| INTRODUCTION
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“Gas! Gas!” This warning cry, so common
in World War I, almost became real to U.S. forces again as they prepared
to liberate Kuwait in late 1990. The threat of chemical, and even
biological, warfare was foremost in the minds of U.S. military personnel
during Operation Desert Shield, the preparation for the Persian Gulf
War. Iraq was known to have a large stockpile of chemical weapons and
had demonstrated during its conflict with Iran that it would use them.
It was not until after the Persian Gulf War that the U.N. Special
Commission on Iraq confirmed that Saddam Hussein also had biological
agents loaded in weapons. The chemical and biological threats were major
concerns to those in the military medical departments who would be
called on to care for poisoned or infected casualties, possibly in a
chemically contaminated environment. Fortunately the ground war of the
Persian Gulf War (Operation Desert Storm) was brief, and even more
fortunately, our adversary did not employ these weapons. |
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During the Arab–Israeli War (also called the Yom
Kippur War) of 1973, chemical weapons were not used. While processing captured
soldiers, however, Israeli troops found that the Egyptians carried personal
protective equipment, a decontamination kit containing items unfamiliar to U.S.
personnel, and an antidote with which we were also unfamiliar. This evidence
suggested that the Egyptians were prepared for a chemical battlefield, and the
components of the antidote suggested that they were prepared for the use of the
nerve agent soman. (The antidote was a mixture of three compounds: atropine,
benactyzine, and the oxime, TMB4.) The U.S. military soon issued the antidote to
U.S. troops, only to withdraw it about 5 years later.
In the mid to late 1970s, reports began to appear
that chemicals were being used against Hmong tribesmen in Laos. The Hmong had
been loyal to the United States and had served this country in many ways during
the Vietnam War; it was suggested that chemicals were being used against the
Hmong in retaliation. Investigations were conducted by U.S. State Department
personnel, by a medical team sent by The U.S. Army Surgeon General, and by
international groups. Little definitive evidence was discovered, primarily
because the alleged attacks took place deep in Laos. The victims took weeks to
travel to Thailand to be examined, and outsiders could not enter Laos to examine
the attack sites. The Hmong who reached Thailand provided graphic accounts of
attacks by sprays and bombs from airplanes and how these “smokes,” which
were of all colors, killed many in their villages. One member of the medical
team brought back a sample of a yellow substance on the outer (barklike) layers
of a bamboo culm (ie, stalk); the sample had been given to him by a Hmong, who
claimed that the material had killed many of his fellow villagers. This yellow
substance, along with samples from many other locations, later became known as
“yellow rain” (see Chapter
34, Trichothecene Mycotoxins, which discusses yellow rain in greater
detail).
Moreover, in the late 1970s and early 1980s,
allegations were made of chemical agent use against refugees fleeing the
barbaric conditions that existed in Kampuchea at that time.1 The
clinical response of the exposed humans did not fit what we understood about the
effects of classic chemical agents. Tearing and itching looked like the effects
of tear gas. Convulsions suggested nerve agents. But the occurrence of internal
hemorrhage and skin lesions could not be explained. Analysis of a leaf sample
collected in Kampuchea 24 hours after an attack implicated trichothecene
mycotoxins, a family of toxins produced by fungi but having characteristics more
like chemical than biological agents.
In August 1981, based on limited physical
evidence, the U.S. government announced that trichothecene mycotoxins had been
used but the findings were less than convincing to some in the scientific
community and the issue became extremely contentious. This controversy was never
totally resolved, and the question of which, if any, agents were used against
civilians was not answered. If mycotoxins were, in fact, used it was the first
recorded use of biological agents since before World War II, when the Japanese
used them against the Chinese in the early 1940s.2
In the 1980s, Soviet troops battled Afghan rebels
protesting the communist Afghan regime. During this lengthy conflict, frequent
allegations were made of the use of chemical agents against the Afghans. One of
these chemicals, known as Blue-X, was said to cause instant immobilization, the
victim remaining in place for a number of hours before recovering. The use of
other, more lethal agents was also alleged, but again no definitive evidence was
found.
The most widespread and most open use of chemical
weapons on a battlefield in recent decades was by Iraq in its conflict with
Iran. This time the evidence of chemical use was conclusive. Undetonated shells
were sampled and their contents were analyzed by several laboratories in Europe.
A vesicant or blister agent (mustard) and a nerve agent (tabun) were identified.
About 100 Iranian soldiers with chemical wounds were sent to European hospitals
for care; their wounds were consistent with vesicant (mustard) injury. A team
appointed by the U.N. secretariat went to Iranian battlefields and hospitals and
found chemical shells and patients with chemical injuries. The public outcry at
the use of these weapons was less than overwhelming. Ignoring protests from the
world community, Iraq continued to use these agents.
Evacuating wounded soldiers to Europe not only
lessened the burden on the medical facilities in Iran (although the number sent
was a small fraction of the total) and provided soldiers with good medical care,
but it also provided the rest of the world with evidence that Iraq was using
these weapons. In general, the casualties were sent privately, not through
governmental connections. Physicians in Europe accepted the patients and assumed
responsibility for their care, usually in private hospitals (a situation that
made a retrospective analysis of the care rendered and the effectiveness of
different treatment regimens difficult).
A similar situation enabled three physicians from
the U.S. Army medical community to examine several casualties from Iraq’s use
of chemical weapons. On March 19, 1988, Iraqi airplanes bombed the village of
Halabja, in Iraq. The inhabitants were Kurdish Iraqi citizens, a tribespeople
who live in the region where the borders of Turkey, Iran, and Iraq meet. The
casualties from this raid received worldwide media attention. The chemical
weapons allegedly used were nerve agents, cyanide, and mustard. The casualties
were cared for by Iran, and five of them (a man, a woman, and three young
children, all unrelated) were sent to the United States for care by an Iranian
physician living here. On examination by three authors of chapters in this
textbook, the casualties were found to have skin lesions and pulmonary
pathological changes (as determined by radiograph) consistent with mustard
exposure.
Other items in the news over the past
decade have suggested that the proliferation of chemical and biological agents
is greater than we might hope. For example, numerous accounts claimed that Libya
had built a facility capable of chemical agent production at Rabta—Libya’s
protestation that this facility was a pharmaceutical plant notwithstanding. One
report even noted that monthly production was about 30 tons of mustard.
In 1979, an accident at a previously undetected
biological weapons plant in Sverdlovsk, Russia, surprised even the intelligence
community.3 At least 66 humans living or working downwind of the
plant died of pulmonary anthrax. Soviet troops quickly attempted to
decontaminate the facility and the city following airborne release of anthrax
spores, and medical teams instituted preventive therapy, but the message was
clear. The Soviet biological warfare program was thriving, more than 6 years
after the Soviet Union had signed the Biological Weapons Convention.
In addition to their being used on the
battlefield, chemical and biological agents might also be used in terrorist
attacks. The nerve agent sarin was twice used in Japan. The first incident, in
Matsumoto in June 1994, produced more than 200 casualties including 7
fatalities. In the second incident—in the Tokyo subway system on 20 March
1995—5,510 people were taken to medical facilities or sought medical
assistance. About 20% of these were hospitalized, and 12 died. The cult that was
accused of both attacks was found to have a large facility for manufacturing
both chemical and biological agents.
In the face of overwhelming evidence, the Soviet
Union continued to officially deny having an offensive biological weapons
program until 1992, when Russian President Boris Yeltsin admitted publicly to
having maintained a program until March of that year. Since then, visits by
teams from the United States and the United Kingdom to former biological warfare
facilities under the Joint United States/United Kingdom/Russia Trilateral
Statement on Biological Weapons have clearly documented the capabilities to
produce biological warfare agents in massive quantities.
Verification of compliance with agreements such
as the Trilateral and with the chemical and biological weapons conventions are
plagued by the “dual-use” nature of the facilities in which these agents are
developed and produced. A legitimate chemical facility can be converted fairly
easily for the manufacture of chemical agents. On threat of inspection by an
international group, the facility can readily be converted back to a legitimate
use. The dual-use nature of production facilities is even more applicable to the
production of biological agents. Partly for this reason, chemical and biological
weapons have been called “the poor man’s atom bomb.” It has also been said
that agents can be made in a bathtub, which may be true to a limited extent for
a skilled microbiologist or chemist. Production of even tactical quantities of
these agents and their deployment on the battlefield, however, is not a trivial
undertaking.
Chemical and biological agents differ in several
important ways. Chemical agents are typically manmade through the use of
industrial chemical processes. Biological agents are either replicating agents
(bacteria or viruses) or nonreplicating materials (toxins or physiologically
active proteins or peptides) that can be produced by living organisms. Some of
the nonreplicating biological agents can also be produced through either
chemical synthesis, solid-phase protein synthesis, or recombinant expression
methods. Almost none of the biological agents are dermally active (the
mycotoxins are a rare exception) and none are volatile. On the other hand, most
of the chemical agents are dermally active, volatile, or both.
Therefore, while many of the dermally active or
volatile chemical agents can be disseminated as liquids or aerosols, and the
biological agents must be dispersed as respirable aerosols (particles
approximately 1–10 µm in diameter). Dispersing a respirable aerosol on a
battlefield requires a high-energy generating system to produce the small
particle size, appropriate weather conditions to assure that the aerosol cloud
stays near the ground, and adequate infectivity or toxicity of the agent to
produce the desired effect. Except for infectivity, these are all important
practical requirements for the field use of chemical, as well as biological,
warfare agents.
In World War I, the use of chemical agents began
with the small-scale use of irritants (known today as riot control agents).
Chlorine, the first agent used on a large scale, and phosgene caused large
numbers of deaths. Cyanide was introduced in midwar, but the agent that caused
the greatest number of casualties was the vesicant mustard, which was introduced
late in the war. Cyanide, phosgene, and mustard are still potential chemical
weapons today.
In the period before World War II,
German scientists synthesized the first nerve agents; during the war, Germany
had thousands of tons of nerve agents stockpiled in munitions. The United States
and the Soviet Union captured the stockpiles and manufacturing facilities late
in the war, and they began to manufacture and stockpile these agents. Nerve
agents are 15- to 100-fold more potent than the chemical agents used in World
War I. In the 1950s, the United States put the incapacitating compound BZ into
munitions (which have been destroyed); late in that decade, the currently used
riot control agent CS was introduced for military use.
Military chemical agents are classified as
“persistent” and “nonpersistent.” Persistent agents are those with low
volatility or which evaporate slowly. Since they do not readily evaporate, they
stay on terrain, materiel, or equipment for days, weeks, or months, depending on
the weather. Chief among the persistent agents are the vesicant mustard and the
nerve agent VX. Nonpersistent agents are those that are volatile and hence
evaporate quickly; they are not expected to be present for more than several
hours. The nonpersistent agents are phosgene, cyanide, and the G series of nerve
agents. Each type has military advantages. Advancing troops might disperse a
nonpersistent agent ahead of their attack to have the advantage of its effects
on the enemy and later to have uncontaminated terrain into which to advance. A
persistent agent might be used to contaminate terrain, supplies, and equipment,
denying the enemy their use.
Biological weapons may contain either replicating
or nonreplicating agents. Although hundreds of naturally occurring bacteria,
viruses, and toxins, as well as “designer compounds,” could potentially be
considered agents by an aggressor, a finite number of these are actually useful
as area weapons on the battlefield. The agents’ utility is limited by ease of
production, stability, and infectivity (bacteria and viruses), or toxicity/effectivity
(toxins and other physiologically active materials). Bacillus anthracis,
for example, is often touted as the best of bacterial agents. Stability of the
spore form and ease of production are its greatest strengths as weapons
material. Among viral agents, Venezuelan equine encephalitis virus is easily
grown to extremely high titers, making it a potential incapacitating agent. The
bacterial agents that cause tularemia, Q fever, and brucellosis are infective at
extremely low doses (1–10 organisms per person). Finally, the extraordinary
toxicity (1,000- to 10,000-fold more toxic than the classic nerve agents) of the
staphylococcal enterotoxins as incapacitants and the botulinum toxins as lethal
agents makes them candidates for weaponization.
Most of the chemical compounds noted above have
characteristics that make them uniquely suited to warfare. Closely related
chemical substances, however, and some of the threat agents, are found
throughout the civilian community. Unlike the chemical warfare agents, which are
not found in nature, essentially all of the biological agents described are
found in nature and cause the same or very similar disease syndromes. Military
medical personnel might encounter persons exposed to the organisms as endemic
disease agents on remote battlefields.
Similarly, civilians as well as military
personnel could be exposed during peacetime to commercial chemicals closely
related to chemical warfare agents. Thousands of tons of cyanide, for example,
are manufactured annually for industrial use and are shipped to users by truck
and train throughout the country. Phosgene is also manufactured in large amounts
and shipped cross-country. The nerve agents are not available outside the
military, but they are closely related to most pesticides or insecticides that
are sprayed on orchards or used by the backyard rose gardener. The effects of
these agricultural compounds are nearly identical to those of nerve agents, and
medical therapy is the same. The incapacitating agent BZ (3-quinuclidinyl
benzilate) is used in small amounts in research pharmacology (where it is known
as QNB). Also, BZ is pharmacologically related to anticholinergic drugs, which
are present in many over-the-counter preparations, such as sleeping medications.
Unlike the chemical warfare agents,
essentially all of the biological agents described cause syndromes that mimic or
are identical to naturally occurring diseases. Outbreaks of disease caused by
bacteria or viruses or isolated intoxications caused by toxins may result in
syndromes similar to those seen in biological warfare attacks. In the case of
these agents, the route of exposure—universally via the airways on the
battlefield—may cause slightly or significantly different clinical
presentations. General principles of prophylaxis and therapy presented in this
text, however, often apply. Although the reader may initially think that the
information presented in this textbook is needed only in wartime, much of the
contents will also be useful to the physician in a busy emergency room.
On the battlefield, knowledge of the chemical or
biological agent threat and its medical and physical countermeasures can
actually reduce the threat. In World War I, the death rate for chemical
casualties was about 3%. Data are not available for the Iran–Iraq War, but
informal reports indicate that the death rate for those chemical casualties who
reached medical care was probably less than 5%, despite the use of the highly
toxic nerve agents against relatively unprotected troops. With well-trained
troops and well-prepared medical personnel, these figures will be lower. For the
chemical agents, real-time detectors allow exploitation of the excellent
individual physical protective mask, effective pretreatment, and therapy.
These countermeasures, in conjunction with
training of our forces, can make an enormous difference and actually serve as a
deterrent to chemical agent use. A chemical attack on a battlefield will not be
the devastating event that some military medical personnel fear. Soldiers will
survive and return to duty. For the biological agents, field detectors are still
not responsive enough to allow timely warning of a cloud moving across the
battlefield. Although the mask is protective, adequate warning may still be a
problem. Knowledge of the meteorological conditions necessary for effective
deployment of biological and chemical agents can at least limit the time during
which a force must be on highest alert. In addition, effective medical
countermeasures (vaccines, drugs, and diagnostics) are available for many of the
agents of greatest concern. An integrated system of countermeasures for the
chemical and biological agents can significantly reduce the threat by raising
the cost/benefit ratio for the would-be aggressor. If the agents are used,
appropriate medical care from well-informed medical care providers that enables
soldiers to survive could be the factor determining whether a battle is won or
lost.
IMPLICATIONS FOR THE MILITARY MEDICAL DEPARTMENTS
From 18 January to 28 February 1991, 39 Iraqi-modified SCUD missiles reached Israel. 4 Although many were off target or malfunctioned, some of them landed in and around Tel Aviv. Approximately 1,000 people were treated as a result of missile attacks, but only 2 died. Anxiety was listed as the reason for admitting 544 patients and atropine overdose for hospitalization of 230 patients. Clearly, these conventionally armed SCUDs were not effective mass casualty weapons, yet they caused significant disruption to the population of Tel Aviv. Approximately 75% of the casualties resulted from inappropriate actions or reactions on the part of the victims. Had one of the warheads contained a chemical or biological agent that killed or intoxicated a few people, the “terror effect” would have been even greater.