Oak Park, Illinois, United States
|Alice Augusta Ball, 1915. (Wikimedia Commons, Public Domain)|
“The leprous person who has the disease shall wear torn clothes and let the hair of his head hang loose, and he shall cover his upper lip and cry out, ‘Unclean, unclean.’ He shall remain unclean as long as he has the disease. He is unclean. He shall live alone. His dwelling shall be outside the camp.” – Leviticus 13: 45-46
For millennia, and in diverse communities and cultures, leprosy has been associated with contagion, exclusion, and sin. Although the Hebrew word tzaraat, which in fact referred to a wide variety of skin rashes, ulcerations, and discolorations, was not translated as leprosy until the sixth century in Greek, and the ninth century in Arabic, the association with a specific and highly stigmatized mycobacterial disease has persisted to modern times. There is no literary, artistic, archeological, or biological evidence that the condition now known as leprosy existed in the regions occupied by the Hebrews at the time the books of the Old Testament were written.1 However, throughout history people with leprosy have been forced to live on the margins of society with a condition that not only slowly and painfully disfigured the body but was long believed to reflect an unclean spirit; a punishment for unspeakable sin.
The earliest descriptions of leprosy are found in ancient texts from China, India, and Egypt dating from 600 BCE. The science of modern genomics has traced the evolution of the causative agent, Mycobacterium leprae, in a fashion that also tells the story of waves of human migration.2 While the clinical manifestations of skin lesions, nerve damage, blindness, and limb disfigurement have been recognized from antiquity, it was not until 1873 that the Norwegian physician Gerhard Armauer Hansen identified a mycobacterium as the causative agent.3 The condition today is commonly referred to as Hansen’s disease, and while Hansen may have discovered its microbial cause in the nineteenth century, the mode of transmission was not yet understood and there was no cure. Hansen’s disease is now known to be less contagious than many other infectious conditions, but those afflicted with the disease were stigmatized, exiled, disowned, and even legally considered dead well into the twentieth century.
One community of forced exile was at Kalaupapa, a settlement on a remote peninsula on the Hawaiian island of Molokai. Mycobacterium leprae was just one of many deadly infectious agents introduced to the native Hawaiian people through European exploration. The population of the archipelago is believed to have been between 400,000 and 800,000 at the time of first European contact; by 1900 the population had dwindled to less than 38,000.4 Leprosy first appeared in Hawaii around 1830, and by the middle of the nineteenth century native Hawaiians were suffering and dying from its effects at such an alarming rate that King Kamehameha V signed the “Act to Prevent the Spread of Leprosy” on January 3, 1865. This law, which would remain in effect until 1969, nearly thirty years after the development of the first successful antibiotic treatment for leprosy, required the arrest of anyone suspected of having the disease. After an evaluation in Honolulu, severely affected people were sent to the settlement on Molokai, where more than 8,000 men, women, and children lived and died during the 103 years of the law’s enforcement.5 It was common for families to disown the afflicted person, both out of fear of suspicion for themselves and because of the strong stigma linking leprosy to sin. Even after the residents of Kalaupapa were successfully treated with antibiotics in the last decades of the twentieth century and no longer infectious, many decided to continue living in their adopted community on Molokai. As stated poignantly by one resident of Kalaupapa who was interviewed in 2001: “We paid for this land. The shame, the abandonment, the exile: we paid for this place.”6
|Leprosy treated with injectable chaulmoogra oil. From Handbook of Medical Treatment, 1919. (Wikimedia Commons, Public Domain)|
Before the introduction of an effective antibiotic in the 1940s, Western scientists had long pursued a treatment for leprosy with chaulmoogra oil. The chaulmoogra tree (Hydnocarpus wightiana) produces seeds that had been used for centuries as a treatment for skin diseases in traditional Chinese and Indian medicine. The seed oil, when applied topically, produced highly inconsistent results in the treatment of leprosy. Some scientists claimed greater success by giving it orally, but a bitter taste and emetic effects limited the usefulness of this route.7 Toward the end of the nineteenth century, some patients were treated by intramuscular or subcutaneous injection. But the oil was not absorbed well, the injections were painful, and many suffered severe localized reactions and infection.8 A method was needed to isolate, extract, and modify the active components, but chaulmoogra oil had proven to top scientists that its secrets were not easily revealed. The solution to this conundrum would come from a young, African American chemist whose story was nearly lost to history.
Alice Augusta Ball was born in Seattle, Washington on July 24, 1892, to a family of successful photographers. Growing up around the chemicals used to develop photographs, she took an early interest in science. She received Bachelor of Science degrees from the University of Washington in both pharmaceutical chemistry and pharmacy, and with her pharmacy instructor co-published a paper in the Journal of the American Chemical Society, an especially remarkable achievement for a woman and a person of color at that time. She received scholarship offers to continue her studies from both the University of California at Berkeley and the College of Hawaii. Having lived in Hawaii with her family for some years when she was a girl, in 1914 she took the long voyage alone to begin advanced studies in Hawaii. She completed her master’s degree in one year and identified the active components of the kava root for her thesis. Few African American women had advanced degrees in chemistry at this time, and after graduation she went on to break barriers as the first African American instructor in the chemistry department at the College of Hawaii (now the University of Hawaii), which was soon followed by her promotion to head the department.9
Ball’s work attracted the attention of physician Harry T. Hollmann, a U.S. Public Health Officer and the medical director of the Kalihi Leprosy Hospital in Hawaii. Hollmann had been following attempts in the scientific community to develop a useful formulation of chaulmoogra oil for the treatment of leprosy and thought Ball had the background, skill set, and energy to take on this important work.10 He was correct in his assessment. Ball, at the age of twenty-three, developed a method to create a water-soluble, injectable form of the active components of chaulmoogra oil, which involved saponification of the oil to make potassium salts of the fatty acids, acidification by successive recrystallizations, and conversion to an injectable form of the ethyl esters. This method would come to be known as the Ball method, but not until Hollmann reclaimed her original work from the hands of a colleague, which occurred years after her untimely death.11
Alice Ball died tragically at the age of twenty-four. Although the circumstances are not entirely clear, her death appears to have been precipitated by the inhalation of chlorine gas in a lab accident. Seriously ill, she returned to Seattle in October and died two months later on December 31, 1916. Her work was taken up by Dr. Arthur Dean, a fellow chemist and the president of the College of Hawaii. Dean published a series of articles using Alice Ball’s research and called the new and innovative treatment “the Dean method.”12 A July 1921 New York Times article touted Dean’s work as a cure for leprosy: “As a result of a series of experiments, Professor Dean determined that the ethyl esters of these acids are thin fluid oils which lend themselves readily to intramuscular injection and are readily absorbed. These ethyl ester derivatives of chaulmoogra oil have now been in use at the United States Public Health Service leprosy investigation station at Kalihi in the Hawaiian Islands for some three years and the results have been very encouraging. During that period some 140 lepers have been paroled and returned to their families, the disease apparently arrested.”13
|Kalaupapa settlement on Molokai, 1905. Hawaii State Archives. (Wikimedia Commons, Public Domain)|
Harry Hollmann, the physician who had first tapped Alice Ball’s innovation and talent in his quest to help patients with leprosy in Hawaii, never forgot who had really made the breakthrough. In a 1922 journal article, Hollmann identified Ball’s crucial contribution in developing this treatment and advised the scientific community to call it “the Ball method.” But even with Hollmann’s input, Alice Ball’s important work was lost for decades and only discovered in the 1970s by a few observant investigators who followed the threads of some obscure references.14 Today there is a plaque recognizing Alice Ball’s accomplishments on a chaulmoogra tree (a gift from the Kingdom of Siam for help in treating leprosy) on the University of Hawaii campus and a scholarship in her honor. Every four years on February 29, Alice Ball Day is celebrated in Hawaii and in 2007 the University of Hawaii posthumously presented her with the Medal of Distinction.15 Her contributions have been recognized internationally as well; in 2019 the London School of Hygiene and Tropical Medicine inscribed Alice Ball’s name on its facade along with Florence Nightingale and Marie Sklodowska-Curie. Their names were added to twenty-three other science and medicine innovators—all men—in celebration of the institution’s ninetieth anniversary.16
Although Ball’s therapy was largely abandoned as a treatment for leprosy when effective antibiotics became available in the 1940s, for decades it offered hope to people worldwide that had suffered physically and emotionally from an ancient scourge. Scores were declared cured and able to return home to their communities if they wished—and if the long and lingering memory of old stereotypes allowed them to do so. The hard work and ingenuity of the woman who developed this breakthrough treatment were nearly lost, likely because of racism, sexism, and the clouding of ethics that stems from cutthroat professional ambition. Science has declared that people who contract Mycobacterium leprae in the twenty-first century should no longer be excluded from society. Likewise, those who have made significant contributions to science but were excluded because of race, gender, or status—scientists like Alice Augusta Ball—should also have their achievements brought into the light and their names chiseled in stone.
- Grzybowski, Andrzej and Nita, Malgorzata. “Leprosy in the Bible,” Clinics in Dermatology 34 , no. 1 (January 2016): 3-7. Accessed August 5, 2020.
- Monot, Mark et al. “On the Origin of Leprosy,” Science 308, 5724 (13 May 2005): 1040-1042. Accessed August 11, 2020. DOI: 10.1126/science/1109759.
- Hansen, G. Armauer. “On the Etiology of Leprosy,” The British and Foreign Medico-Chirugical Review 55, 110 (1875): 459-489. Accessed August 5, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157872/
- Inglis, Kerri A. “A Land and a Disease Set Apart.” In Ma‘i Lepera: A History of Leprosy in Nineteenth-Century Hawai‘i, 17-45. University of Hawai’i Press, 2013. Accessed August 11, 2020. www.jstor.org/stable/j.ctt6wqkmv.8.
- “Hansen’s Disease,” National Park Service, U.S. Department of Interior, Kalaupapa National Historical Park. Accessed August 5, 2020.
- Langlas, Charles, McGuire, Ka’ohulani, and Juvik, Sonia. “Kalaupapa 2002 – 2005: A Summary Report of the Kalaupapa Ethnographic Project,” 2008. Accessed August 5, 2020. https://www.nps.gov/kala/learn/historyculture/upload/KALAsummaryReport.pdf
- Cottle, Wyndham. “Chaulmoogra Oil in Leprosy.” The British Medical Journal 1, 965 (June 28, 1879): 968-969. Accessed August 4, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2239681/
- Parascandola, John. “Chaulmoogra Oil and the Treatment of Leprosy.” Pharmacy in History 45, 2 (2003): 47 – 57. Accessed August 5, 2020. https://www.researchgate.net/publication/277597573_Chaulmoogra_Oil_and_the_Treatment_of_Leprosy
- Brown, Jeannette E. African American Women Chemists. Oxford, Eng.; New York: Oxford University Press, 2012: 20 – 22.
- “UWSOP alumni legend Alice Ball, Class of 1914, solved leprosy therapy riddle,” University of Washington School of Pharmacy, February 13, 2017. Accessed August 5, 2020. https://sop.washington.edu/uwsop-alumni-legend-alice-ball-class-of-1914-solved-leprosy-riddle/
- Notman, Nina. “Alice Ball’s treatment for leprosy,” Chemistry World, May 18, 2020. Accessed August 5, 2020. https://www.chemistryworld.com/culture/alice-balls-treatment-for-leprosy/4011313.article
- Brown, 23.
- “Cure for Leprosy? Assistant Surgeon General Schereschewsky Tells of Apparent With Chaulmoogra Oil,” The New York Times, July 17, 1921. Accessed August 11, 2020. https://timesmachine.nytimes.com/timesmachine/1921/07/17/109813777.pdf
- Kreisels, Susan. “Alice Ball made a stunning find in her early 20s,” Honolulu Star-Bulletin, February 18, 2000. Accessed August 5, 2020. http://archives.starbulletin.com/2000/02/18/news/story3.html
- “A Woman Who Changed the World,” University of Hawaii Foundation, February 21, 2017. Accessed August 4, 2020. https://www.uhfoundation.org/impact/students/woman-who-changed-world
- “Women health pioneers honored on LSHTM’s iconic London building for the first time,” London School of Hygiene and Tropical Medicine, September 6, 2019. Accessed August 4, 2020. https://www.lshtm.ac.uk/newsevents/news/2019/women-health-pioneers-honoured-lshtms-iconic-london-building-first-time
ANNE JACOBSON, MD, MPH, is a family physician, writer, consultant, and editor. Her published works may be found in Hektoen International, The Examined Life Journal, The Journal of the American Medical Association, in the anthology At The End of Life: True Stories About How We Die, and others. A collection of her writing may be found at www.thewritetowander.com. She is the Associate Editor of Hektoen International Journal of Medical Humanities.