Transcript CBW (by popular request)

CBW
CH 339K
CBW - An Ancient Tradition
Sixth Century B.C.
431-404 B.C.
Fourth Century B.C.
Circa 200 B.C.
187 B.C.
7th Century
~ 1040
1347
1672
1767
1855
Assyrians reportedly used ergot fungus (Claviceps purpurea) to poison their enemy’s
water wells
Spartan armies use sulfur and toxic arsenic smoke during Peloponnesian War
Chinese engineers use arsenic against underground sappers.
Officers in Hannibal’s army adulterate the wine of African rebels with mandrake,
which contains belladonna alkaloids causing hallucinations.
Ambraciots (Greece) employ irritating smoke against Roman soldiers
The Byzantine architect, Callinicus (“Kallinikos”), invents the first liquid incendiary—
“Greek Fire.”
Scottish king poisons wine using a belladonna-like (“sleepy nightshade”) herb and
gives to Norwegian enemies as “provisions” under pretense of surrender. Scots then
slaughter the incapacitated Norwegians.
Mongolians lay siege to Kaffa (in modern Ukraine) and throw corpses over city walls
to spread bubonic plague.
Bishop of Münster attempted the use of atropine-like drug in grenades in siege
against city of Groningen. Attack backfires.
British plot to supply cloths from a smallpox hospital ward to American Indian tribes
in hopes of spreading disease.
Sir Lyon Playfair suggests using cyanide-containing chemicals against Russian troops
during Crimean War.
Fritz Haber
• 1868 – 1934
• 1918 Nobel for
synthesis of ammonia
(Haber process)
• Father of modern
chemical warfare
(probably has a
plaque on his office
door in Hell)
Haber’s Law
W  Ct
Where
• W = Haber Product, also known as lethality index
• C = Concentration of the agent in the air
• t = time of exposure
The lower the Haber Product, the more lethal the agent
Lower concentration for a longer time will yield the same effects as a larger
concentration over a shorter exposure
Beginnings
• The large-scale use of poison gas in modern warfare
originated during WWI in the battle of Ypres, April 22, 1915
– 168 tons of Cl2 were released from cylinders along a 4 mile
front
– 5700+ cylinders of gas, weighing 90 lbs. each
– 6000+ French troops were killed within 10 minutes
– Due to the vagaries of wind and the crude delivery
method, a fair number of Germans were also killed or
wounded
• 1.3 million casualties, 91,000 fatalities were attributed to the
use of phosgene, chlorine, and mustard gas during the course
of the war.
• Including my grand uncle Bill
Modern Chemical Agents
• Early Agents (WW1)
– Inhalation (Choking) Agents
• Chlorine
• Chloropicrin
• Phosgene
– Vesicants
• Mustards
• Lewisite
– Blood Agents (Metabolic Poisons)
• Cyanide
Post-WWI Agents
– Nerve “gases”
Chlorine
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Thick greenish vapor
First used by Germans in 1915
Dispensed from gas cylinders
Caused massive casualties due to total lack of
defense
Chlorine Effects (Initial)
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Burning pain in the throat and eyes,
Sensation of suffocation;
Painin the chest, especially behind the sternum.
Rapid, painful, difficult respiration with coughing
Profuse lachrymation.
Retching and vomiting,
Severe headache
Face violet red, ears and finger nails blue
Respiration often over 40 and sometimes even 80 a minute
Dyspnoea lasts about thirty-six hours, after which it gradually
subsides, if death does not occur before. The patient then
falls asleep and wakes up feeling much relieved.
Chlorine Effects (Pneumonial Stage)
• A few hours later acute bronchitis or broncho-pneumonia
develops.
• Sputum viscid, yellow or greenish, and muco-purulent with
occasional streaks of blood.
• Respiration shallow and rapid, up to 80 a minute.
• Rapid pulse
• Fever as high as 104.
• Possible delirium.
• Pleurisy may occur
• Empyema and gangrene of the lung may occur.
• Most survive after long recovery
Use of Chlorine
French cylinder attack on German trenches in Flanders, year unknown.
Note dependence on wind direction for successful attack.
Chloropicrin
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CCl3NO2
pungent, colorless, oily liquid
oral–nasal irritation, coughing, and vomiting
LC50 = 20,000+ mg-min/m3 (i.e. usually sublethal)
First used by Russians in 1916 in hand grenades
Used as secondary agent to make targets remove
their masks to vomit
• Used today as a fumigant
Phosgene
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COCl2
Colorless gas, smells like new mown hay
BP 8o C
LC50 = 3200 mg-min/m3
Common industrial chemical
Reacts with amino groups on surface proteins of
the lung alveolar cells, cross linking them
• Shortness of breath, coughing, tight chest, fluid
buildup in lungs causing asphyxia
• Can be asymptomatic for up to 24 hours
Synthesis
CO + Cl2 → COCl2 (ΔHrxn = −107.6kJ/mol)
• Purified caron monoxide and chlorine gas are passed
together through a porous bed of activated carbon
• Reactor must e cooled to temps of 50 – 150o C
Sulfur Mustards
Bis (beta-chloroethyl) sulfide
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Vesicant (blister agent)
Alkylating agent cross-links lipids, proteins, and DNA
Not very volatile (610 mg/l at 20o C)
Strong smell like horseradish or garlic
Persistant agent
LD50 (human) = 20 mg/kg pericutaneous
LC30 (human) = 900 mg-min/m3 by inhalation
Interestingly, the Canadians in 1942 determined that
anthrax spores can survive in sulfur mustard
Action
• Sulfur mustard readily loses Cl- to form a highly reactive
cyclic sulphonium ion
• This ion reacts with free amino groups on biomolecules –
e.g. guanine nucleotides in DNA, lysine residues in proteins
• Molecular disruption – particularly of DNA – leads to cell
death.
• Blistering of skin
• Blindness from eye damage
• Lung damage and asphyxia due to filling of lungs with fluid
Use of Mustard
• WW1 – both sides
• Second Italo-Abysinnian War 1935-36 (League
of Nations fretted and did nothing)
• Sino-Japanese War
• Iran-Iraq War
• American troops exposed to low levels during
Gulf War 1
Mustard (continued)
Iranian victim of Iraqi mustard attack, 1980’s
Americans blinded by mustard,
France, 1918
Production
Pre-WWII mustard production plant at
Edgewood Arsenal, MD
Synthesis
1)
2)
Lommel-Steinkopf method using 2-chloroethanol
Modern method using ethylene oxide
Synthesis
3)
4)
Levinstein method using ethylene
Radical addition reaction using vinyl chloride
Lewisite
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Talked about before as inhibitor of PDH
LC50 = 1300 mg-min/m3
Severe chemical burns
Inhalation causes a burning pain, sneezing,
coughing, vomiting, and pulmonary edema
• AFAIK, never used (manufacturing process was
being worked out when WW1 ended)
• Significant numbers of Chinese were killed in the
latter years of the 20th century from accidental
exposure to stockpiles left by the Japanese
Cyanide (HCN or salt thereof)
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By inhalation or skin adsorption
LC50 = 3000 mg-min/m3
First used by Austria in 1915
Used by Iraq against both Iran and Iraqi Kurds
More commonly used for assassinations,
murders, and executions (not easy to
disseminate on battlefield)
• Used by KGB to assassinate Stepan Bandera,
Ukranian resistance leader, in Germany in
1959
Nerve Agents
• We talked about these with respect to enzyme
inhibitors
• Organophosphates first developed by IG
Farben in 1936
• Extensively produced by Germans but never
used in WWII
• Russians in Afghanistan (?), Iraq versus Iran
and versus Kurds
• Tokyo subway attacks of 1995 by Aum
Shinrikyo
Irreversible Inhibition at the NM Junction
Nerve Gases
Sarin
Tabun
Soman
VX
Symptoms: Contraction of pupils, profuse salivation, convulsions, involuntary
urination and defecation and eventual death by asphyxiation as control is lost over
respiratory muscles.
Action of Nerve Agents
Common Nerve Agents
Toxicity of Nerve Agents
Agent
LD50 (human)
LC50
Tabun (GA)
1000 mg
400 mg/min-m3
Sarin (GB)
1700 mg
100 mg/min-m3
Soman (GD)
50 mg
70 mg/min-m3
VX
10 mg
50 mg/min-m3
Use of nerve agents
• Iraq produced (admitted values)
– 3.9 tons of VX
– 795 tons of Sarin
– 210 tons of Tabun
– In addition to 2850 tons of good old mustard.
• Sarin and Tabun were loaded into bombs and
ballistic missile warheads.
Synthesis
Synthesis (cont.)
Alternative syntheses for sarin (GB)
Top: binary synthesis (components used in inary munitions)
Bottom: Di-di process using methyl phosphonyl difluoride and methyl
phosphonyl dichloride
Production
US GB (Sarin) Production Plant, Rocky Mountain Arsenal, CO
(now closed)
Delivery
BLU-80B Bigeye Binary Chemical Munition
Could deliver 180 lbs. VX
Delivery (cont.)
Honest John rocket warhead
containing M139 bomblets,
each with about 1.5 lbs of
Sarin
Binary munitions
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Binary munitions contain reactants which produce active agent on mixing
Can e shipped and stored with only one (or no) components present
Final filling at staging are before use
Greater safety in storage and transport
Delivery (cont.)
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M687 Binary 155mm Projectile
Forward chamber contains methyl phosphonyl difluoride
Rear contains mixture of isopropyl alcohol and isopropyl amine
Munition is shipped / stored with rear compartment empty for safe
handling – filled for final use
• Separation between chambers id broken upon firing, creating agent
“on the fly.”
Delivery (cont.)
• M23 Chemical Land Mine
• Last units were destroyed in 2008
• Charged with 10.5 lbs VX
Nerve Gas Antidotes
Atropine sulfate from Atropa belladonna (left)
competes with acetylcholine for the receptor
binding site
Blocks ACH and offsets the effects of the nerve agent
Pralidoxime Hydrochloride
(Pyridine Aldoxime Methyl Chloride)
Usually given along with atropine
Reversibly binds to the enzyme acetylcholinesterase,
competing with organophosphate binding.
Doesn’t inhibit acetylcholinesterase – reactivator.
2-PAM Action
Antidote Delivery
• US Mark 1 anti-nerve agent kit containing (top to
bottom) atropine autoinjector, 2-PAM autoinjector, and
the carrying case. The two autoinjectors are held
together by a safety clip which prevents accidental
discharge
Chemical Agents - Persistence
Classification of agents as “persisting,”
“transitional,” or “volatile” based on
dispersal times.
Wind conditions, rainfall, and
cloudiness will also impact persistence
Persistent agents are best used for
area denial; volatile agents if attacking
troops are to follow through.
Biochemical Weapons
• Split the difference between Chemical and
Biological
• Mostly Protein toxins
Amount of toxin needed to lethally expose humans in a 100 km2 (38 mile2)area.
(from Spertzel RO, Wannemacher RW, Patrick WC, Linden CD,
Franz DR. Technical Ramifications of Inclusion of Toxins in the Chemical Weapons Convention (CWC).
Alexandria, Va: Defense Nuclear Agency; 1992: 18. DNA Technical Report 92-116.)
LCt50 for Selected Aerosols
Botulinum Toxin
• Clostridium botulinum is a spore-forming, anaerobic
bacterium found worldwide in soil.
• Mix of 7 related toxins
• LD50 = 1 ng/kg subq, 3 ng/kg inhaled
• Bind to receptor on nerve cell
• Taken in by receptor-mediated endocytosis
• Prevents release of acetylcholine at synaptic cleft
• Death by flaccid paralysis, respiratory failure
• 6000 liters of concentrate were produced at Al Hakkam in
1990
• Delivery by warhead or from underwing spray tanks
• High terrorist potential but technically difficult to produce
• High lethality, low persistence
Ricin and related toxins
• We’ve discussed extensively
• US and England produced and tested a ricin
bomb in WWII, but never used.
• Inhalation causes death through lung damage
rather than the organ failure seen in internal
exposures
• Diffuse necrotizing pneumonia
• Not as toxic as botulinum, but easy to produce
in large quantities
Georgi Markov
1929-1978
Assassinated by Bulgarian secret police in London ricin
attack
• Modified umbrella used as
delivery device
• Pellet contained ricin (note
size)
Ricinus communis – castor oil plant
Ricin
Ricin B chain
(the attachment bit)
Ricin uptake and release
1.
2.
3.
4.
5.
6.
7.
endocytosis by coated pits and
vesicles or,
endocytosos by smooth pits and
vesicles. The vesicles fuse with an
endosome.
Many ricin molecules are returned
to the cell surface by exocytosis, or
the vesicles may fuse to lysosomes
where the ricin would be destroyed.
If the ricin-containing vesicles fuse
to the Trans Golgi Network, (TGN),
thereís still a chance they may
return to the cell surface.
Toxic action will occur when RTA,
aided by RTB, penetrates the TGN
membrane and is liberated into the
cytosol.
The possibility that
ricin might be used as
an asymmetric
warfare weapon has
not escaped the
attention of the armed
services.
The last time I knew
for sure, there were
no effective antidotes.
Significant Terrorist Incidents Involving Chemical and Biological Agents
Year
1946
1970
1972
1974
1980
1984
1991
1990-1995
1995
1995
1998
2001
2003-2004
Organization
Agents
DIN
Arsenic Compounds
("Revenge" in Hebrew; also
Dahm Y'Israel Nokeam, "Avenging
Israel's Blood")
(Germany)
Weather Underground
Tried to obtain agents from Ft. Detrick by
(United States)
blackmailing a homosexual serviceman.
R.I.S.E
Typhoid, diphtheria, dysentery, meningitis and several
(United States)
others to be delivered by aerosol.
Aliens of America
Nerve Agents
(Alphabet Bomber)
(United States)
R.A.F.
Botulinum toxin
(Rote Armee Faktion)
(Germany)
Rajneshee Cult (United States)
Salmonella enterica serovar typhimurium
Minnesota Patriots Council
(United States)
Aum Shinrikyo
(Japan)
Aryan Nation
(United States)
The Covenant and the Sword
(United States)
Republic of Texas
(United States)
Unknown (United States)
Fallen Angel (United States)
Ricin
Bacteria and viral agents, toxins, organophosphorus
nerve agents.
Yersinia pestis
Ricin
Bacterial and viral agents
Bacillus anthracis
Ricin
Biological Weapons
• Bacterial
–
–
–
–
–
–
Anthrax
Plague
Tularemia
Brucellosis
Glanders
Q Fever
• Viral
– Smallpox
– Encephalitis
– Hemorrhagic Fevers
Biologicals – Modern Use
• Japan dropped plague infected fleas over various parts of China in 1940 –
42
• Several thousand prisoners and POWs died from anthrax, botulism,
brucellosis, cholera, dysentery, gas gangrene, meningococcal infection,
and plague.
• Iraq prepared the following prior to GW1
– 166 bombs (100 botulinum toxin, 50 anthrax, 16 aflatoxin);
– 25 Scud/Al Hussein missile warheads (13 botulinum toxin, 10 anthrax, 2
aflatoxin);
– 122-mm rockets filled with anthrax, botulinum toxin, and aflatoxin;
– 422 spray tanks capable of being fitted to a fighter aircraft or remotely piloted
aircraft, and spraying 2,000 L over a target
– artillery shells.
• The Soviets had an enormous biological program up to the collapse of the
USSR, despite signing the 1972 convention against BW
• Richard Nixon terminated the American offensive BW program in 1969
Anthrax
• Discussed when we talked about bacterial cell
walls
• Spore formers make good weapons
• Produces two exotoxins
– Lethal toxin
– Edema toxin
• Proteins have A and B chains
• B chain is same for both – 83 kdal cell binding
domain
• 90 kdal Lethal factor
• 89 kdal edema factor
Cutaneous anthrax
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Most common non-intended form
Handling of infected animals or animal products
< 1% lethal with treatment
1-2 cm blister that ruptures to leave necrotic ulcer
Inhalation anthrax
• Inhalation of spores
• High lethality even with treatment
• Frequently leads to meningitis
Characteristic widening
of mediastinum
GI anthrax
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Consumption of infected meat
Up to 50% lethality
Nausea and vomiting (possibly bloody)
Anorexia
Bloody diarrhea
Incubation usually 1 week or less
Spore formation
Figure 1. Stages of sporulation. (A) Stage
0/I, (B) stage II, (C) stage
III, (D) stage IV, (E) released spore. The
hatched line around the
spore in panels D and E is the coat.
From: Cell. Mol. Life Sci. 59 (2002)
Bacillus anthracis
Production
Do not try this at home!!!!!
1.
It will not work as shown
2.
You will die
3.
Everyone you know will
go to Gitmo
Delivery
The M33 500-lb biological cluster bomb, which
held 108 of the M114 bombs. Photograph: Chemical
and Biological Defense Command Historical Research
and Response Team, Aberdeen Proving Ground, Md.
Plague
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Black Death killed millions in Europe in 1400’s
Causative agent is Yersinia pestis
Endemic in wild rodent populations
Gram -, does not form spores
Bubonic Plague
• Characterized by formation of
buboes – erthymatous, tender
swollen lymph nodes
• Fever, headache, chills, nausea,
vomiting, prostration, coma
• 5-15% will develop pneumonic
plague
• 11-12% fatal in USA
Septicemic Plague
• Fever, chills, vomiting,
diarrhea, purpura, and
necrosis of extremities
• 33% mortality in USA
• Can be primary, or
secondary effect of
bubonic form
Parient recovering from
septicemic plague – note
necrosis of nose and fingers
Pneumonic plague
• Highly infectious
person-to-person
through aerosol
• Mortality 50% with
treatment, essentially
100% without
Dispersal
• Japanese found that bacterial dispersal was
inefficient
• Clay “bombs” containing infected fleas can be
dropped with 80% flea survival
• Each flea can pass > 20,000 bacteria per feeding
• In the late 80’s, Russians developed a dry,
antibiotic-resistant weaponized form for direct
dispersal
• Direct dispersal (particles suspended in air)
produces very high incidence of pneumonic
disease
Tularemia – rabbit fever
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Francisella tularensis – gram negative
Fever, localized skin lesions, lymphadenopathy, pneumonia
High infectivity
Pneumonic form has high mortality
Low persistence (unlike anthrax)
(Formerly) used in cluster bombs
Vaccine available
Possibly used by Hittites – 14th century BC – sending infected sheep as
gifts
Cutaneous Tularemia
Francisella inside a liver cell
Brucellosis
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Brucella sp. – gram negative coccobacilli
Mainly infects ruminants in nature
Field tested 1944-45, never used
Development terminated in USA in 1967
Aerosols highly infectious
Q fever
• Coxiella burnettii
• Rickettsia, normal reservoir in livestock
• Extremely High infectivity (as low as 1
particle)
• Moderately lethal, but a good incapacitant
Virus weapons
• Good points
– Not readily treatable
– High lethality in some cases
– Easier to engineer
• Bad points
– Difficult to stabilize, store, and disperse
– Many viruses can be stabilized using very high
concentrations of trehalose to form a glasslike
material
Smallpox
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Russians produced in large quantities
Infects only humans
Highly infectious (10-100 particles)
35% mortality
Extinct (hopefully) in the wild
Stocks at Ft. Detrick, CDC in Atlanta, and Vektor – and (I
think) Porton Down
Other Virus Agents
Venezuelan
equine
encephalitis virus
Incubation:
1 to 5 days
10 to 100
organisms
Length of illness:
1 to 2 weeks
Incubation:
3 to 6 days
Length of
illness:
1 to 2 weeks
5% mortality
rate
No specific
therapy exists
Vaccine
available
Nausea,
vomiting,
cough, sore
throat and
diarrhea can
follow
Low mortality
rate
Yellow fever virus
Sudden onset of
fever, severe
headache, and
muscle pain
1 to 10 organisms
Severe fever,
headache, cough,
nausea, vomiting,
vascular
complications
(including easy
bleeding, low
blood pressure)
No specific
therapy exists
Vaccine
available
Hemorrhagic Fever Viruses
• High lethality
– Marburg 50%
– Ebola 60-90% depending on strain
• Tie up medical resources
• Generally non-contagious
• Russians weaponized Marburg virus, probably
others
Delivery
British Canberra Bomber, outfitted for biological
agent delivery (notice spray apparatus)
Particle Penetration - Definitions
Delivery – Criticality of Particle Size
Particle Size
(microns)
Degree of
Infectivity
Target Penetration as a Function of Particle Size
Ideal particle size 15 mm for maximum
lung penetration
Maximizing particle “fluffiness”
• Silica particles in mix minimize van der Waals contacts and prevent
clumping
• Important to keep dry
• Powdered glass or similar materials can carry a charge and help
disperse particles
• Other tricks are no doubt locked in a safe somewhere
Effectiveness
Cost Effectiveness
Modality
Cost per km2 destroyed
Conventional
$6000
Nuclear
$2400
Chemical (Nerve Agent)
$1800
Biological
$3
Note: 1969 dollars not adjusted for inflation
“Destroyed” is defined as 50% casualty rate
Effectiveness by Amount Needed
Effectiveness of Biological Agents by
Infectivity
Recent Terrorist Uses of CBW
Significant Terrorist Incidents Involving Chemical and Biological Agents
Year
Organization
Agents
1946
DIN
("Revenge" in Hebrew; also Dahm Y'Israel
Nokeam, "Avenging Israel's Blood")
(Germany)
Arsenic Compounds
1970
Weather Underground
(United States)
R.I.S.E
(United States)
Aliens of America
(Alphabet Bomber)
(United States)
R.A.F.
(Rote Armee Faktion)
(Germany)
Rajneshee Cult (United States)
Tried to obtain agents from Ft. Detrick by blackmailing a
homosexual serviceman.
Typhoid, diphtheria, dysentery, meningitis and several others to be
delivered by aerosol.
Nerve Agents
Minnesota Patriots Council
(United States)
Aum Shinrikyo
(Japan)
Ricin
Aryan Nation
(United States)
The Covenant and the Sword
(United States)
Republic of Texas
(United States)
Unknown (United States)
Fallen Angel (United States)
Yersinia pestis
1972
1974
1980
1984
1991
1990-1995
1995
1995
1998
2001
2003-2004
Botulinum toxin
Salmonella enterica serovar typhimurium
Bacteria and viral agents, toxins, organophosphorus nerve agents.
Ricin
Bacterial and viral agents
Bacillus anthracis
Ricin
Just to Make You Feel Secure…
Vozrozhdeniye Island Biological Test Facility in Uzbekistan was the CCCP’s
primary biological weapons test site. It is/was located on an island in the
Aral Sea.
What could go wrong?
Thanks to the wonders of Soviet agricultural engineering…
Aral Sea 1971
Aral Sea 2001