07 - Source Answers -
Botulinum toxin is among the most poisonous substances known.
The toxin, which can be ingested or inhaled, and which disrupts
transmission of nerve impulses to muscles, is naturally produced
by the bacterium Clostridium botulinum.
Certain strains of C. baratii and C. butyricum can also be
capable of producing the toxin.
Botulinum toxin has become well known in recent years for two
reasons. First, the toxin has become a weapon in the arsenal of
terrorists. Contamination of food is one route for infection
with the toxin. The toxin can also be released into the air,
which was attempted on at least three occasions between 1990 and
1995 by the Japanese cult Aum Shinrikyo. The government of Iraq
admitted to United Nations inspectors following the 1991 Persian
Gulf War that tens of thousands of liters of botulism toxin had
been produced and loaded into weapons. The toxin was the most
numerous of all the biological weapons then developed by Iraq.
Paradoxically, the other reason for the toxin's fame is the use
of the toxin as a cosmetic enhancement (i.e., "botox").
There are at least seven structurally different versions of
botulinum toxin. The type designated as type A is responsible
for some food-borne outbreaks in the United States and elsewhere.
Improperly canned foods are a particular threat.
Clostridium botulinum is a spore-forming bacterium. Like the
well-known anthrax bacillus, the spores of Clostridium botulinum
can persist in the environment for many years and, when
conditions become more favorable (i.e., in a wound, food, and
the lungs) the spore can germinate and free the toxin. Dried
preparations of the spores can thus represent a terrorist weapon.
The use of botulinum toxin as a weapon began in the 1930s, with
experiments conducted by the Japanese on prisoners during the
occupation of Manchuria. In World War II, plans were made to
vaccinate Allied troops participating in the D-day invasion of
Normandy, because of concerns that Germany had weaponized the
toxin. Even the United States maintained an active biological
weapons program, including the use of botulism toxin, into the
Botulism toxin acts by preventing the transmission of nerve
signals between the nerves that connect with muscle cells.
Progressive functional deterioration of the affected muscles
occurs. Symptoms of botulism intoxication include dizziness,
blurred or double vision, nausea, vomiting, diarrhea, and
weakness of muscles in various areas of the body. The muscle
failure can be so severe as to lead to coma and respiratory
arrest. Even in those who survive exposure to the toxin,
complete recovery can take months.
Tucker, J.B., (ed.). Toxic Terror: Assessing the Terrorist Use
of Chemical and Biological Weapons. Cambridge: MIT Press, 2000.
Byrne, M.P., and L.A. Smith. "Development of Vaccines for
Prevention of Botulism." Biochimie no. 82 (2000): 955–966.
Kahn, A.S., S. Morse, and S. Lillibridge. "Public-health
Prepardness for Biological Terrorism in the USA." Lancet no. 356
Montecucco, C. (ed.). "Clostridial Neurotoxins: The Molecular
Pathogenesis of Tetanus and Botulism." Current Topics in
Microbiology and Immunology no. 195 (1995): 1–278.
Lacy, D.B., W. Tepp, A.C. Cohen, et al. "Crystal Structure of
Botulinum Neurotoxin Type A and Implications for Toxicity."
Nature Structural Biology no. 5 (1998): 898–902.
Centers for Disease Control and Prevention. "Botulism." Public
Health Emergency Preparedness and Response. February 7, 2003. <http://www.bt.cdc.gov/agent/botulism/index.asp>(April
Johns Hopkins University. "Botulinum Toxin." Center for Civilian
Biodefense Strategies. 2002. <http://www.hopkins-biodefense.org/pages/agents/agentbotox.html>(April
07 - Botulinum toxin -
Richard Robinson -
Botulinum toxin is the purified form of a poison created by the
bacterium Clostridium botulinum. These bacteria grow in
improperly canned food and cause botulism poisoning. Minute
amounts of the purified form can be injected into muscles to
prevent them from contracting; it is used in this way to treat a
wide variety of disorders and cosmetic conditions.
Botulinum toxin was developed to treat strabismus (cross-eye or
lazy eye), and was shortly thereafter discovered to be highly
effective for many forms of dystonia. Spasticity can also be
effectively treated with botulinum toxin. Injected into selected
small muscles of the face, it can reduce wrinkling. Other
conditions treated with botulinum toxin include:
* back pain
* excess saliva production
* eyelid spasm
* hemifacial spasm
* palatal myoclonus
* spastic bladder
* uncontrollable eye blinking
It is important to note that as of early 2004, the only Food and
Drug Administration-approved uses for botulinum toxin are for
certain forms of dystonia, hemifacial spasm, strabismus,
blepharospasm (eyelid spasms), and certain types of facial
wrinkles. While there is general recognition that certain other
conditions can be effectively treated with botulinum toxin,
other uses, including for headache or migraine, are considered
A solution of botulinum toxin is injected into the overactive
muscle. The toxin is taken up by nerve endings at the junction
between nerve and muscle. Once inside the cell, the toxin
divides a protein. The normal job of this protein is to help the
nerve release a chemical, a neurotransmitter, which stimulates
the muscle to contract. When botulinum toxin divides the protein,
the nerve cannot release the neurotransmitter, and the muscle
cannot contract as forcefully.
The effects of botulinum toxin begin to be felt several days
after the injection. They reach their peak usually within two
weeks, and then gradually fade over the next 2–3 months. Since
the effects of the toxin disappear after several months,
reinjection is necessary for continued muscle relaxation.
In the United States, purified botulinum toxin is available in
two commercial forms: Botox and MyoBloc. The recommended doses
of the two products are quite different, owing to the differing
potencies of the two products. The size of the muscle and the
degree of weakening desired also affect the dose injected. For
Botox, the maximum recommended dose for adults is 400–600 units
in any three-month period, while for MyoBloc it is 10,000–15,000
units. The maximum dosage may be reached in the treatment of
spasticity or cervical dystonia, while much smaller amounts are
used in the treatment of facial lines, strabismus, and
When injected by a trained physician, botulinum toxin is very
safe. The toxin remains mainly in the muscle injected, spreading
only slightly to surrounding muscles or beyond. Botulism
poisoning, which occurs after ingesting large amounts of the
toxin, is due to the effects of the poison on the breathing
muscles. In medical use, far less toxin is injected, and care is
taken to avoid any chance of spread to muscles needed for
breathing. Injection into the shoulders or neck may weaken
muscles used for swallowing, which patients need to be aware of.
Some patients may need to change to a softer diet to make
swallowing easier during the peak effect of their treatment.
Repeated injections of large amounts of botulinum toxin can lead
to immune system resistance. While this is not a dangerous
condition, it makes further treatment ineffective.
Patients with neuromuscular disease should not receive treatment
with botulinum toxin without careful consultation with a
neurologist familiar with its effects.
Botulinum toxin can cause a mild flu-like syndrome for several
days after injection. Injection of too much toxin causes excess
weakness, which may make it difficult to carry on normal
activities of daily living. In some patients, toxin injection
may cause blurred vision and dry mouth. This is more common in
patients receiving MyoBloc than with Botox.
Patients taking aminoglycoside antibiotics may be cautioned
against treatment with botulinum toxin. These antibiotics
include gentamicin, kanamycin, and tobramycin, among others.
Brin, M. F., M. Hallett, and J. Jankovic, editors. Scientific
and Therapeutic Aspects of Botulinum Toxin. Philadelphia:
WE MOVE. December 4, 2003 (February 18, 2004).
MD Virtual University. December 4, 2003 (February 18, 2004).