Alice Augusta Ball: A trailblazing chemist created a viable treatment for leprosy
Before the discovery of effective treatments, a diagnosis of Hansen’s disease (leprosy) often resulted in shame, stigma, physical disfigurement, and social isolation. Alice Augusta Ball, a Seattle-born chemist with degrees from the University of Washington and the College of Hawai’i (now the University of Hawai’i), devised a method to adapt the single known treatment for the bacteria-driven disease—topical application of an oil from the chaulmoogra tree—so it was more effective and easier to administer. The “Ball Method” yielded a water-soluble form of the active ingredients in chaulmoogra (pronounced “chal-MOO-grah”) oil that could be injected into a person’s body. This chemical modification of chaulmoogra oil would provide the most viable treatment for leprosy in the early 1920s. It remained a key therapy for those with the condition until the discovery of antibiotics decades later.
This Landmark celebrates the scientific contributions of Ball, whose groundbreaking work provided a treatment for leprosy that continues to be used in some areas of the world today. Ball was the first Black and first female chemistry professor at the College of Hawai’i, and her research accomplishments were initially appropriated by others—not an uncommon occurrence in that era. This Landmark underscores the obstacles that women and Black scientists have historically encountered in establishing themselves as leaders in their fields, as well as the importance of correcting the historical record to honor the critical contributions of these scientists for the good of humanity.
History of Hansen's disease
Hansen’s disease (formerly, and more commonly, known as leprosy) is caused by a bacterium (Mycobacterium leprae), which was discovered by Norwegian physician Gerhard Armauer Hansen in the 1870s.
It is particularly prevalent in people living in warm, humid, tropical regions. Descriptions of symptoms consistent with the disease can be found in ancient texts, including the Hebrew Bible and the Nei Ching, an ancient Chinese medical text. Evidence of leprosy has been found in human bone samples dating back to 2000 BCE. Afflicted individuals develop visible skin lesions and misshapen fingers, and in extreme cases require amputation of affected limbs because of damage to the nervous system. Those with leprosy were stigmatized and often kept away from the general population. Historical evidence of social isolation of people with leprosy crossed oceans and centuries. In County Tipperary, Ireland, tourists today can see 12th-century castle ruins at the Rock of Cashel where angled stones shield the windows of upper rooms looking out onto the altar where people with leprosy once hid from congregants while celebrating Mass. In Hawai’i, the remote Kalaupapa peninsula on the island of Moloka’i served to isolate over 8,000 with the disease to slow transmission.
Ethnopharmacology and early treatments
Despite the lack of a cure for leprosy, natural remedies were used for centuries to alleviate some of the outward symptoms of the disease, but to mixed effect. One treatment was the oil found in seeds of the chaulmoogra tree, a tropical evergreen tree. Historical records indicate that chaulmoogra oil was used in traditional Chinese medicine and Indian Ayurvedic medicine as far back as the 14th century to treat lesions from leprosy.
The use of chaulmoogra oil is an example of the science known as ethnopharmacology: the study of substances, particularly naturally occurring folk remedies found in sources such as plants, used as medicinal remedies by ethnic or cultural groups. By the 19th century, Western doctors knew of the oil as a topical treatment to alleviate symptoms, but side effects were significant. Topical applications led to skin irritation and other uncomfortable side effects. Thus, scientists knew an active ingredient in the oil could help alleviate symptoms, but they did not know how to make the treatment strong enough to be effective and safe enough to use without causing more distress.
Alice Augusta Ball and the "Ball Method"
Alice Augusta Ball was born in Seattle in 1892 to James P. Ball, Jr., and Laura Howard. One of four children, she graduated from Seattle High School with exceptional marks in most of her classes, particularly science. She went on to earn a Ph.C. degree in pharmaceutical chemistry in 1912 (a two-year degree that would be called today an associate’s degree) and a bachelor’s degree in pharmacy in 1914, both from the University of Washington in Seattle. She then completed a master’s degree in chemistry in 1915 at the College of Hawai’i, where she also worked as an instructor of chemistry. She was the first Black woman in the U.S. to earn a master’s degree in chemistry, and the first woman and Black person to teach chemistry at the College of Hawai’i.
In Honolulu, Ball became involved with the Leprosy Investigation Station (LIS) and worked with the director George McCoy. Given Ball’s expertise, she was asked to help LIS with their chaulmoogra studies. Specifically, she helped solve the chemical challenge of isolating the active ingredients in chaulmoogra oil to treat people with leprosy.
McCoy and colleague Harry Hollmann had been working on this solution for some time, using non-esterified chaulmoogra for intramuscular injections. Ball devised a method to make ethyl esters from fatty acids. Ethyl esters are a type of compound that include additional oxygen atoms, making the molecule polar and therefore soluble in water. This innovation allowed injected fatty acids isolated from chaulmoogra oil to be more bioavailable to the body due to their increased solubility, a remarkable step in the right direction.
Leaving a legacy
After her untimely death in 1916, Ball’s contributions were initially uncredited by those who built on her accomplishments. But in a 1922 paper, Hollmann credited her ingenuity in creating the esterification method to produce a therapeutic treatment from the chaulmoogra oil’s fatty acids.
Hollmann reported 84 people with leprosy that he treated “have become bacteriologically negative and free from all lesions of the disease … it is positive and undisputable evidence that the ethyl esters of chaulmoogric fatty acids, as isolated by Miss Ball for my use in treating leprosy, are capable…of causing the disappearance of the lesions and the [bacteria].”
Ethyl esterification of the fatty acids in chaulmoogra oil did not require sophisticated equipment, meaning that this improved treatment could be made available in remote locations with few resources. It allowed formerly quarantined people with leprosy to rejoin their families, communities, and the general population. Ball’s innovation—known today as the Ball Method— enabled the difference between a life of discomfort and isolation, and a life of fulfillment.
It is important to note that the chaulmoogra oil treatment using Ball’s esterified fatty acids does not kill the bacteria that causes leprosy but rather stalls its growth. Treatment of early symptoms were most successful and used frequently until the discovery of antibacterial treatments for leprosy in the 1940s.
Chemistry concepts: Esterification and drug development
Ball’s work relied on the chemistry of esterification using an alcohol: a reaction that converts carboxylic acids (such as the fatty acids found in chaulmoogra oil) into esters. Carboxylic acids are usually a linear strand of carbon atoms bound to the functional group -COOH. Chaulmoogric acid (C18H32O2) and hydnocarpic acid (C16H28O2), two key carboxylic acids found in chaulmoogra oil, have unique structures: A ring of five carbon atoms is located at the far end of the long carbon chain. This ring structure plays a role in the acids’ effectiveness at neutralizing leprosy-causing bacteria. Esters are molecules denoted by the chemical formula RCOOR’, where R and R’ represent any combination of atoms, C represents a carbon bound to the R group, and the O’s represent oxygen atoms. The reaction of a carboxylic acid and an alcohol under proper laboratory conditions can yield an ester. This process is known today as Fischer esterification, after Emil Fischer, one of the scientists who first reported on this method in a scientific paper published in 1895.
Ball’s technique required a great deal of skill in chemical methods. While such reactions are straightforward in today’s chemical laboratories, Ball performed her research in 1915, making her accomplishments rather remarkable.
She began by saponifying chaulmoogra oil (that is, making it into a soap) by reacting it with a mixture of potassium hydroxide and an alcohol, a reactant known at the time as “alcoholic potash.” From there, she gently heated the mixture to remove the alcohol via distillation, leaving the potassium soap behind. Ball then poured the soap into water and acidified it with hydrochloric acid. From there, she washed the fatty acids with hot water, dried them, and dissolved them in an alcohol solution before refrigerating them overnight. The fatty acids crystallized (they arranged into solids in a specific formation of molecules that create a lattice-like structure) and could then be removed via filtration. This yielded a purified fraction of the raw oil ready to be reacted with alcohol to produce a substance known as an ethyl ester. This yielded a purified fraction of the raw oil ready to be reacted with alcohol. This substance was then injected into people with leprosy, greatly reducing their symptoms.
Today, esterification is widely used in drug development, especially in the manufacturing of prodrugs: substances that undergo transformation in the body by specific enzymes known as esterases to become active drugs. Ester groups in prodrugs provide several valuable qualities. The prodrugs themselves have better chemical stability, meaning they can be stored longer compared to their active counterparts without undergoing degradation. They can also be administered in a specific area of the body, releasing their active counterparts at a target site. The ester groups improve the drugs’ ability to enter lipid-rich cell membranes, which helps the body absorb the drugs.
A forgotten chemist. Almost.
Ball’s contributions were nearly forgotten by the chemistry community. She died at the age of 24 on December 31, 1916, after perfecting her esterification method. However, there is evidence that Ball was still accelerating her esterification process in early 1916 as more people were being treated.
The cause of her death remains an open question. She came down with an illness that some suspected was tuberculosis and others feared was the result of unknowingly inhaling an extreme form of hydrochloric acid—her lab didn’t have a ventilation hood to protect her from these dangerous fumes. Her death certificate originally listed tuberculosis as the cause of death, but she was active and working without symptoms of that disease through early spring 1916. The word on her death certificate was later deleted by typing a series of “x’s” over the term.
Ball’s research and innovations were initially appropriated by male scientists who wished to take credit for her ideas. Hollmann deserves much credit for posthumously honoring Ball’s contributions to his work in isolating the fatty acids of chaulmoogra oil. But it would be many decades before Ball’s achievements attracted the recognition she deserved. It took historians decades to rediscover Hollmann’s 1922 paper and uncover Ball’s contributions. Ten days before she died, she wrote Hollmann a letter about her methods, and it is believed that part of his 1922 paper quotes her letter, which means her work was published as part of Hollmann’s paper. Hollmann did what he could to honor and memorialize her work and contributions to the treatment.
On the UH Mānoa campus, a plaque in Ball’s memory was dedicated in February 2000 at the base of a chaulmoogra tree gifted by King Prajadhipok of Siam in 1935. Ball was also posthumously awarded the University of Hawai’i Board of Regents Medal of Distinction in 2007. The State of Hawai’i governor has honored Ball with proclamations declaring Alice Augusta Ball Day on February 28. Today, the privately funded Alice Augusta Ball Scholarship is awarded to UH Mānoa students in the fields of chemistry, biochemistry, biology, or microbiology “who typify the characteristics that Ball displayed in her studies and research.”
Ball’s legacy as a chemistry pioneer embraces more than her outstanding achievements in the lab. In an era with few women and few Black people in science in the U.S., Ball excelled at her studies, earned an advanced degree in chemistry, and attained a faculty position in her field. She demonstrated a tenacious commitment to scientific inquiry and impressive research skills for her age and level of experience. As chemistry professor Gregory Petsko told the New York Times in 2023, lamenting her early passing, “Most chemists don’t hit their stride until their 30s or 40s. Just imagine what [else] she could have done if she had lived.”
Landmark dedication
The American Chemical Society (ACS) designated the discovery of the “Ball Method” as a National Historic Chemical Landmark (NHCL) in a ceremony in Honolulu, Hawai’i, on February 26, 2026. The commemorative plaque reads:
Alice Augusta Ball (1892–1916) was a groundbreaking scientist whose contributions went largely unrecognized during her lifetime. The first woman and Black person to earn a master’s degree in chemistry from the College of Hawai’i, Ball worked with Hawai’i health officials to solve the chemical challenges of developing an effective injectable extract of chaulmoogra tree oil for leprosy treatment. Her process, recognized as the Ball Method, remained the primary global treatment until sulfone drugs emerged decades later. A trusted colleague’s contemporaneous record of her work ensured her legacy, enabling many to posthumously honor the achievements of this remarkable chemist.
