The U.S.

Biological Warfare and Biological Defense Programs

Chapter 19

THE U.S. BIOLOGICAL WARFARE AND

BIOLOGICAL DEFENSE PROGRAMS
DAVID R. FRANZ, D.V.M., PH .D. *; CHERYL D. PARROTT†; AND ERNEST T. TAKAFUJI, M.D., M.P.H.‡

INTRODUCTION

A SECRET BIOLOGICAL WARFARE PROGRAM

The Secret Program Is Acknowledged
Field Testing in the United States

AN EXPANDED DEFENSE PROGRAM

A COMPREHENSIVE MEDICAL BIOLOGICAL DEFENSE PROGRAM

Safety in Research and Patient Care
A National Resource

SUMMARY

* Colonel, Veterinary Corps, U.S. Army; Commander, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick,
Maryland 21702-5011
† Formerly, Technical Writer, Public Affairs Office, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick,
Maryland 21702; currently, Biomedical Writer, Office of Communications, National Institute of Allergy and Infectious Diseases, Bethesda,
Maryland 20892
‡ Colonel, Medical Corps, U.S. Army; Commander, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington,
D. C. 20307-5100

425
Medical Aspects of Chemical and Biological Warfare

INTRODUCTION

Biological agents have been used in war for cen- against the United States and its military forces,
turies. After World War I, Major Leon Fox, Medical and to retaliate only if deterrence was unsuccess-
Corps, U.S. Army, prepared a lengthy report1 that ful. The program was characterized by an aggres-
concluded that biological warfare was no longer a sive offensive and defensive research and develop-
concern because of the development of modern ment effort that would be modified to one based
sanitary procedures. However, as he wrote, the on maintaining a strong defense against biological
Japanese were already developing an offensive bio- agents.
logical warfare program involving an extensive list When the biological warfare program was estab-
of biological agents, capable of causing diseases lished, the United States was fighting World War II
such as anthrax, tularemia, plague, botulinum, on two fronts. After the war ended, the Cold War
smallpox, glanders, and typhoid. developed and our security was still threatened. The
The United States conducted a second review of United States maintained an active offensive bio-
the potential of biological warfare during 1941 and logical warfare program until it unilaterally re-
1942 and implemented its program to develop bio- nounced the use of biological weapons in two Na-
logical weapons in 1943. The biological warfare pro- tional Security Memoranda in 1969 and 1970. The
gram of the United States was conducted under United States ratified the Biological Weapons Con-
military auspices and was characterized during its vention in 1975. Although capabilities of the world’s
early years by a high degree of secrecy and contro- military forces have changed significantly in the
versial testing programs. By the 1960s, U.S. scien- years following the disestablishment of the U.S. bio-
tists had clearly established that the development logical warfare program—and despite the Biologi-
of biological weapons was feasible and that their cal Weapons Convention—a biological warfare
use on the battlefield could be effective. threat still exists; therefore, the United States main-
The purpose of the U.S. program in the early tains a program for medical defense against biologi-
years was to deter the use of biological agents cal warfare agents.

A SECRET BIOLOGICAL WARFARE PROGRAM

In 1941, Secretary of War Henry L. Stimson asked American universities, including Harvard, Stanford,
the National Academy of Sciences to evaluate the and other top schools. This agency received con-
feasibility of biological warfare. The academy con- sultative advice from national scientific committees
cluded that biological warfare was feasible and rec- and organizations, including the National Academy
ommended that steps be taken to reduce U.S. vul- of Sciences and the National Research Council.
nerability and also to conduct research to explore The War Reserve Service also empowered the
the offensive potential of bacteriological weapons. U.S. Army’s Chemical Warfare Service to greatly ex-
In April 1942, Stimson recommended to President pand its efforts in regard to biological weapons. The
Franklin D. Roosevelt the creation of a civilian ad- army’s efforts were better funded than those of the
visory group that would coordinate governmental War Reserve Service: in 1942 and 1943, the Chemi-
and privately owned institutions in a biological cal Warfare Service received millions of dollars to
warfare effort.2,3 (What he did not tell Roosevelt was build research facilities. Several locations were se-
that the Army Chemical Warfare Service had be- lected for the army’s biological research, with the
gun its own biological warfare research in 1941.) main headquarters at Camp Detrick, Frederick,
The idea of biological weaponry was controver- Maryland, a small National Guard airfield (desig-
sial, since little was known about the predictability nated Fort Detrick in 1956). The army also made
or effectiveness of biological weapons in wartime. plans to build a manufacturing plant near Terre
President Roosevelt approved the plan in 1942, and Haute, Indiana, and built a 2,000-acre field test site
the War Reserve Service, headed by George W. on Horn Island in Pascagoula, Mississippi. It is
Merck, was established and attached to the Federal ironic that much of the United States’s biological
Security Agency, a New Deal agency of the Depart- warfare effort during World War II was in response
ment of Agriculture. The War Reserve Service to a perceived threat from Germany, when in fact
started out in mid 1942 with a budget of $200,000. the Japanese were much more actively building
Secret work began under Merck’s direction at 28 their biological warfare capability.2

426
 The U.S. Biological Warfare and Biological Defense Programs

In the spring of 1942, President Roosevelt and 400 kg of anthrax spores, which were to be used in
British Prime Minister Winston Churchill an- a specially designed fragmentation bomb.
nounced policies limiting the use of biological In January 1946, the War Department made pub-
weapons to retaliation only, closely paralleling pre- lic for the first time the fact that the United States
vious decisions, such as the Geneva Protocol of had been conducting biological warfare research
1925, on the limited use of chemical weapons. But and testing. The press release emphasized the high
these new policies did not prevent the United States priority placed on safety:
and Great Britain from beginning to amass arsenals
of biological weapons.4 By 1943, the research cen- In all work on biological warfare carried on in the
ter and pilot plant at Camp Detrick employed ap- United States, extreme care was taken to protect
proximately 3,800 military and 100 civilian person- the participating personnel from infection. Many
nel. In 1944, Dugway Proving Ground, Utah, was new techniques were devised to prevent infection
and proved highly successful. Hospitals and dis-
established to replace the Mississippi site, and the
pensaries were maintained at all installations,
production plant was constructed near Terre Haute, staffed with both Army and Navy personnel and
Indiana.2 were equipped to treat accidental infections. As the
The United States exchanged information with result of the extraordinary precautions taken, there
Great Britain and Canada, two other nations con- occurred only sixty cases of proven infection caused
cerned about the biological warfare threat, but the by accidental exposure to virulent biological war-
general public was unaware of a biological warfare fare agents which required treatment. Fifty-two of
program in the United States until 4 months after these recovered completely; of the eight cases re-
the war was over. During World War II, the United maining, all were recovering satisfactorily. There
were, in addition to the sixty proven cases, 159 ac-
States worked primarily on anthrax and botulism;
cidental exposures to agents of unknown concen-
however, brucellosis, psittacosis, tularemia, and trations. All but one of these received prompt treat-
glanders were also studied. There was also consid- ment and did not develop any infection. In one
erable work on agents for use against plants, and instance, the individual did not report exposure,
records show that there were plans drawn up to developed the disease, but recovered after treat-
decimate Japan’s rice crops.2 ment. 3(vol 1, p1-4)
At the end of World War II, construction and test-
ing slowed to a stop, and the effort on biological Mr. Merck, the head of the War Reserve Service,
warfare development was largely limited to re- in his final report6 to the secretary of war noted that
search. The production plant in Indiana was sold although remarkable achievements had been made,
to the Charles A. Pfizer Company for commercial the potential of biological warfare had by no means
use. Although the highly classified program was been completely measured. He recommended that
initially defensive, and closely tied with the chemi- the program be continued on a sufficient scale to
cal weapons program, research continued on devel- provide an adequate defense.
oping an independent retaliatory capability using In 1948, the Research and Development Board
various disease agents. (then under the secretary of defense), which had
been given the responsibility to supervise the gov-
The Secret Program Is Acknowledged ernmental research program, requested an evalua-
tion of biological agents as weapons of sabotage.
Since 1937, Japan had conducted a large biologi- The Committee on Biological Warfare was formed,
cal warfare program, including human testing, at and the Baldwin Report7 prepared by the commit-
its Unit 731 in Manchuria.5 After the war, the United tee stated that the United States was particularly
States granted amnesty to Japanese scientists who vulnerable to covert attack with biological agents.
had participated in the research; however, a condi- It also stated that the current research and devel-
tion of the amnesty was full disclosure of research opment program was “not now authorized to meet
information. Two scientists from Camp Detrick, Dr. the requirements necessary to prepare the defen-
Edwin Hill and Dr. Joseph Victor, went to Japan in sive measures against special [biological warfare]
1945 and interviewed 22 scientists. They learned operations.”7(p1)
that many of the classical biological warfare agents The Baldwin Report recommended7 that
had been studied, and that approximately 1,000
autopsies had been performed in Unit 731, most of • means be developed to detect and identify
these on humans who had been exposed to anthrax. biological warfare agents;
They also learned that the Japanese had stockpiled • methods be developed for decontamina-

427
Medical Aspects of Chemical and Biological Warfare

tion, protection, prophylaxis, and treat-

ment; and
• methods be assessed for dissemination of
biological agents, with emphasis on appli-
cation to special operations.

Specifically recommended were research programs,

such as the testing of “innocuous organisms”7(p7) in
ventilation systems, subway systems, and public
water supplies. This guidance influenced several
subsequent administrations over the next 20 years,
and the United States conducted a sequence of
highly classified scientific tests on unknowing
populations throughout the country, with agents
and materials believed to be nonpathogenic. In fact,
not until early 1977 was the extent of the military
biological weapons testing program publicly dis-
closed before Congress.3,4
The biological warfare research program in the
early 1940s and 1950s involved antipersonnel,
anticrop, and, for a brief period, antianimal stud-
ies.8 Field trials included open-air vulnerability test-
ing, and contamination of public water systems
with live organisms such as Serratia marcescens.
Covert programs were conducted by the Central In-
telligence Agency. Pathogenic organisms were also
Fig. 19-1. These workers are standing outside the “8-
tested in Florida and the Bahamas in the 1940s. Ball,” a 1-million-liter sphere used for testing static aero-
Chemical anticrop studies evaluated defoliation sols of biological agent preparations during the United
and crop destruction. Explosive munitions tests States’s offensive biological warfare program. The build-
with pathogens were begun in 1949. ing enclosing the 8-Ball and its supporting infrastructure
In 1950, the first open-air tests with biological were destroyed by fire in 1974. The sphere remains to-
simulants were conducted in various locales, one day as a historical monument at Fort Detrick, Frederick,
of which was off the coast of Norfolk, Virginia. This Maryland. Photograph: Public Affairs Office, Fort De-
was followed by limited zinc cadmium sulfide dis- trick, Frederick, Md. circa 1968.
persal tests in Minneapolis, Minnesota, and St.
Louis, Missouri, in 1953; and Bacillus subtilis var
niger dispersal in the New York City subway sys- During the early 1950s, Major General George E.
tem in 1966.3,4 The Special Operations Division at Armstrong, The U.S. Army Surgeon General (1951–
Camp Detrick conducted much of the research on 1955) became concerned about medical defense
possible methods of covert attack and sabotage, and issues. Lieutenant Colonel Abram S. Benenson,
many environmental studies—often without in- a medical officer from the Walter Reed Army Insti-
forming local or state governmental agencies or the tute of Research, was appointed medical liaison
general population. with the biological warfare laboratories at Fort De-
Between 1948 and 1950, several reviews were con- trick. A joint agreement was signed, and beginning
ducted by the Research Review Board of the biologi- in 1953, studies on medical defense against biologi-
cal, chemical, and radiological warfare programs. cal weapons were conducted cooperatively by the
Recommendations included the creation of a specific Chemical Corps and the U.S. Army Medical Depart-
biological warfare production facility, continued field ment. In 1954, a congressionally approved medical
tests with biological warfare agents and munitions, volunteer program, designated “Project Whitecoat,”
and expansion of the overall program. In 1949, an was established after a series of meetings with rep-
enclosed, 1-million-liter steel test sphere was built at resentatives of the General Conference of the Sev-
Camp Detrick, and biological warfare explosive mu- enth-Day Adventist Church and The Surgeon Gen-
nitions tests with agents were begun (Figure 19-1). eral, U.S. Army.

428
 The U.S. Biological Warfare and Biological Defense Programs

Field Testing in the United States logical warfare agents. While many of the efforts
involved military researchers, others from the Pub-
The Korean War, which began in June 1950, lic Health Service, other Federal departmental agen-
added justification for continuing the biological cies, and civilian scientific institutions were also
warfare program, when the possible entry of the involved in the research.
Soviet Union into the war was feared. Concerns The general public was uninformed of these on-
over the Soviet Union were justified, for the Soviet going studies, especially the environmental and
Union would pronounce in 1956 that chemical and open-air experiments that were being conducted.
biological weapons would, indeed, be used for mass A controversial environmental test occurred in 1951,
destruction in future wars. 9 In October 1950, the when army researchers deliberately exposed a dis-
secretary of defense approved continuation of the proportionate number of black citizens to the fun-
program, based largely on the Soviet threat and a gus Aspergillus fumigatus, to see if African Ameri-
belief that the North Korean and Chinese commu- cans were more susceptible to such infection, like
nists would use biological weapons.10 they were already known to be to coccidioi-
The first large-scale aerosol vulnerability test was domycosis (Coccidioides immitis). Some in the scien-
conducted in the San Francisco Bay area in Septem- tific community believed that such knowledge
ber 1950, using two species of bacteria (Bacillus would assist in preparing defenses against a more
globigii and Serratia marcescens) and fluorescent virulent form of this fungus. Similarly, in 1951, un-
particles. Various Bacillus species were used in suspecting workers at the Norfolk Supply Center,
many experiments because of their spore-forming Norfolk, Virginia, were exposed to crates contami-
capabilities and their similarities to Bacillus nated with A fumigatus spores.
anthracis. S marcescens was used because its red pig- Needless to say, there was a public outcry sev-
ment made it readily identifiable. What was unex- eral years later when much of this information was
pected was the increased number of cases of Serratia released, and the biological warfare research pro-
infections over the next few years in communities gram would be forever tainted as operating within
that had been sprayed earlier with the organisms.4 “clouds of secrecy.”4 The first lawsuit against the
The military considered the situations coinciden- U.S. government was filed by family members of
tal, but many civilian physicians believed them to an individual who had died, allegedly as a result
be directly related. Other limited-scale field of the San Francisco experiments in 1950. The court
tests with pathogenic organisms were conducted decided that the U.S. government could not be sued
at Dugway Proving Ground, Utah. Antianimal (under the Federal Tort Claims Act), since the deci-
studies were conducted at Eglin Air Force Base, sion to spray S marcescens was a part of national
Florida. defense planning. Several of the organisms (such
The biological warfare research facilities at Camp as S marcescens and A fumigatus), which were con-
Detrick were expanded, and a biological warfare sidered at one time to be innocuous, are now rec-
production facility was created at Pine Bluff Arse- ognized to cause infections in humans, on occasion.
nal, Arkansas, in 1951. The first limited, biological Immunocompromised or debilitated persons ap-
warfare retaliatory capability was achieved when pear to be at greatest risk. Early experiments con-
an anticrop bomb was developed, tested, and placed ducted with such organisms involving subjects or
in production for the U.S. Air Force. Anticrop–agent populations who were unaware of the ongoing ex-
production sites were carefully selected for safety periments may have posed a health risk to highly
with the coordination and approval of the U.S. De- susceptible persons.
partment of Agriculture. This marked the first During the two decades following the second
peacetime biological weapons production by the World War, laboratories for biological and chemi-
United States.11 cal warfare research continued to increase in
By 1954, the Pine Bluff laboratory produced Bru- size, and programs were expanded with a multi-
cella suis (the causative agent of brucellosis, also million dollar budget. The Fort Detrick research
called undulant fever) and Francisella tularensis (tu- program was complemented by contractual civil-
laremia, or rabbit fever). Hardware for antiperson- ian institutions; for example, Ohio State University
nel biological cluster bombs was delivered to Pine was tasked with making vaccines. Human volun-
Bluff for filling with Brucella suis to support air force teers were used in many of the studies. Vaccines
requirements. By 1955, the accelerated program was against diseases, such as Q fever and tularemia,
producing stocks of B suis and F tularensis as bio- were developed.

429
Medical Aspects of Chemical and Biological Warfare

AN EXPANDED DEFENSE PROGRAM

With expansion of the biological warfare retalia- The U.S. Army Chemical Corps was given the
tory program, the scope of the defensive program responsibility to conduct biological warfare re-
was nearly doubled. Data were obtained on person- search for all of the services.3 In 1962, the responsi-
nel protection, decontamination, and immuniza- bility for the testing of promising biological war-
tion. Early detection research produced prototype fare agents was given to a separate Testing and
alarms for use on the battlefield, but progress was Evaluation Command. Depending on the particu-
slow, apparently limited by technology. lar program, different test centers were used, such
The U.S. Army Medical Unit, under the direction as the Deseret Test Center at Fort Douglas, Utah,
of The U.S. Army Surgeon General, began formal the headquarters for the new biological and chemi-
operations in 1956. One of the Unit’s first missions cal warfare testing organization. In response to in-
was to manage all aspects of Project CD-22, the ex- creasing concerns over public safety and the envi-
posure of volunteers to aerosols containing a patho- ronment, the Testing and Development Command
genic strain of Coxiella burnetii, the etiologic agent implemented a complex system of approval of its
of Q fever. The volunteers were closely monitored research programs that included the U.S. Army
and antibiotic therapy was administered when ap- Chief of Staff, the Joint Chiefs of Staff, the Secre-
propriate. All volunteers recovered from Q fever tary of Defense, and the President of the United
with no adverse aftereffects. One year later, the Unit States.
submitted to the U.S. Food and Drug Administra- During the last 10 years of the offensive research
tion an Investigational New Drug application for a and development program, many scientific ad-
Q fever vaccine. vances were made that proved that biological war-
The United States was now accumulating invalu- fare was clearly feasible, although dependent on
able data on personnel protection, decontamination, careful planning, especially with regard to meteo-
and immunization; and, in the offensive program, rological conditions. Large-scale fermentation, pu-
on the potential for mosquitoes to be used as bio- rification, concentration, stabilization, drying, and
logical vectors. A new Department of Defense Bio- weaponization of pathogenic microorganisms could
logical and Chemical Defense Planning Board was be done safely. Furthermore, modern principles of
created in 1960 to establish program priorities and biosafety and containment were established at Fort
objectives. Preventive approaches toward infections Detrick that have greatly facilitated biomedical re-
of all kinds were funded under the auspices of bio- search; still today, these are copied throughout the
logical warfare. As concern increased over the bio- world. Arnold G. Wedum, M.D., Ph.D., a civilian
logical warfare threat during the Cold War, so did scientist who was Director of Industrial Health and
the budget for the program: to $38 million by fiscal Safety at Fort Detrick, was the leader in the devel-
year 1966. opment of containment facilities (Figure 19-2).

Fig. 19-2. Technicians in Class III hood lines

are seen working with preparations of bio-
logical agents at Fort Detrick, Frederick,
Maryland, circa 1968, when the United
States had an offensive biological warfare
program. The completely enclosed hood
lines provide total containment of hazard-
ous organisms. Hoods were maintained at
a pressure negative to ambient by con-
stantly drawing air out through high-effi-
ciency particulate air (HEPA) filters. Work-
ers wore heavy rubber gloves to access
material inside the hoods. Photograph:
Public Affairs Office, Fort Detrick, Freder-
ick, Md.

430
 The U.S. Biological Warfare and Biological Defense Programs

During the 1960s, the country experienced a ing to $11.8 million by fiscal year 1973. Although
philosophical change, and attention was now di- the offensive program had been stopped in 1969,
rected toward biological agents that could incapaci- both offensive and defensive programs continued
tate but not kill. In 1964, research programs in- to be defended. John S. Foster, Director of Defense
volved staphylococcal enterotoxins capable of Research and Engineering, responded to a query by
causing food poisoning. Research initiatives also in- Congressman Richard D. McCarthy:
cluded new therapy and prophylaxis. Pathogens
studied included the agents causing anthrax, glan- It is the policy of the U.S. to develop and maintain
ders, brucellosis, melioidosis, plague, psittacosis, a defensive chemical-biological (CB) capability so
Venezuelan equine encephalitis, Q fever, coc- that our military forces could operate for some pe-
cidioidomycosis, and a variety of plant and animal riod of time in a toxic environment, if necessary;
to develop and maintain a limited offensive capa-
pathogens.10,12
bility in order to deter all use of CB weapons by
Particular attention was directed at chemical and the threat of retaliation in kind; and to continue a
biological detectors during the 1960s. The first de- program of research and development in this area
vices were primitive field alarms to detect chemi- to minimize the possibility of technological
cals. Although the development of sensitive biologi- surprise.13(pp153–154)
cal warfare agent detectors was at a standstill, two
systems were, nonetheless, investigated. The first On 25 November 1969, President Nixon visited
was a monitor that detected increases in the num- Fort Detrick to announce a new policy on biologi-
ber of particles sized 1 to 5 µm in diameter, based cal warfare. In two National Security Memo-
on the assumption that a biological agent attack randa,14,15 the U.S. government renounced all devel-
would include airborne particles of this size. The opment, production, and stockpiling of biological
second system involved the selective staining of weapons and declared its intent to maintain only
particles collected from the air. Both systems lacked small research quantities of biological agents, such
enough specificity and sensitivity to be of any prac- as are necessary for the development of vaccines,
tical use.8 drugs, and diagnostics.
But in 1966, a research effort directed at detect- Ground was broken in 1967 for construction of a
ing the presence of adenosine triphosphate (a new, modern laboratory building at Fort Detrick.
chemical found only in living organisms) was be- The building would open in phases during 1971 and
gun. By using a fluorescent material found in fire- 1972. With the disestablishment of the biological
flies, preliminary studies indicated that it was pos- warfare laboratories, the name of the U.S. Army
sible to detect the presence of a biological agent in Medical Unit, which was to have been housed in
the atmosphere. The important effort to find a sat- the new laboratories, was formally changed to U.S.
isfactory detection system continues today, for Army Medical Research Institute of Infectious
timely detection of a biological attack would allow Diseases (USAMRIID) in 1969. The institute’s new
the attacked force to use its protective masks effec- mission was stated in General Order 137, 10 No-
tively, and identification of the agent would allow vember 1971 (since superseded):
any pretreatment regimens to be instituted.
The army also experimented with and developed Conducts studies related to medical defensive as-
highly effective barrier protective measures against pects of biological agents of military importance
both chemical and biological agents. Special imper- and develops appropriate biological protective
vious tents and personal protective equipment were measures, diagnostic procedures and therapeutic
methods.16
developed, including individual gas masks even for
military dogs.
The emphasis shifted away from offensive weap-
During the late 1960s, funding for the biological
ons to development of vaccines, diagnostic systems,
warfare program decreased temporarily, to make up
personal protection, chemoprophylaxis, and rapid
for the accelerating costs of the Vietnam War. The
detection systems.
budget for fiscal year 1969 was $31 million, decreas-

A COMPREHENSIVE MEDICAL BIOLOGICAL DEFENSE PROGRAM

In response to President Nixon’s decision in 1969, laboratory at Pine Bluff Arsenal, Arkansas, was con-
all antipersonnel biological warfare stocks were de- verted to a toxicological research laboratory, and
stroyed between 10 May 1971 and 1 May 1972. The was no longer under the direction or control of the

431
Medical Aspects of Chemical and Biological Warfare

Department of Defense. Biological anticrop agents wear filtered positive-pressure total body suits,
were destroyed by February 1973. Biological war- which isolate the worker from the internal air of
fare demilitarization continued through the 1970s, the laboratory. BL-3 laboratories have a similar de-
with input provided by the U.S. Department of sign, but do not require that personnel wear posi-
Health, Education and Welfare; Department of the tive-pressure suits. Workers in BL-3 suites are pro-
Interior; Department of Agriculture; and the Envi- tected immunologically by vaccines. U.S. govern-
ronmental Protection Agency. Fort Detrick and mental standards provide guidance as to which or-
other installations involved in the biological war- ganisms may be handled under various contain-
fare program took on new identities, and their mis- ment levels in laboratories such as USAMRIID.17
sions were changed to biological defense and the The unique facilities available at USAMRIID also
development of medical countermeasures. The nec- include a 16-bed clinical research ward capable of
essary containment capability, Biosafety Levels 3 BL-3 containment, and a 2-bed patient care isola-
and 4 (BL-3 and BL-4, which are discussed below) tion suite where ICU-level care can be provided
continued to be maintained at USAMRIID. under BL-4 containment. Here, healthcare person-
In 1984, the Department of Defense requested nel wear the same positive-pressure suits as are
funds for the construction of another biological worn in BL-4 research laboratories. The level of
aerosol test facility in Utah. The proposal submit- patient isolation required depends on the infecting
ted by the army called for BL-4 containment, al- organism and the risk to healthcare providers. Pa-
though maintaining that the BL-4 inclusion was tient care can be provided at BL-4. There is no pa-
based on a possible need in the future and not on a tient-care category analogous to BL-3; humans who
current research effort. The proposal was not well are ill as a result of exposure to BL-3 agents are cared
received in Utah, where many citizens and govern- for in an ordinary hospital room with barrier nurs-
ment officials still recalled the secretive projects of ing procedures.
the military: the areas on Dugway Proving Ground USAMRIID guidelines have been prepared to
still contaminated with anthrax spores, and the determine which level of containment should be
well-publicized accidental chemical poisoning of a employed for individual patients who require BL-4
flock of sheep in Skull Valley, Utah, in March 1968.10 isolation or barrier nursing care (Exhibit 19-1). Staff
Questions arose over the safety of the employees augmentation for BL-4 critical care expertise comes
and the surrounding communities, and a sugges- from Walter Reed Army Medical Center, Washing-
tion was even made to shift all biological defense ton, D.C., under an existing Memorandum of
research to a civilian agency, such as the National Agreement. Patients can be brought directly into the
Institutes of Health. The plan for a new facility was BL-4 suite from the outside through specialized
revised to utilize a Biosafety Level 3 (BL-3) facility, ports with unique patient-isolation equipment.
but not before congress had instituted more surveil- Finally, USAMRIID maintains a unique evacua-
lance, reporting, and control measures on the army tion capability called the Aeromedical Isolation
to ensure compliance with the Biological Weapons Team (AIT). Led by a physician and a registered
Convention of 1972. nurse, each of the two teams consists of eight vol-
unteers who train intensively to provide an evacu-
Safety in Research and Patient Care ation capability for casualties suspected of being in-
fected with highly transmissible, life-threatening
Currently, the medical biological defense re- BL-4 infectious diseases (eg, hemorrhagic fever vi-
search effort (part of the U.S. Army’s Biological ruses). The unit uses special adult-sized Vickers iso-
Defense Research Program [BDRP]) is concentrated lation units (Vickers Medical Containment Stretcher
at USAMRIID at Fort Detrick. The army maintains Transit Isolator, manufactured by Isolators Ltd.,
state-of-the-art containment laboratory facilities at Shropshire, U.K.) (Figure 19-3). These units are air-
USAMRIID, with more than 10,000 ft2 of BL-4 and craft transportable and isolate a patient placed in-
50,000 ft2 of BL-3 laboratory space. BL-4, the high- side from the external environment. The AIT can
est containment level, includes laboratory suites transport two patients simultaneously; obviously,
that are isolated by internal walls and protected by it is not designed for a mass casualty situation.
rigorous entry restrictions, air-locks, negative-pres- During the 1995 outbreak of Ebola fever in Zaire,
sure air-handling systems, and filtration of all out- the AIT remained on alert to evacuate any Ameri-
flow air through high-efficiency particulate air cans who might have become ill while working to
(HEPA) filters. Workers in BL-4 laboratories also control the disease in that country.

432
 The U.S. Biological Warfare and Biological Defense Programs

EXHIBIT 19-1
ISOLATION PROCEDURES FOR PATIENT CARE AT USAMRIID, BY DISEASE AGENT OR
TYPE OF EXPOSURE

Biosafety Level 4 (BL-4) isolation suite admission; care providers in positive-pressure protective suits
Ebola virus
Marburg virus
Crimean-Congo hemorrhagic fever virus
Variola (smallpox) and monkeypox viruses
A patient presumed to be a victim of biological agent attack until definitive diagnosis is made

Biosafety Level 4 (BL-4) isolation suite admission; barrier nursing procedures*

Yersinia pestis (pneumonic form) †
Lassa fever virus
Argentine hemorrhagic fever (Junin) virus
Bolivian hemorrhagic fever (Machupo) virus
Venezuelan hemorrhagic fever (Guanarito) virus

Normal hospital room; barrier nursing procedures* or secretion precautions, ‡ depending on the agent
Tick-borne encephalitis complex
Yellow fever virus §
Venezuelan equine encephalitis virus §
Rift Valley fever virus§
Chikungunya virus§
Dengue virus§
Brucella species
Vibrio cholerae
Bacillus anthracis (pulmonary or cutaneous forms)
Francisella tularensis (pulmonary form)
Yersinia pestis (bubonic or septicemic form)

Normal hospital room; no special precautions

Eastern equine encephalitis virus
Western equine encephalitis virus
Hemorrhagic fever with renal syndrome (Hantaan, Seoul, Puumala viruses)
Japanese encephalitis virus
Sandfly fever viruses
Coxiella burnetii (Q fever)
Chlamydia psittaci
Botulinum toxin
Staphylococcal enterotoxin B
Ricin toxin
Saxitoxin
Trichothecene mycotoxins

* Barrier nursing procedures: wearing gown, gloves, and surgical mask, but caring for patients in isolation suites.
†Pneumonic plague initially requires respiratory protection: full-face respirator or Racal hood (manufactured by Racal Health
and Safety, Inc, Frederick, Md).
‡ Secretion precautions: wearing gown and gloves; special handling of potentially infectious dressings, drainage, and/or
excreta.
§ The patient must be protected from potential arthropod vectors: windows should be screened and/or closed.
USAMRIID: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Md.

433
Medical Aspects of Chemical and Biological Warfare

Fig. 19-3. Members of the Aeromedical Iso-

lation Team (AIT) prepare to transfer a pa-
tient from a stretcher isolator into the
Biosafety Level 4 (BL-4) isolation suite at the
U.S. Army Medical Research Institute of In-
fectious Diseases, Fort Detrick, Frederick,
Maryland. The interior of the isolator is main-
tained at a pressure negative to the external
environment by a high-efficiency particu-
late air (HEPA) filtered blower. The isola-
tor can be attached directly to a transfer
port, visible on the external wall of the
building, to allow movement of the patient
into the suite without exposing the envi-
ronment to the patient. Team members are
seen wearing protective suits and positive-
pressure, HEPA-filtered Racal hoods (manu-
factured by Racal Health & Safety, Inc,
Frederick, Md). Photograph: Public Affairs
Office, Fort Detrick, Frederick, Md.

Some biological defense research also continues • antiviral drugs against multiple viral
at the U.S. Army Medical Research Institute of agents.
Chemical Defense, Edgewood Arsenal, Maryland,
and the Walter Reed Army Institute of Research, Some vaccines also have applicability for diseases
Washington, D. C. USAMRIID and these laborato- of domestic animals (eg, Rift Valley fever and Ven-
ries conduct basic research in support of the medi- ezuelan equine encephalitis). In addition, vaccines
cal component of the Biological Defense Research are provided to persons who may be occupation-
Program, which develops strategies, products, in- ally exposed to such agents (eg, laboratory work-
formation, procedures, and training for medical ers, entomologists, and veterinary personnel)
defense against biological warfare agents. The prod- throughout government, industry, and academe.
ucts include diagnostic reagents and procedures, USAMRIID also provides diagnostic and epide-
drugs, vaccines, toxoids, and antitoxins. Emphasis miological support to federal, state, and local agen-
is placed on protecting personnel before any poten- cies and foreign governments. Examples of assistance
tial exposure to the biological agent occurs.18 rendered to civilian health efforts by the former U.S.
Army Medical Research and Development Command
A National Resource (renamed the U.S. Army Medical Research and Ma-
teriel Command in October 1994) include
Since biological warfare agents are often etiologic
agents for naturally occurring diseases, the military • the massive immunization program insti-
research effort provides substantive benefits for ci- tuted during the Venezuelan equine en-
vilian populations also. Products produced or be- cephalitis outbreak in the Americas in 1971;
ing developed through military research include • the laboratory support provided to the U.S.
Public Health Service during the outbreak
• vaccines to prevent tularemia, Q fever, Rift of Legionnaire’s disease in Philadelphia,
Valley fever, Venezuelan equine encephali- Pennsylvania, in 1976;
tis, Eastern and Western equine encephali- • the management of patients suspected of
tis, chikungunya fever, Argentine hemor- having African viral hemorrhagic fever in
rhagic fever, the botulinum toxicoses, and Sweden during the 1980s;
anthrax;18,19 • international support during the outbreak
• antitoxins for diseases such as botulism; of Rift Valley fever in Mauritania in 1989;
• human immune globulin preparations (pas- • assistance with the outbreak of Ebola infec-
sive antibody protection) against various tions among monkeys imported to Reston,
bacteria and viruses; and Virginia, in 1990; and

434
 The U.S. Biological Warfare and Biological Defense Programs

• epidemiological and diagnostic support to in view of

the World Health Organization–Centers for
Disease Control and Prevention field team • evidence that some countries are not com-
that studied the Ebola outbreak in Zaire in plying with the Biological Weapons Con-
1995. vention;
• the difficulty of verifying compliance with
The current research effort combines new tech- the Convention;
nological advances, such as genetic engineering and • the potential use of biological warfare by
molecular modeling, applying them toward devel- terrorists;
opment of prevention and treatment of diseases of • the increased possibility of new threat
military significance. The program is conducted in agents based on advances in biotechnology;
full compliance with requirements set forth by the and
U.S. Food and Drug Administration, U.S. Public • the belief that a strong defense serves as a
Health Service, Nuclear Regulatory Commission, deterrent.
U.S. Department of Agriculture, Occupational
Safety and Health Administration, and Biological While some of the military’s biological defense
Weapons Convention.18 programs remain classified, based on world-
Even though the United States stopped all offen- wide threats and uncertainties, the medical Biologi-
sive biological warfare research in 1969, the Biologi- cal Defense Research Program is unclassified and con-
cal Defense Research Program must remain strong tinues to be an invaluable resource for the nation.

SUMMARY

Although biological agents have been used in actual agents disseminated over wide areas. A small
warfare for centuries to produce death or disease defensive effort paralleled the weapons develop-
in humans, animals, or plants, the United States did ment and production program.
not begin a biological warfare offensive program With the presidential decision in 1969 to halt of-
until 1941. It was concern about the Japanese bio- fensive biological weapons production, and the
logical warfare threat that motivated the United agreement in 1972 at the international Biological
States to begin to develop biological weapons. Dur- Weapons Convention never to develop, produce,
ing the next 28 years, the United States initiative stockpile, or retain biological agents or toxins,
evolved into an effective, military-driven research the program became entirely defensive, with medi-
and acquisition program, shrouded in controversy cal and nonmedical components. The U.S. Biolog-
and secrecy. Most research and development was ical Defense Research Program exists today, con-
done at Fort Detrick, Maryland, while production ducting research to develop physical and medical
and testing occurred at Pine Bluff, Arkansas, and countermeasures to protect service members and
Dugway Proving Ground, Utah. Field testing was civilians from the threat of modern biological
done secretly and successfully with simulants and warfare.

REFERENCES

1. Fox LA. Bacterial warfare: The use of biologic agents in warfare. Milit Surg. 1933;72(3):189–207.

2. Bernstein BJ. The birth of the US biological-warfare program. Sci Am. 1987;256:116–121.

3. Department of the Army. Special Report to Congress. US Army Activity in the US Biological Warfare Programs,
1942–1977. Vols 1 and 2. Washington, DC: DA. 24 Feb 1977. Unclassified.

4. Cole LA. Clouds of Secrecy: The Army’s Germ Warfare Tests Over Populated Areas. Totowa, NJ: Rowman and
Littlefield; 1988.

5. Williams P, Wallace D. Unit 731: Japan’s Secret Biological Warfare in World War II. New York, NY: Free Press; 1989.

435
Medical Aspects of Chemical and Biological Warfare

6. Report to the Secretary of War by Mr. George W. Merck, Special Consultant for Biological Warfare, 3 Jan 1946.
Cited in: Department of the Army. Special Report to Congress. US Army Activity in the US Biological Warfare
Programs, 1942–1977. Vol 2, annex 1. Washington, DC: DA. 24 Feb 1977. Unclassified.

7. Baldwin IL. Special BW Operations. Washington, DC: The National Military Establishment Research and Devel-
opment Board; 5 Oct 1948. Memorandum for Executive Secretary, Research and Development Board. Unclassified.

8. Hersh SM. Chemical and Biological Warfare: America’s Hidden Arsenal. Indianapolis, Ind: Bobbs-Merrill; 1968.

9. Geissler E, ed. Biological and Toxin Weapons Today (Stockholm International Peace Research Institute). Oxford,
England: Oxford University Press; 1986.

10. Harris R, Paxman J. A Higher Form of Killing: The Secret of Chemical and Biological Warfare. New York, NY: Hill
and Wang; 1982.

11. Cowdrey AE. The Medics’ War. Washington DC: Center of Military History, US Army; 1987.

12. Stockholm International Peace Research Institute (SIPRI). The Rise of CB Weapons. Vol 1. In: The Problem of Chemical
and Biological Warfare. New York, NY: Humanities Press; 1971.

13. Foster JS, Director of Defense Research and Engineering, US Department of Defense. Letter dated 15 April
1965 to Honorable Richard D. McCarthy, US House of Representatives. Cited in: McCarthy RD. The Ultimate
Folly: War by Pestilence, Asphyxiation, and Defoliation. New York, NY: Alfred A. Knopf; 1969: 153–154.

14. Kissinger HA. N.S. Decision Memorandum 35. 25 November 1969.

15. Kissinger HA. N.S. Decision Memorandum 44. 20 February 1970.

16. Department of the Army. General Order 137. Washington, DC: Headquarters, DA; 10 November 1971.

17. Centers for Disease Control and Prevention. Biosafety in Microbiological and Biomedical Laboratories. 3rd ed. Wash-
ington, DC: US Department of Health and Human Services, Public Health Service, Centers for Disease Control
and Prevention. May 1993. HHS Publication (CDC) 93-8395.

18. Huxsoll DL, Parrott CD, Patrick WC III. Medicine in defense against biological warfare. JAMA. 1989;265:677–679.

19. Takafuji ET, Russell PK. Military immunizations: Past, present and future prospects. Infect Dis Clin North Am.
1990;4:143–157.

436