Issues in Biotechnology:

The Way We Work With Life

Dr. Albert P. Kausch

life

edu.org
OnCampus
Live
BCH 190, MIC 190, AFS 190, NRS 190, PLS 190
OnLine BCH 190
A Sweeping General Survey on Life and Biotechnology
A Public Access College Course

The University of Rhode Island

Issues in Biotechnology:
Biotechnology, Our Society and Our Future

Issues in Biotechnology:
The Way We Work With Life
Dr. Albert Kausch
Kimberly Nelson

BCH 190

Section I. The Mechanics of DNA: What is Life?

Section II. The Applications of Biotechnology

A Sweeping General Survey on Life and Biotechnology

A Public Access College Course

The University of Rhode Islandlife

Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch

life edu.org
Section II

The Applications of
Biotechnology
A Sweeping General Survey on Life and Biotechnology
The University of Rhode Island

Agricultural Biotechnology
life_edu

Lectures 13 and 14

Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch

life edu.org
Medical Biotechnology
24. Part Ia. Some Background and Historical Highlights
25 . Part Ib. Stem Cells-Therapy and Medical Research
26. Part Ic. Animal and Human Cloning and Genetic Engineering
27 . Part II. Gene Therapy, Tissue Engineering and Nanotechnology
Part III. Biotechnology Applications in Tough Times.
28. Part IIIa. Pandemic Flu
29. Part IIIb. Bioweapons
Part IV Cancer Biology and Emergent Treatments.
30. Part IVa. Cancer Basics and Socio-Economic Burdens
31. Part IVb. Applications of Biotechnology in Cancer Treatment

Issues in Biotechnology:
The Way We Work With Life
Dr. Albert P. Kausch

life edu.org
Biotechnology Applications in Tough Times
Pandemic Flu
Bioweapons
A Sweeping General Survey on Life and Biotechnology

The University of Rhode Island

Application of Biotechnology

BIOTERRORISM: HISTORY AND UPDATE

BIOWEAPONS: NOW AND THE FUTURE
Dr. Albert Kausch
Department of Cell and Molecular Biology
The University of Rhode Island

IssuesinBiotechnology
Since the Anthrax attacks in 2001, if a large scale
biological weapons attach were to occur in New York,
Boston or Providence, I am informed for proper
evacuation and response procedures
A
B
C
D
F

Well informed
Somewhat informed
Unchanged
Confused
Totally unprepared

IssuesinBiotechnology
Since the Anthrax attacks in 2001, I feel that the treat of a
major bioweapons attack as addressed by Homeland
Security
A
B
C
D
F

Has been eliminated

Is greatly reduced
Is unchanged
Has worsened
Has significantly increased

IssuesinBiotechnology
Since September 11 2001, I feel that our threat from
terrorist attacks
A
B
C
D
F

Has been eliminated

Is greatly reduced
Is unchanged
Has worsened
Has significantly increased

IssuesinBiotechnology
Since 9/11 I would grade The US Government on
addressing Homeland Security as:
A
B
C
D
F

BIOTERRORISM: OVERVIEW
Deliberate use of microbial agents and toxins as
weapons
US vulnerable due to international political and
economic instability, state-supported and tolerated
terrorism, freedom of access
Global vulnerability due to increased
technological capabilities
Effective response requires coordination of
medical/public health system, emergency
management and law enforcement.

HISTORY
Exodus 9:3 - -5th plague visited upon Pharoah,
murrained carcassespestilence
14th century: Tartars catapult plague-infected
corpses into city of Kaffa
18th century: British use blankets to transmit
smallpox to hostile Native Americans
WWI: Germany uses glanders to infect livestock
bound for Allied forces
1932-45: Japan conducts large-scale human BW
field trials in Manchuria and China

History
1942-73: US program of offensive and defensive
BW, including human volunteer exposures
Cold War: superpowers active in research and
production of offensive weapons
1972: Biological Weapons and Toxin Convention
formally bans use or development of BW
1979: 68 deaths in Sverdlovsk due to
inadvertent release of Anthrax spores from
military facility

History
1984: Rajneeshee Cult in The Dalles, Oregon
deliberately contaminates commercial salad bars
with Salmonella to tilt election in Wasco county
Persian Gulf War: Iraq weaponizes BW agents
1995: Sarin nerve gas attacks in Tokyo subway
kills 12; Aum Shinrikyo cult developing BW.
1998-99:~50 Anthrax hoax threats in U.S.
11 Sept 2001: Multiple, massive terrorist attacks
in NYC, Wash DC
Sept-Dec 2001: deadly Anthrax attack in US

BIOWEAPONS AND IRAQ

BIOWEAPONS AND IRAQ

BIOWEAPONS
AND
THE UNITED STATES

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction

Al Hakam Single-Cell Protein
Plant. Iraq's major facility for the
production of biological warfare
agents.
Under the watchful eye of the
United Nations Special
Commission, this plant was
destroyed by Iraqi workers in May
and June of 1996. (Photo courtesy of Davis
Franz, DMV, PhD)

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction

Chronology of Germ Weapons in Iraq
According to the UN Special Commission on Iraq (UNSCOM) ,
Iraq's biological weapon program ran from 1973 until at least
1991. Iraq claimed that the program began with the establishment
of the Al-Hazen Institute as a dedicated BW facility. From 1974 to
1978, the Institute studied several germs - botulinum toxin,
anthrax spores, Shigella, and cholera - as well as viruses. The
Institute was closed on 16 January 1979 because of fraud by its
Chairman (Major Ghazan Ibrahim) and some senior staff.

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction

Chronology of BioWeapons in Iraq
In 1987, Iraq transferred the bulk of its biological weapon work to
Al-Salman's Technical Research Center in order to maintain the
program's secrecy and pushed work on anthrax spores and
botulinum toxin. In April 1988, began research on gas gangrene and
mycotoxins in 1987/88, then viruses and genetic engineering in 1990.
The virus studies at Al Salman focused on camelpox, infectious
hemorrhagic conjunctivitis and rotavirus
Factory at Al Hakam actually produced biological agents in 1988. In 1999
produced 19,000 liters of botulinum toxin, 8,500 liters of anthrax, and had
experimented with gases that produced gangrene. The facility reportedly
produced hundreds of liters of gas gangrene before the first Gulf war.

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction

Chronology of BioWeapons in Iraq

Iraq admitted that it weaponized biological agents between December

1990 and January 1991. The types of munitions under development
for use with biological weapons included Al Hussein missile warheads,
R-400 aerial bombs, aircraft drop tanks, pilotless aircraft, helicopterborne spraying systems ("The Zubaidy Device"), 122 mm rockets,
LD-250 aerial bombs, and fragmentation weapons.

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction

BioWeapons in Iraq
Aflatoxin: Iraqi scientists studied how to produce liver cancer using aflatoxin. Aflatoxin has no
direct military value, as its cancerous effects take years to develop. Iraq produced more than 2000
liters of aflatoxin, and admitted putting it into missile warheads and R-400 bombs.

Anthrax spores: One gram of dried anthrax spores has been estimated to contain about 10 million
lethal doses. The US Army estimates that a person inhaling 8,000 spores (weighing about .08
millionths of a gram) would be likely to die in less than a week. However, as the attacks on the
United States made clear, far fewer spores can cause death in some victims
Botulinum toxin: the most poisonous substance known - the average man would only have to
inhale about 70 billionths of a gram for it to be fatal. Eighty percent of victims die within 1-3 days
of being infected. Botulinum toxin attacks the central nervous system and blocks
neurotransmission. However, the toxin decomposes quickly when exposed to sun, air or heat,
which limits its effectiveness.

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction

BioWeapons in Iraq
Cholera: Cholera is passed naturally via contaminated food and water, and as a weapon would
most likely be used to poison water supplies. It causes diarrhea, which could cause death from
dehydration if not treated. However, cholera is not usually fatal - only debilitating and disruptive.
Iraq studied cholera at the Al Hazen Institute, but little is known about production or
weaponization.

Clostridium perfringens (gas gangrene): The Clostridium perfringens bacterium can cause gas
gangrene, which in turn causes toxic gases to form in the body's tissues. The result can be acute
lung distress, leaking blood vessels, the breakdown of the red blood cells or platelets (which enable
the blood to clot to stop bleeding), and liver damage. Inspectors believed Iraq could have produced
some 5,000 liters of clostridium perfringens, though it declared it had made far less.
Mycotoxins: Trichothecene mycotoxins are a family of poisonous compounds made from a mold
that grows on wheat, millet and barley. Mycotoxins can be absorbed by the skin, inhaled or
ingested. These toxins attack the cells of bone marrow, skin, and the G-I tract. They also block
blood clotting. It takes only about 35 milligrams in aerosol form to kill an average man, but
mycotoxins are considered only moderately lethal.

BIOWEAPONS
AND
IRAQ
IRAQ AND BIOWEAPONS:
A SPECIAL REPORT
WHAT WAS THE SITUATION? BioWeapons in Iraq
Camelpox: Camelpox causes fever and skin rash in camels but rarely infects humans. It is a virus
closely related to smallpox; thus, Iraq may have been studying camelpox in order to learn more
about using smallpox as a biological weapon.

Enterovirus 70: Enteroviruses are common human viruses that can cause flu, colds, or
pneumonia. While not fatal, they might weaken an enemy's military forces or disrupt its population
and medical care facilities. Iraq conducted research on Enterovirus 70 at the Daura site.
Infectious hemorrhagic conjunctivitis virus: This virus attacks the victim's eyes, causing a loss
of sight and in some cases bleeding. Iraq conducted preliminary studies on infectious hemorrhagic
conjunctivitis virus beginning in 1990 but is not known to have advanced farther.
Rotavirus: This virus causes diarrhea, which could theoretically cause death from dehydration if
not treated. However, rotavirus is more likely to simply debilitate its victims.
Smallpox: The virus can be inhaled or absorbed by the skin. Its initial symptoms are like a severe
flu, then a rash appears. Smallpox kills about a third of unvaccinated victims, but the vaccine is
highly effective. The virus can be stored over long periods of time if it is freeze-dried, and it is
easy to produce, making it a good candidate for biological warfare.

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction Iraq's Chemical Weapons

Well before Operation Desert Storm or the U.N. inspections that followed it, Iraq
had already begun to build chemical weapons.
After launching a research effort in the 1970s, Iraq was able to use chemical
weapons in its war against Iran and to kill large numbers of its own Kurdish
population in the 1980s.
By 1991, the United Nations had established its Special Commission (UNSCOM)
By the time UNSCOM left Iraq in December 1998, it had eliminated a large
portion of Iraq's chemical weapon potential. UNSCOM had overseen the
destruction or incapacitation of more than 88,000 filled or unfilled chemical
munitions, over 600 tons of weaponized or bulk chemical agents, some 4,000 tons
of precursor chemicals, some 980 pieces of key production equipment, and some
300 pieces of analytical equipment.

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction

Chronology of BioWeapons in Iraq

Iraq admitted that it weaponized biological agents between December

1990 and January 1991. The types of munitions under development
for use with biological weapons included Al Hussein missile warheads,
R-400 aerial bombs, aircraft drop tanks, pilotless aircraft, helicopterborne spraying systems ("The Zubaidy Device"), 122 mm rockets,
LD-250 aerial bombs, and fragmentation weapons.

BIOWEAPONS AND IRAQ

IRAQ AND BIOWEAPONS:

A SPECIAL REPORT

WHAT WAS THE SITUATION?

Weapons of Mass Destruction

Chronology of BioWeapons in Iraq

Iraq admitted that it weaponized biological agents between December

1990 and January 1991. The types of munitions under development
for use with biological weapons included Al Hussein missile warheads,
R-400 aerial bombs, aircraft drop tanks, pilotless aircraft, helicopterborne spraying systems ("The Zubaidy Device"), 122 mm rockets,
LD-250 aerial bombs, and fragmentation weapons.

BIOWEAPONS
AND
THE UNITED STATES

BIOWEAPONS
AND
THE UNITED STATES
An offensive biological program was begun in 1942 under the
direction of a civilian agency, the War Reserve Service (WRS).
The program was expanded during the Korean War (1950-53). A new
production facility incorporating adequate biosafety measures was
constructed at Pine Bluff, Arkansas
Volunteer studies were performed in a 1-million liter sphere at Fort
Detrick known as the "eight-ball" to test weapons systems
disseminating Francisella tularensis, Coxiella burnetti, and other
pathogens. Animal experiments were conducted at Fort Detrick and at
remote desert and Pacific sites.

BIOWEAPONS
AND
THE UNITED STATES
Cities were unwittingly used as laboratories to test aerosolization and
dispersal methods; Aspergillus fumigatus, B. subtilis var. globigii, and
Serratia marcescens were used as stimulants and released during
experiments in New York City, San Francisco, and other sites
There were 456 cases of occupational infections acquired at Fort
Detrick during the offensive biological program, at a rate of less than
10 infections per million hours worked.
In 1969, President Richard Nixon closed the American offensive
biological warfare program, The 1969 budget for Chemical/Biological
Warfare research was reported to be $300 million with $5 million for
herbicides designed to kill food crops or strip trees of foliage to
deprive enemy forces of ground cover.

BIOWEAPONS
AND
THE UNITED STATES

A series of field tests took place under the auspices of the Biological
Laboratories from 1943 to the mid-1960s: In one such test, travelers at
Washington National Airport were subjected to a harmless bacterium. Traps were
placed throughout the facility to capture the bacterium as it flowed in the air.
Laboratory personnel, dressed as travelers carrying brief cases, walked the corridors
and without detection sprayed the bacterium into the atmosphere. In the New York
Subway, a light bulb filled with the same harmless bacterium was dropped on the
tracks. The organism spread throughout the system within 20 minutes. Traps and
monitoring devices showed the amount of organismif it were one of the
predictable, dangerous organisms, could have killed thousands of persons. No one
was injured or became ill as a result of the test. In San Francisco, a U.S. Navy ship,
equipped with spray devices operated by Fort Detrick personnel, sprayed Serratia
marcescens, a non-pathogenic microorganism that is easily detected, while the ship
plied the San Francisco Bay. It spread more than 30 miles to monitoring stations. A
jet aircraft equipped with spray devices, flew a course near Victoria, Texas, and the
harmless particles were monitored in the Florida Keys

BIOWEAPONS
AND
THE UNITED STATES
Front of main building at
USAMRIID (United States
Army Medical Research
Institute of Infectious Diseases)
on the grounds of Fort Detrick,
Maryland.

BIOWEAPONS
AND
THE UNITED STATES
PLUM ISLAND: BIOWARFARE
LABORATORY?
Plum Island is a legend, but not a myth. Just off Orient Point,
Long Island, and six miles from the Connecticut coast, Plum
Island is the site of a United States Agriculture Department
Animal Disease Research Center. The USDA acquired the
island from the War Department at the end of World War II
with a charter from Congress to study animal diseases such as
Foot and Mouth Disease. In surrounding communities,
distrust of Plum Island runs deep. Lyme Disease takes its
name from a Connecticut town across from the island: many
wonder whether birds or swimming animals could have
brought the disease from Plum Island. Some suspect this
might be the case with West Nile Virus as well. Plum Island
officials, of course, dismiss such hypotheses as fantasy.

BIOWEAPONS
IN
THE UNITED STATES
What about the possible threat to
Agriculture in the US?
What about the use of Agricultural
Bioweapons as an offensive
weapon?

IssuesinBiotechnology
A notorious attack that used bioweapons in Oregon in
1984 was perpetrated by a cult in an attempt to sway an
upcoming election. Cult members were found to have
contaminated commercial salad bars with what
organism?
(A) Ebola virus
(B) Salmonella
(C) Yersinia pestis
(D) Small pox
(E) Anthrax

BIOWEAPONS IN THE UNITED STATES

Anthrax Attacks 2001
The 2001 anthrax attacks in the United States, also known as Amerithrax
from its Federal Bureau of Investigation (FBI) case name, occurred over the
course of several weeks beginning on Tuesday, September 18, 2001, one week
after the September 11 attacks. Letters containing anthrax spores were
mailed to several news media offices and two Democratic U.S. Senators,
killing five people and infecting 17 others. According to the FBI, the ensuing
investigation became "one of the largest and most complex in the history of
law enforcement.
A major focus in the early years of the investigation was a bio-weapons
expert named Steven Hatfill, who was eventually exonerated. Another
suspect, Bruce Edwards Ivins became a focus of investigation around April 4,
2005. Ivins was a scientist who worked at the government's biodefense labs at
Fort Detrick in Frederick, Maryland. On April 11, 2007, Ivins was put under
periodic surveillance and an FBI document stated that "Bruce Edwards Ivins
is an extremely sensitive suspect in the 2001 anthrax attacks". [2] On July 27,
2008, Ivins killed himself with an overdose of acetaminophen

BIOWEAPONS
IN
THE UNITED STATES
Bruce Edwards Ivins
Ivins at a 2003 awards ceremony at USAMRIID
Born

April 22, 1946(1946-04-22)

Lebanon, Ohio, U.S.

Died

July 29, 2008(2008-07-29)

(aged 62)
Frederick Memorial Hospital
Frederick, Maryland, U.S.

Cause of death

Suicide by overdose

Education

University of Cincinnati
(Ph.D.)

Employer

United States Army Medical

Research Institute of
Infectious Diseases

Religion

Roman Catholic

We now realize
the insidious possibility
of suicide delivery
agents

Why?

Infection Threats
The ideal offensive agent: aerosol/easy to
disseminate; stable over wide temperature range
and long shelf life; inexpensive; able to be
produced in large quantities; and reliably causes
high mortality, morbidity and social disruption
CDC has prioritized biologicals into category A
(high mortality, major impact) B (moderate
morbidity), C (emerging pathogens)

Infection Threats
Category A
Anthrax Bacillus anthracis
Botulism Clostridium botulinum
Plague Yersinia pestis
Poxvirus (smallpox) Variola major and
Variola minor

Tularemia Francisella tularensis

Viral hemorrhagic fevers
VHFs -RNA viruses:

the families Arenaviridae,

Filoviridae, Bunyaviridae, and Flaviviridae.

Category B
Q fever Coxiella burnetii
Brucellosis Brucella abortus
Glanders Burkholderia mallei
Viral encephali
Ricin toxin Ricinus communistides
Staphylococcus
enterotoxin B

Infection Threats
Category B
Epsilon toxin of C.
perfringens
Food/waterborne
pathogens: Cholera
Salmonella, Shigella
E.coli 0157:H7,
Cryptosporidia

Category C
Hantaviruses
Tickborne viruses
Yellow fever
Tuberculosis
(Drug Resistant)

Casualties from Hypothetical

Aerosol Attack
Agent

Downwind
reach (km)

#Dead

#Incapacitate
d

Rift Valley
fever

400

35,000

Brucellosis

10

500

125,000

Q fever

>20

150

125,000

Tularemia

>20

30,000

125,000

Anthrax

>20

95,000

125,000

DETECTION
Illness likely to occur before circumstances known
Characteristic symptom complex suggestive of
BW agent
Occurrence of rare infection
Temporal clustering of common symptoms/signs
Occurrence of an infection not endemic to the area
Concurrent disease in humans and animal
population in a region

IssuesinBiotechnology
In a bioweapons attack, there are the unique challenges
with first response because
(A) The release of biological agents is not likely to be
immediately discernible
(B) Casualties will immediately overwhelm medical
attention
(C) Firefighters, police and paramedics would most likely
desert immediately.
(D) Physicians specifically ID specialist, are likely to be
out of town

Diagnostic Problems
Civilian targets may be unaware of release; military
theater more predictable
Casualties will be staggered in their presentation and
may be geographically dispersed
Initial symptoms non-diagnostic
Physicians clinically inexperienced due to rarity of
these infections in U.S.
Suspicion of even one case should prompt
notification of state health dept and local law
enforcement agencies including FBI office

Problems With First Response

The release of biological agents is not likely
to be immediately discernible
Casualties will not immediately present for
medical attention
Firefighters, police and paramedics may not
be involved initially.
Physicians specifically ID specialist, are
likely to be the first responders

Comparison of Weapons of Mass

Destruction
Nuclear

Chemical

Biological

Area
involved

Large

Limited

Moderately
large

Rapid
Detection

Easy

Moderate

Difficult

Clinical
Incubation

Varies
w/dose

Minutes

Days to
weeks

Medical RX

Limited

Limited

Effective
v.some

The Naturally Occurring Possibilities

The Sentinel Six

1) Anthrax
2) Small Pox
3) Plague
4) Tularemia
5) Botulism
6) Hemorrhagic Fever

Anthrax

Bacillus anthracis

Anthrax: Epidemiology
Infected animals or contaminated animal
products.
Most infection comes from skin contact.
Eating raw or rare meat.
Inhaling spores from the soil.
No person to person transmission.

Anthrax: Clinical Presentations

Skin infection- starts as itchy bump, progresses to
a blister and then forms an ulcer with a black dead
center
Intestinal infection- nausea, no appetite, vomiting.
Later severe diarrhea and vomiting blood.
Inhalation infection- starts with flu symptoms.
One day to weeks later becomes severe with
breathing problems and shock.

Cutaneous Anthrax

Anthrax: Aerosolization
Greatest risk of infection during primary
aerosolization: within 24 h of release
Exposure depends on duration that spores
remain airborne and distance spores travel
from release point (intrinsic aerosol
properties, meteorological conditions)
Secondary aerosolization unlikely; ongoing
epidemiologic monitoring essential

Anthrax: Aerosolization
Delivery Methods

Inhalational Anthrax

Anthrax as a Biological Agent

The initial evidence of the release of
aerosolized anthrax spores as bioterrorism
or as biological warfare is likely to be a
clusters of cases of an acute flu-like illness
with a fulminant course and without
pneumonia that rapidly progress to death
within days without appropriate treatment.
There is no effective warning system to
detect aerosol cloud.

Anthrax: As a Weapon
Not contagious, so only those exposed to
the spores get sick- no unintended victims.
Spores last a long time.
Early symptoms not specific- identity not
disclosed.
85% fatal as aerosol.
Easy and cheap to produce.

Anthrax Vaccine
Made from a bacterial strain that cannot cause the
disease.
Vaccine is painful and given on an extensive
schedule.
Need yearly booster.
Used for prevention- not treatment.
Currently reserved for military, lab workers who
handle the bacteria and decontamination crews.

Treatment of Anthrax
Doxycycline- drug of choice in treating
people who have been exposed.
Cipro- best drug of choice for documented
infection.
Penicillin- is the cheapest alternative if
cultures prove to be sensitive.
Antibiotics- need to be used discriminately.
Dont stock pile for personal use.

Genetic Engineering of
Bioweapons

Anthrax: Infection Control

No patient-to-patient transmission of inhalational
disease; isolation unnecessary
Standard precautions for cases; no contact or
airborne precautions indicated
No need for PEP of close contacts unless common
source aerosol exposure
Suspicion of even once case should prompt
notification of state health dept and local law
enforcement agencies including FBI office

Anthrax: Contaminated Mail

Contaminated letters- do not shake contents,
do not attempt to clean up powder or fluid,
cover with plastic or trash can, leave the
room and close the door, prevent others
from entering, wash hands with soap and
water, report incident to police, give list of
people in room with mail to the local state
public health, contaminated clothing in
plastic bag, shower with soap and water.

Plague

Plague

Yersinia pestis

Wright's stain peripheral

blood smear of a patient
with septicemic plague
demonstrating bipolar,
safety-pin staining of
Yersinia pestis. While
Wright's stain will often
demonstrate this
characteristic appearance,
Giemsa's and Wayson's
stains most consistently
highlight this pattern.
(Courtesy Ken Gage, PhD.,
CDC, Fort Collins, CO. )

Plague as Biological Weapon

Plague as Biological Weapon

Outbreak would pose serious threat.
Could create wide spread panic because of
its known reputation and devastation.
Attack of aerosolized Y pestis would cause
highly lethal pneumonic plague.
Attack rate dependent on the agent used,
meteorological conditions and method of
aerosol dissemination.

Plaque: Transmission
Pneumonic plague would be highly
contagious.
Spread is by sneezing or bites from infected
flea.
Almost 100% fatal if not treated within 24
hours of onset.

Plague Transmission

Primary Pneumonic Plaque

Incubation period 1-6 days, typically brief
Prominent systemic and respiratory sx with
hemoptysis and GI sx common
CXR with bilat, patchy infiltrates or consolidation
Rapid progression to resp failure, MOSF shock
and death, without expeditious treatment, over 2-6
days.
Purpuric skin lesions and necrotic digits in
advance disease

Primary Bubonic Plague

Pneumonic Plaque: Detection

Problems
Unable to pick up aerosolized plague cloud.
No readily available wide spread rapid
testing.
Clinically aggressive with little time for
diagnosis.

Plaque as a BW Agent: Therapy

Recommendations
Setting
Contained
casualties

Preferred

Alternates

Gentamicin Doxy 100 mg

IV or
IV q 12h or
Streptomycin Cipro 400 mg
IM
IV q 12 h (or
other FQ)

Mass
Doxy 100 mg Chloramphen
casualties or
PO bid or
icol 25mg/kg
PEP (fever or Cipro 500 mg
PO qid
cough)
PO bid

Duration
10 d

10 d (7 for
PEP)

Pneumonic Plaque: Infection

Control
PEP indicated for household, hospital or close
contacts (<2 meters) of cases
Contagious until 48 h into antimicrobials and
evidence of clinical improvement
Droplet precautions via disposable surgical masks
and other standard measures
Isolation or cohorting of cases until non-infectious
Disinfect surfaces with 0.5% hypochlorite; no spore
form and Y. pestis vulnerable to heat, sunlight and
does not survive long environment

Small Pox

Variola major and Variola minor

Smallpox as a Biological Weapon

Stability in aerosol form (inversely related to
temp/humidity), infective dose low ~10-100 organisms,
efficient person-to-person spread
Secondary attack rates 25%-40% (amplified)
Essentially all children and most adults are non-immune
Only limited vaccine supplies available and production
facilities inadequate
No proven effective antiviral therapy
Case fatality rates >25%-30%
Transmissible person can infect 20

Smallpox as a Biological Weapon

Smallpox: Transmission
Person-to-Person spread via droplet nuclei, resp
aerosols or direct contact with infectious lesions or
drainage (formites)
Incubation period 7-17 d (10-12 d to prodrome and
2-4 d more to rash)
Viral prodrome symptoms and acute systemic
toxicity maculopapular rash; synchronous onset
and evolution, centrifugal distribution (includes
oral mucosa, palms and soles) vesicles
pustules crusts (~d 8)

Smallpox Clinical Presentation

Fatal Smallpox

Smallpox: Transmission and

Clinical Presentation
Rash scabbed over 10-14 d after onset
Rash may be attenuated or atypical in variola
minor or partially immune
Hemorrhagic and malignant varieties frequently
fatal
Communicable from onset of rash until separation
of all scabs (~3 wks); most contagious during
week 1 due to high viral titers in saliva

Smallpox: Diagnosis and

Therapy
Clinical Dx requires index of suspicion and acumen:
distinguish from varicella (centripetal and
asynchronous)
Specimens of vesicular/pustular fluid sent to BL-4
facilit EM culture, PCR, RFLP
Suspected case of smallpox is public health
emergency and possibly indicative of BW
No proven antimicrobial Rx: cidofovir shows some
promise in vitro and animals
Antibacterials for secondary infections

Smallpox: Vaccination
Vaccine highly effective; large scale preventive
program not currently feasible
VIG limited and recommended for severe cutaneous
complications of vaccination
Post-exposure vaccination, within 3-5 days, may
attenuate disease and prevent mortality
Vaccine complications occur in 0.004% death in ~1%
of those
Needs: new vaccine using tissue culture-grown virus,
possibly attenuated and vaccine stockpiles

Smallpox as BW: Infection

Control
Isolate suspect cases at home if poss; in hospital,
neg pressure with HEPA filter
? Designated sites for smallpox care
All patients and HCWs should be vaccinated; VIG
in contraindicated
Contact + airborne precautions + particulate
respirator (N95 mask)
Autoclave or incinerate equipment or patient
materials

IssuesinBiotechnology
The reasons that small pox is considered such a
dangerous threat as a bioweapon include: its stability in
aerosol form; infective dose low ~10-100 organisms; and,
efficient person-to-person spread. The fact that a
transmissible person can infect many other persons has
created what possible threat since 9/11 that was not
previously seriously considered?
(A) that a reliable vaccine against small pox can not be constructed
(B) that suicide terrorists could inject themselves with a virulent strain to
spread it through an unsuspecting population
(C) that the ultimate suicide mission would be to unleash a bioweapon
that would kill everyone on the planet
(D) that a strain of small pox could be fused with portions of the bird flu
virus to be deployed as a bioweapon

Botulism as Weapon
Very unlikely to be effective as biological
agent.
Weaponized by several countries including
Iraq in aerosol.
Would kill about 10% of population
exposed.
Could be used to contaminate food supply.
Clostridium botulinum

Botulism: Clinical Presentation

Early symptoms- drooping eye lids,
weakened jaw clench, trouble swallowing,
and speaking. Blurred vision and trouble
breathing.
Nausea and vomiting would be a sign that
the germ was eaten.

Botulism: Clinical Presentation

Botulism: Safe Guards

Not contagious and required direct exposure
which is difficult to achieve on a mass
scale.
It is treatable with mortality rates 10% or
less.
Anti-toxin supply available at CDC.
Botulism vaccine is available.

Tularemia: Biological Weapon

Weaponized by both US and USSR.
Small animal reservoir better known as
rabbit fever.
Transmission by aerosols or direct contact
with animal tissue.
Can live for weeks in water, soil, hides, and
carcasses.
Francisella tularensis

Tularemia: Inhalation
Highly infectious.
Incubation period 3-5 days.
Fatality rate 30% without treatment, but less
than 5% with treatment.

Tularemia: Clinical Presentation

Begins as flu like illness.
Over next few days, painful breathing and
cough begins.
May progress to pneumonia- respiratory
failure- death.

Tularemia Clinical Presentation

Tularemia: Treatment
Doxycylcine
Cipro
Respiratory Support

Tularemia: Infection Control

No person- to- person transmission.
Standard precautions.
Culture manipulation in the lab requires
high level of containment.
Limited availability of vaccine.

Hemorrhagic Fevers- Ebola Virus

VHFs -RNA viruses:

the families Arenaviridae,

Filoviridae, Bunyaviridae, and Flaviviridae

Ebola Virus: Scenarios

As BW extremely unlikely.
Terrorist would have to deliberately infect himself,
travel to a major city and spread disease by sexual
contact or sharing needles.
Most people infected with Ebola die within one
week with grave suffering, making the window of
opportunity to infect others brief.

Ebola: Clinical Presentation

Sudden fever, headache and muscle pain.

Nausea, vomiting, diarrhea.
Cough with chest pain.
Bumpy, red rash.
Profuse bleeding from GI tract and lungs
leading to death.

Ebola: Safe Guards

Can spread from person to person, but only
via blood or body fluids.
No known cure.

IssuesinBiotechnology
The use of Ebola virus as a bioweapon is would be
horrific and is nearly unthinkable. Which of the
following statements about Ebola as a bioweapon is not
true?
(A) Genetically engineered strains have been made that
can be carried by mosquitoes
(B) As a BW, Ebola attacks are extremely unlikely.
(C) A terrorist would have to deliberately infect himself,
travel to a major city and spread disease by sexual
contact or sharing needles.
(D) Most people infected with Ebola die within one week
with grave suffering, making the window of opportunity
to infect others very brief.

BIOTERRORISM
and
COUNTERDEFENSE

WHAT GOALS MIGHT AN ATTACK ON THE

AGRICULTURAL SECTOR SERVE?
Attack the food supply of an enemy belligerent
The classical rationale for the inclusion of anti-plant programs in national biological weapons programs.

Destabilize a government by initiating food

shortages or unemployment
Disruption of the agricultural sector can cause profound dislocation of societies.

Alter supply and demand patterns for a commodity

The imposition or relaxation of trade restrictions

Control an undesirable plant or animal (biocontrol)

The use of legitimate, peaceful biocontrol is expanding steadily

HOW WILL GENOMICS AND GENETIC

TECHNOLOGY CHANGE THE BIOLOGICAL
WARFARE THREAT?
Genomics and proteomics make genotype-specific weapons
possible.
Agriculture is highly vulnerable to genotype-specific weapons
High-tech agent design is an option available only to
sophisticated playerseg states and multinational corporations.

Course of Action for Biological

Attack

Contain
Confirm
Clean up
Direct appropriate prophalactic treatment
Direct appropriate treatment as needed

Panic- the Real Enemy

Objective of terrorist is to destroy normal day to day life.
Psychological reaction- mass sociogenic illness.
Over reactions- frighten people and make then
suspicious.
Reassurances- suspect a cover up.
Fear is from lack of knowledge.

How to Make a Bioweapon

Can you pick out the flaws here?
Let's make a biological weapon
by Matt Giwer, 2005 We get hysterical mention of bioweapons and terrorists every day. So it
must be easy to do. So lets make one.
Diseases are contagious and if we use it we and all our fellow terrorists will eventually be
exposed to it and be at risk of dying of it. So the first rule of a bioweapon is it cannot be
contagious. That rules out smallpox, influenza and just about every other know disease.
So right up front the crap about smallpox as a threat is out the window. And the US agrees with
this as the top priority in the military is not smallpox vacination, it is anthrax. Botulism? The
only interest is in the toxin not in the bacteria. The bacteria is killed by air, period. There is no
way to change that.
It is anthrax because a few rare strains of it kills most infected people and it is not contagious.
The effort in weaponizing anthrax is to produce spore clumps of exactly the right size to lodge in
the lungs, not too large or too small. And after decades of research no country, not the US not
Russia has accomplished this. Pardon me but I don't think a man in a cave in Afghanistan can do
it either. Certainly not even Saddam Hussein either.
But if you still want to take a shot at it you will have to come up with an entirely new disease
which no one else knows about. This is before you invest the hundreds of millions into the R&D
and production facilities.

How to Make a Bioweapon

Start with a known bioweapon (pick one)

Bacterial- Start with a known agent
Genetically engineer with multiple antibiotic resistance
Weaponize for distribution (mass aerosol, water or
suicide delivery)
Engineer in antibiotic sensitivity for self protection
Viral- Start with a known agent
Genome sequence
Mutagenize to increase transmissiblity
Make appropriate vaccine for self protection
Use of synthetic biology for creative components
Agricultural- Start with a known agent
Target large disruptive markets (i.e. mad cow disease,
corn leaf blight etc.
Design appropriate delivery method and timing

Synthetic Biology
A Larger Threat to World Peace than Nuclear War?

Pandemic Flu as a Bioweapon

What Made the 1918 flu Virus So Deadly?

Did we really
need to do this?

It could help
prevent a
future disaster.

What happens if it
escapes to re-infect
the world again?

Could it be a
recipe for
bioterorrists?

It could be a
recipe for a
future disaster.
Nature 6 October 2005 p794

The Dual Use Dilemma

Could the world stop it even it could?

Science 14 October 2005 p195

Nature 6 June 2005 p860

CREDIT: COLLAGE: N. KEVITIYAGALA/SCIENCE, PHOTOS (LEFT TO RIGHT) ISTOCK

Pandemic: Only a Matter of Time

The Ferret Model

Science 3 February 2012: 512-513

H5N1 Virus Attachment to Lower Respiratory Tract
Debby van Riel, Vincent J. Munster, Emmie de Wit, Guus F. Rimmelzwaan, Ron A. M. Fouchier, SCIENCE March 12 2012

Pandemic: Only a Matter of Time

H5N1 Ron Fouchier: In the Eye of the Storm
Martin Enserink

Researchers find a limited

ofcome
mutations
render
It's number
a pity that it has
to this. RON
FOUCHIER, ERASMUS MC
H5N1 more transmissible
Spurs Controversy on
Publication and Dual-Use

The continuous threat of an influenza pandemic represents one of the biggest challenges in
public health. Influenza pandemics are known to be caused by viruses that evolve from animal
reservoirs, such as in birds and pigs, and can acquire genetic changes that increase their ability
to transmit in humans
In two independent studies conducted in two leading influenza laboratories at the University of
Wisconsin-Madison and Erasmus MC in Rotterdam, the Netherlands, investigators have
proved that viruses possessing a hemagglutinin (HA) protein from highly pathogenic avian
H5N1 influenza viruses can become transmissible in ferrets
Science 27 January 2012:
Vol. 335 no. 6067 pp. 400

Pandemic: Only a Matter of Time

Engineered Avian Flu Could Kill

Half the Worlds Humans
It's a pity that it has come to this. RON FOUCHIER, ERASMUS MC

Controversy on Dual-Use

Pandemic: Only a Matter of Time

The Obligation to Prevent the Next Dual-Use Controversy
Policy Forum
Public Health and Biosecurity
Ruth R. Faden1,*,, and Ruth A. Karron2

Currently, the avian influenza virus H5N1 is not easily transmitted from human to human, but a
high mortality rate in those who have been infected with H5N1 viruses has raised fears of possible
naturally occurring mutations that would increase transmissibility

Science 17 February 2012:

Vol. 335 no. 6070 pp. 802-804

Pandemic: Only a Matter of Time

H5N1Flu Controversy Spurs Research Moratorium
David Malakoff*

Taking a break. Leading flu researchers will halt controversial studies involving
H5N1 viruses (blue) for 2 months.

Science 27 January 2012:

Vol. 335 no. 6067 pp. 387-389

Pandemic: Only a Matter of Time

What if this
were a weapon?

How would that

change things?

Is evolution
faster than a
terrorist?

Maybe the real

terrorist is a
chicken in
Southeast Asia

Fire and Ice

Some say the world will end in fire,
Some say in ice.
From what I've tasted of desire
I hold with those who favor fire.
But if it had to perish twice,
I think I know enough of hate
To say that for destruction ice
Is also great
And would suffice.
Robert Frost

IssuesinBiotechnology
17. There is a so-called Sentinel Six Infectious Agents that
are considered Category A bioweapons which do not
include:
(A) H1N5 avian flu virus
(B) Anthrax and Small Pox
(C) Plague and Tularemia
(D) Botulism
(E) Ebola: Hemorrhagic Fever

17. Bruce Ivans

(A) won the Nobel prize in medicine for research on bioweapons
(B) was the highly suspected perpetrator of 2001 Anthrax attack in
the US
(C) conducted research on Iraqi bioweapons with Saddam Hussein's
regime at the Al-Shazam Institute that led to the Iraq war
(D) was a senator for Rhode Island during the first Gulf War leading
policies against bioweapons research
(E) won the Nobel Peace prize for his stance against bioweapons

18. The United States

(A) has conducted significant research on the use of bioweapons
(B) has never experienced a bioweapons attack yet on its own soil
(C) has effectively prevented bioweapons attacks in the US
(D) secretly attacked the former Soviet Union because of their
research on bioweapons in 2005
(E) has no known research on bioweapons

19. Synthetic biology

(A) will most likely never be used on bioweapons
(B) can never be applied to bioweapons research
(C) is a problem considered in the Dual Use Dilemma
(D) is not a large threat to the deployment of future
bioweapons
(E) was used to develop weaponized bioweapons to
produce the Anthrax used in the 2001 US attack
Saddam Hussein's regime

by

20. During the historical development of bioweapons it is

known that:
(A) in 142-73: US program of offensive and defensive BW, including
human volunteer exposures with Ebola virus
(B) 1942-73: US program of offensive and defensive BW, including
human volunteer exposures
(C) 1992-73: US program of offensive and defensive BW, including
human prisoner exposures to Yersinia pestis and syphllis
(D) 1998-03: US program of offensive and defensive BW, including
human military exposures genetically
(E) Anthrax was developed and weaponized by a cult in Oregon to
secure land during a controversial election

21. The reasons that small pox is considered such a

dangerous threat as a bioweapon include: its stability in
aerosol form; infective dose low ~10-100 organisms; and,
efficient person-to-person spread. The fact that a
transmissible person can infect many other persons has
created what possible threat since 9/11 that was not
previously seriously considered?
(A) that a reliable vaccine against small pox cannot be constructed
(B) that suicide terrorists could inject themselves with a virulent
strain to spread it through an unsuspecting population
(C) that the ultimate suicide mission would be to unleash a
bioweapon that would kill everyone on the planet
(D) that a strain of small pox could be fused with portions of the bird
flu virus to be deployed as a bioweapon
(E) it is not important enough

22. In a bioweapons attack, there are the unique

challenges with first response because
(A) The release of biological agents is not likely to be immediately
discernible
(B) Casualties will immediately in the first 24 hours, overwhelm
medical attention
(C) Firefighters, police and paramedics would most likely desert
immediately.
(D) Physicians specifically ID specialists, are likely to be out of town
(E) There are no know treatments for any of the sentinel six
bioweapons agents

23. A notorious attack that used bioweapons in Oregon in

1984 was perpetrated by a cult in an attempt to sway an
upcoming election. Cult members were found to have
contaminated commercial salad bars with what
organism?
(A) Ebola virus
(B) Salmonella
(C) Yersinia pestis
(D) Small pox
(E) Anthrax

24. Since the Anthrax attacks in 2001, if a large scale

biological weapons attach were to occur in New York,
Boston or Providence, I feel informed for proper
evacuation and response procedures. Pick one.*
(A ) Well informed
(B) Somewhat informed
(C) Unchanged
(D) Confused
(F) Totally unprepared
* There is no right answer

25. Since the Anthrax attacks in 2001, I feel that the treat
of a major bioweapons attack as addressed by Homeland
Security. Pick one.*

(A) Has been eliminated

(B) Is greatly reduced
(C) Is unchanged
(D) Has worsened
(E) Has significantly increased
* There is no right answer