1. Possible Treatment for Cancer?
Ricin
Possible Treatment for Cancer?

2. What is Ricin?
A poison found naturally in beans of caster bean plant, Ricinus communis
Family Euphorbiaceae
Native to tropical Africa
Can be in form of powder, mist, or pellet, or dissolved in water or weak acid
A stable substance under normal conditions

3. Where is Plant Found and How is it Used?
Castor beans are processed throughout world to make castor oil
Castor beans grow wild everywhere
Castor Oil was once used as an oral laxative, but is now used mainly as an industrial lubricant and for preparing leather products

4. How is Ricin Purified?
Part of waste “mash” produced when castor oil is made
Does not need to be purified
Mashing up beans produces crude toxin powder that is very stable
An estimated 50,000 tons available in world today

5. How Can You Be Exposed to Ricin?
Not contagious; Can not be spread by person to person contact
Can be used to expose people through air, food, or water
Possibly as warfare agent

6. Chemical Nature of Ricin
Tertiary structure is globular, heterodimer
Ribotoxic A chain (RTA) and B chain (RTB)
Ricin A is of extremely low toxicity as long as B chain is not present
Many plants have A chain but not B chain (i.e. Barley)
Entering cell depends on hydrogen bonding interactions between RTB and carbohydrates on eukaryotic cell surface

7. How Does Ricin Work?
Inhibits protein synthesis by inactivating ribosomes
Effects of poisoning depend on dose and whether ricin was inhaled, ingested, or injected
Perhaps one milligram of ricin can kill an adult

8. Signs and Symptoms of Ricin Exposure
Death could take place 36 to 72 hours of exposure
Initial symptoms by inhalation occur within 8 hours of exposure
Respiratory distress, fever, cough, nausea, and tightness in chest
Heavy sweating and pulmonary edema follow
Low blood pressure and respiratory failure

9. Signs and Symptoms Cont.
Initial symptoms by ingestion occur in less than 6 hours
Vomiting and diarrhea
Severe dehydration and low blood pressure
May include hallucinations, seizures, and blood in urine
Several days after, liver, spleen, and kidneys may stop working, resulting in death
Skin and eye contact cause redness and pain

10. How Do Authorities Confirm Cases of Suspected Ricin Poisoning?
No widely available, reliable medical test
People observed for signs of poisoning
Environmental testing by public health and law enforcement
Try to detect ricin in powders or materials released into environment

11. Disease Control and Prevention
Biothreat
Easily produced
Readily available
Highly stable
More than 750 cases of documented ricin intoxication

12. How is Ricin Poisoning Treated?
No vaccine or prophylactic antitoxin available
Immunization appears promising in animal models
Most important factor is getting ricin off or out of body as quickly as possible
Symptomatic poisoning treated by supportive medical care
Types of supportive care depends on type of exposure

13. What Should You Do In Case of Exposure?
Leave area where ricin was released
Remove clothing, rapidly wash entire body with soap and water, and get medical care as quickly as possible

14. Ricin Benefits Use as immunotoxin Medical research
Abundant and easy to manipulate
Vaccine research
Protection for troops and public against bioterrorist attack

15. Other Uses Suicidal and homicidal purposes United Kingdom
Death of Georgi Ivanov Markov in 1978
Ricin via a tiny pellet
London in 2003
Suspicion of manufacturing toxin for terrorist purposes
United States
Ricin detected in mail at white house in 2003

16. Experimental Uses in Medicine
Dr David Flavell, University of Southampton
Potential for immunotoxins
Binds to cancer cell, is internalized and kills cell
Antibody targets only cancer cells and normal cells spared

17. Experimental Uses Cont.
Conjugate RTA subunit and antibodies or growth factors bind cancer cells
Worked well for in vitro 
Successful in destroying T lymphocytes in bone marrow

18. Experimental Uses Cont.
Some given treatment developed vascular leak syndrome
Walls of blood vessels allow plasma to seep into the tissues
Fluid retention, increase in body weight, interstitial edema

19. Experimental Uses Cont.
Team from the University of Texas Southwestern Medical Center
Engineered toxin lacking proteins that caused vascular leak syndrome
Modified toxin was efficient at killing tumor cells
Concluded dose of toxin in future cancer drug should be increased, making it more effective against disease
Research was published in the journal Nature Biotechnology

20. Experimental Uses Cont.
Immunotoxins are completing Phase I and II trials in patients with Hodgkin’s and non-Hodgkin’s lymphoma
Preclinical studies for clinical trial in pediatric lymphocytic leukemia
Immunotoxins under development to prevent graft-versus-host disease

21. Pilot Clinical Trial of Recombinant Ricin Vaccine
Ellen S. Vitetta UT Southwestern
Recombinant A chain (RTA) with two amino acid substitutions disrupts ribotoxic site
Recombinant RTA (named RiVax) produced and purified in E. coli 
RiVax injected i.m. into mice
Proved effective and safe

22. Pilot Clinical Trial of Vaccine Cont.
Pilot clinical trial under investigational new drug application by Food and Drug Administration
Study:
Three groups of five volunteers injected three times monthly with 10, 33, or 100 μg of RiVax
Vaccine was safe and elicited Abs in one of five individuals in the low-dose group, four of five in the intermediate-dose group, and five of five in high-dose group
Results justify further development of vaccine

23. References http://www.bt.cdc.gov/agent/ricin/qa.asp