Biosynthesis
Physostigmine biosynthesis is proposed from tryptamine methylation and post-heterocyclization catalyzed by an unknown enzyme:

History
The Calabar bean
The Efik people, living in Cross River State and the Ibibio people in Akwa Ibom State, in what is now the south-south of Nigeria, were the first to come in contact with physostigmine, the active ingredient in the Calabar bean. The Calabar bean, or chopping nut, was very prevalent in Efik culture as an ordeal poison. Individuals accused of witchcraft would drink the white, milky extract of the bean, made by crushing the bean in a mortar and soaking the remains in water. If the accused died, it was considered proof of their use of witchcraft. If they lived, usually due to vomiting up the poison, then they were declared innocent and sent free. Western medicines discovery
In 1846, European missionaries arrived in what was referred to as Old Calabar, now part of Nigeria. These missionaries wrote about the use of the Calabar bean as a test for witchcraft. These beans eventually made their way back to Scotland, the home of these particular missionaries, where in 1855 Robert Christison, a toxicologist, tested the toxicity of the poison on himself by eating one. He survived to document the experience.
Furthermore, effective medications are often in short supply in developing countries, which carry the majority of the disease burden from Shigella. Antidiarrheal agents may worsen the sickness, and should be avoided.In most cases, the disease resolves within four to eight days without antibiotics. Severe infections may last three to six weeks. Antibiotics, such as trimethoprim-sulfamethoxazole, ciprofloxacin may be given when the person is very young or very old, when the disease is severe, or when the risk of the infection spreading to other people is high. Additionally, ampicillin (but not amoxicillin) was effective in treating this disease previously, but now the first choice of drug is pivmecillinam. Epidemiology
Insufficient data exist, but it is estimated to have caused the death of 34,000 children under the age of five in 2013, and 40,000 deaths in people over five years of age. Shigella also causes about 580,000 cases annually among travelers and military personnel from industrialized countries.An estimated 500,000 cases of shigellosis occur annually in the United States. Infants, the elderly, and the critically ill are susceptible to the most severe symptoms of disease, but all humans are susceptible to some degree. Individuals with acquired immune deficiency syndrome (AIDS) are more frequently infected with Shigella. Shigellosis is a more common and serious condition in the developing world; fatality rates of shigellosis epidemics in developing countries can be 5–15%.Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in these communities in Israel, with sporadic outbreaks occurring elsewhere in among these communities.