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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
Issues in Biotechnology:
The Way We Work With Life
Dr. Albert Kausch
Kimberly Nelson
BCH 190
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
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
IssuesinBiotechnology
Since September 11 2001, I feel that our threat from
terrorist attacks
A
B
C
D
F
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
THE UNITED STATES
A SPECIAL REPORT
A SPECIAL REPORT
A SPECIAL REPORT
A SPECIAL REPORT
A SPECIAL REPORT
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.
A SPECIAL REPORT
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.
A SPECIAL REPORT
A SPECIAL REPORT
A SPECIAL REPORT
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
Bruce Edwards Ivins
Ivins at a 2003 awards ceremony at USAMRIID
Born
Died
Cause of death
Suicide by overdose
Education
University of Cincinnati
(Ph.D.)
Employer
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
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)
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
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
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.
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 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
Plague
Plague
Yersinia pestis
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
Preferred
Alternates
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)
Small Pox
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)
Fatal Smallpox
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
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
Tularemia: Inhalation
Highly infectious.
Incubation period 3-5 days.
Fatality rate 30% without treatment, but less
than 5% with treatment.
Tularemia: Treatment
Doxycylcine
Cipro
Respiratory Support
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
Contain
Confirm
Clean up
Direct appropriate prophalactic treatment
Direct appropriate treatment as needed
Synthetic Biology
A Larger Threat to World Peace than Nuclear War?
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 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
Controversy on Dual-Use
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
Taking a break. Leading flu researchers will halt controversial studies involving
H5N1 viruses (blue) for 2 months.
What if this
were a weapon?
Is evolution
faster than a
terrorist?
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
by
25. Since the Anthrax attacks in 2001, I feel that the treat
of a major bioweapons attack as addressed by Homeland
Security. Pick one.*