Wednesday, February 7, 2018

Chemist Alice Ball, chaulmoogra and the first effective method for treating leprosy

Alice Ball, 11" x 14", linocut by Ele Willoughby, 2018, shows the chemist, branches of the chaulmoogra tree and
how she formed the ethyl ester of chaulmoogric acid (the acid plus alcohol produces the ethyl ester with water)

Leprosy is a disfiguring disease which has afflicted people for millenia. Though her work was stolen and she died tragically young, we now recognize Alice Ball, the young black woman chemist, for her discovery of the first effective treatment for leprosy just over a century ago. Today we know that leprosy (or Hansen's disease) is a long-term infection of bacterium Mycobacterium leprae or Mycobacterium lepromatosis, which can usually be treated with a mix of modern antibiotics. It's likely however that leprosy is as old as human history and descriptions of the symptoms of the disease appear in ancient texts, including Hippocrates (460 BCE) and the Hindu scripture the Atharva Veda from 2,000 BCE. Signs of the disease have been found in skeletal remains from 2,000 BCE. Those infected may not show symptoms for as many as 5 to 20 years, which hindered our understanding of how it was transmitted. Sufferers develop inflammation of the nerves, respiratory track, skin and eyes, as well as skin lesions and can loose the sensation of pain in those areas. This puts them in danger of loosing extremities as repeated injuries, wounds and infection can go unnoticed. People wrongly feared that leprosy was highly contagious, and quarantined the infected in "leper colonies," a practice which persists in some developing countries. There has been significant social stigma associated with the disease, which disproportionately afflicts those living in poverty and and the term "leper" for a person affected with leprosy. Jack London in The Cruise of the Snark described a Hawaiian leper colony as ‘the pit of hell, the most cursed place on Earth’.

In the West, the traditional treatment for leprosy, like syphilis, was mercury, which is of course poisonous. In traditional Indian and Chinese medicine, the oil from the seeds of the chaulmoogra tree (Hydnocarpus wightianus) was used as a treatment. While the oil did indeed combat the disease, it could not be effectively applied. As early as the 1300s, people tried applying chaulmoogra oil topically but it was too sticky. The acrid oil usually lead to vomiting when taken orally. Since it is viscous and can't dissolve in water (or blood), when injected it merely clumped under the skin and the patients were left with rows of oily blisters, with skin resembling bubble wrap. The painful injections were described as "burning like fire through the skin." This partial and flawed, disfiguring treatment for a disfiguring disease was adopted in Western medicine in the 19th century and there were no better options until a 23 year old chemist, Alice Ball was recruited to study chaulmoogra oil in 1915.

Alice Augusta Ball (July 24, 1892 - December 31, 1916) was one of four children in a middle to upper-middle class, black family in Seattle. Her father was a newspaper editor, photographer, and a lawyer, her mother was a photographer and her grandfather was a famous photographer. As such, she grew up around chemicals and the magic of chemistry. The family moved to Honolulu while she was a girl, because they hoped it would help with her grandfather's arthritis, but he died shortly thereafter and they returned to Seattle. Ball studied chemistry at the University of Washington, earning a bachelor's degree in pharmaceutical chemistry and a second degree in pharmacy two years later. She published "Benzoylations in Ether Solution," in the prestigious Journal of the American Chemical Society with her pharmacy instructor, at a time when it was quite an unusual accomplishment for any woman, let alone a woman of colour, to publish in the peer review literature. She was offered various scholarships and opted to return to Hawaii to pursue her master's in chemistry, investigating the active principle of Piper methysticum (a medicinal plant known as kava  or ╩╗awa). She was both the first woman and the first African American to graduate with a master's degree from the University of Hawai'i. She also became the first Black chemistry professor at the school.

Kalawao, Molokai, ca. 1922.jpg
Island of Molokai where people diagnosed with leprosy were held
was once known as the "Land of Living Death."
Albert Pierce Taylor (1922) Under Hawaiian Skies: A Narrative of the Romance,
Adventure and History of the Hawaiian Islands
, Board of Education of the
Hawaiian Kingdom, Page 348, Public Domain, Link

From 1866 to 1942, people diagnosed with leprosy in Hawai'i were arrested and quarantined on the Island of Molokai. Physician Dr. Harry T. Hollmann of the Kalihi Hospital in Hawai'i and acting director of the Kalihi leprosy clinic, was unsatisfied with using chaulmoogra oil in its natural form to treat leprosy patients and wanted to isolate the active ingredients. He recruited the graduate student Ball to help. Within a year, she was able to do what chemists and pharmacologists had been unable to do for centuries. She not only isolated the active ingredients but convert them to a form which could be circulated in the body. By taking the fatty acids present in the oil and exposing them to an alcohol and a catalyst, she produce ethyl esters which are soluble in water, and hence could effectively be injected. My print shows how she formed the ethyl ester of chaulmoogric acid (the acid plus alcohol produces the ethyl ester with water). This breakthrough was so significant, she was offered an instructor position in chemistry at the university. By 1922, her method was widely used to prepare chaulmoogra oil, and patients would might have been subjected to exile, a life of regular painful injections and being trapped in quarantine were instead being effectively cured and discharged!

Tragically, Ball did not live to see the affects of her research. She became ill during her research and returned to Seattle for treatment. She may have been exposed to chlorine gas while demonstrating the use of a gas mask in case of attack (as WWI was raging), but the cause of her death is unknown. Her death certificate was altered and lists tuberculosis as the cause of death, at age 24. She had yet to publish her results when she met her untimely death.

The chemist and president of the University of Hawaii, Arthur L. Dean completed and published her study - but he did not give Ball credit for her work, calling it the "Dean Method"! Dr. Hollmann objected and published an article documenting how the technique should in fact be known as the "Ball Method". The Ball Method relieved the thousands of patients removed from the homes in Hawai'i, forcing their families to hold funerals before their exile. Ball's Method was the preferred treatment for Hansen's disease until the advent of antibiotics in the 1940s. Despite Hollmann's efforts to defend her legacy, Ball's achievements did not receive much recognition until historians learned of and highlighted her work in the 1970s. Almost 90 years after her discovery, the University of Hawai'i finally recognized her work with a plaque on the school's lone chaulmoogra tree in 2000, and the Lieutenant Governor  declared February 29 "Alice Ball Day," now celebrated every four years.

Esther Inglis-Arkell, "We Had A Cure For Leprosy For Centuries, But Couldn't Get It To Work", io9,  
"Ball, Alice Augusta," ScholarSpace at University of Hawaii at Manoa, accessed February 7, 2018
"Alice Ball", "Hydnocarpus wightianus", and "Leprosy," Wikipedia, accessed February 7, 2018
"Meet Alice Ball - The pharmaceutical Chemist who developed the first effective treatment for Leprosy," Women Rock Science, December 3, 2013 
"Alice Ball and the Fight against Leprosy," blue stocking, Posted on

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