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PREFACE

The contents of this document are not be

construed as an official Department of the Army 

position unless so designated by other authorized 

documents. Opinions are those of the author and do 

not necessarily reflect doctrine.

ACKNOWLEDGMENTS

The author wishes to thank the investigators and 

staff of the Toxinology Division, USAMRIID for 

providing the backdrop for the accumulation of the 

information contained herein; Drs. Ed Eitzen, Robert 

Wannemacher, Carol Linden and Robert Boyle for 

technical review; Ms. Kathy Kenyon and Ms. Cherly 

Parrott for editorial assistance, and Mr.

Gene Griffith for cover design.

 

 First Printing 1994

Reprinted 1995

Revised 1997

 U.S. Army Medical Research

 and Materiel Command 

 ATTN: U.S. Army Medical Research Institute 

 of Infectious Diseases 

 1425 Porter Street

 Fort Detrick, Maryland 21702-5011 

 MCMR-UIZ-A
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DEFENSE AGAINST TOXIN WEAPONS

David Franz DVM, PhD

 Colonel (ret), U.S. Army

INTRODUCTION 1

UNDERSTANDING THE THREAT 5

Toxins Compared to Chemical Warfare Agents 5

Toxins on the Battlefield 7

Toxicity, Ease of Production and Stability 8

Classes and Examples of Toxins 13

How Toxins Work 17

Many Toxins, But Not an Overwhelming Problem 22

Populations at Risk 22

COUNTERMEASURES 25

Physical Protection 25

Real-Time Detection of an Attack 26

Diagnosis: General Considerations 28

Approaches to Prevention and Treatment 31

Decontamination: Is It Necessary? 38

ANSWERS TO OFTEN-ASKED QUESTIONS 39

Protecting Health-Care Providers 39

Sample Collection: General Rules for Toxin 40

Toxin Analysis and Identification 42

Water Treatment 43

THE FUTURE 44

Intelligence: Information that Protects Soldiers 44

Toxins as Weapons 46

Countermeasures to Toxins 47

Protecting Soldiers 48
5

 DEFENSE AGAINST TOXIN 

WEAPONS

INTRODUCTION

The purpose of this manual is to provide basic 

information on biological toxins to military leaders 

and health-care providers at all levels to help them 

make informed decisions on protecting their troops 

from toxins. Much of the information contained 

herein will also be of interest to individuals charged 

with countering domestic and international terrorism. 

We typically fear what we do not understand. 

Although understanding toxin poisoning is less 

useful in a toxin attack than knowledge of cold injury 

on an Arctic battlefield, information on any threat 

reduces its potential to harm. I hope that by 

providing information 

about the physical characteristics and biological 

activities of toxins, the threat of toxins will actually be 

reduced. I did not intend to provide detailed 

information on individual threat toxins or on medical 

prevention or treatment. This primer puts toxins in 

context, attempts to remove the elements of mystery 

and fear that surround them, and provides general 

information that will ultimately help leaders make 

rational decisions, protect their soldiers and win 

battles.
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The mission of the U.S. Army Medical Research 

and Development Command's Medical Biological 

Defense Research Program is to study and develop 

means of medically defending the U.S. Armed 

Forces from toxins and infectious threats posed by 

adversaries. It is our responsibility to develop 

medical countermeasures to toxins of plant, animal 

and microbial origin. We believe that there is a 

biological toxin threat and we know of countries that 

are not in compliance with the Biological Weapons 

Convention of 1972. Therefore, prudence mandates 

a strong defensive program. The toxins described 

herein are all nonreplicating agents; some have 

been identified by the intelligence community as 

biological warfare threats.

Physical measures, such as the protective mask 

and decontamination systems, developed for the 

chemical threat are, for the most part, effective 

against toxin threats. Research to develop individual 

medical countermeasures to toxins is complicated 

by several factors. A number of toxins could be 

selected by an adversary for use in low-tech, 

relatively inexpensive weapons. Many more are 

potentially available through genetic engineering or 

chemical synthesis. Biological weapons are far 

more easily obtained and used than nuclear 

weapons. They actually may be more easily 

produced and used than conventional explosive 

weapons. Colorless, tasteless, odorless, smallscale aerosols may be generated relatively easily 

with a cheap plastic 
7

nebulizer attached to a pump or pressurized air 

bottle. However, production and use of toxins as true 

mass casualty weapons is not a trivial undertaking.

The likely route of intoxication for soldiers or 

victims of terrorist attack is through the lung by 

respirable aerosols; another possibility is through 

the gastrointestinal tract by contamination of food or 

water supplies, although the latter would be difficult 

in chlorinated water, or in rivers, lakes or reservoirs 

because of dilution effects. The effects of most 

toxins are more severe when inhaled than when they 

are consumed in food or injected by bites or stings. 

Some toxins can elicit a significantly different clinical 

picture when the route of exposure is changed, a 

phenomenon that may confound diagnosis and 

delay treatment. 

Finally, because the primary population

at risk is relatively small (military troops, not the 

general public, as with childhood infectious 

diseases), there is little commercial incentive to 

produce vaccines, antisera or therapeutic drugs to 

counter toxin threats.

There are still many unknowns regarding toxins 

and their weaponization. Statements in this 

document on the nature of a “typical toxin attack” are 

based on my understanding of the physical 

characteristics of toxins, recent studies of 

aerosolized toxins in small laboratory chambers to 

test protective drugs and vaccines, and historical 
8

data from larger-scale studies with toxin or simulant 

aerosols.

The following three descriptions, Toxin, Mass 

Casualty Biological (toxin) Weapon and 

Militarily Significant Weapon, define these terms 

for the purposes of this primer.

1. A Toxin is any toxic substance that can be 

produced by an animal, plant or microbe. Some 

toxins can also be produced by molecular biologic 

techniques (protein toxins) or by chemical synthesis 

(low molecular weight toxins). Chemical agents, 

such as soman, sarin VX, cyanide and mustard 

agents, typically man-made for weaponization, are 

not included in this discussion 

except for comparison.

2. A Mass Casualty Biological (toxin) 

Weapon (MCBW) is any toxin weapon capable of 

causing death or disease on a large scale, such that 

the military or civilian infrastructure of the state or 

organization being attacked is overwhelmed. (Note: 

The commonly accepted term for this category of 

weapons is ”Weapons of Mass Destruction,” 

although that term brings to mind destroyed cities, 

bomb craters and great loss of life; MCBWs might 

cause loss of life only. I do not anticipate that 

”MCBW” will replace the term “Weapon of Mass 

Destruction” in common usage, but it is technically 

more descriptive of toxin weapons).
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3. A Militarily Significant (or Terrorist) 

Weapon is any weapon capable of affecting-directly 

or indirectly, physically or through psychological 

impact-the outcome of a military operation.

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.
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TABLE 1: Comparison of Chemical 

Agents and Toxins

Toxins Chemical Agents

Natural Origin Man-made

Difficult, small-scale Large-scale industrial 

production production

None volatile Many volatile

Many are more toxic Less toxic than many toxins

Not dermally active* Dermally active

Legitimate medical use No use other than mony toxins

Odorless and tasteless Noticeable odor or taste

Diverse toxic effects Fewer types of effects

Many are effective Poor immunogens

immunogens** Mist/droplet/aersol delivery

Aerosol 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.
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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 μm in diameter 

are typically retained within the lung. Smaller 

particles can be inhaled, but most are exhaled. 

Particles larger than 5-15 μm lodge in the nasal 

passages or trachea and do not reach the lung. A 

large percentage of aerosol particles larger than 15-

20 μm 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.
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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 μg/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 

μg dose of a toxin with an LD50 of 1.0 μg/kg. Note 

that for toxins less toxic than botulinum hundreds of 

kilograms or even ton quantities would be need to 

cover an area of 10x10 km (100 km2) with an 

effective lethal 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 
13

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.

 
14

 

 Í kilogram ä Í metric ton ä

Figure 1. Toxicity in LD50 (see Table 2) vs. quantity 

of toxin required to provide a theoretically effective 

open-air exposure, under ideal meteorological 

conditions. to an area 100 km2 (Patrick and 

Spertzel, 1992: based on Calder K.L., BWL Tech 

Study #3, Mathematical models for dosage and 

casualty coverage resulting from single point and 

line source release of aerosol near ground level, 

DTIC#AD3 10-361, Dec. 1957.) Ricin, saxitoxin and 

botulinum toxins kill at the concentrations depicted.
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TABLE 2: Comparative Lethality Of Selected 

Toxins And Chemical Agents In Laboratory 

Mice

AGENT LD50 MOLECULAR SOURCE

 (μg/kg) WEIGHT

Botulinum Toxin 0.001 150,000 Bacterium

Shiga Toxin 0.002 55,000 Bacterium

Tetanus Toxins 0.002 150,000 Bacterium

Abrin 0.04 65,000 Plant (Rosay Pea)

Diphtheria Toxin 0.10 62,000 Bacterium

Maitotoxin 0.10 3,400 Marine Dinoflagellate

Palytoxin 0.15 2,700 Marine Soft Coral

Ciguatoxin 0.40 1,000 Fish/Marine Dinoflagellate

Textilotoxin 0.60 80,000 Elapid Snake

C. perfringens toxins 0.1-5.0 35,000-40,000 Bacterium

Batrachotoxin 2.0 539 Arrow -Poison Frog

Ricin 3.0 64,000 Plant (Castor Bean)

Conotoxin 5.0 1,500 Cone Snail

Taipoxin 5.0 46,000 Elapid Snake

Tetrodotoxin 8.0 319 Puffer Fish

αTityustoxin 9.0 8,000 Scorpion

Saxitoxin 10.0 (Inhal;2.0) 299 Marine Dinoflagellate

VX 15.0 267 Chemical Agent

SEB (Rhesus/Aerosol) 27.0 (ED50∼pg) 28,494 Bacterium

Anatoxin-A(s) 50.0 500 Blue-Green Alga

Microcystin 50.0 994 Blue-Green Alga

Soman (GD) 64.0 182 Chemical Agent

Sarin (GB) 100.0 140 Chemical Agent

Aconitine 100.0 647 Plant (Monkshood)

T-2 Toxin 1,210.0 466 Fungal My cotoxin

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
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the lung may greatly reduce gas transport without 

causing death. Less potent toxins could also be 
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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 
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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
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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 
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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 
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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
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cone snail; 2) the presynaptic phospholipase A2 

neurotoxins of the banded krait. Mojave 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.)
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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. Although 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 
24
25

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 
26

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.
27

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.
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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. 
29

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 
30

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 μg/kg), 

Highly Toxic (LD50 , 0.025-2.5 μg/kg) and 

Moderately Toxic (LD50 >2.5 μg/kg). From DNA-TR92-116, Technical Ramifications of Inclusion of 

Toxins in the Chemical Weapons Convention 

(CWC).
31
32

COUNTERMEASURES

PHYSICAL PROTECTION

As stated above, most toxins are neither volatile 

nor dermally active. Therefore, an aggressor would 

most likely attempt to present them as respirable 

aerosols. Toxin aerosols should pose neither 

significant residual environmental threat, nor remain 

on the skin or clothing. The typical toxin cloud would, 

depending on meteorologic

conditions, either drift with the wind close to the 

ground or rise above the surface of the earth and be 

diluted in the atmosphere. There may, however, be 

residual contamination near the munition release 

point. Humans in the target area of a true aerosol 

would be exposed as the agent drifted through that 

area. The principal way humans are exposed to 

such a cloud is through breathing. Aerosol particles 

must be drawn into the lungs and retained to cause 

harm.

The protective mask, worn properly, is effective 

against toxin aerosols. Its efficacy is, however, 

dependent on two factors: 1) mask-to-face fit and 2) 

use during an attack. Proper fit is vital. Because of 

the extreme toxicity of some of the bacterial

toxins, a relatively small leak could easily result in a 

significant exposure. Eyes should be protected 

when possible. Definitive studies have not been 

done to assess the effects of aerosolized toxins
33

on the eyes. One would expect that, in general, 

ocular exposure to a toxin aerosol, unless the 

exposed individual is near the release point, would 

result in few systemic effects because of the low 

doses absorbed. Certain toxins have direct effects 

on the eyes, but these are generally not toxins we 

would expect to face as aerosols. Donning the 

protective mask prior to exposure would, of course, 

protect the eyes.

Because important threat biological warfare 

agents are not dermally active, special protective 

clothing, other than the mask, is less important in at 

toxin attack than a chemical attack. Presently

available clothing should be effective against 

biological threats as we know them. Commanders 

should carefully consider the relative impact of 

thermal load and the minimal additional protection 

provided by protective clothing.

REAL-TIME DETECTION OF AN 

ATTACK

Because of the nature of the threat, soldiers may 

be dependent on a mechanical detection and 

warning system to notify them of impending or 

ongoing attack. Without timely warning, their most

effective generic countermeasure, the protective 

mask, may be of limited value. There have been 

successful efforts in the past to develop real-time 

detectors of a chemical agent attack. It will be more 

difficult to develop such detectors for toxins for 
34

several reasons. As stated above, toxins must be 

presented as respirable aerosols, which act as 
35

a cloud, not as droplets (as the chemical agents) 

that fall to the ground and evaporate with time. The 

toxin cloud, typically delivered at night with a slight 

wind, would be expected to move across the 

battlefield until it either rises into the atmosphere to 

be diluted or settles, relatively harmlessly, to the 

ground. Unlike chemical agents, which might be 

detectable for hours, toxins might be detectable in 

the air at one location only for a few minutes. 

Definitive, specific toxin detectors would have to 

sample continuously or be turned on by a continuous 

sampler of some kind. 

Furthermore, toxin detectors (assuming the 

present state of technology) would likely have to 

have the specificity of immunoassays to identify a

toxin and differentiate it from other organic material 

in the air. Continuous monitoring by such equipment 

would be extremely costly, reagent intensive, and 

logistically very difficult to support because of 

reagent requirements. Identifying each toxin would 

require a different set of reagents if an 

immunoassay system were used. Analytical assays 

would necessarily be more complex and less likely 

to identify distinct toxins, but might detect that 

something unusual was present. Imagine the 

difficulty of developing a detection system based on 

molecular weight or other physical characteristics to 

differentiate among the seven botulinum toxins 

(molecular weight is the same for all of the botulinum 

toxins, while all seven require a different antibody for 

identification
36

or therapy). Finally, to be effective, a detector would 

have to be located where it could ”sniff” a toxin cloud 

in time to warn the appropriate population. This 

might be possible on a battlefield, but would be 

nearly impossible, except in selected facilities, in the 

case of a terrorist attack. It is possible that, if all the 

capabilities described were developed and 

available at the right place and time, an aerosol 

cloud of almost any of the toxins of concern could be 

detected and identified. Future advances in 

technology could well resolve our present technical 

difficulties.

DIAGNOSIS: General Considerations

Health-care providers often ask whether they will 

be able to tell the difference among cases of 

inhalation botulinum, staphylococcal enterotoxin 

intoxication, and chemical nerve agent poisoning 

Table 4. describes these differences. In general, 

nerve agent poisoning has a rapid onset (minutes) 

and induces increased body secretions (saliva, 

airways secretions), pinpoint pupils and convulsions 

or muscle spasms. Botulinum intoxication has a 

slow onset (24-72 hours) and manifests as visual 

disturbance and muscle weakness, (often seen first 

as droopy eyelids). SEB poisoning has an 

intermediate (few hours) time of onset and is 

typically not lethal, but severely incapacitating. 

Chemical nerve agent poisoning is a violent illness 

resulting in respiratory failure because of muscle 

spasm, 
37

airway constriction and excessive fluid in the 

airways. Botulinum-intoxicated patients simply get 

very tired, very weak and, if they die, it is because 

the muscles of respiration fail. SEB-intoxicated 

patients become very sick, but typically survive.

TABLE 4: Differential Diagnosis of Chemical Nerve 

Agent, Botulinum toxin and Staphylococcal 

Enterotoxin B Intoxication.

CHEMICAL NERVE BOTULINUM TOXIN STAPHYLOCOCCAL 

 AGENT ENTEROTOXIN B

 Time to Symptoms Minutes Hours (24-72) Hours (1-6)

 Nervous Convulsions, Progressive Paralysis Headache, Muscle

 Muscle Twitching Aches

 Cardiovascular Slow Heart Rate Normal Rate Normal or Rapid Heart 

 Rate

 Respiratory Difficult Breathing, Normal, Then Nonproductive Cough,

 Airways Contriction Progressive Paralysis Severe Cases; Chest 

 Pain/difficult breathing

 Gastrointestinal Increased Motility, Dec reased Motility Nausea, Vomiting 

and/or Pain, Diarrhea Diarrhea

 Ocular Small Pupils Droopy Eyelids May see "red eyes" 

 (Conjuntival Injection)

 Salivary Profuse, watery Normal, but swallowing May be slightly

 saliva difficult 

Increased quantities of 

saliva

 Death Minutes 2-3 days Unlikely

 Response to Yes No Atropine may reduce 

 Atropine/2PAM - C1 gastrointestinal 

 

symptoms
38
39

Health-care providers should consider toxins in 

the differential diagnosis, especially when multiple 

patients present with a similar clinical syndrome. 

Patients should be viewed epidemiologically

and asked about where they were, whom they were 

with, what they observed, how many other soldiers 

were and are involved, etc. Inhaled and retained 

doses of toxins will differ among soldiers

exposed to the same aerosol cloud. Those who 

received the highest dose typically will show signs 

and symptoms first. Others will present somewhat 

later, while others in the same group may show

no signs of intoxication. The distribution of severities 

within the group of soldiers may vary with type of 

exposure and type of toxin. For example, exposing a 

group of individuals to the

staphylococcal enterotoxins would likely make a 

large percentage (80%) of them sick, but would 

result in few deaths. Exposing a group of soldiers to 

a cloud of botulinum toxin might kill half, make 20% 

very sick, and leave 30% unaffected. 

One must consider the varying latent periods 

before onset of clinical signs. For patients exposed 

to toxins by aerosol, the latent or

asymptomatic period varies from minutes (saxitoxin, 

microcystin) to hours (the staphylococcal 

enterotoxins), even to days (ricin, the botulinum 

toxins). 

Save clinical and environmental samples for 

diagnosis. Both immunoassays and analytical tests 

are available for many of the toxins. Toxin 
40

samples taken directly from a weapon are often 

easier to test than biological samples because they 

do not contain body proteins and other interfering 

materials. The best early diagnostic sample for most 

toxins is a swab of the nasal mucosa. In general, the 

more toxic toxins are more difficult to detect in 

tissues and body fluids, because so little toxin needs 

to be present in the body to exert its effect. The 

capability exists

however, to identify most of the important toxins in 

biological fluids or tissues, and many other toxins in 

environmental samples. Definitive laboratory 

diagnosis might take 48-72 hours; however, 

prototype field assays that can identify some toxins 

within 30 minutes have been developed recently. 

For individuals who survive an attack with toxins of 

lower toxicity, immunoassays that detect IgM or IgG 

(immunoglobulins produced by the body after 

exposure to a toxin) offer a means of diagnosis or 

confirmation or indirect identification of agent within 

2-3 weeks after exposure.

APPROACHES TO PREVENTION AND 

TREATMENT

In developing medical countermeasures, each 

toxin must be considered individually. Some 

incapacitate so quickly that there would be little time 

for therapy after an attack. Others cause few or no 

clinical signs for many hours, but set off irreversible 

biochemical processes in minutes or a 
41

few hours which lead to severe debilitation or death 

several days later. Fortunately, some of the most 

potent bacterial protein toxins act slowly enough 

that, if they are identified, therapy is usually 

successful 1224 hours after exposure.

It is always better to prevent casualties than to 

treat injured soldiers. For most of the significant 

threat toxins in military situations, vaccination is 

the most effective means of preventing

casualties. Unlike the chemical warfare agents, 

many of the important threat toxins are highly 

immunogenic (exposing the body to small doses of 

the inactivated toxin causes the body to make 

antibodies that protect against subsequent actual 

toxin exposure). Immunized laboratory animals are 

totally protected from high-dose aerosols of these 

toxins. Immunization requires a knowledge of the 

threat, availability of a vaccine, and time. The time 

needed to allow the body to make its own protective 

antibodies to a toxin may range from a minimum of 

4-6 weeks to 12-15 weeks or longer. Some 

vaccines currently in use require multiple injections, 

often weeks apart. The logistical burden of assuring 

that troops are given

booster immunizations at the correct time could be 

overwhelming in a fast-moving build-up to hostilities.

It may be possible to reduce the time required 

for immunization. For example, antigens (materials 

that stimulate the body to develop antibodies) are 

being microencapsulated 
42

(entrapped in a synthetic polymer that breaks down, 

slowly releasing the material) to form timed-release 

vaccines that might provide the primary 

immunization, a boost two weeks later, and another 

boost 10 weeks after that-all with one injection. 

Another approach is being evaluated with current 

Medical Biological Defense Research Program 

vaccines. Soldiers could be given a priming dose 

and the first boost two weeks apart while in basic 

training. The response generated by the immune 

system's memory cells might last for many months or 

even years, although not all soldiers would develop 

fully protective immunity at that time after two 

immunizations. Shortly before the onset of hostilities, 

or when the soldier is assigned to a rapidly 

deployable unit, one boost could provide protective 

immunity quickly, and preclude the need for 

additional boosts after deployment. Preliminary data 

suggest that a boost up to 24 months (the greatest 

interval thus far tested) after two initial priming 

doses will be effective, even with moderately 

immunogenic vaccines such asthe current botulinum 

toxoid. Studies are ongoing to determine the 

maximum reasonable interval between initial 

immunization series and the predeployment boost.

Passive antibody prophylaxis (the soldier 

doesn't make his own antibodies, but is given 

antibody preparations produced in animals or

other humans) is generally quite effective in 

protecting laboratory animals from toxin exposure. 

However, this option is of little real utility for large 
43

groups of people for several reasons. The protection 

provided by human antibody may last for only 1-2 

months, and protection afforded by despeciated 

(animal antibodies altered chemically to reduce the 

likelihood of the human body identifying them as 

foreign protein) horse antibody may last for only a 

few weeks. Therefore, antibody

prophylaxis would be practical only when the threat 

is clearly understood and imminent. Furthermore, it 

is unlikely that animal antibody would be used in an 

individual before intoxication because of the risk, 

albeit small, of an adverse reaction to foreign 

protein. The latter problem may be overcome within 

the next few years, as the

production of human monoclonal antibodies 

(homogeneous populations of antibodies directed 

against one, very specific site on the toxin) or

”humanization” of mouse monoclonal antibodies 

become practical. Unfortunately, single monoclonal 

antibodies are seldom as effective against toxins as 

polyclonal antibodies, such as those produced 

naturally in other humans or horses. However, 

combined antibody therapy, or ”cocktails”of more 

than one monoclonal antibody,

may overcome this problem in the future.

Pretreating soldiers with drugs is feasible, 

but little success has been achieved in the discovery 

or development of drugs that block the effects of 

toxins. Many toxins affect very basic mechanisms 

within body cells, tissues and organs; therefore, 

drugs that block these effects often have debilitating 

or toxic side effects. An exception 
44

is rifampin, the anti-tuberculosis drug, which protects 

laboratory animals exposed to the blue-green algal 

toxin, microcystin, and is safe for use in humans.

Pretreatment (treatment after exposure) with 

antibodies from human or animal sources is 

feasible for some of the 35 threat toxins. Passive 

immunotherapy (treatment with other than one's own 

antibodies) is very effective after exposure to 

botulinum toxin if treatment is begun soon enough, 

up to 24 hours after high-dose aerosol exposure to 

the toxin. The utility of antibody therapy drops 

sharply at or shortly after the onset of the first signs 

of disease. It appears that a significant amount of 

the toxin has, at that time, been taken up by areas of 

the body that cannot be reached by circulating 

antibodies. Even so, we have preliminary evidence 

that antibody therapy is at least partially effective 

after onset of signs of

intoxication (36-48 hours after aerosol exposure) in 

monkeys exposed to botulinum toxin. The available 

antibody to botulinum toxin is produced in horses, 

and then despeciated to make a product with a 

reduced risk of adverse reaction that can be given 

to humans. Human monoclonal antibodies, or 

cocktails of two or more monoclonal

antibodies, may be the next generation of antibody 

therapy. Passive antibody therapy such as that 

described here is more likely to be effective against 

neurotoxins like the botulinum toxins, which do not 

cause tissue damage, than against toxins that 

induce mediator release (the 
45

staphylococcal enterotoxins) or directly damage 

tissues (ricin).

Specific therapy with drugs (drugs that alter 

the action of the toxin o reverse its toxic effects 

directly) present) has little value because most of the 

toxins either physically damage cells and tissues 

very quickly (ricin), or affect such basic mechanisms 

within the cell (the neurotoxins) that drugs designed 

to reverse their effects are toxic themselves. 

Nevertheless, we have shown that rifampin stops the 

lethal intoxication by microcystin if given to 

laboratory animals therapeutically soon after toxin 

administration

(within 15-30 min). Development of therapeutic 

drugs for toxins is presently aimed at several 

more general approaches. Where the mechanism 

of action of the toxin is understood and covalent 

(permanent) bonding of the toxin to cellular protein 

does not occur (example: ion-channel toxins), 

attempts are being made to discover drugs that 

compete or block the toxin from binding to its site of 

action. For toxins with enzymatic activities, such as 

ricin and the botulinum toxins, drugs that serve as 

alternate targets of such enzymatic action may be 

developed. For toxins such as botulinum, which 

block the release of a neural transmitter, attempts 

can be made to enhance the release of the needed 

transmitter by other means; the diaminopyridines 

are temporarily effective in reversing botulinum 

intoxication by this mechanism.
46

Finally, for toxins like staphylococcal enterotoxins 

and ricin, which induce the release of secondary 

mediators (actually, a natural part of the body's 

defense mechanism that overreacts), specific 

mediator blockers are being studied. It is likely that, 

in the next few years, drugs may find a place in the 

therapy of some intoxications as adjuncts to 

vaccination or passive antibody therapy, or they may 

be used to delay onset of toxic effects.

Other general supportive measures 

(Symptomatic Therapy) are likely to be effective in 

therapy of intoxication. Artificial ventilation

could be life-saving in the case of neurotoxins, which 

block nerves that drive muscles of respiration 

(botulinum toxins and saxitoxin).

Oxygen therapy, with or without artificial ventilation, 

may be beneficial for intoxication with toxins that 

directly damage the alveolar-capillary membrane 

(the site of movement of molecules

between the inhaled air and the blood) of the lung. 

Vasoactive drugs (drugs that cause blood vessels to 

dilate or contract) and volume expanders could be 

used to treat the shock-like state that accompanies 

some intoxications. These measures could be used 

in conjunction with more specific therapies.
47

DECONTAMINATION: Is It Necessary?

Recall that a true respirable aerosol will leave 

less residue on clothing and environmental objects 

than would the larger particles produced by a 

chemical munition. This suggests that 

decontamination would be relatively unimportant 

after a toxin aerosol attack. Because we lack field 

experience, however, prudence dictates that

soldiers decontaminate themselves after an attack. 

As a general rule, the decontamination procedure 

recommended for chemical warfare

agents (Army FM 8-285) effectively destroys toxins. 

Exposure to 0.1% sodium hypochlorite solution 

(household bleach) for 10 minutes

destroys most protein toxins. The trichothecene 

mycotoxins require more stringent measures to 

inactivate them, but even they can be removed from 

the skin (although not inactivated) simply by

washing with soap and water. Soap and water, or 

even just water, can be very effective in removing 

most toxins from skin, clothing and equipment. 

Again, because most toxins are not volatile or

dermally active, decontamination is less critical than 

after a chemical attack.
48
49

Answers to Often-Asked Questions

PROTECTING HEALTH-CARE 

PROVIDERS

For the same reason that decontamination is 

only moderately important after personnel are 

exposed to a respirable toxin aerosol, health-care 

providers are probably at only limited risk from 

secondary aerosols. Because toxins are not volatile, 

casualties can, for the most part, be handled safely 

and moved into closed spaces or buildings, unless 

they were very heavily exposed. Prudence dictates, 

however, that patients be handled as chemical 

casualties or, at a minimum, that they be washed 

with soap and water. The risk to health-care 

providers is of greater concern with some agents. 

Secondary exposure might be a hazard with very 

potent bacterial protein toxins, such

as botulinum toxin or the staphylococcal 

enterotoxins. (Note that decontamination and 

isolation of patients or remains could be much more 

important and difficult after an attack with a bacteria 

or virus that replicates within the body.)

Remains of persons possibly contaminated with 

toxins should be handled as chemically 

contaminated remains. For the most part, toxins are 

more easily destroyed than chemical agents, and 

they are much more easily destroyed than 
50

spores of anthrax. Chemical disinfection of remains 

in 0.2% sodium hypochlorite solution for

10 minutes would destroy all surface toxin (and even 

anthrax spores), greatly reducing the risk of 

secondary exposure.

SAMPLE COLLECTION: General Rules 

for Toxins

Identifying toxins or their metabolites (breakdown products) in biological samples (blood, urine, 

feces, saliva or body tissues) is difficult for several 

reasons. In the case of the most toxic toxins, 

relatively few molecules of toxin need be present in 

the body to cause an effect, therefore, ”finding” them 

requires extremely sensitive assays. Secondly, the 

most toxic, and most likely to be seen on the 

battlefield, are proteins, a class of molecules which 

our bodies break down and process. Therefore, 

these toxins and pieces of them after breakdown 

often ”blend into the scenery” of the body and, at 

some point, are no

longer identifiable.

Typically, we must look for the toxin itself or its 

metabolites, not an antibody response, as can be 

done with infectious agents. It is very unlikely that 

anyone receiving a lethal dose of any of the toxins 

would live long enough to be able to mount an 

antibody response. However, with certain protein 

toxins (ricin and the staphylococcal enterotoxins) 

that are highly immunogenic and less lethal, one 
51

might expect to see antibodies produced in soldiers 

who received a single exposure and survived. These 

might be seen as early as two weeks after 

exposure.

Certain toxins can be identified in the serum of 

animals, therefore probably humans, exposed by 

inhalation. Blood samples should be collected in 

sterile tubes and kept frozen, or at least cold,

preferably after clotting and removal of cells. If 

collected within the first day, swab samples taken 

from the nasal mucosa may be useful in identifying 

several of the toxins. These too, should

be kept cold. As a general rule, all samples that are 

allowed to remain at room temperature 

(approximately 75-800F) or above for any length of 

time will have little value.

Biological samples from patients are generally 

not as useful for diagnosis of intoxications as they ar 

for diagnosis of infectious diseases. The same is 

true of postmortem samples. The literature

suggests that botulinum toxins can be isolated from 

liver and spleen, even when they cannot be isolated 

from blood. We can identify ricin with immunoassays 

in extracts of lung, liver, stomach and intestines up to 

24 hours after aerosol exposure. We have identified 

high doses of ricin in fixed lung tissue of aerosolexposed laboratory

animals by immunohistochemical methods. The 

staphylococcal enterotoxins can be detected by 

immunoassay in bronchial washes. Like blood
52

and swab samples, postmortem tissue or fluid 

samples should be kept cold, preferably frozen, until 

they can be assayed.

Environmental samples from munitions or swabs 

from environmental materials should be placed in 

sealed glass or Teflon containers, and kept dry and 

as cold as possible. Handling a dry or powdered 

toxin can be very dangerous, because the toxin may 

adhere to skin and clothing and could be inhaled.

TOXIN ANALYSIS AND 

IDENTIFICATION

Immunological and/or analytical assays are 

available for most of the toxins discussed in this 

document. Immunological methods, typically 

enzyme-linked immunosorbent assays (ELISA) or 

receptorbinding assays, are sensitive to 1-10 

nanograms/milliliter and require approximately 4 

hours to complete; these are being developed as

the definitive diagnostic tests for deployment. 

Analytical (chemical) methods are sensitive at low 

microgram to high nanogram amounts, and take 

approximately 2 hours to run, plus time for 

instrument setup and isolation or matrix removal 

when necessary; the latter can add days to the 

process. A small, sensitive, far-forward, fieldable 

assay for several toxins has been developed and 

similar kit assays are being developed for many of 

the other toxins described in this document. The 

polymerase chain reaction (PCR) technique,
53

which provides very sensitive means of detecting

and identifying the genetic material (DNA) of any 

living organism, can be used to detect remnants of 

the bacterial, plant or animal cells that might remain 

in the crude, impure toxin one would expect to find in 

a weapon. Finally, a new method of combining 

immunoassays with PCR may allow us to detect 

extremely small quantities of the toxins themselves. 

In their present state, PCR assays are primarily 

suited for use in the reference laboratory.

WATER TREATMENT

Questions often arise regarding the protection of 

water supplies from toxins. It is unlikely that a typical 

small-particle aerosol attack with toxins would 

significantly contaminate water supplies.

Furthermore, as a general rule, direct contamination 

of water supplies by pouring toxins into the water 

would require that it be done downstream of the 

processing plant and near the end user, even for the 

most toxic bacterial toxins-and normal chlorination 

methods are effective against some of the most 

potent toxins. Because of dilution, adding toxins to a 

lake or reservoir would be unlikely to cause human 

illness. Natural production of algal toxins (e.g., 

microcystin) in stagnant bodies of water could 

produce enough toxin to cause illness if that water 

were used for drinking. The following methods of 

water purification have been tested for the toxins 

listed.
54

Reverse osmosis systems are effective against:

Ricin - 64,000 daltons(molecular weight)

Microcystin - 1,000 daltons

T-2 - 466 daltons

Saxitoxin - 294 daltons

(Botulinum toxin - 150,000 daltons and SEB-

 28,494 daltons not tested:expect same result)

Coagulation/flocculation

Not effective for removing ricin, microcystin, T-2 

or saxitoxin from water.

Chlorine

Five milligrams/liter (5 parts per million) free, 

available chlorine (household bleach) for 30 minutes 

destroys botulinum toxin. This

concentration does not inactivate ricin, microcystin, 

T-2 or saxitoxin.

The Future

INTELLIGENCE: Information that 

protects soldiers

Readers of this document should now understand 

several important points about protecting soldiers 

and targets of terrorist attack from toxin weapons:

1) Fifteen to twenty of some 400 known toxins 

have the physical characteristics that make them 
55

threats against U.S. forces as potential MCBWs. 

However, many toxins could be used in weapons

to produce militarily significant/terrorist 

(psychological) effects -especially in poorly 

educated troops or in uninformed civilian 

populations.

2) Effective individual physical protective gear is 

available; soldiers must receive timely warning of an 

attack, however, if they are to use their protective 

masks effectively.

3) Most of the toxins with the characteristics that 

make them threats as MCBW are proteins, which is 

to our advantage; vaccines or passive antibody 

therapy are developed relatively easily.

4) Immunizing troops, much preferred to treating 

intoxicated troops after exposure, typically requires 

a minimum of 4-15 weeks.

5) Development of medical countermeasures 

against likely MCBWs is feasible.

In addition, research for and development of a 

vaccine or passive antibody therapy through final 

approval by the U.S. Food and Drug Administration 

as a product for human use is likely to require a 

minimum of 4-7 years (8-10 years in some cases). 

Because developing and producing 

countermeasures takes years, intelligence 

information regarding toxin research for weapons 

development and aggressor capability analysis is 

invaluable. Our own understanding of the physical 

characteristics of toxins, even without intelligence

information, allows us to deduce what may be 

possible for the aggressor; this information 
56

reduces the list of toxins from hundreds to less than 

20. Good intelligence on threat research and 

development can, at a minimum, help those 

responsible for research and development of 

medical countermeasures prioritize finite resources, 

and thus reduce the time of the research and 

development cycle. Good intelligence on 

weaponized toxins held by an aggressor will also 

greatly assist leaders who must make decisions to 

immunize troops as they prepare for conflict. 

Therefore, as regards medical defense against toxin 

weapons, a strong and effective intelligence effort is 

both necessary and cost-effective.

TOXINS AS WEAPONS

Research literature suggests that we have 

discovered the majority of the “most toxic” 

(LD50<0.0025 micrograms/kilogram) naturally 

occurring toxins. New toxins of lesser toxicity, 

especially the venom toxins, are being discovered at 

the rate of perhaps 10-30 per year. There is little 

precedence in the literature for artificially increasing 

the toxicities of naturally occurring

toxins; however, it might be possible to increase the 

physical stability of toxins that are toxic enough but 

too unstable to weaponize. This could increase the 

effectiveness of the threat toxins.

It is unlikely that chemical synthesis of complex 

nonprotein toxins will become significantly easier 
57

in the near future. It is likely, however, that largescale biosynthesis of peptide toxins of 10-15

amino acids (some of the venom toxins) will become 

possible in the next few years.

I have attempted to present a rationale for 

focusing our medical biological defense resources 

on the development of medical countermeasures

for those toxins that our soldiers are most likely to 

face on the battlefield in the next 5 years. We must 

also continue limited basic research efforts and 

maintain “technical watch” of the peptide and other 

toxins that could become the next generation of toxin 

weapons. Medical defense against biological 

weapons requires constant vigilance, especially 

today, because biotechnology is now available 

worldwide.

COUNTERMEASURES TO TOXINS

Although the threat of toxin weapons of the future 

is formidable, the prospect of new and better 

medical countermeasures is brighter than ever 

before. Biotechnology may have more value to those 

of us developing countermeasures than to those 

who would use toxins maliciously. Molecular 

biological techniques developed in the last few 

years now allow us to produce more effective and 

less expensive vaccines against the protein and 

peptide toxins. Such vaccines will likely be available 

for the most important toxins within the next few 

years. We are making good 
58

progress on developing recombinant vaccines for 

certain highthreat toxins. Similar technology allows 

us to produce human antibodies, which will 

eventually replace those now produced in animals. 

Human antibodies will be a significant advance over 

despeciated horse antibodies, allowing us to protect 

unvaccinated soldiers by simply giving them an 

injection before they go into battle, thereby providing 

immediate protection. Human

antibodies could also find application in 

counterterrorism as therapy.

PROTECTING SOLDIERS

Protecting soldiers on the battlefield from toxinsand replicating agents-is possible if we use our 

combined resources effectively. Physical 

countermeasures such as the protective mask, 

clothing and decontamination capabilities exist and 

are effective; as we improve our battlefield detection 

systems, early warning of our soldiers may become 

a reality, at least in subpopulations within our forces. 

These assets, unlike most medical 

countermeasures, are generally generic and protect 

against most or all of the agents.

Among the medical countermeasures, vaccines are 

available and effective for some of the most 

important agents and therapies exist for others. 

Because of limited resources available to develop

vaccines, diagnostics and therapies, we can field 

specific medical countermeasures only to a 
59

relatively small group of threat agents. Our efforts in 

this area must be carefully focused. A third and

complementary element of our defensive program 

must be good intelligence. Only through knowledge 

of specific threat agents, delivery systems, and 

national capabilities can we assure effective 

development and use of our physical and medical 

countermeasures.

Finally, our renewed understanding of the real 

strengths and weaknesses of toxins as weapons 

allows us to put them in perspective in educating

our soldiers, removing much of the mystique-and 

associated fear-surrounding toxins. Knowledge of 

the threat thus reduces the threat to our soldiers.
60

About the Author...

Colonel David R. Franz, former Commander of the 

U.S. Army Medical Research Institute of Infectious 

Diseases, has served within the Medical Research 

and Development Command for 23 of his 27 years 

on active duty. He was assigned to four of the 

Command's laboratories as well as the 

headquarters and has personally conducted 

research and published in the areas of frostbite 

pathogenesis, organophosphate chemical warfare 

agent effects on pulmonary and upper airways 

function, the role of cell-mediated small vessel 

dysfunction in cerebral malaria, and most recently, 

medical countermeasures to the biological toxins. 

Before joining the Command, he served as Group 

Veterinarian for the 10th Special Forces Group. 

Colonel Franz served as Chief Inspector on three 

United Nations Special Commission biological 

warfare inspection missions to Iraq and as 

technical advisor on long-term monitoring. He also 

served as a member of the first two US/UK teams 

which visited Russia in support of the Trilateral 

Joint Statement on Biological Weapons and as a 

member of the Trilateral Experts' Committee for 

BW negotiations. Colonel Franz holds the D.V.M. 

degree from Kansas State University and the 

Ph.D. in Physiology from Baylor College of 

Medicine. COL Franz retired from active duty in 

August, 1998 and remains actively employed in 

the biodefense community.