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Defense Against Toxic Weapons: Understanding the Threat
by David R. Franz
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Defense Against Toxic Weapons
Understanding the Threat
The following is a theoretical discussion based on an understanding of physical and biochemical characteristics of toxins. It is not an intelligence assessment of the threat.
TOXINS COMPARED TO CHEMICAL WARFARE AGENTS
Toxins differ from classical chemical agents by source and physical
characteristics. When considering how to protect soldiers from
toxins, physical characteristics are much more important than source.
TABLE 1: Comparison of Chemical Agents and Toxins Toxins
Chemical Agents Natural Origin
Difficult, small-scale production Man-made
Large-scale industrial production None volatile
Many are more toxic Many volatile
Less toxic than many toxins Not dermally active*
Legitimate medical use Dermally active
No use other than mony toxins
Noticeable odor or taste Odorless and tasteless Noticeable odor or taste
Diverse toxic effects
Many are effective immunogens**
Aerosol delivery Fewer types of effects
Poor immunogens
Mist/droplet/aersol delivery * Exceptions are trichothecene
mycotoxins, lyngbyatoxin and some of the blue-green algal toxins.
The latter two cause dermal injury to swimmers in contaminated waters, but are generally unavailable in large quantities and have low toxicity, respectively.
** The human body recognizes them as foreign material and makes protective antibodies against them.
The most important differences to understand are volatility and
dermal activity. Toxins also differ from bacterial agents (e.g.: those
causing anthrax or plague) and viral agents (such as those that cause
VEE, smallpox, flu, etc.), in that toxins do not reproduce themselves.
TOXINS ON THE BATTLEFIELD
Because toxins are not volatile, as are chemical agents, and with rare
exceptions, do not directly affect the skin, an aggressor would have to
present toxins to target populations in the form of respirable aerosols,
which allow contact with the more vulnerable inner surfaces of the
lung. This, fortunately, complicates an aggressor's task by limiting the
number of toxins available for an arsenal. Aerosol particles between
0.5 and 5 m in diameter are typically retained within the lung. Smaller
particles can be inhaled, but most are exhaled. Particles larger than 5-
15 gm lodge in the nasal passages or trachea and do not reach the
lung. A large percentage of aerosol particles larger than 15-20 m
simply drop harmlessly to the ground. Because they are not volatile,
they are no longer a threat, even to unprotected troops. Although
there are few data on aerosolized toxins, it is unlikely that secondary
aerosol formation caused by vehicular or troop movement over ground
previously exposed to a toxin aerosol would generate a significant
threat; this may not be true with certain chemicals or with very heavy
contamination with infectious agents such as anthrax spores.
TOXICITY, EASE OF PRODUCTION AND STABILITY
Because they must be delivered as respirable aerosols, toxins' utility
as effective MCBW are limited by their toxicities and ease of
production. The laws of physics dictate how much toxin of a given
toxicity is needed to fill a given area of space with a small-particle
aerosol. Figure 1 presents a theoretical calculation of the approximate
quantities of toxins of varying toxicities required to intoxicate people
exposed in large open areas on the battlefield under optimal
meteorological conditions. The figure is based on a mathematical
model that has been field tested and found to be valid. It shows that a
toxin with an aerosol toxicity of 0.025 g/kg would require 80 kg of
toxin to cover 100 km2 with an effective cloud exposing individuals
to approximately a lethal dose 50 (LD50). LD50 means, for example,
that a person weighing 70 kg would have a 50% chance of surviving
after receiving a 70 1lg dose of a toxin with an LD50 of 1.0 11g/kg.
Note that for toxins less toxic than botulinum or the staphylococcal
enterotoxins, hundreds of kilograms or even ton quantities would be
need to cover an area of 10x10 km (100 km2) with an effective
aerosol. Assuming this to be true, the number of toxins which can be
used as MCBW is very limited; most of the less toxic agents either
cannot be produced in quantity with current technology, or delivered
to cover large areas of the battlefield. That could change, however,
especially for the peptide toxins, as techniques for generating genetic
recombinants improve. Stability of toxins after aerosolization is also
an important factor, because it further limits toxin weapon
effectiveness.
It is readily apparent that, ignoring other characteristics, if a toxin is
not adequately toxic, sufficient quantities cannot be produced to
make even one weapon. Because of low toxicity. hundreds of toxins
can be eliminated as ineffective for use in MCBWs. Certain plant
toxins, with marginal toxicity, could be produced in large (ton)
quantities. These toxins could possibly be weaponized. At the other
extreme, several bacterial toxins are so lethal that MCBW quantities
are measured not in tons, but in kilograms-quantities more easily
produced. Such toxins are potential threats to our soldiers on the
battlefield.
Incapacitation, as well as lethality, to humans must be considered. A
few toxins cause illness at levels many times less than the
concentration needed to kill. For example, toxins that directly affect
membranes and/or fluid balance within the lung may greatly reduce
gas transport without causing death. Less potent toxins could also be
significant threats as aerosols in a confined space, such as the air-
handling system of a building. Finally, breakthroughs in delivery
vehicle efficiency or toxin "packaging" by an aggressor might alter the
relationship between toxicity and quantity, as depicted in Figure 1;
but even at best, quantities needed could likely be reduced only by
one-half for a given toxicity. For now, however, the figure provides a
reasonable and valid way of sorting toxins.
Some toxins are adequately toxic and can be produced in sufficient
quantities for weapons, but are too unstable in the atmosphere to be
candidates for weaponization. Although stabilization of naturally
unstable toxins and enhanced production of those toxins now
difficult to produce are possible ties for the future, there exists no
evidence at this time for successful amplification of toxicity of a
naturally occurring toxin. Militarily significant weapons need not be
MCBW From 18 January to 28 February 1991, some 39 Iraqi-
modified Scud missiles reached Israel. 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 two died. Anxiety was listed as the reason for
admitting 544 patients and atropine overdose for hospitalization of
230 patients. (Karsenty et al., Medical Aspects of the Iraqi Missile
Attacks on Israel, Isr J Med Sci 1991: 27: 603-607). Clearly, these
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 toxin
which killed or intoxicated a few people, the "terror effect" would
have been even greater. Therefore, many toxins that are not
sufficiently toxic for use in an open-air MCBW could probably be
used to produce a militarily significant weapon. However, the
likelihood of such a toxin weapon causing panic among military
personnel decreases when the leaders and troops become better
educated regarding toxins.
CLASSES AND EXAMPLES OF TOXINS
The most toxic biological materials known are protein toxins
produced by bacteria. They are generally more difficult to produce on
a large scale than are the plant toxins, but are many, many times more
toxic. Botulinum toxins (seven related toxins), the staphylococcal
enterotoxins (also seven different toxins), diphtheria and tetanus
toxin are well-known examples of bacterial toxins. The botulinum
toxins are so very toxic that lethal aerosol MCBW weapons could be
produced with quantities of toxin that are attainable relatively easily
with present technology. They cause death through paralysis of
respiratory muscles. Staphylococcal enterotoxins, when inhaled,
cause fever, headache, diarrhea, nausea, vomiting, muscle aches,
shortness of breath, and a nonproductive cough within 2-12 hours
after exposure; they can also kill, but only at much higher doses.
Staphylococcal enterotoxin B (SEB) can incapacitate at levels at least
one hundred times lower than the lethal level. These too would likely
be delivered as a respirable aerosol.
Other bacterial toxins, classified generally as membrane-damaging,
are derived from Escherichia coli (hemolysins), Aeromonas,
Pseudomonas and Staphylococcus alpha, (cytolysins and
phospholipases), and are moderately easy to produce, but vary a great
deal in stability. Many of these toxins affect body functions or even
kill by forming pores in cell membranes. In general, their lower
toxicities make them less likely battlefield threats.
A number of the toxins produced by marine organisms or by bacteria
that live in marine organisms might be used to produce terrorist
biological weapons. Saxitoxin, the best known example of this group,
is a sodium-channel blocker and is more toxic by inhalation than by
other routes of exposure. Unlike oral intoxication with saxitoxin
(paralytic shellfish poisoning), which has a relatively slow onset,
saxitoxin can be lethal in a few minutes by inhalation. Saxitoxin
could be used against our troops as an antipersonnel weapon, but
because it cannot currently be chemically synthesized efficiently, or
produced easily in large quantities from natural sources, it is unlikely
to be seen as an area aerosol weapon on the battlefield. Tetrodotoxin
is much like saxitoxin in mechanism of action, toxicity and physical
characteristics. Palytoxin, from a soft coral, is extremely toxic and
quite stable in impure form, but difficulty of production or harvest
from nature reduces the likelihood of an aggressor using it as an
MCBW. The brevetoxins, produced by dinoflagellates, and the
bluegreen algal toxins like the hepatotoxin, microcystin, have limited
toxicity. For many of these toxins, either difficulty of production or
lack of sufficient toxicity limits the likelihood of their use as
MCBW.
The trichothecene mycotoxins, produced by various species of fungi,
are also examples of low molecular weight toxins (molecular weight:
400-700 daltons). The yellow rain incidents in Southeast Asia in the
early 1980s are believed to have demonstrated the utility of T-2
mycotoxin as a biological warfare agent. T-2 is one of the more stable
toxins, retaining its bioactivity even when heated to high
temperatures. High concentrations of sodium hydroxide and sodium
hypochlorite are required to detoxify it. Aerosol toxicities are
generally too low to make this class of toxins useful to an aggressor
as an MCBW as defined in Figure 1; however, unlike most toxins,
these are dermally active. Clinical presentation includes nausea,
vomiting, weakness, low blood pressure, and burns in exposed areas.
Toxins derived from plants are generally very easy to produce in large
quantities at minimal cost in a low-tech environment. A typical plant
toxin is ricin, a protein derived from the bean of the castor plant.
Approximately 1 million tons of castor beans are processed annually
worldwide in the production of castor oil. The resulting waste mash is
3-5% ricin by weight. Because of its marginal toxicity, at least a ton
of the toxin would be necessary to produce an MCBW (as defined in
Figure 1). Unfortunately, the precursor raw materials are available in
those quantities throughout the world.
Animal venoms often contain a number of protein toxins as well as
nontoxic proteins. Until recently, it would have been practically
impossible to collect enough of these materials to develop them as
biological weapons. However, many of the venom toxins have now
been sequenced (their molecular structure is known) and some have
been cloned and expressed (produced by molecular biological
techniques). Some of the smaller ones could also be produced by
relatively simple chemical synthesis methods. Examples of the venom
toxins are 1) the ion channel (cationic) toxins such as those found in
the venoms of the rattlesnake, scorpion and cone snail; 2) the
presynaptic phospholipase A2 neurotoxins of the banded krait.
Moiave rattler and Australian taipan snake; 3) the postsynaptic
(curare-like alpha toxin) neurotoxins of the coral, mamba, cobra, sea
snake and cone snail; 4) the membrane damaging toxins of the
Formosan cobra and rattlesnake and 5) the
coagulation/antlcoagulation toxins of the Malayan pit viper and
carpet viper. Some of the toxins in this group must be considered
potential future threats to our soldiers as large-scale production of
peptides becomes more efficient; however, difficulty of production in
large quantity presently may limit the threat potential of many of
them.
HOW TOXINS WORK
Unlike chemical agents, there are many classes of toxins, and they
differ widely in their mechanisms of action. makes the job of
medically protecting soldiers difficult, as there are seldom instances
where one vaccine or therapy would be effective against more than
one toxin. Time from exposure to onset of clinical signs may also
vary greatly among toxins.
(Note that, unlike a terrorist threat, one can prepare for a battlefield
threat through development of specific medical countermeasures.
Vaccines and other prophylactic measures can be given before
combat, and therapies kept at the ready.)
Some neurotoxins, such as saxitoxin, can kill an individual very
quickly (minutes) after inhalation of a lethal dose. This toxin acts by
blocking nerve conduction directly and causes death by paralyzing
muscles of respiration. Yet, at just less than a lethal dose, the
exposed individual may not even feel ill or just dizzy. Because of the
rapid onset of signs after inhalation, prophylaxis (immunization or
pretreatment with drugs) would be required to protect soldiers from
these rapidly acting neurotoxins. Unprotected soldiers inhaling a
lethal dose would likely die before they could be helped, unless they
could be intubated (a breathing tube placed in the airway) and
artificially ventilated immediately. A1though the mechanism of death
after inhalation of saxitoxin is believed to be the same as when the
toxin is administered intravenously, it is more toxic (a smaller dose
will kill) if inhaled.
Other neurotoxins, such as the botulinum toxins, must enter nerve
terminals before they can block the release of neurotransmitters which
normally cause muscle contraction. Botulinum neurotoxins generally
kill by relatively slow onset (hours to days) respiratory failure. The
intoxicated individual may not show signs of disease for 24-72 hours.
The toxin blocks biochemical action in the nerves that activate the
muscles necessary for respiration, leading to suffocation.
Intoxications such as this can be treated with antitoxin (a preparation
of antibodies from humans or animals) that can be injected hours (up
to 24 hours in monkeys, and probably humans) after exposure to a
lethal dose of toxin, and still prevent illness and death. Although the
mechanisms of toxicity of the botulinum toxins appear to be the same
after any route of exposure, unlike saxitoxin, the actual toxicity is
less by inhalation (i.e., the lethal dose of botulinum toxin is slightly
greater by inhalation).
While neurotoxins effectively stop nerve and muscle function without
causing microscopic damage to the tissues, other toxins destroy or
damage tissue directly. For these, prophylaxis (pretreatment of some
kind) is important because the point at which the pathological change
becomes irreversible often occurs within minutes or a few hours after
exposure. An example of this type of toxin is microcystin, produced
by blue-green algae, which binds very specifically to an important
enzyme inside liver cells; this toxin does not damage other cells of
the body. Unless uptake of the toxin by the liver is blocked,
irreversible damage to the organ occurs within 15-60 minutes after
exposure to a lethal dose. In this case, the tissue damage to a critical
organ, the liver, is so severe that therapy may have little or no value.
For this toxin, unlike most, the toxicity is the same, no matter what
the route of exposure.
The consequences of intoxication may vary widely with route of
exposure, even with the same toxin. The plant toxin, ricin, kills by
blocking protein synthesis in many cells of the body, but no lung
damage occurs with any exposure route except inhalation. If ricin is
inhaled, as would be expected during a biological attack, microscopic
damage is limited primarily to the lung, and that damage may be
caused by a mechanism different from that which occurs if the toxin
is injected. Furthermore, when equivalent doses of toxin are used,
much more protective antibody must be injected to protect from
inhalation exposure compared to intravenous injection of the toxin.
Finally, although signs of intoxication may not be noted for 12-24
hours, microscopic damage to lung tissue begins within 8-12 hours or
less. Irreversible biochemical changes may occur in 6090 minutes
after exposure, again making therapy difficult.
The toxicities of some bacterial toxins are too low to make them
effective lethal MCBWs, according to the standards described in
Figure 1. However, some cause incapacitating illness at extremely low
levels. Therefore, lethality alone is not an appropriate criterion on
which to base a toxin's potential as a threat. The staphylococcal
enterotoxins are examples. They can cause illness at extremely low
doses, but relatively high doses are required to kill. These toxins are
unusual, in that they act by causing the body to release abnormally
high levels of certain of its own chemicals, which, in very small
amounts, are beneficial and necessary for life, but at higher levels are
harmful.
Only one class of easily produced toxins, the trichothecene
mycotoxins, is dermally active. Therefore, trichothecenes must be
considered by different standards than all other toxins. They can
cause skin lesions and systemic illness without being inhaled and
absorbed through the respiratory system. Skin exposure or ingestion
of contaminated food are the two likely routes of exposure of
soldiers; oral intoxication is unlikely in modern, welltrained armies.
Nanogram (one billionth of a gram) quantities per square centimeter
of skin cause irritation, and microgram (one millionth of a gram)
quantities cause necrosis (destruction of skin cells). If the eye is
exposed, microgram doses can cause irreversible injury to the cornea
(clear outer surface of the eye). The aerosol toxicity of even the most
toxic member of this group is low enough that large-quantity
production (approximately 80 metric tons to expose a 10 km2 area
with respirable aerosol) makes an inhalation threat unlikely on the
battlefield. These toxins, therefore, might be dispersed as larger
particles, probably visible in the air and on the ground and foliage. In
contrast to treatment for exposure to any of the other toxins, simply
washing the skin with soap and water within 1-3 hours after an
exposure would eliminate or greatly reduce the risk of illness or
injury.
MANY TOXINS, BUT NOT AN OVERWHELMING PROBLEM
Because there are hundreds of toxins available in nature, the job of
protecting troops against them seems overwhelming. One would think
that an aggressor would need only to discover the toxins against
which we can protect our troops and pick a different one to
weaponize. In reality, it is not quite that simple. The utility of toxins
as MCBWs is limited by toxicity (Figure 1). This criterion alone
reduces the list of potential open-air weaponizable toxins for
MCBWs from hundreds to fewer than 20. Issues related to stability
and weaponization will not be addressed here, but would only further
reduce the list and make the aggressor's job more difficult.
POPULATIONS AT RISK
An armored or infantry division in the field is not at great risk of
exposure to a marine toxin whose toxicity is such that 80 tons are
needed to produce an MCBW covering 10 km2. Most marine toxins
are simply too difficult to produce in such quantities. Military leaders
on today's battlefield should be concerned first about the most toxic
bacterial toxins and possibly some of the plant toxins that are slightly
less toxic but available in large quantities in nature. The more
confined the military or terrorist target (e.g., inside shelters,
buildings, ships or vehicles) the greater the list of potential toxin
threats which might be effective. This concern is countered, however,
by the fact that toxins are not volatile like the chemical agents and are
thus more easily removed from air-handling systems than are volatile
agents. It is probably most cost-effective to protect our personnel
from these toxins through the use of collective filtration systems.
Nonetheless, we must consider subpopulations of troops and areas
within which they operate when we estimate vulnerability to a given
toxin threat. Situations could well occur in which different
populations of troops require protection from different toxins,
because of differences in operational environments. To protect them
effectively, decision makers and leaders must understand the nature of
the threat and the physical and medical defense solutions.
Table 3 lists the approximate number of known toxins by toxicity
level and source. To simplify our approach to development of medical
countermeasures, we have divided them into "Most Toxic," "Highly
Toxic" and "Moderately Toxic" categories (also see Figure 1). The
Most Toxic toxins could probably be used in an MCBW; it is
feasible to develop individual medical countermeasures against them.
The Highly Toxic toxins could probably be used in closed spaces
such as the air-handling system of a building or as ineffective terror
weapons in the open; collective filtration would be effective against
these toxin aerosols targeted to enclosed spaces. The Moderately
Toxic toxins would likely be useful only as assassination weapons
which would require direct attack against an individual; it is not
feasible to develop medical countermeasures against all of the toxins
in this group. Such reasoning allows us to use limited resources most
effectively and maximize protection, and thus effectiveness, of our
fighting force.
SOURCE Most Toxic Highly Toxic Moderately Toxic Total
(Number of toxins in each category)
Bacterium 17 >12 >20 >49
Plant >5 >31 >36
Fungus >26 >26
Marine Organism >46 >65 >111
Snake >8 >116 >124
Alga >2 >20 >22
Insect >22 >22
Amphibian >5 >5
Total 17 >73 >305 >395
Table 3. Approximate number of toxins arbitrarily categorized as
Most Toxic (LD50 <0.025 æg/kg),
Highly Toxic (LD50, 0.025-2.5 æg/kg) and
Moderately Toxic (LDso >2.5g/kg).
From DNA-TR-92-116, Technical Ramifications of Inclusion of Toxins in the Chemical Weapons Convention (CWC).
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