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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

FOREWORD

U.S. Senate,

Committee on Veterans' Affairs,

Washington, DC, December 8, 1994

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

------------------------------------------------------------------------

CONTENTS

I. Introduction

II. Background

* A. Codes, declarations, and laws governing human experimentation

* B. Mustard gas and lewisite

* C. Seventh-Day Adventists

* D. Dugway Proving Ground

* E. Radiation exposure

* F. Hallucinogens

* G. Investigational drugs

III. Findings and conclusions

* A. For at least 50 years, DOD has intentionally exposed military

personnel to potentially dangerous substances, often in secret

* B. DOD has repeatedly failed to comply with required ethical standards

when using human subjects in military research during war or threat of

war

* C. DOD incorrectly claims that since their goal was treatment, the use

of investigational drugs in the Persian Gulf War was not research

* D. DOD used investigational drugs in the Persian Gulf War in ways that

were not effective

* E. DOD did not know whether pyridostigmine bromide would be safe for

use by U.S. troops in the Persian Gulf War

* 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

* G. Pyridostigmine may be more dangerous in combination with pesticides

and other exposures

* H. The safety of the botulism vaccine was not established prior to the

Persian Gulf War

* I. Records of anthrax vaccinations are not suitable to evaluate safety

* J. Army regulations exempt informed consent for volunteers in some

types of military research

* 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

* 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

* M. The Federal Government has failed to support scientific studies that

provide timely information for compensation decisions regarding

military personnel who were harmed by various exposures

* 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

* O. DOD has demonstrated a pattern of misrepresenting the danger of

various military exposures that continues today

IV. Recommendations

* A. Congress should deny the DOD request for a blanket waiver to use

investigational drugs in case of war or threat of war

* B. FDA should reject any applications from DOD that do not include data

on women, and long-term followup data

* C. Congress should authorize a centralized database for all federally

funded experiments that utilize human subjects

* D. Congress should mandate all Federal agencies to declassify most

documents on research involving human subjects

* E. Congress should reestablish a National Commission for the Protection

of Human Subjects

* F. VA and DOD should implement regular site visits to review

Institutional Review Boards

* G. The Feres Doctrine should not be applied for military personnel who

are harmed by inappropriate human experimentation when informed consent

has not been given

Appendix -- Survey of 150 Persian Gulf War Veterans

------------------------------------------------------------------------

IS MILITARY RESEARCH HAZARDOUS TO VETERANS' HEALTH? LESSONS SPANNING HALF A

CENTURY

I. INTRODUCTION

During the last 50 years, hundreds of thousands of military personnel have

been involved in human experimentation and other intentional exposures

conducted by the Department of Defense (DOD), often without a

servicemember's knowledge or consent. In some cases, soldiers who consented

to serve as human subjects found themselves participating in experiments

quite different from those described at the time they volunteered. For

example, thousands of World War II veterans who originally volunteered to

"test summer clothing" in exchange for extra leave time, found themselves in

gas chambers testing the effects of mustard gas and lewisite. (Note 1)

Additionally, soldiers were sometimes ordered by commanding officers to

"volunteer" to participate in research or face dire consequences. For

example, several Persian Gulf War veterans interviewed by Committee staff

reported that they were ordered to take experimental vaccines during

Operation Desert Shield or face prison. (Note 2)

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.

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:

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)

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)

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.

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)

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)

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)

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)

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."

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)

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.

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.

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)

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)

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.

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.

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.

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.

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.

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.

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)

B. DOD HAS REPEATEDLY FAILED TO COMPLY WITH REQUIRED ETHICAL STANDARDS WHEN

USING HUMAN SUBJECTS IN MILITARY RESEARCH DURING WAR OR THREAT OF WAR.

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)

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.

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.

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)

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.

* 1. Military personnel were not given the opportunity to refuse

investigational drugs.

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.

* 2. Military personnel were not informed about the risks of the

investigational drugs.

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)

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.

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.

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.

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)

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)

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.

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.

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.

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.

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)

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.

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)

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.

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.

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.

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.

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)

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)

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):

* a. Research and nonresearch programs, tasks, and tests which may

involve inherent occupational hazards to health or exposure of

personnel to potentially hazardous situations encountered as part of

training or other normal duties, e.g., flight training, jump training,

marksmanship training, ranger training, fire drills, gas drills, and

handling of explosives.

* b. That portion of human factors research which involves normal

training or other military duties as part of an experiment, wherein

disclosure of experimental conditions to participating personnel would

reveal the artificial nature of such conditions and defeat the purpose

of the investigation.

* c. Ethical medical and clinical investigations involving the basic

disease process or new treatment procedures conducted by the Army

Medical Service for the benefit of patients. (Note 145)

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.

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.

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.

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.

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.

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.

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)

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.

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.

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.

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.

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)

IV. STAFF RECOMMENDATIONS

A. FDA SHOULD DENY THE DEPARTMENT OF DEFENSE REQUEST FOR A "BLANKET WAIVER"

TO USE INVESTIGATIONAL DRUGS WITHOUT INFORMED CONSENT IN CASE OF WAR OR

THREAT OF WAR.

If investigational drugs are deemed necessary for protection or treatment, a

waiver of informed consent should be sought only on a case-by- case basis.

While the military might order individuals to take an investigational drug

or use an investigational device if it is clearly safe and potentially

efficacious, under no circumstances should the DOD fail to inform

individuals about the known short-term and long-term risks prior to its

administration.

In 1990, DOD applied to FDA for a waiver of informed consent, claiming they

would provide warnings orally and in writing regarding the risks of

pyridostigmine, even though they would not give soldiers the choice of

whether or not to take it. According to reports from various sources,

including DOD's own study, DOD did not fulfill its promise. In addition, DOD

personnel apparently distributed these drugs to civilians without any

warnings. These failures and broken promises should be sufficient to

persuade FDA to reject the DOD request for a blanket waiver, and should be

taken into consideration any time DOD applies for a waiver of informed

consent. In addition, FDA should investigate these problems and work with

DOD to prevent similar problems in the future.

In addition, third-party or "deferred" consent should not be considered

unless the individual receiving the drug is physically or mentally

incompetent to make an informed decision on his/her behalf. If the DOD fails

to obtain the necessary waivers, or fails to adequately inform those

receiving the investigational products, DOD should be required to provide a

written explanation to the appropriate congressional committees.

B. FDA SHOULD REJECT IND AND NDA APPLICATIONS FROM DOD THAT DO NOT INCLUDE

DATA ON WOMEN AND LONG-TERM FOLLOWUP DATA.

When DOD submits an IND (investigational new drug) application or NDA (new

drug application) to FDA for any product that they plan to use, they should

always be required to include women in their research, since it is likely

that the product will be used by women. On the basis of that requirement,

FDA should reject the currently pending NDA for pyridostigmine's use as an

antidote enhancer, which was submitted to FDA in early 1994.

At a Senate briefing in November 1994, Dr. Ruth Merkatz, FDA's Associate

Commissioner for Women's Health, stated that FDA will always require data on

women in future drug approval applications, if the product under review is

intended for use by women. However, Dr. Merkatz was not specific about

whether this policy would apply to DOD.

In addition to data on women, it is increasingly clear that drugs can have

long-term adverse reactions that are not immediately obvious. Given the

responsibility of the Federal Government to provide medical care to veterans

who were harmed during military service, DOD and FDA need to ensure that the

VA and the public are aware of any potential long-term adverse reactions of

any medical products that are given to military personnel.

In the case of pyridostigmine, a drug that DOD wants to have the authority

to use in future conflicts in the Persian Gulf and elsewhere, FDA should

immediately urge DOD to conduct the kinds of research that is needed to

prove its safety for future military use, including research on its

potentially toxic effects when combined with insecticides and other chemical

agents that are commonly used by military personnel.

C. CONGRESS SHOULD AUTHORIZE A CENTRALIZED DATABASE FOR ALL FEDERALLY FUNDED

EXPERIMENTS THAT UTILIZE HUMAN SUBJECTS.

Currently, the U.S. Department of Agriculture maintains a database which can

identify the number of research grants awarded for studying various species,

such as beef and dairy cattle, poultry, sheep, swine, and others. (Note 166)

However, a database which identifies the types of human subjects does not

exist.

Congress should authorize a database which would provide crucial information

on federally funded research utilizing human subjects. Included in this

database should be the amount of Federal dollars spent on various research

efforts and the type of human subjects utilized, such as women, minorities,

children, prisoners, military personnel, and others.

Annual reports from the data collected should be provided to Congress. Such

information would enable legislators to understand better the use of human

subjects in federally sponsored research.

D. CONGRESS SHOULD MANDATE ALL FEDERAL AGENCIES TO DECLASSIFY MOST DOCUMENTS

ON RESEARCH INVOLVING HUMAN SUBJECTS.

Information involving human subjects in military research, which remains

classified for purported reasons of national security, needs to be

reevaluated and declassified whenever possible. All Federal agencies should

scrutinize classified information and make information available which might

benefit individuals who participated in such research.

E. CONGRESS SHOULD REESTABLISH A NATIONAL COMMISSION FOR THE PROTECTION OF

HUMAN SUBJECTS, WITHOUT A TERM LIMIT, WHICH HAS THE AUTHORITY TO INVESTIGATE

POTENTIAL VIOLATIONS OF HUMANS SUBJECTS' RIGHTS IN FEDERALLY FUNDED

RESEARCH.

A National Commission should standardize Federal regulations (45 CFR 46),

and consider adding military personnel as a vulnerable population. Policies

for the conduct of research in war or for the purposes of national security

should receive greater public debate. No existing regulations governing

military personnel should be finalized without such public dialogue.

Congress should provide authorization and appropriations for the National

Commission, and require annual reports on potential violations of human

subjects' rights. The administrative body of the Commission should consist

of nine members, three appointed by the majority party in Congress, three

appointed by the minority party in Congress, and three appointed by the

executive branch.

F. THE DEPARTMENT OF VETERANS AFFAIRS AND THE DEPARTMENT OF DEFENSE SHOULD

IMPLEMENT REGULAR SITE VISITS TO REVIEW THE PERFORMANCE OF INSTITUTIONAL

REVIEW BOARDS.

DOD and VA authorized site visits should include an evaluation of military

and VA research onsite, and a random sample review of actual research and

medical records, interviews with human subjects, and signed consent forms to

assure investigator compliance. A mechanism should be in place whereby human

subjects can express concern over perceived or actual violations of the

informed consent contract. This mechanism should allow human subjects to

register complaints to a regulatory agency and the National Commission,

rather than solely the investigator of the research project. All military

personnel and veterans involved in research should receive a copy of the

"Experimental Subject's Bill of Rights." (Note 167)

G. THE FERES DOCTRINE SHOULD NOT BE APPLIED FOR MILITARY PERSONNEL WHO ARE

HARMED BY INAPPROPRIATE HUMAN EXPERIMENTATION WHEN INFORMED CONSENT HAS NOT

BEEN GIVEN.

The U.S. Supreme Court has interpreted the Feres Doctrine to mean that

soldiers "injured in the course of activity incident to service" may not sue

the Government for compensation. (Note 168) However, when inappropriate

experimentation has resulted in suffering for military personnel, this

interpretation stands in violation of established ethical standards,

including the Nuremberg Code, the Declaration of Helsinki, and the "Common

Rule." Congress should not apply the Feres Doctrine for military personnel

who are harmed by inappropriate experimentation when informed consent has

not been given.

The U.S. Supreme Court mentioned the Nuremberg Code in United States v.

Stanley in 1987. James Stanley, an Army serviceman, volunteered to test the

effectiveness of protective clothing and equipment against chemical warfare

in February 1958. (Note 169) In the process, he unknowingly received LSD as

part of an Army study to determine the effects of the drug on humans.

Although Stanley suffered from periods of incoherence and memory loss for

years, he only learned in 1975 that he had participated in the LSD study

when the Army solicited his cooperation in a followup study. Having been

denied compensation for injury by the Army, Stanley filed under the Federal

Tort Claims Act. Justice Antonin Scalia wrote the opinion for the Court,

split 5 to 4. (Note 170) Justice Scalia wrote that permitting Stanley to sue

the Army would disrupt the Army itself and "would call into question

military discipline and decision-making." However, Justice Sandra Day

O'Connor, writing for herself as one of the dissenting judges, stated that

the Feres doctrine bar

"surely cannot insulate defendants from liability for deliberate and

calculated exposure of otherwise healthy military personnel to medical

experimentation without their consent, outside of any combat, combat

training, or military exigency..." (Note 171)

Justice O'Connor also commented on the Nuremberg Code in her writing,

stating that voluntary consent of the human subject is absolutely essential,

even for the U.S. military. It was, after all, the U.S. military who played

an instrumental role in the criminal prosecution of the Nazi officials who

experimented with human beings during World War II.

APPENDIX

Survey of 150 Persian Gulf War Veterans

Male respondents: 120 [80%]

Female respondents: 30 [20%]

Active duty servicemembers: 46 [31%]

Retired: 4 [3%]

Temporarily disabled retirement list: 2 [1%]

Active reservists: 46 [31%]

Veteran: 15 [10%]

Individual ready reserves: 10 [7%]

National Guard: 27 [18%]

Those ill since returning from Gulf: 136 [91%]

Those who had ill family members: 60 [40%]

Those who identified at least one investigational drug that they took:

75 [50%]

ANTHRAX--

Number of respondents who received anthrax: 68 [45%]

1 vaccination: 31 [46% of those who received anthrax]

2 vaccinations: 31 [46%]

3 vaccinations: 2 [ 3%]

Unknown number: 4 [ 6%]

Of those receiving anthrax vaccinations, those who:

received no oral or written information about the vaccine: 61 [90%]

were told they could not refuse it: 58 [85%]

described immediate side effects: 29 [43%]

Of the women receiving anthrax vaccination, those who received no

warning on risk if pregnant: 12/16 [75%]

BOTULINUM TOXOID--

Number of respondents who received botulinum toxoid: 17

1 vaccination: 10 [59% of those who received botulinum toxoid]

2 vaccinations: 3 [18%]

Unknown number: 4 [24%]

Of those receiving botulinum toxoid, those who:

received no oral or written information about the vaccine: 13 [76%]

were told they could not refuse it: 15 [88%]

described immediate side effects: 6 [35%]

Of the women receiving botulinum toxoid, those who received no warning

on risk if pregnant: 4/4 [100%]

PYRIDOSTIGMINE BROMIDE--

Number of respondents who took pyridostigmine bromide: 73 [49%]

Of those taking pyridostigmine bromide, those who:

received no oral or written information on side effects: 63 [86%]

were told they could not refuse it: 54 [74%]

described immediate side effects: 38 [52%]

did not comply and take drugs when they were supposed to: 14 [19%]

Of the women receiving pyridostigmine bromide, those who received no

warning on risk if pregnant: 14/18 [78%]

OTHER SURVEY INFORMATION--

Number of respondents who received a vaccination but did not know what

it was: 25 [17%]

Number of respondents who received a drug but did not know what it was:

28 [19%]

Number of respondents who have not received any information following

the Persian Gulf War concerning investigational drugs from either VA or

DOD: 128 [85%]

Concerning medical records:

Medical record is incomplete/inaccurate: 48 [32%]

Medical record [part or all] is missing/lost: 28 [19%]

 

25 MOST COMMON SYMPTOMS REPORTED

[number of respondents reporting]

Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

Skin problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

rashes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

Memory loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

blackouts, forgets where they are . . . . . . . . . . . . . . . . . . 5

Joint pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

Headaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

Personality changes . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Diarrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Muscle pain, weakness, spasms, tremors . . . . . . . . . . . . . . . . 29

Pain [back, shoulder, neck, etc] . . . . . . . . . . . . . . . . . . . 28

Trouble with vision . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Shortness of breath . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Sleep disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Hair loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Numbness [hands, fingers, feet] . . . . . . . . . . . . . . . . . . . . 19

Dental problems/bleeding gums . . . . . . . . . . . . . . . . . . . . . 18

Reproductive problems . . . . . . . . . . . . . . . . . . . . . . . . . 18

Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Sores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Chest problems [pain] . . . . . . . . . . . . . . . . . . . . . . . . . 12

Abdominal/stomach pain . . . . . . . . . . . . . . . . . . . . . . . . 12

Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Nausea/vomiting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Dizziness/staggering . . . . . . . . . . . . . . . . . . . . . . . . . 10

Sinus, nasal discharge . . . . . . . . . . . . . . . . . . . . . . . . . 9

Sensitivity to light, smell, noise . . . . . . . . . . . . . . . . . . . 9

Children born with birth defects . . . . . . . . . . . . . . . . . . . . 7

Partners with reproductive problems . . . . . . . . . . . . . . . . . . 16

NOTES

1. Veterans at Risk: The Health Effects of Mustard Gas and Lewisite,

Pechura, C.M. & Rall, D.P. (Eds.) Institute of Medicine, National

Academy Press, Washington, DC, 1993, p. 65.

2. In a survey of 150 Persian Gulf War veterans conducted by Committee

staff, 15 of 17 military personnel receiving botulinum toxoid in the

Gulf war were told they could not refuse the vaccination; 54 of 73

military personnel receiving pyridostigmine were told they could not

refuse the drug.

3. Veterans at Risk, op. cit., p. 36.

4. Testimony of Deanne Siemer, general counsel, Department of Defense,

hearing before the Subcommittee on Health and Scientific Research,

Committee on Human Resources, U.S. Senate, "Human Testing by the CIA,

1977," September 20-21, 1977, pp. 157-168.

5. Testimony of Sidney Gottlieb, M.D., former CIA agent, hearing before

the Subcommittee on Health and Scientific Research, Committee on Human

Resources, U.S. Senate, "Human Drug Testing by the CIA, 1977,"

September 20-21, 1977, pp. 169-217.

6. The Nuremberg Code, from Trials of War Criminals before the Nuremberg

Military Tribunals, U.S. Government Printing Office, Washington, DC,

1948.

7. 55 Federal Register 52,814-52,817 (December 21, 1990), "Informed

Consent for Human Drugs and Biologics: Determinations that Informed

Consent is Not Feasible."

8. Declaration of Helsinki, in European and Nordic Regulations and

Guidelines for Good Clinical Practice, Pharmaco Dynamics Research,

Inc., July 1990.

The Declaration of Helsinki was amended at the Twenty-Ninth World

Medical Assembly held in Tokyo, Japan, in 1975, the Thirty-Fifth World

Medical Assembly held in Venice, Italy, in 1983, and the Forty-First

World Medical Assembly held in Hong Kong in 1989.

9. Declaration of Helsinki, World Medical Association, in Biomedical

Ethics, Third Edition, Mappes, T.A. & Zembaty, J.S., McGraw-Hill, Inc.,

1991, pp. 211-213.

10. 56 Federal Register 28,002-28,032 (June 18, 1991), "Federal Policy for

the Protection of Human Subjects."

11. "Research Involving Human Subjects," statement of Robyn Y. Nishimi,

Ph.D., Office of Technology Assessment, hearing before the Subcommittee

on Energy, Committee on Science, Space, and Technology, U.S. House of

Representatives, "Human Radiation, Experimentation, and Gene Therapy,"

February 10, 1994.

12. 45 CFR 46 (Public Welfare), subparts B,C, and D, revised October 1,

1991.

13. 10 U.S.C. (Armed Forces) and 32 U.S.C. 980 (National Guard) put limits

on the use of humans as experimental subjects.

14. Veterans at Risk, op. cit., pp. 3-4, 6-8, 50-52, 224-226.

15. Ibid., p. 65.

16. Ibid., p. 7.

17. 59 Federal Register 41,497-42,500 (August 18, 1994), "Claims Based on

Chronic Effects of Exposure to Vesicant Agents."

18. Gene Wars, Military Control Over the New Genetic Technologies, Piller,

C. & Yamamoto, K.R., Beech Tree Books, William Morrow, New York, 1988,

pp 44-45, 53.

19. Ibid.

20. Ibid.

21. At least one Seventh-Day Adventist Church has held reunions of those

human subjects who participated in Operation Whitecoat. (Phone

interview by Committee staff with Dr. Frank Damazo, Frederick, MD,

March 21, 1994.)

22. Hearing before the Subcommittee on Conservation and Natural Resources,

Committee on Government Operations, U.S. House of Representatives,

"Environmental Dangers of Open-Air Testing of Lethal Chemicals," May

20-21, 1969.

23. Ibid., pp. 6-7.

24. Testimony of Dr. D.A. Osguthorpe, veterinarian and consultant to Utah

State Department of Agriculture, hearing before the Subcommittee on

Conservation and Natural Resources, Committee on Government Operations,

U.S. House of Representatives, "Environmental Dangers of Open-Air

Testing of Lethal Chemicals," May 20-21, 1969, pp 63-66.

25. Ibid., pp. 64-65.

26. Testimony of Hon. Richard D. McCarthy, a Representative in Congress

from the State of New York, hearing before the Subcommittee on

Conservation and Natural Resources, Committee on Government Operations,

U.S. House of Representatives, "Environmental Dangers of Open-Air

Testing of Lethal Chemicals," May 20-21, 1969, pp 6-7.

27. Cole, L.A., "Risk and biological defense program," Physicians for

Social Responsibility Quarterly, Vol 2, No. 1, March 1992, pp. 40-50.

28. Compilation of Local Fallout Data From Test Detonations 1945-1962,

extracted From DASA 1251, Vol I-Oceanic U.S. Tests, Contract No. DNA

001- 79-C-0081, May 1, 1979, sponsored by the Defense Nuclear Agency.

29. Ibid.

30. Secret document, Department of Defense, Research and Development Board,

Committee on Medical Sciences, Joint Panel on the Medical Aspects of

Atomic Warfare, 8th Meeting, Washington, DC, February 24, 1951.

31. "Health Effects of Exposure to Low Levels of Ionizing Radiation," BEIR

V, National Research Council, National Academy Press, Washington, DC,

1990.

32. Letter from Hon. Jesse Brown, Secretary of Veterans Affairs, to Sen.

John D. Rockefeller IV, Chair, Senate Committee on Veterans' Affairs,

May 31, 1994.

33. News release, Office of Public Affairs, Department of Veterans Affairs,

Washington, DC, October 11, 1994.

34. "Nuclear Health and Safety, Examples of Post World War II Radiation

Releases at U.S. Nuclear Sites," U.S. General Accounting Office,

November 1993, GAO/RCED-94-51FS.

35. Information from the Office of the Assistant Secretary for

Congressional Affairs, Department of Veterans Affairs, received at the

Senate Committee on Veterans' Affairs, September 21, 1994; in Committee

files.

36. Letter from Hon. Jesse Brown, Secretary of Veterans Affairs, to Sen.

John D. Rockefeller IV, Chair, U.S. Senate Committee on Veterans'

Affairs, May 26, 1994.

37. Gene Wars, op. cit., pp 50-51.

38. Statement of David Gries, Director, Center for the Study of Human

Intelligence, CIA, hearing before the Subcommittee on Administrative

Law and Governmental Relations, Committee on the Judiciary, U.S. House

of Representatives, "Government-Sponsored Tests on Humans and Possible

Compensation for People Harmed in the Tests," February 2, 1994.

39. Summary of testimony, Lloyd B. Gamble, LSD test subject, hearing before

the Subcommittee on Administrative Law and Governmental Relations,

Committee on the Judiciary, U.S. House of Representatives, "Government-

Sponsored Tests on Humans and Possible Compensation for People Harmed

in the Tests," February 2, 1994.

40. Ibid.

41. Testimony of Sidney Gottlieb, M.D., former CIA agent, before the

Subcommittee on Health and Scientific Research, Committee on Human

Resources, U.S. Senate, "Human Drug Testing by the CIA, 1977,"

September 20-21, 1977, p. 169. Actual wording is "convert means," which

we took to mean "covert means."

42. Ibid., pp. 169-217.

43. 55 Federal Register 52,814-52,817 (December 21, 1990).

44. Sidell, F.R., "Clinical Considerations in Nerve Agent Intoxication,"

Chemical Warfare Agents, Somani, S.M. (Ed.), Academic Press, Inc.,

1992, pp. 155-194.

45. Ibid.

46. Ibid.

47. Ibid.

48. Ibid.

49. Das Gupta, S., Bass, K.N., Warnick, J.E. "Interaction of reversible and

irreversible cholinesterase inhibitors on the monosynaptic reflex in

neonatal rats," Toxicology and Applied Pharmacology, Vol. 99, 1989, pp.

28- 36.

50. 55 Federal Register 52,814-52,817 (December 21, 1990).

51. Drachman, D.B. "Medical Progress, review article: Myasthenia gravis,"

New England Journal of Medicine, Vol. 330, No. 25, June 23, 1994, pp.

1797- 1810.

52. Scadding, G.K., Havard, C.W.H., Lange, M.J., & Domb, I. "The long term

experience of thymectomy for myasthenia gravis," Journal of Neurology,

Neurosurgery, and Psychiatry, Vol. 48, 1985, pp. 401-406.

53. Wacks, I., Oster, J.R., Perez, G.O., & Kett, D.H. "Spurious

hyperchloremia and hyperbicarbonatemia in a patient receiving

pyridostigmine bromide therapy for myasthenia gravis," American Journal

of Kidney Diseases, Vol. XVI, No. 1, July 1990, pp. 76-79.

54. Ibid.

55. Mestinon is the brand name for one form of pyridostigmine bromide

available in the United States.

56. Minutes of meeting of the Informed Consent Waiver Review Group (ICWRG),

Food and Drug Administration, December 31, 1990.

57. Ellis, R.J. Immunobiologic agents and drugs available from the Centers

for Disease Control: Descriptions, recommendations, adverse reactions,

and serologic response. Third Edition. Centers for Disease Control,

Public Health Service, U.S. Department of Health and Human Services,

Atlanta, GA, March 1982.

58. Middlebrook, J.L. "Contributions of the U.S. Army to Botulinum Toxin

Research," Botulinum and Tetanus Neurotoxins, Das Gupta, B.R., (Ed.),

Plenum Press, New York, 1993, pp. 515-519.

59. Informational material for the use of pentavalent (ABCDE) botulinum

toxoid aluminum phosphate adsorbed, Protocol #392, Centers for Disease

Control, Public Health Service, U.S. Department of Health and Human

Services, May 1992.

60. Review by Ann Sutton to the IND record, November 14, 1990; in Committee

files.

61. Informational material for the use of anthrax vaccine adsorbed,

Michigan Department of Public Health, U.S. License No. 99, 1978.

62. Friedlander, A.M., Welkos, S.L., Pitt, M.L.M., et al. "Postexposure

prophylaxis against experimental inhalation anthrax," Journal of

Infectious Diseases, Vol. 167, 1993, pp. 1239-1242.

63. Anthrax vaccine adsorbed, package insert, Michigan Department of Public

Health, Lansing, MI, 1978.

64. "Summary of the issues impacting upon the health of Persian Gulf War

veterans," Version 1.1, March 3, 1994.

65. "Human Experimentation, An Overview on Cold War Era Programs," U.S.

General Accounting Office, September 28, 1994, GAO/T-NSIAD-94-266.

66. Ibid.

67. Veterans at Risk, op. cit., pp. 7-8.

68. Statement of Rudolph R. Mills, hearing before the Committee on

Veterans' Affairs, U.S. Senate, "Is Military Research Hazardous to

Veterans' Health? Lessons from World War II, the Persian Gulf War, and

Today," May 6, 1994; hereinafter referred to as Hearing, May 6, 1994.

69. Ibid.

70. Hearing, May 6, 1994; John T. Harrison, written statement submitted for

the record.

71. Although the study was published in the Journal of the American Medical

Association, these results were not reported in the published article.

They are reported in an unpublished report, Survey #1, Food and Drug

Administration IND 23,509, Operation Desert Storm/Shield, May 27, 1992.

72. The Nuremberg Code, op. cit.

73. "Annas, G.J. & Grodin, M.A. "The Nazi Doctors and the Nuremberg Code,"

Human Rights in Human Experimentation, Oxford University Press, 1992, p

152.

74. Hearing, May 6, 1994; Nathan J. Schnurman, written statement submitted

for the record.

75. Testimony of Nathan Schnurman, WWII veteran, mustard gas test subject,

hearing before the Subcommittee on Administrative Law and Governmental

Relations, Committee on the Judiciary, U.S. House of Representatives,

"Government-Sponsored Tests on Humans and Possible Compensation for

People Harmed in the Tests," February 2, 1994.

76. Hearing, May 6, 1994; John William Allen, written statement submitted

for the record.

77. Pyridostigmine is approved by the FDA at a one-time dosage of 15 mg to

reverse the effects of certain drugs given during anesthesia.

78. 55 Federal Register 52,814-52,817 (December 21, 1990).

79. Memorandum for Record, August 30, 1990, submitted by Craig R. Lehmann,

Lt. Col., USAF, BSC; in Committee files.

80. FDA memorandum from Richard Klein and Ann Graham to Stuart Nightingale,

September 7, 1990; in Committee files.

81. Draft of minutes, meeting between officials of DOD and FDA, December

31, 1990, provided by FDA to Committee; in Committee files.

82. Ibid.

83. 55 Federal Register 52,814-52,817 (December 21, 1990).

84. Letter in Committee files.

85. Letter from Enrique Mendez, Jr., M.D., to David Kessler, M.D.,

Commissioner, Food and Drug Administration, March 15, 1991; in

Committee files.

86. Survey #1, Food and Drug Administration IND 23,509, Operation Desert

Storm/Shield, May 27, 1992.

87. Response to Committee survey completed by Carol Picou, Persian Gulf War

nurse; in Committee files.

88. Hearing, May 6, 1994; statement of Neil Tetzlaff, Persian Gulf War

veteran.

89. Memoranda describing phone conversations with journalists are in

Committee files.

90. Letters, summaries of phone conversations, and supporting documents are

in Committee files. These include an "Aircrew Symptoms Checklist on AF

Form 1666 (TEST) FEB 86, which instructs the pilots to "[t]ake one (1)

pyridostigmine bromide tablet (30 mg) every eight (8) hours over a 24

hour period."

91. One of the men has provided records of these studies to the Committee;

although the records specify that all pilots participating in the study

were removed from flight status and given informed consent about the

risks of pyridostigmine, those records are not consistent with the

descriptions of the study provided by the pilots who contacted the

Committee. Moreover, the records themselves do not include an informed

consent form or information about the risks of pyridostigmine.

92. Letter and medical records of Craig Crane are in Committee files.

93. Hearing, May 6, 1994; statement of Dr. Edward Martin, Acting Principal

Assistant Secretary of Defense for Health Affairs.

94. Letter from John M. Bachkosky, Deputy Director, Office of the Director

of Defense Research and Engineering, U.S. Department of Defense, to

Sen. John D. Rockefeller IV, Chair, Senate Committee on Veterans'

Affairs, May 19, 1994.

95. Letter from John Deutch, Deputy Secretary of Defense, to Sen. John D.

Rockefeller IV, Chair, Senate Committee on Veterans' Affairs, November

17, 1994; in Committee files.

96. Hearing, May 6, 1994; statement of Arthur Caplan, Ph.D. Dr. Caplan is

now Director of the Center of Biomedical Ethics at the University of

Pennsylvania.

97. Minutes, Meeting (July 27, 1992) on Finalizing Interim Rule on Waiver

of Informed Consent, signed July 28, 1992, by William H. Habig.

98. Koplovitz, I., Harris, L.W., Anderson, D.R., Lennox, W.J., & Stewart,

J.R. "Reduction by pyridostigmine pretreatment of the efficacy of

atropine and 2-PAM treatment of sarin and VX poisoning in rodents,"

Fundamental and Applied Toxicology, Vol. 18, 1992, pp. 102-106.

99. Sidell, F.R., op. cit.

100. "Summary of the issues impacting upon the health of the Persian Gulf

veterans," Version 1.1: March 3, 1994.

101. The actual data from this study was not provided to our Committee, and

apparently not provided to FDA either.

102. IND Amendment, Reference to IND# 28480, March 28, 1988, Letter from

Thomas H. Gray, Chief, Operational Unit Training Branch, Department of

the Air Force, to Mr. David Banks, Consumer Safety Officer, FDA.

103. Answers from the Department of Defense to followup questions submitted

by Sen. John D. Rockefeller IV, after the Committee's May 6, 1994,

hearing. The answers were received by the Committee on September 19,

1994.

104. A 150-pound man weighs 68 kg; 68 x 0.4 = 27 mg.

105. Sidell, F.R., op. cit.

106. The administration of additional atropine some hours after exposure to

chemical weapons might have been helpful, but it is not clear how many

soldiers would have been fortunate enough to receive medical treatment

within hours of combat, or how effective that later treatment would

have been.

107. Minutes of Meeting of the Informed Consent Waiver Review Group (ICWRG),

Food and Drug Administration, December 31, 1990.

108. In a letter dated July 27, 1992, FDA asked whether an IND should be

required to test the anthrax vaccine against aerosolized anthrax.

109. Department of Defense briefing with staff of the Senate Committee on

Veterans' Affairs, 414 Russell Senate Office Building, April 20, 1994.

110. A list of many of these studies is in Appendix A.

111. Barbarino, A., Corsello, S.M., Tofani, A., et al. "Sexual dimorphism of

pyridostigmine potentiation of growth hormone (GH)-releasing hormone-

induced GH release in humans," Journal of Clinical Endocrinology and

Metabolism, Vol. 73, No. 1, 1991, pp. 75-78.

112. O'Keane V. & Dinan, T.G. "Sex steroid priming effects on growth hormone

response to pyridostigmine throughout the menstrual cycle," Journal of

Clinical Endocrinology and Metabolism, Vol. 75, No. 1, 1992, pp. 11-14.

113. Ibid.

114. These instructions are consistent over time, and were included in many

different studies between 1985-90. Copies are in Committee files.

115. IND Amendment, 28 March 1988, IND 28,480.

116. IND Annual Report, 1987-1988, IND 23,509.

117. DAMD17-85-C-5133, Task Order 2, Kornhauser.

118. Israeli Journal of Medical Science, Vol. 27, 1991, pp. 659-663.

119. Keeler, J.R., Hurst, C.G., & Dunn, M.A. "Pyridostigmine used as a nerve

agent pretreatment under wartime conditions," Journal of the American

Medical Association, Vol. 266, No. 5, 1991, pp. 693-695.

120. Letter from the author of the published research, Dr. Thomas Tiedt, to

Sen. John D. Rockefeller IV, Chair, Senate Committee on Veterans'

Affairs, June 8, 1994; in Committee files.

121. Abbreviated Protocol, signed by Roger W. Wiley and Darcelle Delrie, and

other documents regarding "The Effects of Pyridostigmine Bromide on

Vision"; attached to a cover letter from Martha H. Myers, Acting Chief,

Human Use Review and Regulatory Affairs Office, Department of the Army,

August 15, 1990. Documents are in Committee files.

122. There are several studies of the effects of a one-time dose of

pyridostigmine on growth hormone in women, but the conditions of these

studies, including fasting and use during one phase of the menstrual

cycle, were not relevant to use of pyridostigmine in the Gulf War.

123. to Protocol HURC #378," memorandum from William K. Prusaczyk, research

physiologist, October 23, 1989; in Committee files.

124. Sharabi, Y., Danon, Y., Berkenstadt, H., et al., "Survey of symptoms

following intake of pyridostigmine during the Persian Gulf War,"

Israeli Journal of Medical Science, Vol. 27, 1991, pp. 656-658.

125. Information amendment from the Department of the Army to FDA, IND

23509-pyridostigmine bromide-WR 270,710, May 27, 1992.

126. Keeler, J.R., et al., op. cit.

127. Ibid.

128. Barbarino, A., et al., op. cit.

129. All the men and women in the study were between 19-25 years old, were

free of other medications, and were fasting; the women were all in the

luteal phase of their menstrual cycle.

130. Although the DOD does plan to follow up on research on pyridostigmine

and DEET conducted by Dr. James Moss (previously with the Agricultural

Research Service, USDA) by conducting a study of rats, that research

has not yet been initiated. Dr. Moss' research is described in the next

section of this report.

131. M.A. & Stephenson, L.A. "Cardiovascular and thermoregulatory responses

to repeated anticholinesterase administration," Journal of Thermal

Biology, Vol. 17, No. 6, pp. 333-337.

132. Hearing, May 6, 1994; testimony of James Moss, Ph.D., researcher,

Agricultural Research Service, U.S. Department of Agriculture,

Gainesville, FL.

133. Additional information about his results are provided in Dr. Moss'

answers to Sen. Rockefeller's posthearing questions, included in the

transcript of the Committee's May 6, 1994, hearing, and in documents

provided by Dr. Moss which are in the Committee files.

134. "U.S. Chemical and Biological Warfare-related Dual Use Exports to Iraq

and Their Possible Impact of the Health Consequences of the Persian

Gulf War," a report of Sen. Donald W. Riegle, Jr., Chair, and Sen.

Alfonse M. D'Amato, ranking Republican member, U.S. Senate Committee on

Banking, Housing, and Urban Affairs, May 25, 1994.

135. List of pesticides procured during Desert Shield/Storm (acquired

through the Federal supply system), information submitted to the Senate

Committee on Veterans' Affairs, April 6, 1994, from the Department of

the Army, Office of the Surgeon General.

136. Hearing, May 6, 1994; document submitted for the record.

137. Correspondence between Secretary Espy and Senator Rockefeller are in

Committee files.

138. Hearing, May 6, 1994; document submitted for the record by Craig Crane.

139. Minutes of Meeting of the Informed Consent Waiver Review Group (ICWRG),

Food and Drug Administration, December 31, 1990.

140. BBIND 3723, Food and Drug Administration, memorandum from Lawrence A.

D'Hoostelaere on "General safety testing of botulinum toxoid," March 2,

1994.

141. Review by Ann Sutton, Vaccines and Allergenics, DBIND, Food and Drug

Administration, to the IND record, November 14, 1990.

142. Informational material for the use of pentavalent (ABCDE) botulinum

toxoid aluminum phosphate adsorbed, U.S. Department of Health and Human

Services, Centers for Disease Control, Atlanta, Georgia, Revised May

1982, protocol #392.

143. Briefing, Maj. Gen. Ron Blanck, Commanding General, Walter Reed Army

Hospital, to Committee staff, 414 Russell Senate Office Building,

Washington, DC, February 4, 1994.

144. Hearing, May 6, 1994, testimony of the Rev. Dr. Barry Walker, Persian

Gulf War veteran.

145. Army Regulation 70-25, "Research and Development, Use of Volunteers as

Subjects of Research," Department of the Army, Washington, DC, March

26, 1968.

146. Letter from Sara E. Lister, Assistant Secretary of the Army, to Sen.

John D. Rockefeller IV, Chair, Senate Committee on Veterans' Affairs,

June 15, 1994.

147. The two provisions described in this section are part of Public Law

103-446, the Veterans' Benefits Improvement Act of 1994.

148. Veterans at Risk, op. cit.

149. Veterans and Agent Orange, Health Effects of Herbicides Used in

Vietnam, Institute of Medicine, National Academy Press, Washington, DC,

1993.

150. News Release, Office of Public Affairs, Department of Veterans Affairs,

Washington, DC, June 13, 1994.

151. "Health Effects of Exposure to Low Levels of Ionizing Radiation," op.

cit.

152. Hearing, May 6, 1994; prepared statement of Robert J. Temple, M.D.,

Director, Office of Drug Evaluation, Center for Drug Evaluation and

Research, Food and Drug Administration.

153. Public Law 102-585, 706, November 4, 1992, Agreement with National

Academy of Sciences for Review of Health Consequences of Service during

the Persian Gulf War.

154. "It is likely that a great majority of ground personnel [in the Persian

Gulf] received at least one dose and probably up to the full 21 tablets

[of pyridostigmine] dispensed," National Institutes of Health

Technology Assessment Workshop, "The Persian Gulf Experience and

Health," final statement issued June 22, 1994, p. 10. The workshop was

held April 27-29, 1994.

155. News Release, Office of Public Affairs, Department of Veterans Affairs,

July 20, 1994.

156. B-257173, GAO letter to Senator John D. Rockefeller IV, Chair, Senate

Committee of Veterans' Affairs, on the location of veterans' service

medical records, May 4, 1994.

157. Hearing, May 6, 1994; testimony of Leonard A. Cole, Ph.D., professor,

Rutgers University.

158. Ibid.

159. San Francisco Chronicle, December 22, 1976, page 1.

160. Cole, L.A. Clouds of Secrecy, The Army's Germ Warfare Tests Over

Populated Areas, Rowman and Littlefield, 1988, pp. 75-104.

161. Hearing, May 6, 1994; testimony of Earl P. Davenport, veteran and

former employee, Dugway Proving Ground.

162. Memorandum of phone interview with Dr. Michael Vance, Good Samaritan

Hospital, Phoenix, AZ, March 21, 1994; in Committee files.

163. "UMA Seeks Health and Safety Controls at Dugway," Bulletin of the Utah

Medical Society, May 1992, Vol. 40, No. 5, p. 1; "UMA Joins Lawsuit

Against Army," Bulletin of the Utah Medical Society, June 1992, Vol.

40, No. 6, p. 1; in Committee files.

164. Hearing, May 6, 1994; testimony of Dr. Cole.

165. Ibid.

166. Phone interview, Patrick Casula, Office of Grants and Program Systems,

U.S. Department of Agriculture, October 12, 1994.

167. "Summary of Findings and Recommendations, Review of the Office of

Health and Environmental Research Program, Protection of Human Research

Subjects," Subcommittee of the Health and Environmental Research

Advisory Committee, U.S. Department of Energy, May 1994.

168. Annas, G.J. & Grodin, M.A. "The Nazi Doctors and the Nuremberg Code,"

Human Rights in Human Experimentation, Oxford University Press, 1992,

p. 209.

169. Ibid., pp. 212-214.

170. United States v. Stanley, 107 S. Ct. 3054 (1987), cited in "The Nazi

Doctors and the Nuremberg Code," Human Rights in Human Experimentation,

Annas, G.J. & Grodin, M.A., Oxford University Press, 1992, pp. 212-214.

171. Ibid.