Alice Ball: The Chemist Who Revolutionised Leprosy Treatment and Changed Pharmacological History

Alice Augusta Ball, an African-American chemist [Figure 1], made a groundbreaking contribution to the treatment of leprosy (Hansen’s disease) during her short yet impactful life. Born in 1892, she became the first woman and first African American to earn a Master’s degree in chemistry from the College of Hawaii, now the University of Hawaii. At just 23 years old, Ball revolutionized the use of chaulmoogra oil in leprosy treatment, offering hope to those suffering from this stigmatized and misunderstood disease¹.
 

Figure 1- Alice Ball portrait. Reproduced from: Mushtaq, S. and Wermager, P. (2022). Alice Augusta Ball: The African-American chemist who pioneered the first viable treatment for Hansen’s Disease. Clinics in Dermatology, 41.¹

Leprosy, caused by Mycobacterium leprae, had long been a source of social ostracism due to ability of the disease to cause visible deformities and its contagious nature. Before the 20th century, leprosy patients were often segregated in colonies or asylums, with few effective treatments available.² Chaulmoogra oil, derived from the seeds of the Hydnocarpus tree, had been used for centuries in traditional medicine across Asia for leprosy treatment¹. However, its application in Western medicine was problematic—oral intake caused severe gastrointestinal distress, and injections were painful due to the oil’s viscosity, leading to inconsistent results³ [Figure 2]. The search for a more effective treatment seemed futile until 1915, when a young chemist, Alice Ball, changed everything.
 

Figure 2 – A) Hydnocarpus fruits from which the seeds are derived. Reproduced from: India Biodiversity Portal; B) Hyndocarpus tree as seen from the University of Hawaii campus dedicated to Alice Ball. Reproduced from:  Mushtaq, S. and Wermager, P. (2022). Alice Augusta Ball: The African-American chemist who pioneered the first viable treatment for Hansen’s Disease. Clinics in Dermatology, 41¹.C) Painful injections of oil Lancet; C) Painful chaulmoogra oil injections. Reproduced from: Ferry, G. (2023). Alice Ball: chemist who developed a treatment for leprosy. The Lancet, 402(10404), p.767.

Ball’s genius lay in her ability to chemically modify the active components of chaulmoogra oil, altering its pharmacokinetic properties to significantly enhance the agent's bioavailability. In 1915, she developed a method to extract the ethyl esters from the fatty acids in the oil, making it water-soluble. This formulation could be safely injected, absorbed more effectively by the body, and caused fewer side effects than the earlier versions of chaulmoogra oil treatments. Known as the "Ball Method," her breakthrough in 1915 provided the first effective and viable treatment for leprosy, continuing to be used until the introduction of sulfone drugs in the 1940s^1,3.
From a pharmacological perspective, chaulmoogra oil's key components, chaulmoogric and hydnocarpic acids, belong to a unique class of cyclopentenyl fatty acids (CFAs) with a cyclic 5-carbon ring structure⁴. This structure plays a crucial role in the oil’s bactericidal effect on M. leprae. The oil’s fatty acids may interfere with the bacterium’s ability to synthesize its fatty capsule, which is essential for its survival⁵.

Despite her remarkable discovery, Alice Ball did not live to see the full impact of her work. Tragically, she died at the young age of 24 before she could publish her findings. After her death her colleague, Arthur Lyman Dean, took credit for her groundbreaking method, rebranding it as the “Dean Method”^6,7. Dean made only a slight modification to Ball’s method, using distillation in vacuum, a step that Hollmann, a physician involved in leprosy treatment, later criticized. In 1922, Hollmann published a paper refuting Dean's claims, strongly defending the efficacy of Ball’s original method⁸ [Figure 3]. He argued that Dean’s adjustment did not improve the process and, in fact, made it more complicated without offering any therapeutic advantage. Hollmann emphasized that the extraction technique should rightfully be called the "Ball Method." Despite Hollmann’s efforts to set the record straight, Alice Ball’s name was lost in time for 85 years, until her contributions were rediscovered and finally recognised¹.
 

Figure 3 - An excerpt from Hollmann’s 1922 contribution, crediting Alice Augusta Ball for the first time in medical literature. Reproduced from: HOLLMANN, H.T. (1922). THE FATTY ACIDS OF CHAULMOOGRA OIL IN THE TREATMENT OF LEPROSY AND OTHER DISEASES. Archives of Dermatology and Syphilology, 5(1), p.94.
 
Today, leprosy is treated with multidrug therapy (MDT), which combines antibiotics such as dapsone, rifampicin, and clofazimine. MDT is used because monotherapy is not effective, as Mycobacterium leprae can quickly acquire resistance to individual antibiotics. These drugs in combination are highly effective in curing the disease and preventing its transmission, allowing patients to reintegrate into society without fear of contagion⁹. Ball’s pioneering work paved the way for these advancements, as her method provided a foundation for further research into the treatment of leprosy.

Alice Ball's legacy continues to inspire future generations of scientists, particularly Black women in STEM, showing that perseverance and innovation can change the course of history, even in the face of adversity. Her contributions to the treatment of leprosy remain a testament to the power of science in alleviating human suffering.

References:

1. Mushtaq, S. and Wermager, P. (2022). Alice Augusta Ball: The African-American chemist who pioneered the first viable treatment for Hansen’s Disease. Clinics in Dermatology, 41(1).

2. Santacroce, L., Del Prete, R., Charitos, I.A. and Bottalico, L. (2021). Mycobacterium leprae: A historical study on the origins of leprosy and its social stigma. Le Infezioni in Medicina, 29(4), pp.623–632.

3. Ferry, G. (2023). Alice Ball: chemist who developed a treatment for leprosy. The Lancet, 402(10404), p.767.

4. Govil, J. and Singh, V. (2011). Recent progress in medicinal plants. Fixed Oils and Fats of Pharmaceutical Importance ed. Houston, Tex.: Studium Press Llc, pp.339–356.

5. Sahoo, M.R., Dhanabal, S.P., Jadhav, A.N., et al (2014). Hydnocarpus: An ethnopharmacological, phytochemical and pharmacological review. Journal of Ethnopharmacology, 154(1), pp.17–25.

6. McDonald, J.T. and Dean, A.L. (1920). The Treatment of Leprosy: With Especial Reference to Some New Chaulmoogra Oil Derivatives. Public Health Reports (1896-1970), 35(34), p.1959.

7. Mcdonald, J.T. (1920). Treatment of Leprosy with the Dean Derivatives of Chaulmoogra Oil ; Apparent Cure in 78 Cases. JAMA, 75(22).

8. HOLLMANN, H.T. (1922). THE FATTY ACIDS OF CHAULMOOGRA OIL IN THE TREATMENT OF LEPROSY AND OTHER DISEASES. Archives of Dermatology and Syphilology, 5(1), p.94.

9. Smith, C.S., Aerts, A., Saunderson, P., et al (2017). Multidrug therapy for leprosy: a game changer on the path to elimination. The Lancet Infectious Diseases, 17(9), pp.e293–e297.

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