerve agents in the spinal
cord. (Note 49)
Safety. Pyridostigmine bromide is approved by the FDA for treating
myasthenia gravis, a neurological disease characterized by extreme
weakness. This disease occurs when individuals develop antibodies that
prevent ACh from causing muscle impulses at the neuromuscular junction.
Therefore, treatment with relative high doses of pyridostigmine increases
ACh to levels that are able to overcome the "block" created by the
antibodies. An analogy might be that of a fishing pond. The two ways to
increase the number of fish caught are to increase the number of fishing
poles or to increase the number of fish in the pond.
FDA and DOD officials claimed they were confident of the safety of
pyridostigmine as an antidote enhancer for chemical warfare protection
because it would be used at a much lower dose (Note 50) in combat
than normally used for treating patients with myasthenia gravis. However,
normal patients and those with myasthenia gravis may not respond similarly
to the same dose of pyridostigmine bromide. Whereas the dosage of
pyridostigmine bromide for patients with myasthenia gravis may reach 120 mg
every three hours, (Note 51) the dose for U.S. troops was only 30
mg every 8 hours. A good analogy is the use of insulin for diabetes
mellitus; very high doses of insulin are sometimes necessary to treat
diabetics, but similar doses could be fatal for non-diabetic individuals.
Some scientists also question whether pyridostigmine is completely safe
even for treating patients with myasthenia gravis. The proportion of
patients with myasthenia gravis that recover after surgical treatment
(thymectomy) has decreased since pyridostigmine therapy was introduced
several decades ago. (Note 52) Experts speculate that whereas the
problems caused by myasthenia gravis can be corrected by surgery,
pyridostigmine may cause immune damage to the neuromuscular junction that
cannot be corrected by surgery. Since the symptoms of pyridostigmine damage
would be similar to the symptoms of myasthenia gravis, any damage from the
pyridostigmine would be extremely difficult if not impossible to diagnose.
In addition to its use for myasthenia gravis, pyridostigmine bromide has
been approved by FDA for use with surgical patients; it is administered
after surgery to reverse the effect of anesthesia, which are neuromuscular
blocking agents. The dose is relatively small (15 mg) and not repeated.
This treatment does not provide relevant information about the safety of
repeated use of pyridostigmine by healthy individuals, since the dosage is
small and the patients have received neuromuscular blocking agents.
The bromide that is included in pyridostigmine bromide pills is known to
sometimes cause problems referred to as "bromide intoxication" when used
for the treatment of myasthenia gravis. (Note 53) Bromide
intoxication may cause confusion, irritability, tremor, memory loss,
psychotic behavior, ataxia, stupor, and coma. Some patients with bromide
intoxication have a skin disorder of the face and hands resembling acne. A
60 mg tablet of the commercially available pyridostigmine bromide contains
18.4 mg bromide (30.6 percent). (Note 54), (Note 55)
FDA has not approved pyridostigmine bromide for repeated use in healthy
individuals as an antidote enhancer or for any other reason. Since it would
be unethical to expose individuals to potentially lethal chemical weapons
in order to evaluate the efficacy of pyridostigmine, this use has only been
studied on animals. The product is therefore an investigational drug when
used as an antidote enhancer for treating nerve gas poisoning.
Botulinum toxoid is an unapproved vaccine that is used to protect
laboratory workers and others who are likely to be exposed to botulism.
Botulism is caused by at least one of seven neurotoxins produced by the
bacteria Clostridium botulinum. When home-canning of food was common, food
poisoning was the most common cause of botulism in the United States; the
bacteria in the food produces a toxin which is eaten. Today, the most
common form of botulism occurs in infants, since the bacteria that produces
the toxin can thrive in a baby's intestinal tract.
A botulism vaccine that is intended to protect against five of seven
neurotoxins (called A,B,C,D,E) is produced by the Michigan Department of
Health. This is called pentavalent toxoid. This vaccine is not a licensed
product and must be distributed as an Investigational New Drug (IND).
Efficacy. Desert Shield began on August 8, 1990. Since the air war did
not begin until January 16, 1991, and the ground war took place from
February 24-27, 1991, the Pentagon had several months to review the
possible use of investigational drugs and vaccines. In December 1990,
the FDA advised the Department of Defense that it would be unable to test
the botulism vaccine for efficacy, presumably because of limited time
before the onset of the war. The FDA agreed to test the vaccine for safety,
but these tests were not completed until late January 1991. At a meeting of
the Informed Consent Waiver Review Group (ICWRG) on December 31, 1990, a
representative of FDA's Center for Biologics Evaluation and Research
discussed the vaccine, explaining that the existing supply was nearly 20
years old and consisted of three lots, stored under continuous
refrigeration. (Note 56) Given the age of these vaccines, there
were concerns about their safety.
The recommended schedule for immunization with the pentavalent vaccine
includes a series of three initial injections at 0, 2, and 12 weeks,
followed by a booster 12 months after the first injection. According to the
Centers for Disease Control's Center for Infectious Diseases, subjects
given the vaccine did not have detectable antitoxin titers after the first
two shots in the initial series, which means that they were unlikely to be
protected at week 2. (Note 57) If for any reason only two
immunizations can be given, at least 4 to 8 weeks should elapse between
injections if most individuals are to be protected against the
disease. (Note 58)
Safety. The Michigan Department of Health reported that 4.2 percent of
patients reported a sore arm or other local reactions to the initial series
of three shots, and 12.1 percent had local reactions to the booster
shots. (Note 59) Almost 3 percent had systemic reactions, such as
general malaise, after either the initial three shots or the booster shots.
Because of the relatively large percentage of adverse reactions, new lots
of the vaccine were manufactured in 1971. However, there is no evidence
that the newer lots produced fewer adverse reactions than the older lots.
In her review of the DOD's application for use of botulinum toxoid in
the Persian Gulf, an FDA reviewer pointed out that in 1973, the Centers for
Disease Control had considered terminating the distribution of the vaccine
because of the relatively large number of individuals who had negative
reactions to it. (Note 60) The FDA reviewer also pointed out that
"there are no efficacy data in humans" and that the dose for humans was an
estimate based on results from guinea pigs. In addition, potency testing
had suggested that the vaccine would not be effective against two of the
five botulism toxins.
According to the Michigan Department of Health, the effects of the
botulism vaccine on pregnant women had not been studied prior to its use in
the Persian Gulf War.
Anthrax vaccine is an FDA-approved vaccine that is considered safe and
effective for individuals whose skin may come in contact with animal
products such as hides, hair, or bones likely to contain the anthrax
infection. It is also recommended for veterinarians and others who are
likely to touch infected animals. (Note 61) However, the
vaccine's effectiveness against inhaled anthrax is unknown. Unfortunately,
when anthrax is used as a biological weapon, it is likely to be aerosolized
and thus inhaled. Therefore, the efficacy of the vaccine against biological
warfare is unknown.
It appears that there is only one relevant animal study which showed
that anthrax vaccine apparently provided additional protection against
relapse in monkeys exposed to inhalation anthrax and treated with
antibiotics. (Note 62) Although the results of this study suggest
the vaccine might protect against anthrax that has been sprayed, it is not
sufficient to prove that anthrax vaccine is safe and effective as used in
the Persian Gulf. The vaccine should therefore be considered
investigational when used as a protection against biological warfare.
The anthrax vaccine is given as three injections 2 weeks apart, followed
by three additional injections given 6, 12, and 18 months after the initial
injection. If immunity is to be maintained, subsequent booster injections
of anthrax vaccine are recommended at 1-year intervals. (Note 63)
According to the Interagency Task Force on Persian Gulf War Illnesses, one
dose provides some immunity in 85 percent of those individuals
vaccinated. (Note 64)
According to the Michigan Department of Public Health which manufactures
anthrax vaccine, it is not known whether anthrax vaccine is safe for
pregnant women or their offspring.
For example, Rudolph R. Mills participated in gas chamber experiments as
an 18-year-old in 1945, one year after he joined the U.S.
Navy. (Note 68) He was sworn to secrecy and did not learn until
46 years later that approximately 4,000 servicemen were human subjects in
mustard gas experiments conducted from 1942 through 1945 by the Chemical
Warfare Service. Although his health began to deteriorate even before his
discharge from the Navy in 1946, he did not learn that mustard gas might be
responsible for his physical problems until more than 40 years later.
At a May 6, 1994, hearing of the Senate Committee on Veterans' Affairs,
entitled "Is Military Research Hazardous to Veterans' Health? Lessons from
World War II, the Persian Gulf War, and Today," Mr. Mills testified, "I had
on an experimental mask and the Navy was trying to determine if people
wearing these masks could communicate with each other. I was enticed to
sing over the intercom....No one ever told me that the mask became less
effective against the gas with each use....We were sworn to secrecy....At
the age of 43 I underwent a long series of radiation treatments and later
surgery to remove part of my voice box and larynx....It didn't occur to me
that my exposure to mustard gas was responsible for my physical problems
until June 1991, when I read an article in my hometown
newspaper." (Note 69)
John T. Harrison participated in Navy chemical tests in 1943 to get an
extra week pass. He was also sworn to secrecy. According to written
testimony submitted to the Senate Committee on Veterans' Affairs by Mr.
Harrison, "[I] was never warned or told anything about the dangers of what
[I] volunteered for....told never to reveal what [I] did or where [I] was;
if anyone asked [I] was to say [I] was on rowing
maneuvers." (Note 70) At the time of his discharge from the
military, he could not even describe his exposures to a Navy doctor who was
trying to determine the cause of his severe respiratory illnesses. Although
Mr. Harrison has suffered from recurrent breathing problems and has greatly
diminished pulmonary function, he has never received any compensation for
his illness. According to the VA and DOD, his medical and services records
have been lost, making it difficult to prove that his disability is
service-connected.
Similarly, military personnel were intentionally given hallucinogenic
drugs to determine the effects of those drugs on humans. The servicemembers
were not told that they would be given experimental drugs, they had no
choice of whether or not to take them, and even after the unusual effects
of the drugs were obvious to researchers, the unwitting human subjects were
given no information about the known effects of the drugs. Even if the DOD
did not know about the potential long-term effects of the drugs, that would
not justify their failure to provide information to thousands of
servicemembers about the known short-term effects of the drugs.
B. DOD HAS REPEATEDLY FAILED TO COMPLY WITH REQUIRED ETHICAL STANDARDS WHEN
USING HUMAN SUBJECTS IN MILITARY RESEARCH DURING WAR OR THREAT OF WAR.
These standards are more than 50 years old. For example, the Nuremberg
Code was based on testimony of two U.S. physicians, Drs. Leo Alexander and
Andrew Ivy, who served as expert medical witnesses for the Nazi crime
prosecutors. The code was not the outcome of an attempt to frame a new code
of ethics, but rather a description of criteria said to be widely accepted
by the medical profession at the time. (Note 73) Therefore, DOD
research during the 1940's was clearly conducted in an era when researchers
were well aware of ethical codes regarding the use of human subjects.
The Department of Defense has violated these well-established ethical
principles each time soldiers are required to participate in military
research or take investigational drugs or vaccines or are not adequately
informed about the risks of the experiments.
For example, in 1944, Nathan Schnurman was a 17-year-old sailor who was
recruited to test Navy summer clothing, in exchange for a 3-day pass.
Instead, he participated in the testing of gas masks and clothing while he
was locked in a gas chamber and exposed to mustard gas and lewisite. Mr.
Schnurman believes that he was not really a volunteer since the research
was misrepresented. Additionally, Mr. Schnurman stated in written testimony
submitted to the Committee that "many were denied the 3-day pass, and many
went to their graves without revealing this story." (Note 74)
Perhaps most outrageous, Mr. Schnurman was not allowed to leave the gas
chamber when he became violently ill. Mr. Schnurman testified before the
Committee on the Judiciary of the U.S. House of Representatives that,
"During my sixth exposure in the chamber, I determined something was wrong.
I called to the corpsman, via an intercom, and informed him of my
condition, and what was happening and requested I be released from the
chamber, now. The reply, was `No' as they had not completed the experiment.
I became very nauseous. Again, I requested to be released from the chamber.
Again, permission was denied. Within seconds after the denial, I passed out
in the chamber. What happened after that, I don't know. I may only assume,
when I was removed from the chamber, it was presumed I was already
dead." (Note 75)
John William Allen enlisted in the U.S. Navy in 1945 at the age of 17.
Immediately after boot camp, he volunteered to test summer uniforms so he
could go home before shipping out. His test clothing consisted of one pair
of pants, undershorts, a gas mask, and a shirt that had been used in
previous experiments and was therefore impregnated with toxic chemicals.
According to Mr. Allen, the actual testing consisted of determining the
amount of sulfur mustard that would cause illness ("man-break" test), not
the testing of summer uniforms. He was exposed several times to sulfur
mustard and was removed from further exposure on May 5, 1945, when he
passed out in the gas chamber. A physical examination on May 14, 1945,
revealed many wounds as the result of exposure to mustard gas.
Mr. Allen stated in written testimony submitted to the Committee, "The
government has lied to us for 50 years over and over again. If I would have
been shot on the front lines at least I would had it on my record and would
have received medical treatment." (Note 76)
When the Department of Defense began preparations for Desert Shield and
Desert Storm in 1990, officials were extremely concerned about the need to
protect U.S. troops against chemical and biological weapons that were
believed to have been developed by Iraq. However, the DOD lacked drugs and
vaccines that were proven safe and effective to safeguard against expected
weapons, such as soman and botulism.
Under the Food, Drug, and Cosmetics Act, all vaccines and medical
products must be proven safe and effective by the Food and Drug
Administration (FDA) in order to be sold and distributed in the United
States, or used by U.S. troops. However, DOD officials were interested in
using a botulinum toxoid, which is a vaccine to prevent botulism, that was
not approved by FDA. They also wanted to use pyridostigmine bromide, a
medication to protect U.S. troops against chemical nerve agents. Although
approved by the FDA for treating patients with a neurological disorder
called myasthenia gravis, pyridostigmine is not proven safe or effective
for repeated use by healthy persons under any circumstances, and is
normally unavailable in doses that would be likely to be safe for healthy
individuals. (Note 77)
Under current law, the unapproved vaccine and the investigational use of
pyridostigmine for healthy individuals could only be administered under an
Investigational New Drug (IND) procedure. (Note 78) Under an IND,
any individual who is given the investigational product must give informed
consent, i.e., must be told of the potential risks and benefits of the
product, orally and in writing, and choose freely whether or not to
participate. In addition, the IND requires that the medical product be
distributed under carefully controlled conditions where safety and
effectiveness can be evaluated.
In August 1990, the DOD contacted FDA to review regulatory restrictions
of DOD's plan to use pyridostigmine and botulinum toxoid for U.S. troops in
the Persian Gulf. The major focus of the meeting was informed consent. The
DOD sought a waiver of requirements for informed consent for the use of
pyridostigmine bromide and botulinum toxoid, arguing that these
investigational products had well-established uses and were safe. They also
claimed that there were no reasonable alternatives. According to minutes of
the meeting, "FDA expressed some concern about liability and the need to
comply with the regulations," and FDA's Deputy Director for Drug Review
"pointed out the need to establish an appropriate investigational framework
to collect observational data and evaluate the military medical products in
question." (Note 79)
In summary, DOD informed FDA that they did not want to abide by informed
consent regulations, and FDA officials pointed out that pyridostigmine and
botulinum toxoid were investigational and that there are laws regulating
how they can be used. DOD claimed that "under the DOD directive the
Secretary of Military Departments [could] dictate the use of unapproved FDA
regulated products" in the Persian Gulf, but "DOD's current position is
that this not their primary choice at this time." (Note 80)
The issue was debated by the two agencies for several months. Finally,
at a meeting on December 31, 1990, an agreement was reached. According to
minutes of that meeting, DOD officials agreed that the botulism vaccine
would be administered by trained individuals with a health care background,
and that information would be provided orally "at minimum, and in written
form if feasible, to all personnel receiving the
vaccine." (Note 81) Officials from the DOD said that the
feasibility of distributing an information sheet would depend on many
factors, and would vary from location to location within the military
theater of operation. DOD officials "reiterated that at least verbal [sic]
information would be provided to each person receiving the vaccine."
The FDA Informed Consent Waiver Review Group recommended that pregnant
women be excluded from receiving the vaccine and that information about the
vaccine be "posted at places where vaccine is administered." However, DOD
argued that pregnant women would be at greater risk from exposure to
botulism toxins than to the vaccine, and FDA agreed that instead of
excluding pregnant women, a statement would be added to the information
sheet stating that, "If you are pregnant, it is not known if this vaccine
will hurt the unborn baby, however, most vaccines do
not." (Note 82)
In their application for a waiver, DOD described the safeguards that
would be in place regarding the distribution of the botulism vaccine. In
addition to oral warnings regarding the vaccine, DOD promised that the
soldiers would be observed for 30 minutes after receiving the vaccine, and
if possible, they would also be checked again 48 hours later. In addition,
DOD claimed that they would provide all three vaccine injections and stated
that all three were necessary to provide protection.
FDA granted the waiver on a temporary basis, concurring that obtaining
informed consent during wartime is not feasible in a specific military
operation involving combat or the threat of combat. (Note 83) On
January 8, 1991, Dr. David Kessler, FDA Commissioner, wrote to the
Assistant Secretary of Defense for Health Affairs regarding the waiver for
informed consent for pyridostigmine. In his letter, Dr. Kessler agreed that
since there was "no available satisfactory alternative therapy" for
protection against organophosphorus nerve gas, he would "concur with your
assessment that informed consent is not feasible." This agreement was
apparently based on DOD officials' promise to "provide and disseminate
additional information to all military personnel concerning the risks and
benefits of pyridostigmine." (Note 84)
Although FDA agreed to waive informed consent for both the
pyridostigmine bromide and the botulism vaccine, the Assistant Secretary of
Defense for Health Affairs notified Dr. Kessler on March 15, 1992, that
"Central Command" had decided that the vaccine would be administered on a
voluntary basis. (Note 85) However, based on interviews with 150
Persian Gulf War veterans by Committee staff (Appendix), 88 percent of
those who said they received a botulism vaccine were told they had no
choice.
According to the DOD, all 696,562 U.S. troops in the Persian Gulf War
were issued pyridostigmine bromide as a pretreatment for nerve agent
poisoning, and officials estimate that approximately two-thirds took the
drug for varying periods of time. Of 150 who were interviewed by Committee
staff, 73 took pyridostigmine and 74 percent of them were told they could
not refuse to take it. Approximately 8,000 individuals received botulinum
toxoid in the Persian Gulf. Given the high proportion who have reported
that they had no choice, it appears that hundreds of thousands of U.S.
troops were ordered to take an investigational drug or vaccine without
having the opportunity to refuse.
Although DOD officials convinced FDA they need not offer choice, DOD had
promised to provide extensive information about potential risks orally and
in writing. In addition to being ordered to take an investigational product
without informed consent, most Persian Gulf War military personnel surveyed
claim they received no oral or written information about the drug or
vaccine, despite the DOD promises to FDA to provide information about
potential risks. These claims are supported by a survey conducted by the
Department of Defense following the Persian Gulf War. Sixteen of 23
selected Persian Gulf War medical personnel surveyed by the DOD indicated
that no information on the side effects of pyridostigmine bromide was
provided to those who were ordered to take the drug. (Note 86)
These medical personnel were responsible for 8,366 military personnel
during the Persian Gulf War.
There are two kinds of risks associated with lack of information. One is
a lack of trust. In the survey conducted by Committee staff, 14 of 73 (19
percent) Persian Gulf War veterans who had been ordered to take
pyridostigmine bromide indicated that they did not take all the
pyridostigmine bromide they were ordered to take, fearful that the drug was
responsible for the symptoms they experienced (Appendix). Because no one
would answer their questions about the safety and efficacy of the
pyridostigmine bromide, they feared they were receiving a potentially
harmful drug. Therefore, if pyridostigmine bromide had been crucial for
surviving nerve agent exposure, an unknown number of individuals would have
lacked protection because they had received inadequate information about
the drug.
The other risk is that even if serious side effects were rare, they
could have been treated if medical personnel were able to diagnose the
problem. For example, Carol Picou, a nurse who was stationed in the Gulf
for 5 months, had obvious side effects from the pyridostigmine starting on
the third day that she took it. These side effects included incontinence,
drooling, and blurry vision, among others. The side effects became worse 1
hour after she took each pill. One day, she did not take the pill as
scheduled, and the side effects stopped; unfortunately, her commanding
officer ordered her to continue taking the pills, and watched to make sure
she swallowed them. She was ordered to take the pills for 15 days. She now
has many permanent medical problems, including incontinence, muscle
weakness, and memory loss, that might have been avoided had she been
allowed to stop taking the pills. (Note 87)
Similarly, Lt. Col. Neil Tetzlaff had immediate side effects when he
started taking pyridostigmine bromide on the plane ride over to Saudi
Arabia. His nausea and vomiting became so severe that he needed emergency
surgery to repair a hole in his stomach. When he became ill, the military
doctor told him to continue to take the pills, because the doctor
apparently did not know that nausea and vomiting were known side effects.
According to Tetzlaff's sworn testimony, the doctor acted as if the
pyridostigmine was as safe as a cough drop. (Note 88)
For example, according to journalists who covered the Gulf War, some
were given the pills by the U.S. military. Several of these journalists
experienced serious medical problems similar to Persian Gulf War
veterans. (Note 89) The Committee has also received letters from
civilians who are suffering from "Gulf War syndrome" who report the
widespread use of pyridostigmine by civilians working for DOD during the
Gulf War.
The descriptions of these studies are disturbing because, if accurate,
they indicate that even during peacetime, the Air Force totally ignored the
requirements of informed consent that are a central provision of the
Nuremberg Code, the Declaration of Helsinki, and the "Common Rule" which
had been in effect in at least some U.S. Government agencies at the time.
In addition to being unethical, these studies were reportedly
unscientific; there were apparently no safeguards to ensure that the pilots
took the pills or accurately reported the side effects. Many pilots who
participated in these studies were on flight status; if they reported any
side effects, they could lose their flight pay. (Note 91)
Obviously, this provided an incentive for them not to report any side
effects, since they did not want to lose their flight pay. Similarly, those
who experienced side effects had an incentive to stop taking the drug
without notifying the researchers conducting the study. Moreover, pilots
who contacted the Committee staff reported that many of their friends and
colleagues did not take any of the pills at all, and many of those who did
take at least one pill stopped taking them when they experienced headaches
and other side effects. Despite the pressure to obey orders, many of the
pilots apparently believed that they should not trust the Pentagon
regarding the safety of these experimental pills.
One member of the air crew who was given pyridostigmine as part of these
studies, Craig Crane, notified the Committee that he now has memory loss,
joint pain, sensitivity to chemicals, and other symptoms that are commonly
associated with Gulf War syndrome, although he is only 32 years old and did
not serve in the Gulf War. He has left the Air Force because of his
disabilities. (Note 92)
In a letter to Sen. Rockefeller dated November 17, 1994, DOD continues
to claim that its use of pyridostigmine was not research. John Deutch,
Deputy Secretary of Defense, wrote that, "Although pyridostigmine and
botulinum toxoid were classified as investigational drugs as required by
FDA regulations, they were not used for experimental purposes in [Operation
Desert Storm] and the military personnel who received these products were
not experimental subjects." (Note 95) Mr. Deutch added that, "The
fact that these drugs were used for treatment purposes, not research
purposes, was clearly understood by all parties involved and specifically
approved by the courts in litigation challenging the governments [sic]
actions." Once again, it appears that the DOD confuses the goals of using
these medical products with the process, which was clearly considered
investigational by FDA.
Dr. Arthur Caplan, who at the time he testified was Director of the
Center of Biomedical Ethics at the University of Minnesota, addressed that
issue at the May 6 hearing. He explained that the fact that the goal is
treatment and that DOD believed the benefits of the pills and vaccines
would outweigh the risks "doesn't transform the use of experimental,
innovative, investigational agents into therapies. These agents were used,
as we have heard, in large populations for purposes other than those for
which they were originally designed in some cases, and circumstances under
which they had never before been tried out in the desert. This seems to me
to cinch the case that what took place fell into the category of
experimental, innovative and investigational, and that makes them
research." (Note 96)
Since the end of the Persian Gulf War, DOD has repeatedly requested that
the waiver of informed consent be made permanent, arguing that "to not
finalize it provides an arguable defect under the Administrative Procedures
Act and leaves both DOD and FDA open to greater
liability." (Note 97) To finalize the interim rule would grant
unrestricted use of investigational drugs by military personnel, even
though investigational status means that efficacy and safety have not been
proven. FDA has not yet decided whether to concur with DOD's request.
Pyridostigmine bromide, according to DOD, improves the survival of
animals exposed to soman and treated with atropine and 2-PAM. However,
pyridostigmine pretreatment makes individuals more vulnerable to other
nerve agents, such as VX and sarin. (Note 98) The DOD scientists
who studied pyridostigmine and sarin therefore concluded that
pyridostigmine should only be used when the chemical warfare threat is
soman. (Note 99)
The Pentagon, however, had no reason to believe that the Iraqis were
more likely to use soman rather than sarin. According to a report by the
Persian Gulf Veterans Coordinating Board, Iraq had several chemical
weapons, including sarin. (Note 100) Moreover, at a briefing for
Senators and staff on November 10, 1993, Under Secretary of Defense John
Deutch stated that the Czechoslovakian military detected low levels of
sarin in the Saudi theater during the opening days of the air war against
Iraq. This statement was also made by Joseph Corrivean, U.S. Army Foreign
Science and Technology Center, on April 27, 1994, at a National Institutes
of Health workshop on "The Persian Gulf Experience and Health."
Even if U.S. troops had been exposed to soman, it is unclear that the
pyridostigmine would have provided adequate protection against nerve
damage. When DOD began the second phase of research on pyridostigmine, it
was noted that the atropine and 2-PAM did not seem to save the lives of
animals that were exposed to soman. As a result, the dose of atropine was
increased to 0.40 mg/kg, which according to FDA, increased the survival of
Rhesus monkeys exposed to soman. (Note 101) However, when the
Department of Defense developed a treatment regimen for U.S. troops during
the Persian Gulf War, it was based on the inadequate dose of atropine in
the animal studies (0.096 mg/kg) rather than the higher, effective
dose. (Note 102) Therefore, even if Persian Gulf soldiers had
been exposed to soman, it is questionable if the pyridostigmine
pretreatment would have provided any protection, since the dose of atropine
was apparently inadequate.
In response to posthearing questions about this dosage discrepancy from
Sen. Rockefeller, the DOD stated "the dose of atropine in the Mark I kit
was established based exclusively on safety, rather than on efficacy,
considerations." (Note 103) This statement suggests that
hundreds of thousands of servicemembers were put at risk by requiring them
to take a drug with known risks (pyridostigmine bromide) in a situation
where it might have done little good since the atropine dose in the Mark I
kits, 6 mg, was inadequate. Based on the monkey data, a dose of 27 mg would
have been required for a 150-pound man. (Note 104) However, the
side effects of only 2 mg of atropine in a normal young person (without
nerve-agent exposure) include increased heart rate, decreased sweating,
visual blurring, and others. (Note 105) Apparently, DOD
officials decided that the high dosage required for protection would impair
performance, so they selected the much lower dosage, even though its
effectiveness was questionable. Although results for monkeys may not be
exactly comparable to those for humans, it seems unlikely that humans would
respond dramatically differently. It is therefore likely that the dose of
atropine in the Mark I kits was inadequate for efficacy, and even with this
very low dose could have compromised the ability of servicemembers during
war. (Note 106)
Botulism vaccine was given too late to U.S. troops to be of any use had
the Iraqis actually used biological warfare during Desert Storm. At a
briefing on April 20, 1994, DOD officials informed Committee staff that
botulism vaccine was not administered to most military personnel in the
Persian Gulf until January 23, 1991, which was 7 days after the onset of
the air war. Approximately 8,000 individuals received the vaccine, but most
received only one or two inoculations. Because the war ended on February
27, 1991, before the third injection was scheduled to be given, it is
unlikely that these soldiers were adequately immunized. Moreover, because
of the severe shortage of the product, the remainder of those deployed
received no inoculations, and hence no protection against botulism.
According to the Department of Veterans Affairs, 696,562 individuals
participated in Operation Desert Shield/Desert Storm. Therefore, 99 percent
of the military personnel deployed would have received no protection due to
the shortage of botulinum toxoid, and the remaining 1 percent were probably
not protected because the vaccine distribution started too late.
Additionally, in December 1990, the FDA advised the Department of
Defense that it would be unable to test the botulism vaccine for efficacy,
presumably because of limited time before the onset of the
war. (Note 107) Therefore, in addition to the limited supply of
vaccine and late onset of inoculations, efficacy of the existing supply was
not determined prior to the onset of the war.
Anthrax vaccine was given to approximately 150,000 military personnel in
the Persian Gulf. Anthrax vaccine is considered effective for protecting
against anthrax exposure of the skin; however it is unclear whether it
provides protection against inhaling aerosolized
anthrax. (Note 108) According to the Department of Defense, in
biological warfare the anthrax would be sprayed, so the efficacy of the
vaccine against aerosolized anthrax would have been the relevant
test. (Note 109) As stated earlier in this report, the DOD has
only one study indicating that the vaccine might be useful against
aerosolized anthrax, but there are no data on humans.
According to the materials that FDA provided to the Committee, virtually
all the studies excluded women. The lack of studies on women is a problem,
because dosage should be based on the weight of the person taking the drug,
and because some scientists believe that pyridostigmine may affect men and
women differently. (Note 111), (Note 112) For
example, women on birth control pills may have different levels of AChE
than other women or men. Similarly, women in different stages of their
reproductive cycle respond differently to
pyridostigmine. (Note 113) Since studies excluded women, there
is no information on the potential long-term side effects of pyridostigmine
on diseases unique to women (such as menstrual cycle irregularities or
breast cancer).
Because of the DOD researchers' concerns about serious adverse reactions
to pyridostigmine bromide, many of the studies screened the men to
determine whether they were hypersensitive to pyridostigmine bromide before
allowing their participation in the experiment. In some cases they used
test doses; in other cases they asked questions regarding similar
medications and sensitivity to bromide. In many of the studies, patients
were excluded if they were taking any medications, since adverse reactions
could occur when pyridostigmine was administered with other drugs (i.e.,
propranolol, birth control medications, or anti-malarial drugs). In some
studies, smokers were excluded; in many studies, participants were told not
to drink any alcoholic beverages. Most research study participants were
less than 35 years of age. In addition, individuals with abnormal blood
pressure, asthma, glaucoma, low serum AChE levels, gastrointestinal
disorders, urinary or intestinal blockage, or hyperthyroidism, were
excluded from the studies. (Note 114)
Despite these precautions, serious adverse reactions were reported for
several of the studies. For example, in one study, pyridostigmine bromide
was administered to a group of 28 active duty Air Force
pilots. (Note 115) One pilot experienced respiratory arrest 91
minutes after swallowing the third in a series of three 30-mg
pyridostigmine tablets. This pilot had shown no sensitivity to the test
dose of pyridostigmine prior to the study. In another study of 32 male
subjects, one subject lost consciousness following vision problems and
headache. (Note 116) In other studies, abnormal liver tests,
unusual electrocardiograms, gastrointestinal disturbances, and anemia were
reported. (Note 117), (Note 118), (Note 119)
Results also showed that pyridostigmine impaired performance, including
tasks which require short-term memory, and prevented a number of test
subjects from exercising in hot environments during the second or third day
of treatment. A study of the impact of pyridostigmine on swimming in cold
water had to be terminated when it was determined that its use caused
severe cramps that could cause drowning.
Research published in 1978 on neostigmine, a "close relative" of
pyridostigmine, found that the drug caused "profound physiological,
electrophysiological, and electron microscopic disruption of nerve endings
and muscles." Some of these changes increased in severity over time with
continued treatment. (Note 120) The author of that study
believes this study has worrisome implications for pyridostigmine.
In August 1990, just before U.S. troops were sent to the Gulf, DOD
scientists requested approval for a study of four men that would evaluate
the effects of pyridostigmine on vision. This study was deemed urgent
because of the situation in Kuwait, and it was approved quickly. It is
important to note that this study, conducted just prior to the Gulf War,
included extensive safety precautions, including giving medical exams to
the men before giving the pyridostigmine. The researchers indicated that
pyridostigmine should not be given to individuals who had bronchial asthma,
peptic ulcer, liver, kidney, heart disease, or hypersensitivity to
pyridostigmine or related drugs. They informed study volunteers that
possible adverse side effects include nausea, vomiting, slow heart rate,
sweating, diarrhea, abdominal cramps, increased salivation, increased
bronchial secretions, and pupil constriction. They also warned of other
side effects, including "weakness, muscle cramps, and muscle twitches" and
explained that, "Because of these side effects, all subjects will be
admitted to Lyster Army Hospital as in-patients so that they will be
medically monitored during evening periods of nontesting. A drug will be
available at the test site to counteract the possible adverse side
effects." (Emphasis added) (Note 121) In addition, the Human
Subjects Committee that reviewed this study considered whether the
possibility of pyridostigmine causing death should be mentioned in the
informed consent form; after some discussion, it was decided that such a
warning was unnecessary since death was unlikely.
In contrast to the extensive precautions taken before giving
pyridostigmine every 8 hours for 3 days to four volunteers, a few months
later approximately 400,000 U.S. soldiers were ordered to take the same
dosage of the drug for days, weeks, or months, none of whom had been
screened for any of the diseases mentioned in the informed consent form
given to the four men, none of whom were warned about the risks associated
with the drug, and none of whom were given a choice of whether or not to
take it. Additionally, approximately 28,000 of the 400,000 receiving the
pyridostigmine were women, who were required to take an investigational
drug that DOD had never tested on healthy women. (Note 122)
The repeated claims by DOD and FDA at the Committee's May 6, 1994,
hearing and at other times since the war that they were sure pyridostigmine
was perfectly safe as used is not consistent with the concerns of DOD
scientists regarding the potential serious adverse reactions and drug
interactions while conducting research. It does not make sense that the
researchers would establish such elaborate safeguards when giving the drug
to four men, and then have none of those safeguards when giving the drug to
more than 400,000 U.S. troops, none of whom had been tested for sensitivity
to pyridostigmine, and most of whom were not screened for medical problems
or medication use that could preclude the safe use of pyridostigmine. DOD
researchers were aware of the shortcomings of their research. For example,
in 1989 William K. Prusaczyk suggested, "Because of the existing incidence
of asthma in soldiers in the U.S. Army," the medical monitor believes that
pyridostigmine should be studies on individuals who have
asthma. (Note 123)
The safety of pyridostigmine was evaluated during and after the Persian
Gulf War. In one study, approximately 37 percent of 213 soldiers reported
at least one severe symptom 24 hours after beginning to take the 30-mg
pyridostigmine tablets. (Note 124) Additionally, the DOD
conducted three surveys concerning the use of pyridostigmine in Operation
Desert Shield/Storm which were reported in 1992. (Note 125)
These surveys indicated that side effects were frequently experienced by
military personnel taking pyridostigmine bromide. One published article,
based on reports from medical personnel providing care to 41,650 soldiers
(6.5 percent women) who took pyridostigmine bromide in the Persian Gulf,
found that over half experienced gastrointestinal
disturbances. (Note 126) Urinary urgency and frequency,
headaches, nasal discharge, profuse sweating, and tingling of hands and
feet were reported to occur in a range of 5 to 30
percent. (Note 127) Several doctors who were interviewed for the
study expressed concerns that the dose for women may have been too high.
In the 3 years that have elapsed since the Gulf War, the DOD has
apparently not conducted research on the safety of pyridostigmine for
healthy women. In early 1994, DOD submitted an NDA (new drug approval)
application to FDA, urging that FDA determine that pyridostigmine bromide
is safe and effective as an antidote enhancer. The studies provided in that
application did not include women.
In the last few year, several studies have been published on the effects
of pyridostigmine on growth hormones of women and men. In one study, three
of the eight women who received one 120 mg dose of pyridostigmine bromide
became so ill they had to be excluded from the study. (Note 128)
The entire study consisted of eight women and eight men who received
pyridostigmine in single doses of 30, 60, or 120 mg. The women in the study
experienced more severe and prolonged symptoms than men, especially at the
120 mg dose, such as severe abdominal cramps, nausea, vomiting, asthenia,
and muscle cramps. Three subjects who received 120 mg had vision impairment
that lasted several hours. (Note 129)
In addition, none of the studies of pyridostigmine evaluated the safety
of pyridostigmine if taken over a period of weeks or months, as was done in
the Gulf War. Moreover, none of the studies evaluated the long-term safety
of pyridostigmine by providing followup information about men who had taken
the drug years earlier.
Despite the Committee's hearing in May and numerous television news
magazine reports and newspaper articles reporting our concerns about the
safety of pyridostigmine, the DOD has apparently not yet conducted any
studies that provide any more information than was previously
available. (Note 130) Several studies of pyridostigmine
conducted by DOD under conditions of heat and/or exercise have been
published, but they studied only four to seven young men. In one study of
four men, one man became so fatigued on the third day that he was told to
stop exercising; this problem was barely mentioned in the published study,
and the implication for soldiers during wartime was not
discussed. (Note 131)
The results were similar but not as alarming for permethrin, another
insecticide that was used in the Gulf War. Permethrin was used in the
military uniforms, impregnating the fabric before it was cut and sewn. In
his cockroach studies, Dr. Moss found that DEET became twice as toxic when
used with permethrin.
Dr. Moss also studied the combination of DEET and pyridostigmine with
other toxic substances that were present in the Gulf War, such as lindane
(a treatment for lice) and a wide range of insecticides. These substances
also became more toxic when used at the same time than when used
individually. Even caffeine was found to have a potential impact on the
toxicity of other substances.
Dr. Moss believes his findings regarding cockroaches are likely to be
relevant to humans; however, more research is needed to determine if humans
would be similarly affected. Nevertheless, his findings are consistent with
concerns that have been raised by military researchers, who have stated
publicly that carbamates such as pyridostigmine must never be used after
nerve agent exposure, presumably because the pyridostigmine could further
decrease AChE from nerve agent poisoning. If military personnel were
exposed to low levels of nerve agents due to bombing of nerve agent
stockpiles as proposed by some, (Note 134) as well as numerous
pesticides procured by the Army, (Note 135) and pyridostigmine
bromide, it is likely that the combination could have been much more toxic
than any of those substances would have been individually.
Dr. Moss' findings regarding pesticides are also consistent with a note
in the Air Force records of Craig Crane, an Air Force crewman who
participated in a pyridostigmine experiment in 1986. According to a
description of the pyridostigmine study that was signed by medical
personnel and included in Mr. Crane's records, "There is no sensitivity to
pesticides or recent significant exposure." This medical notation suggests
that Air Force medical personnel were concerned about a possible
interaction between pyridostigmine and pesticides, and therefore avoided
including men who had been exposed to pesticides. (Note 136)
Dr. Moss testified about his findings at the Committee's May 6, 1994,
hearing, despite efforts by USDA to prevent him from doing so. On June 31,
1994, his 3-year contract with USDA expired, and it was not renewed. Dr.
Moss' repeated efforts to continue working at USDA were unsuccessful. Sen.
Rockefeller wrote to Secretary Espy in May, June, and July to ask how USDA
planned to continue Dr. Moss' research, but received no reply until after a
CBS Evening News story on the subject on October 14, 1994. Secretary Espy
then wrote to Sen. Rockefeller saying that the USDA had no plans to follow
up on Dr. Moss' research, but would ensure that the data were provided to
DOD. (Note 137)
Although Dr. Moss made no accusations against USDA at the Committee
hearing, he has subsequently expressed his views that he lost his job at
USDA because of his research findings. He also now reports that his
supervisor warned him that he should not discuss his research findings with
anyone. Moreover, in an internal USDA memo dated December 30, 1993, Dr.
Moss stated that he was advised to "keep quiet." (Note 138) USDA
and the Johnson Wax Company are the co-inventors of DEET, an ingredient in
most commercially available insecticides, such as Raid.
While the results of FDA's general safety testing were encouraging, the
problem with adverse reactions to the vaccine were not resolved. In her
review of the DOD's application for use of the botulism vaccine in the
Persian Gulf, an FDA reviewer pointed out that in 1973, the Centers for
Disease Control had considered terminating its distribution because of
adverse reactions. (Note 141) New lots of the vaccine were
manufactured in 1971, but research was not conducted to determine whether
the newer lots produced fewer adverse reactions than the older
lots. (Note 142)
Since no records were kept for most of the Gulf War soldiers who
received the vaccine, there is no new information about the safety of the
botulism vaccine resulting from its use by U.S. troops. Therefore, its
safety remains unknown.
Unfortunately, medical records and shot records of individuals who
served in the Persian Gulf frequently do not report the vaccines they
received. In some cases, anthrax was recorded as "Vac-A." However, in many
cases, veterans who believe they received anthrax vaccinations did not have
them recorded in their medical records. According to testimony received at
the Committee hearing on May 6, 1994, vaccines were recorded in separate
vaccine records, for soldiers who had such records with them and insisted
that the information be recorded. (Note 144)
If the military collects data to determine how to better train
individuals, the "training" is then defined as contributing information to
generalizable knowledge, and is hence "research." For the optimal
protection of U.S. troops, one would hope that training exercises are
improved based on reliable information. However, during the testing of new
training methods or equipment, exercises utilizing potentially dangerous
substances, such as chemical weapons, should be considered research rather
than training. Participants must be fully apprised of the nature of the
experiments and have the opportunity to refuse without reprisal, in order
to conform with the Nuremberg Code and other ethical standards.
It is the responsibility of DOD and VA to identify and keep track of
veterans exposed to potentially dangerous substances so that they can
receive medical care if needed. Even in situations where DOD believes an
investigational drug is safe, such followup is necessary to establish with
certainty whether exposures were safe, or whether they resulted in long-
term side effects.
Similarly, many atomic veterans believe that infertility, miscarriages,
stillbirths, and birth defects resulted from exposure to ionizing
radiation.
Although these reports have received media attention for years, the VA
and DOD have not conducted research on these questions, nor have they
supported independent research. Finally, 50 years after veterans were
intentionally exposed to ionizing radiation, the VA will be required by law
to enter into a contract with the Institute of Medicine (IOM), or a similar
independent agency, to evaluate whether it is feasible to support research
on the reproductive problems associated with exposure to ionizing
radiation. If the IOM determines that such research is feasible, the VA and
the Congress will then determine whether such research should be
funded. (Note 147)
In November 1994, President Clinton signed a law that would require VA
to conduct research on birth defects and miscarriages among Gulf War
families. A preliminary study will be required, in which information about
these reproductive outcomes will be included in the Persian Gulf War
Veterans' Health Registry. In addition, VA will be required to include
semen analysis and other reproductive evaluations in a standard protocol
used to evaluate Gulf War veterans with mysterious illnesses.
Similarly, the use of Agent Orange and other herbicides in Vietnam has
stimulated concern and controversy ever since the United States began the
military herbicide program in 1961, but a comprehensive review and
evaluation of available scientific and medical information regarding the
health effects of herbicides and the contaminant dioxin was not conducted
until it was authorized by Congress in 1991. (Note 149) The
Department of Veterans Affairs has recently announced new rules for
awarding compensation for more Agent Orange-related diseases, three decades
after military personnel were exposed to the defoliant in
Vietnam. (Note 150)
Reports of the National Research Council's Committee on the Biological
Effects of Ionizing Radiation (BEIR), written to advise the U.S. Government
on the health consequences of radiation exposure, frequently relied on
mortality and morbidity experiences of exposed individuals, some of which
took decades to accumulate. (Note 151) Information is continuing
to be gathered, which will be incorporated into future BEIR reports.
When investigational drugs and vaccines were given to thousands of
military personnel during the Persian Gulf War, this provided an
unprecedented opportunity to learn more about the safety of those products.
Unfortunately, no effort was made to gather objective information, despite
the fact that data gathering is required as part of the IND process for
investigational drugs and vaccines. (Note 152) Any research that
is conducted years after the war is over will be less scientifically valid
and much more expensive as a result of the lack of objective information
gathered during the war about which servicemembers took which drugs or
vaccines, and the adverse reactions that they experienced.
The Medical Follow-up Agency (MFUA) of the Institute of Medicine will
take 3 years to issue its final report on whether there is a scientific
basis for an epidemiological study on the health consequences of service in
the Persian Gulf. (Note 153) If the MFUA determines such a study
or studies should be conducted, it will take several more years to gather
the necessary data.
Even if medical records contain relevant information regarding health
consequences from various investigations, these medical records may be
difficult to obtain. Of the 150 individuals who were interviewed for the
Committee's survey, not all respondents had tried to obtain their medical
records, but 28 (19 percent) indicated that part or all of their medical
record were lost and 48 (32 percent) respondents indicated that their
medical records were incomplete or inaccurate (Appendix). Some of those
surveyed believed their records had been deliberately altered or contained
inaccurate information.
The VA Office of Inspector General recently investigated the possible
illegal removal of official documents from certain veterans' appeals files
assigned to two Board of Veterans' Appeals attorneys. (Note 155)
It is unknown whether such intentional removal is a rare occurrence;
clearly, any removal of medical information would make it difficult and
perhaps impossible for a veteran to receive the medical care and
compensation that he or she is entitled to.
In addition to any intentional removal of information, veterans' service
medical records are difficult to find. According to the U.S. General
Accounting Office, veterans' service medical records can potentially be in
thousands of locations. (Note 156) The DOD has attempted to
simplify the retrieval of medical records by modifying the route for
medical records of individuals who have left the military. The simplified
route was initiated for the Army in October 1992, for the Navy in February
1994, and for the Air Force and Marines in late 1994. Although the new
procedures should simplify the process, the GAO concluded that the
possibility of misplaced medical records remains because there are still
thousands of locations where records could be found within the new system.
For example, the military has released chemicals and biological agents
through outdoor "open air" tests for over four decades. Some of these
supposedly safe chemicals and biological agents, referred to as simulants,
were also released over populated areas and cities. (Note 158)
Although scientific evidence suggested that the tests may have caused
illnesses to exposed citizens, the Army repeatedly claimed that these
bacteria and chemicals were harmless until adverse health effects convinced
them to change the simulants used. The death of Edward J. Nevin was
associated with the release of one simulant, Serratia marcescens, over San
Francisco in 1950. (Note 159) A subsequent court trial revealed
that on September 26 and 27, 1950, the Army sprayed Serratia marcescens
from a boat off the coast of San Francisco. (Note 160) On
September 29, patients at the Stanford University Hospital in San Francisco
began appearing with Serratia marcescens infections. Although the judge
denied the validity of the plaintiffs' claims that the exposures were
related to the death of Mr. Nevin, the trial raised frightening questions
about the selection of simulants. Serratia marcescens is no longer used by
the military as a simulant.
Dugway Proving Ground has been a site for "open air" testing of chemical
and biological agents for decades. The purpose of the tests is to determine
how the agents spread and survive, and their effect on people and the
environment. Earl Davenport is a veteran who participated in tests at
Dugway Proving Ground in Utah, first as a military employee and later as a
civilian employee. He became ill in 1984 after being exposed to a chemical
simulant called DMMP (dimethyl methylphosphate). He had been spraying the
chemical into the path of a laser beam when a sudden change in wind blew
the chemical all over his face and hair before he was able to put on a
protective mask. Although he was "wheezing and coughing" the next day, and
his symptoms lasted for weeks, the Dugway Army Hospital merely gave him
cough medicine and antibiotics. The Dugway Safety Office assured him that
the chemical was safe. However, by 1988, officials at Dugway had
reevaluated the simulant's danger, and were becoming concerned that DMMP
could cause cancer and kidney damage. (Note 161) Mr. Davenport
is currently attempting to obtain compensation for his illness from the
Department of Labor, since his exposure occurred when he was employed at
Dugway as a civilian.
In 1992, several military personnel from the Arizona National Guard
experienced chemical burns during a summer training exercise at the Dugway
Proving Grounds. According to two physicians, a daughter from one of the
guardsmen also received chemical burns when she later handled her father's
duffle bag. One of these doctors, Dr. Michael Vance, was contacted by
military officials and encouraged to modify his written findings on the
possible cause of the daughter's injury. (Note 162) He refused.
According to scientists and doctors from the University of Utah, there
is great concern over the potential health consequences not only for
military personnel who work and train at Dugway, but also for civilians who
live in a small town and on an Indian reservation near the Proving Grounds.
Moreover, physicians from the Utah Medical Society have complained about
the lack of information provided to the medical community about the agents
that are used in Dugway, despite repeated requests. (Note 163)
According to Dr. Cole, the use of potentially harmful chemical and
biological agents continues at Dugway even today. For example, he testified
that the Army uses a simulant called Bacillus subtilis, "which is fairly
harmless in many natural conditions, [but] is recognized as a potential
source of infection and can cause serious illness in some people when they
are exposed to it in large numbers and they inhale large numbers of those
microorganisms." (Note 164)
Dr. Cole also testified about the lack of informed consent at Dugway in
recent months. For example, in November 1993, a test that was intended to
evaluate whether chemical agents could penetrate protective clothing used
informed consent forms that did not mention the
chemicals. (Note 165) II. BACKGROUND
A. CODES, DECLARATIONS, AND LAWS GOVERNING HUMAN EXPERIMENTATION
The Nuremberg Code is a 10-point declaration governing human
experimentation, developed by the Allies after World War II in response to
inhumane experiments conducted by Nazi scientists and physicians. The Code
states that voluntary and informed consent is absolutely essential from all
human subjects who participate in research, whether during war or peace.
The Code states:B. MUSTARD GAS AND LEWISITE
According to a report published by the Institute of Medicine (IOM) last
year, approximately 60,000 military personnel were used as human subjects
in the 1940's to test two chemical agents, mustard gas and lewisite. Most
of these subjects were not informed of the nature of the experiments and
never received medical followup after their participation in the
research. (Note 14) Additionally, some of these human subjects
were threatened with imprisonment at Fort Leavenworth if they discussed
these experiments with anyone, including their wives, parents, and family
doctors. (Note 15) For decades, the Pentagon denied that the
research had taken place, resulting in decades of suffering for many
veterans who became ill after the secret testing. According to the 1993 IOM
report, such denial by the DOD continues: "This committee discovered that
an atmosphere of secrecy still exists to some extent regarding the WWII
testing programs. Although many documents pertaining to the WWII testing
programs were declassified shortly after the war ended, others were
not." (Note 16)C. SEVENTH-DAY ADVENTISTS
Many experiments that tested various biological agents on human
subjects, referred to as Operation Whitecoat, were carried out at Fort
Detrick, MD, in the 1950's. The human subjects originally consisted of
volunteer enlisted men. However, after the enlisted men staged a sitdown
strike to obtain more information about the dangers of the biological
tests, Seventh-Day Adventists who were conscientious objectors were
recruited for the studies. (Note 18) Because these individuals
did not believe in engaging in actual combat, they instead volunteered to
be human subjects in military research projects that tested various
infectious agents. At least 2,200 military personnel who were Seventh-Day
Adventists volunteered for biological testing during the 1950's through the
1970's. (Note 19) D. DUGWAY PROVING GROUND
Dugway Proving Ground is a military testing facility located
approximately 80 miles from Salt Lake City. For several decades, Dugway has
been the site of testing for various chemical and biological agents. From
1951 through 1969, hundreds, perhaps thousands of open-air tests using
bacteria and viruses that cause disease in human, animals, and plants were
conducted at Dugway. (Note 22) For example, antigens produced by
animals that had come in contact with Venezuelan equine encephalomyelitis
(VEE), a disease usually found in horses, were later found in animals
around Dugway. Prior to the identification of these substances in the
Dugway vicinity, VEE had only been identified in the rat population in
Florida. Such a finding suggested that VEE had been used in the open-air
tests at Dugway or within laboratories, and transferred to the nearby
animal population. (Note 23)E. RADIATION EXPOSURE
ATOMIC VETERANS
From 1945 to 1962, the United States conducted numerous nuclear
detonation tests: Crossroads (Bikini); Sandstone, Greenhouse, and Ivy
(Eniwetok Atoll); Castle (Bikini Atoll); Pacific Ocean 400 miles southwest
of San Diego; Redwing and Hardtack I (Eniwetok and Bikini Atolls); Argus
(South Atlantic); and Dominic (Christmas Island, Johnston Island, 400 miles
west of San Diego). (Note 28) The main goal was to determine
damage caused by the bombs; however, as a result, thousands of military
personnel and civilians were exposed to radioactive fallout. Similar tests
were conducted within the continental United States, including sites in New
Mexico and Nevada. (Note 29) Veterans who participated in
activities that directly exposed them to radioactive fallout are referred
to as "atomic veterans." RADIATION RELEASES AT U.S. NUCLEAR SITES
In addition to detonation testing, radioactive releases were also
intentionally conducted at U.S. nuclear sites in the years following World
War II. According to the U.S. General Accounting Office (GAO), at least 12
planned radioactive releases occurred at three U.S. nuclear sites during
1948-1952. These tests were conducted at Oak Ridge, TN; Dugway, UT; and Los
Alamos, NM. (Note 34) Additionally, a planned release occurred at
Hanford, WA, in December 1949, which has been referred to as the Green Run
test. It is not known how many civilians and military personnel were
exposed to fallout from these tests. OTHER EXPOSURES TO IONIZING RADIATION
In January 1994, the Clinton administration established a Human
Radiation Interagency Working Group to coordinate a Government-wide effort
to uncover the nature and extent of any Government-sponsored experiments on
individuals involving intentional exposure to ionizing radiation. The
working group represents the Administration's response to Secretary of
Energy Hazel O'Leary's promise to comb Government files for information on
hundreds of experiments conducted on people in the 1940's and 1950's.F. HALLUCINOGENS
Working with the CIA, the Department of Defense gave hallucinogenic
drugs to thousands of "volunteer" soldiers in the 1950's and 1960's. In
addition to LSD, the Army also tested quinuclidinyl benzilate, a
hallucinogen code-named BZ. (Note 37) Many of these tests were
conducted under the so-called MKULTRA program, established to counter
perceived Soviet and Chinese advances in brainwashing techniques. Between
1953 and 1964, the program consisted of 149 projects involving drug testing
and other studies on unwitting human subjects. (Note 38)G. INVESTIGATIONAL DRUGS USED IN THE PERSIAN GULF WAR
Under the Food, Drug, and Cosmetics Act, all vaccines and medical
products must be proven safe and effective by the Food and Drug
Administration (FDA) in order to be sold and distributed in the United
States. This law also applies to medical products used by the Department of
Defense, even if given to U.S. troops who are stationed in other countries. III. FINDINGS AND CONCLUSIONS
A. FOR AT LEAST 50 YEARS, DOD HAS KNOWINGLY EXPOSED MILITARY PERSONNEL TO
POTENTIALLY DANGEROUS SUBSTANCES, OFTEN IN SECRET.
The U.S. General Accounting Office issued a report on September 28,
1994, which stated that between 1940 and 1974, DOD and other national
security agencies studied hundreds of thousands of human subjects in tests
and experiments involving hazardous substances. (Note 65) GAO
stated that some tests and experiments were conducted in secret. Medical
research involving the testing of nerve agents, nerve agent antidotes,
psychochemicals, and irritants was often classified. Additionally, some
work conducted for DOD by contractors still remains classified today. For
example, the Central Intelligence Agency (CIA) has not released the names
of 15 of the approximately 80 organizations that conducted experiments
under the MKULTRA program, which gave psychochemical drugs to an
undetermined number of people without their knowledge or consent. According
to the GAO report, the CIA has not released this information because the
organizations do not want to be identified. (Note 66) WORLD WAR II VETERANS
As recently as 1993, the Institute of Medicine of the National Academy
of Sciences reported that an atmosphere of secrecy still existed regarding
World War II testing of mustard gas and lewisite. (Note 67)
Although many documents pertaining to the World War II testing programs
were declassified shortly after World War II ended, others remain
"restricted" even today. In addition to the classified or restricted
documents, World War II veterans who participated in the research were
sworn to secrecy. These classified documents and promises of secrecy have
impeded medical care for thousands of veterans during half of the last
century. COLD WAR VETERANS
During the years immediately following World War II, military personnel
were intentionally exposed to radiation during the testing of atomic bombs
and during radioactive releases. While it is unclear how many of these
servicemembers were intentionally exposed to what were known to be harmful
levels of radiation, there is clear evidence that in some cases military
personnel were ordered to locate themselves in areas of high radioactive
fallout. They were given no choice in the matter, and they were not told of
the potential risks of those exposures. PERSIAN GULF WAR VETERANS
Persian Gulf veterans were also given investigational vaccines and
ordered not to tell anyone. In a Committee survey of 150 individuals who
served in the military during the Persian Gulf War (see Appendix), many of
those surveyed indicated they were ordered, under threat of Article 15 or
court martial, to discuss their vaccinations with no one, not even with
medical professionals needing the information to treat adverse reactions
from the vaccine. Similarly, 86 percent of the military personnel who told
the Committee that they were ordered to take pyridostigmine bromide
reported that they received no information on what they were taking or the
drug's potential risks. According to a DOD study published in the Journal
of the American Medical Association, commanding officers and medical
personnel were also inadequately informed about the investigational drugs;
as a result, they were ill-prepared to recognize or treat military
personnel who experienced side effects. (Note 71)
The major principle of all research ethics involving human subjects, as
described by the Nuremberg Code, the Declaration of Helsinki, and the
"Common Rule" of the U.S. Government, states that the voluntary, competent,
informed, and understanding consent of the subject is absolutely essential,
whether during war or peace. (Note 72) WORLD WAR II VETERANS
Many individuals were recruited for various military experiments of
mustard gas and lewisite under the guise of testing clothing, without being
warned beforehand that they would be exposed to dangerous chemicals.
Additionally, young servicemembers frequently reported that they were
enticed to volunteer for experiments by being promised extra leave time
from duty. PERSIAN GULF WAR VETERANS
Almost 50 years after World War II veterans were exposed to unethical
research, the Department of Defense again failed to comply with the well-
established ethical requirement that all soldiers and civilians make an
informed choice of whether or not to use investigational medical treatment.
CIVILIANS IN THE GULF WAR
Numerous civilians have reported to Committee staff that they also were
given investigational drugs during the Persian Gulf War without informed
consent. For example, civilians who worked for DOD contractors and news
media personnel were apparently instructed to take the pyridostigmine
bromide tablets. They usually were not told it was experimental or that the
pyridostigmine bromide was being administered in a regime that was not
proven efficacious or safe, and received no information on potential side
effects of the drug. OTHER STUDIES OF PYRIDOSTIGMINE
Following the Committee's May 6, 1994, hearing, several individuals who
were in the Air Force during the 1980's contacted Committee staff to report
they had also received pyridostigmine bromide without their
consent. (Note 90) They indicated that they did not volunteer for
any research study, were ordered to take the pyridostigmine pills as part
of a research project, and were ordered to report any side effects to the
flight surgeons. One individual estimated that several hundred individuals
in his squadron participated in the pyridostigmine studies, and reported
that the studies were conducted over a period of at least 2 years. C. DOD INCORRECTLY CLAIMS THAT SINCE THEIR GOAL WAS TREATMENT, THE USE OF
INVESTIGATIONAL DRUGS IN THE PERSIAN GULF WAR WAS NOT RESEARCH.
Despite the fact that pyridostigmine was an investigational drug whose
safety and effectiveness had not been proven to FDA, the DOD claims that
its use in the Persian Gulf War was prevention and treatment, not research.
For example, Dr. Edward Martin, Acting Principal Assistant Secretary of
Defense for Health Affairs, stated at the Committee's hearing on May 6,
1994, that "..investigational products were employed during the Persian
Gulf War as prophylactic treatments against biological and chemical warfare
agents. This was not research but direct prevention and
treatment." (Note 93) Additionally, John M. Bachkosky, Deputy
Director, Office of the Director of Defense Research and Engineering, wrote
to Sen. Rockefeller on May 19, 1994, that "[botulinum toxoid and
pyridostigmine bromide] were used for direct prevention and treatment and
were not employed as part of any research effort." (Note 94) D. DOD USED INVESTIGATIONAL DRUGS IN THE PERSIAN GULF WAR IN WAYS THAT WERE
NOT EFFECTIVE.
The DOD persuaded FDA that informed consent should be waived for
pyridostigmine bromide and botulism vaccine because these investigational
products had been used safely in the past. However, based on documents
provided to the Committee staff, it is doubtful that either of these
products would have been effective as used in the Persian Gulf War.E. DOD DID NOT KNOW WHETHER PYRIDOSTIGMINE BROMIDE WOULD BE SAFE FOR USE BY
U.S. TROOPS IN THE PERSIAN GULF WAR.
Committee staff reviewed all the clinical studies and related research
regarding pyridostigmine on healthy individuals which DOD provided to FDA
to support their IND and their NDA (new drug approval)
application. (Note 110) The number of human subjects in most
studies was less than 35; several studies included as few as two or four
individuals. F. WHEN U.S. TROOPS WERE SENT TO THE PERSIAN GULF IN 1994, DOD STILL DID
NOT HAVE PROOF THAT PYRIDOSTIGMINE BROMIDE WAS SAFE FOR USE AS AN ANTIDOTE
ENHANCER.
When U.S. troops were sent to the Persian Gulf in the fall of 1994
because of concern about Kuwait, the DOD considered the use of
pyridostigmine to protect against chemical weapons. However, in the 3 years
since the Persian Gulf War of 1991, the DOD had not conducted studies that
proved the safety of pyridostigmine bromide for that use.G. PYRIDOSTIGMINE MAY BE MORE DANGEROUS IN COMBINATION WITH PESTICIDES OR
OTHER EXPOSURES.
In 1993, Dr. James Moss, a scientist at the U.S. Department of
Agriculture, conducted research on cockroaches that could have important
implications for Persian Gulf War veterans. (Note 132) He found
that when pyridostigmine was used in combination with a common insect
repellent called DEET (diethyl-m-tolamide), the DEET became almost seven
times as toxic as when it was used alone. Similarly, pyridostigmine became
four times as toxic when used in combination with
DEET. (Note 133) DEET and many other insect repellents and
pesticides were widely used in the Gulf War as protection against sand
flies, scorpions, and other pests. If individuals who took pyridostigmine
bromide became more vulnerable to pesticides, or those exposed to
pesticides became more vulnerable to pyridostigmine bromide, this could
explain the serious neurological symptoms experienced by so many Gulf War
veterans.H. THE SAFETY OF THE BOTULISM VACCINE WAS NOT ESTABLISHED PRIOR TO THE
PERSIAN GULF WAR AND REMAINS UNCERTAIN.
At a meeting with DOD officials regarding informed consent in December
1990, the FDA agreed to test the botulinum toxoid (botulism vaccine) for
safety. (Note 139) A representative of FDA's Center for
Biologics Evaluation and Research explained that the existing supply of the
vaccine was nearly 20 years old and consisted of three lots, stored under
constant refrigeration. There was concern that the vaccine would break down
into toxic products due to prolonged storage. General safety testing was
performed by the FDA on all of the lots of botulinum toxoid used in the
Persian Gulf; however, the FDA did not complete these tests until January
24, 1991, (Note 140) after the war had started.I. RECORDS OF ANTHRAX VACCINE ARE NOT SUITABLE TO EVALUATE SAFETY.
Although anthrax vaccine had been considered approved prior to the
Persian Gulf War, it was rarely used. Therefore, its safety, particularly
when given to thousands of soldiers in conjunction with other vaccines, is
not well established. Anthrax vaccine should continue to be considered as a
potential cause for undiagnosed illnesses in Persian Gulf military
personnel because many of the support troops received anthrax vaccine, and
because the DOD believes that the incidence of undiagnosed illnesses in
support troops may be higher than that in combat
troops. (Note 143) J. ARMY REGULATIONS EXEMPT INFORMED CONSENT FOR VOLUNTEERS IN SOME TYPES OF
MILITARY STUDIES.
Army regulation (AR) 70-25 provides guidelines for the use of volunteers
as subjects in military research. Section 3 describes three exemptions
whereby military researchers are exempt from the provisions of these
protective regulations (the following is a direct quote from the
regulation):
It is sometimes difficult to differentiate training from research. For
example, military personnel at the U.S. Chemical School, Fort McClellan,
AL, are currently exposed to nerve agent poisons as part of their training,
so that they will learn how to cope with similar situations in combat.
Soldiers who refuse to participate or do not complete live agent training
are subject to reclassification in another military occupational specialty
and cannot graduate. (Note 146) To determine if the students
used correct procedures during the training exercise, blood samples are
obtained from some students before and after the procedure, and are
analyzed for red blood cell cholinesterase to determine if the soldier was
exposed to the nerve agents. K. DOD AND DVA HAVE REPEATEDLY FAILED TO PROVIDE INFORMATION AND MEDICAL
FOLLOWUP TO THOSE WHO PARTICIPATE IN MILITARY RESEARCH OR ARE ORDERED TO
TAKE INVESTIGATIONAL DRUGS.
A common theme voiced by military personnel who have participated in
military research or training exercises over the last 50 years is the lack
of information about the risks they faced and the lack of medical followup.
World War II veterans frequently reported that they heard about the adverse
health effects of mustard gas and lewisite from newspapers and television
decades after they were exposed, not from the Department of Defense or
Department of Veterans Affairs. Veterans and civilians who worked at the
Dugway Proving Ground and were exposed to a variety of biological and
chemical simulants began to question the association of poor health with
work as they compared information among themselves, not because of
information provided by military officials. Veterans who were inside atomic
clouds from atomic testing heard nothing at all from their government after
they returned home from duty. Similarly, soldiers who unknowingly
participated in military research designed to test the effects of
hallucinogens on human behavior were never given information to explain
their hallucinations and suffered from severe psychological disorders as a
result. Even today, most of those who served in the Persian Gulf indicate
they have received no followup information about the investigational drugs
they received.L. THE FEDERAL GOVERNMENT HAS FAILED TO SUPPORT SCIENTIFIC STUDIES THAT
PROVIDE INFORMATION ABOUT THE REPRODUCTIVE PROBLEMS EXPERIENCED BY VETERANS
WHO WERE INTENTIONALLY EXPOSED TO POTENTIALLY DANGEROUS SUBSTANCES.
In the last year, Gulf War veterans have reported that exposures during
military service have resulted in miscarriages and birth defects, as well
as excruciating pain during sexual intercourse. For example, at a Committee
hearing on August 5, 1994, Kelli Albuck, the wife of a Gulf War veteran,
described the miscarriage and pregnancy problems she had experienced since
her husband returned from the Gulf War. She also described what she called
"burning semen" or "shooting fire." Mrs. Albuck stated that many wives of
Gulf War veterans complained that their husbands' semen caused a burning
sensation, and in her case that the semen itself could cause a rash or
blood blister on her husband's leg or her skin. Steve Miller, an Army nurse
who also testified at that hearing, had no problems with burning semen, but
his son was born with extensive birth defects, including having only one
eye and one ear. The doctors told him that the combination of severe birth
defects was very unusual and suggestive of a toxic exposure. Mr. Miller
believes that his son's birth defects could be related to his use of
investigational drugs or vaccines, perhaps in combination with pesticide
exposures. M. THE FEDERAL GOVERNMENT HAS ALSO FAILED TO SUPPORT SCIENTIFIC STUDIES
THAT PROVIDE TIMELY INFORMATION FOR COMPENSATION DECISIONS REGARDING
MILITARY PERSONNEL WHO WERE HARMED BY VARIOUS EXPOSURES.
For decades, military personnel who were injured from various exposures
have been denied compensation until scientific evidence could support their
claims for service-connected disabilities. Although 60,000 military
subjects were involved as human subjects in testing programs involving
mustard gas and lewisite over 50 years ago, the initiation of a study to
review research regarding the long-term health consequences from these
military experiments did not occur until 1991, and the results of the study
were not published until 1993. (Note 148)N. PARTICIPATION IN MILITARY RESEARCH IS RARELY INCLUDED IN MILITARY
MEDICAL RECORDS, MAKING IT IMPOSSIBLE TO SUPPORT A VETERAN'S CLAIM FOR
SERVICE-CONNECTED DISABILITIES FROM MILITARY RESEARCH.
Although hundreds of thousands of U.S. military personnel have been
involved in military research, their medical records usually do not contain
information about the studies they participated in, or the investigational
drugs or vaccines they received. (Note 154) There are currently
no standardized guidelines imposed by either the DOD or VA to include a
copy of the informed consent form or research proposal in the medical
records of exposed human subjects.O. DOD HAS DEMONSTRATED A PATTERN OF MISREPRESENTING THE DANGER OF VARIOUS
MILITARY EXPOSURES THAT CONTINUES TODAY.
According to Dr. Leonard Cole, professor at Rutgers University, the DOD
has denied the possibility of harm from various exposures. However, in many
instances the military belatedly recognized that some exposures may be
causing disease and death. (Note 157) Such denial, however,
delays the availability of medical assistance to those harmed.