Calabar Bean

Scientific Name: Physostigma venenosum

Also Known as: Calabar bean, Esere (Efik language), ordeal bean

Parts used: Seeds, also known as “beans”

Native to: West Africa, especially southeastern Nigeria

Some Traditional Uses: glaucoma; myasthenia gravis; acute tetanus; played a part in the development of synthetic sex hormones such as those used in the birth control pill 

Current Medicinal Uses and Purposes:  The synthetic Alzheimers Disease drug Exelon is based on the physostigmine molecule and actions. Pyridostigmine and neostigmine, both used in the treatment of myasthenia gravis, are “cousins” of physostigmine.

Side Effects and Contraindications: Poisonous

Areas of Further Research: Alzheimers Disease

Calabar bean has a dramatic history of human use. Listen to the show

 

   

How does the calabar toxin (physostigmine) work? Our bodies get things done by sending messages--demands for action--via neurotransmitters. These couriers run all over the body--to receptors in muscles, for example, and glands, and the brain. After messages are delivered and the requested action has begun, enzymes usually break the neurotransmitters down, stopping them. Physostigmine destroys these enzymes, so the nervous system never stops being stimulated. Finally, fatally, it floods.


In the early twentieth century, physostigmine’s ability to stimulate the nervous system led to new understanding of how to treat the autoimmune disease myasthenia gravis (MG). MG causes weakness in voluntary muscles such as the limbs, neck, and chest. Some sufferers can barely hold up their heads. In 1934, aware of research on physostigmine as an antidote for curare poisoning–another situation in which muscles weaken–Scottish doctor Mary Walker dared to inject physostigmine into a patient with MG, with miraculous results. Drug research for MG has moved on from physostigmine, but the main drugs that people with the condition use today, pyridostigmine and neostigmine, are related to physostigmine.

Photo credit: Dr. Mary Walker circa 1950. Courtesy Pamela Furtek

For photos and more detail about Dr. Walker’s breakthrough experimentation

Read more about Dr. Walker in a 2002 Myasthenia Gravis Association newsletter 

                  

Research on physostigmine led to important understanding about how the nervous system works. Unfortunately, the same knowledge led to the development, before World War II, of nerve gas. Sarin, used by a cult group in 1995 in the Tokyo subway, is one such gas. The attack killed 12 people and injured more.

Photo credit: Emergency workers in Japan rush sarin victim to the hospital.   japanfocus.org

                    

Most recently, physostigmine has been a subject of research related to Alzheimer’s Disease. In the 1970s and 1980s, researchers found it was one of the few drugs of its kind able to cross the blood-brain barrier. Its interaction with certain neurotransmitters led to improved cognitive function in people with the disease.

                     

Study of physostigmine also resulted in the development of insecticides. They operate the same way the calabar bean toxin does.

By 1846, calabar was growing in the Royal Botanic Garden in Edinburgh, Scotland, from seeds delivered by missionaries, and soon, toxicologic studies began. It was found that a small amount of seed extract administered to the eye produced constriction in the pupil. In 1864, researchers isolated physostigmine, calabar’s major constituent, and in the 1870s, a German scientist used it successfully to relieve glaucoma, a condition involving too much pressure in the eye.

                        

“Every time I have tackled a new natural product and marveled at its biogenesis, the memory of the Sunday afternoon walks through the woods and field has remained with me.”

Dr. Percy Lavon Julian

          

That's Dr. Percy Julian (1899-1975) talking about the walks he used to take with his father in the woods around their Montgomery, Alabama, home. His father pointed out native plants as they walked. Later, Dr. Julian became one of the foremost chemists of his time, with a specialty in plant chemistry. In 1935, he synthesized physostigmine.

Why did it become important to synthesize physostigmine–that is, to manufacture it versus collecting it from the wild? Because of its usefulness with glaucoma and the expense of extracting the natural compound from actual calabar plants.

Julian did other important work in plant chemistry. Like Russell Marker and Carl Djerassi, he was involved in the effort to synthesize sex hormones. His studies of soy contributed to this research as well as other uses for that plant. Julian Hall, on the campus of Illinois State University, is named for Percy Julian.

Photo credits: Young Percy Julian at DePauw University. DePauw University Archives and Special Collections (at top of story). Immediately above: US stamp issued in 1993.

Julian’s story is told in great illustrated detail on the great Science Alive! website. Kids especially will like it. And here's another excellent webpage about Julian and Djerassi.

 

Calabar Bean References for The Plant Detective Radio Show

Holmstedt, B. The Ordeal Bean of Old Calabar: The Pageant of Physostigma venenosum in Medicine. In: Plants in the Development of Modern Medicine, Swain, Tony, ed. Cambridge, MA: Harvard University Press, 1972, 303-60.

Mann, J. Murder, Magic, and Medicine. Oxford, UK: Oxford University Press, 1992, 29-35.

Further References

Rosenthal, Anne M. “Starting with Nature’s Molecules.” NIBR Perspective. Novartis Institutes for BioMedical Research 2004. Online at www.nibr.novartis.com.

Personal communication, Myasthenia Gravis Foundation of America (www.myasthenia.org), 9/22/04