Download ricin - UNM Biology

RICIN
Donald Luna
Kathryn Frazier
Sasha Sokolowski
Natalya Trujillo
What is a toxin?
 Substance produced by an organism that has
an adverse affect on other organisms.
 Any substance is capable of becoming a toxin
under the right conditions and in the
appropriate organism.
 Toxins can be produced for various reasons
 Defensively
 Offensively
 Both defensively and offensively
Why we chose Ricin?
We chose to do our project on Ricin because it
comes from castor beans , which are very
common around the world. We found it
interesting that castor oil has been used as a
folk remedy for years and yet Ricin poisoning
is not common. As we researched Ricin we
became intrigued by the medical uses of
Ricin.
What is Ricin?
 Ricin is a type II ribosome inactivating protein
 It contains two subunits called
A and B chains
 The A and B chains are linked
by a disulfide bond
 Ricin is freely soluble in water
Where does Ricin come from?
 Comes from castor beans on the castor bean
plant, Ricinus communis
 Is released when the beans are crushed
 Castor bean plants are currently found
throughout the world, originating from Asia
and Africa
Mechanism of Ricin
1. Ricin utilizes the A-
B mechanism to
enter the cell, in
which the B chain
attaches to the cell
and then the
protein undergoes
endocytosis into
the cell.
2. It then enters the
Golgi apparatus
and undergoes
retrograde
transport to the
endoplasmic
reticulum (ER)
Mechanism of Ricin (continued)
3. In the ER the A and B
chains dissociate and
then the A chain
translocates to the
cytosol.
4. The A chain inactivates
ribosomes by
removing an adenine
from position 4324 of
the 28S rRNA in the
60S ribosomal subunit.
5. The rRNA is unable to
bind protein
elongation factors,
thus seizing protein
synthesis.
History of the
castor bean
 Production of castor oil
 Folk uses/ Home remedies
 Industrial uses
Production of castor oil
 Castor oil is made up of
 Rhicinoleic acid: 85-95%
 Oleic acid: 2-6%
 Linoleic acid: 1-5%
 Ricin is found in the mash that
is produced when castor beans
are processed
Folk remedies
Skin remedies
Other uses
 Sunburn
 Laxative
 Skin abrasions/
 Arthritis
inflammation
 Acne
 Reduction in scar
tissue
 Ringworm
 Hair loss
 Athlete’s foot
Industrial uses
 Motor oil- Castrol
 Lubricant
 Biofuel
 Varnishes
Uses for
Ricin
Biological warfare
 During WWII, the British military developed a
Ricin bomb. It was code-named the W-bomb
 However, it was never used on soldiers or civilians
 During WWII, U.S. and Canada undertook
studying Ricin in cluster bombs.
 Development of Ricin into a military weapon
is no longer funded due to the fact that it is
less potent than other agents such as
botulinum or anthrax.
Terrorism
 In recent years, Ricin turned up in an
envelope in the mailroom that serves Senator
Bill Frist’s office and in the post office in
Greenville, SC.
 In 2002, plans by the al Qaeda terror network
to produce Ricin were found in Kabul
 In 1991, four members of the Patriots Council,
an extremist and anti-government group,
were arrested for allegedly plotting to kill a
U.S. marshall with Ricin
Ricin assassination
 In 1978, Ricin was used to assassinate Georgi
Markov, a Bulgarian dissident. The Ricin was
injected through a poison dart that was shot
from an umbrella. The Russian KGB and the
Bulgarian secret police are suspected.
Ricin vaccine
 A Ricin vaccine, RiVax, was developed at the
University of Texas Southwestern.
 RiVax contains a genetically inactivated
subunit Ricin A chain that is enzymatically
inactive and lacks residual toxicity of the
holotoxin.
 It is currently undergoing its second trial at
the University of Texas.
Medical uses for Ricin
 Ellen Vitetta, director of the Cancer
Immunobiolgy Center at UT Southwestern, is
working on developing a cancer treatment using
ricin.
 Developed a portion of the Ricin toxin into a new class
of immunotoxins
 Immunotoxins are made by linking a portion of the
Ricin toxin to a tumor-seeking antibody.
 The antibody binds to the tumor cell and then the Ricin
portion of the immunotoxin is taken into the cell. This
results in the tumor cell’s death.
Continued cancer research
 Vitetta has also developed a way to
genetically modify the Ricin A chain so that it
is less dangerous to humans, but still as lethal
to cancer cells. This would allow for higher
doses of the treatment to be given without
the risk of increased side effects.
 This new version has been successful in
human and mice trials.
Civilian Poisoning
 Easy access from websites allows anyone the
knowledge to synthesize toxic Ricin
 This knowledge allows people to potentially use
it as a deadly weapon
 Some websites that contain directions:
http://ishare-world.blogspot.com/2008/02/whypeople-want-to-know-how-to-make.html
http://www.zoklet.net/totse/en/bad_ideas/irrespon
sible_activities/163208.html
**Please DO NOT Try This At Home!!!!**
Exposure To Ricin
 In its natural form, Ricin has to be ingested
for an organism to be exposed to it
 Purified Ricin can be exposed to organisms
through the air, food and water
 Ricin is not contagious (transmitted from
human to human)
Exposure Pathways
Increasing Lethality from Left to Right
Pathways:
 Inhalation
 The symptoms and
severity of Ricin
poisoning are routeand dose-dependent
 Ingestion
 Skin contact
 Ricin poisoning can
lead to death within 36
to 72 hours.
Inhalation Symptoms
 Symptoms begin within 12
hours of exposure
 Intoxication through
inhalation of aerosolized
powder or mist is the most
lethal route
 Symptoms include:
respiratory distress, fever,
cough, nausea, tightness in
the chest, heavy sweating
and pulmonary edema
resulting in cyanosis. Low
blood pressure and
respiratory failure may
occur, leading to death.
Ricin
Ingestion Symptoms
 Oral ingestion is the least deadly
route
 Swallowing significant amounts
of Ricin may result in vomiting &
diarrhea that may become
bloody.
 Severe dehydration may result,
followed by low blood pressure.
 Other signs or symptoms may
include hallucinations, seizures,
and blood in the urine.
 Multi-organ failure and death
may follow shortly after.
Ricin
Subdermal Injection Symptoms
 Ricin is unlikely to be
absorbed through intact
skin though contact may
cause redness and pain
 Intravenous exposure
results in fever, tachycardia,
tachypnea, hypotension,
hepatitis, pancreatitis,
nephritis, myocardial injury,
cerebral edema, vomiting,
diarrhea, and bone marrow
suppression.
Ricin
Treatment
 There are currently no U.S.
Food and Drug Administration
(FDA) approved treatments
specifically for Ricin poisoning.
 Patients suffering from Ricin
poisoning should be provided
supportive therapy.
 Supportive Therapy: an
intervention to relieve
symptoms of infection in
patients. Supportive care can
include intravenous fluids or
medicine for pain or fever
relief.
What To Do If Exposed
 Leave the area




immediately
Remove clothing
Wash skin and eyes
Do NOT induce vomiting
or drink fluids
Seek medical attention
immediately
 Death can take place
within 36-72 hours
 No antidote
Conclusion
 What is it: Ricin
 Where it comes from: “Mash” of Castor Beans
 What it does: Ceases protein synthesis by
inactivating ribosomal translation
Conclusion
 The good: Currently being tested as a cancer
treatment option
 The bad: In the past, was developed by militaries as
a biological weapon BUT never actually used
 The ugly: Within the past decade, there have been
numerous terrorist groups that have utilized Ricin
poisoning
References

http://www.compchemcons.com/ricin.html

http://www3.interscience.wiley.com (image)

http://faculty.ucc.edu/biology-ombrello/POW/castor_bean.htm (image)

http://www.onlinehardware.ie/shop/images/eco_varnish.jpg (image)

http://www.performance-oils.co.uk/acatalog/a747.jpg (image)

http://www.dcmilitary.com/dcmilitary_archives/stories/090105/36813-1.shtml

http://www.cnn.com/2003/WORLD/europe/01/07/terror.poison.extremists/index.html

http://www.dorbiopharma.com/prod_def_rivax.shtml

http://www.upmc-biosecurity.org/website/focus/agents_diseases/fact_sheets/ricin.html

Audi, J., Belson, M., Patel, M. et al. 2005. Ricin Poisoning: A Comprehensive Review. Journal of American Medical
Association. Vol 294: 2342-2351.

Coopman, V., Cordonnier, J., De Leeuw, M., Jacobs, W. 2009. Suicidal death after injection of a castor bean extract
(Ricinnus communis ) . Forensic Science International. Vol 189: e13-e20.

Credle, J., Danielsen, M., Dretxhen, K., Leshin, J., O’Connell, K., Weeks, A. 2010. Characterization of Ricin toxin
family members from Ricinus communis. Toxicon. Vol 55: 658-661.

Madea, B., and Musshoff, F. 2009. Ricin Poisoning and Forensic Toxicology. Drug Testing and Analysis. Vol 1: 184191.