RICIN

1. RICIN Name 1 Name 2 Name 3 Name 4

2. 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

3. 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.

4. 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

5. Where does Ricin come from? • Comes from castor beans on the castor bean plant, Ricinuscommunis • Is released when the beans are crushed • Castor bean plants are currently found throughout the world, originating from Asia and Africa

6. Mechanism of Ricin 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. It then enters the Golgi apparatus and undergoes retrograde transport to the endoplasmic reticulum (ER)

7. Mechanism of Ricin (continued) In the ER the A and B chains dissociate and then the A chain translocates to the cytosol. The A chain inactivates ribosomes by removing an adenine from position 4324 of the 28S rRNA in the 60S ribosomal subunit. The rRNA is unable to bind protein elongation factors, thus seizing protein synthesis.

8. History of the castor bean Production of castor oil Folk uses/ Home remedies Industrial uses

9. 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

10. Folk remedies Skin remedies Other uses Sunburn Skin abrasions/ inflammation Acne Reduction in scar tissue Laxative Arthritis Ringworm Hair loss Athlete’s foot

11. Industrial uses • Motor oil- Castrol • Biofuel • Lubricant • Varnishes

12. Uses for Ricin

13. 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.

14. 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

15. 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.

16. 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.

17. 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.

18. 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.

19. 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/why-people-want-to-know-how-to-make.html http://www.zoklet.net/totse/en/bad_ideas/irresponsible_activities/163208.html **Please DO NOT Try This At Home!!!!**

20. 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)

21. Exposure Pathways Increasing Lethality from Left to Right Increasing Lethality from Left to Right Pathways: • Inhalation • Ingestion • Skin contact • The symptoms and severity of Ricin poisoning are route- and dose-dependent • Ricin poisoning can lead to death within 36 to 72 hours.

22. Inhalation Symptoms Ricin 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.

23. Ingestion Symptoms Ricin 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.

24. Subdermal Injection Symptoms Ricin 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.

25. 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.

26. 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

27. Conclusion What is it: Ricin Where it comes from: “Mash” of Castor Beans What it does: Ceases protein synthesis by inactivating ribosomal translation

28. 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

29. 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 (Ricinnuscommunis ) . 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 Ricinuscommunis. Toxicon. Vol 55: 658-661. Madea, B., and Musshoff, F. 2009. Ricin Poisoning and Forensic Toxicology. Drug Testing and Analysis.Vol 1: 184- 191.