While googling another topic, I came across the research and contributions of Alice Augusta Ball, a chemist and university professor who made a significant contribution to medicine and science. In 1915, Ball worked with an assistant surgeon and U.S. Public Health officer in Hawaii to research the properties of chaulmoogra oil. Her claim to fame would be developing an injectable form of the oil for the treatment of leprosy or Hansen’s disease while working as a chemistry instructor at the University of Hawaii.
Since the 14th century in China and even earlier in India, chaulmoogra oil was used topically or administered orally with moderate and inconsistent success to lessen the effects of leprosy. Ball’s development of a dosage that could be injected into the dermis greatly enhanced the efficacy of the oil which cured countless leprosy patients around the world or reduced the negative effects of the disease. It remained the primary treatment for leprosy for three decades until the invention of sulfone drugs in the 1940s.
As life and other events would have it, Ball’s work would remain hidden for almost a century before she received proper credit for her medical research. Some highlights of the history of leprosy are provided as a prelude to Alice Ball’s her-story.
Early History and Treatment of Leprosy
According to the Centers for Disease Control (CDC), leprosy or Hansen’s disease can affect the nerves, skin, eyes, and lining of the nose (nasal mucosa). The bacteria attack the nerves, which can become swollen under the skin. This can cause the affected areas to lose the ability to sense touch and pain, which can lead to injuries, like cuts and burns.
If left untreated, the nerve damage can result in paralysis of hands and feet. In very advanced cases, the person may have multiple injuries due to lack of sensation, and eventually an infected person can lose his toes and fingers. It is known to affect people of all ages from newborns to the elderly. It is most common in warm, wet areas in the tropics and subtropics.
Although it is not clear as to when leprosy was first recorded, it has tormented humans throughout recorded history. The earliest possible account of a disease that many scholars believe is leprosy appears in an Egyptian Papyrus document written around 1550 B.C. Around 600 B.C. Indian writings describe a disease that resembles leprosy. In Europe, leprosy first appeared in the records of ancient Greece after the army of Alexander the Great came back from India and then in Rome in 62 B.C. coinciding with the return of Pompeii’s troops from Asia Minor. [Ref 1]
The word, leprosy, is mentioned in both the Old and New Testaments of the Bible about 50 times. As an example, the case of Naaman (2 Kings 5:1) shows that lepers were not isolated and excluded from society among the Syrians:
Now Naaman was commander of the army of the king of Aram. He was a great man in the sight of his master and highly regarded, because through him the Lord had given victory to Aram. He was a valiant soldier, but he had leprosy. (NIV)
In the Middle Ages [Ref 2], instead of leprosy colonies, shelters existed that were known as leprosy asylums, or leprosaria. Lepers who were wealthy often stayed at home in isolated parts, but poorer lepers were sent to these asylums, where they were mixed in with a larger number of poor, depraved, or ill people. These asylums were run by monks, and were almost always associated with spiritual or religious significance. By the year 1200, there were some 19,000 leprosy asylums throughout Europe.
As if the skin disfiguration and boils of the disease weren’t enough to stigmatize the victims, people in the Middle Ages believed that leprosy was a punishment from God and that patients were literally embroiled in sin. People with the disease were considered dead to society — and their disease was known as the “living death.” Lepers often carried a bell they rang to warn healthy people that a diseased person was coming. Between 1200 and 1600, however, the disease in Europe began to decline, though scientists aren’t entirely sure why.
The modern history of leprosy began in 1873 and is chronicled below [Ref 1]. Before this time, the only way to “treat” the disease was to separate the victims from the rest of healthy society. Oils for the skin were largely used in an attempt to treat boils from the disease, but not much research exists as to whether they were very effective. Targeting the infection itself, however, wasn’t yet put in place.
1873 – Dr. Gerhard Henrik Armauer Hansen of Norway was the first person to identify the germ that causes leprosy under a microscope. Hansen’s discovery of Mycobacterium leprae (or M-leprae as it is often called) proved that leprosy was caused by a germ, and was thus not hereditary, from a curse, or from a sin.
Early 20th Century – Until the late 1940s, doctors all over the world treated leprosy patients by injecting them with oil from seeds of the chaulmoogra tree. This course of treatment was painful, and although some patients appeared to benefit, its long-term efficacy was questionable.
1921 – U.S. Public Health Service established the Gillis W. Long Hansen’s Disease Center in Carville, LA, which became known as “Carville.” It became a center of research and testing to find a cure for leprosy and a live-in treatment center for leprosy patients.
1941 – Promin, a sulfone drug, was introduced as a treatment for leprosy. It was first identified and used at Carville. Promin successfully treated leprosy, but unfortunately treatment with Promin required many painful injections.
1950s – Dapsone pills, pioneered by Dr. R.G. Cochrane at Carville, became the treatment of choice for leprosy. Dapsone worked wonderfully at first, but unfortunately, M. leprae eventually began developing dapsone resistance.
1970s – The first successful multi-drug treatment (MDT) regimen for leprosy was developed through drug trials on the island of Malta.
1981 – The World Health Organization began recommending MDT, a combination of three drugs: dapsone, rifampicin, and clofazimine. MDT with these drugs takes from six months to a year or even more, depending on strength of leprosy infection.
1989 – [added] Former U.S. Surgeon General Dr. C. Everett Koop noted in a visit to Kalaupapa, HI that “AIDS is the modern-day leprosy.” The difference between the two is that AIDS is caused by a virus, and leprosy is caused by a bacterium.
Current practice – MDT with a combination of dapsone, rifampicin, and clofazimine is still the best treatment for preventing nerve damage, deformity, disability and further transmission. Researchers are working on developing a vaccine and ways to detect leprosy sooner to start treatment earlier.
Much stigma and prejudice about the disease is still prevalent in many places around the world, and those suffering from it are isolated and discriminated. Continued commitment to fighting the stigma through education and improving access to treatment will lead to a world free of this completely treatable disease.
Alice Augusta Ball was born on July 24, 1892 in Seattle, Washington to James Presley and Laura Louise (Howard) Ball. Her grandfather was one of the first African American men to learn how to create daguerreotype (early photographic images were developed on silver-coated glass or copper plates) images. Her father was a lawyer and editor of the Colored Citizen newspapers. Her mother was a well-regarded photographer of Black leaders. [Ref 3, 4]
Alice graduated at the top of Seattle High School’s senior class in 1910, acing all of her classes. Given her family background in photography, she grew up around chemicals. She probably helped out in the family photo gallery, mixing fresh developers and preparing photographic plates. Her father and aunt were also photographers. Her early experience with photography chemicals is possibly what propelled her interest in chemistry. Following graduation from high school, Alice attended the University of Washington to study science, earning not one but two bachelor degrees – one in pharmaceutical chemistry (1912) and the other in pharmacy (1914). [Ref 3]
In 1914, and as an undergraduate student, she co-published an 11-page article in the Journal of the American Chemical Society: Benzoylations in Ether Solution with one of her instructors. [Ref 3, 4] As a reminder, she did all of this in the early 1900s, a time when race and sex discrimination were rampant and legal in the United States.
Alice decided to pursue a master’s degree in chemistry. She was offered scholarships from both the Universities of Berkeley and Hawaii. She chose the latter and in 1915, she became the first woman to graduate with a master’s degree from the University of Hawaii. She was offered a teaching position which she accepted. This also made her the first black professor of chemistry at this institution. [Ref 3]
As timing would have it, the paths of Alice Ball and Dr. Harry T. Hollmann, an Assistant Surgeon at Kalihi Hospital in Hawaii where new Hansen’s disease patients were sent, would cross in 1915. Later, in his 1922 medical article, Hollmann explained how it all began: “I interested Miss Alice Ball, M.S., an instructress in chemistry at the College of Hawaii in the chemical problem of obtaining for me the active agents in the oil of chaulmoogra. After a great amount of experimental work, Miss Ball solved the problem for me by making the ethyl esters of the fatty acids found in the chaulmoogra oil, employing the technique herewith described.” [Ref 3]
Ball’s solution to the problem involved preparing the ethyl esters of the fatty acids present in the oil. An ester can be prepared from a carboxylic acid by reacting it with an alcohol, usually in the presence of another acid as a catalyst. An alcohol has an -OH functional group, and a carboxylic acid functional group has the general formula -COOH, or -CO2H. The ethyl ester of an acid is formed using ethanol as the alcohol.
Scientists around the world had been searching for years to find an effective way to administer chaulmoogra oil in an injectable form. While working on her thesis, Ball accomplished what many researchers, chemists, and pharmacologists working in some of the world’s most sophisticated and well-equipped laboratories had been unable to do! Ball almost appeared as a modern day heroine who was put on earth to solve this very complex problem.
At the ripe old age of 23 or 24, Ball developed the first preparation of a water-soluble, injectable form of chaulmoogra oil to treat leprosy. This was quite remarkable considering she had a full-time job teaching chemistry classes and labs during the day leaving her to conduct the chaulmoogra experiments in her free time. Because she solved the chaulmoogra puzzle rather quickly— between 1915 and early 1916—we can presume that she was gifted at project planning and strategy.
Alice Ball’s story would take another unusual twist! Before she was able to publish her results, she fell ill after accidentally inhaling chlorine gas during a lab demonstration. During this time, ventilation hoods were not a mandatory safety feature in laboratories. She would return home to Seattle and later died on December 31, 1916, at the age of 24.
Ball’s unpublished results on the ethyl ester isolation process for chaulmoogra oil held great promise for patients of Hansen disease. Following her untimely death, Dr. Arthur L. Dean, a chemist and president of the College of Hawaii, carried on Alice’s pioneering work. [Ref 3, 4] A laboratory at the college began producing large quantities of the new injectable chaulmoogra oil to supply the numerous requests that were coming from all over the world.
While it was good that someone was appointed to finish the project that Alice started, what was informally referred to as the Ball Method for treating leprosy became the Dean Method. Dr. Hollmann would later point out this error in a paper he wrote in 1922: The Fatty Acids of Chaulmoogra Oil in Treatment of Leprosy and Other Diseases. Hollman pointed out that he saw no improvement over the original technic that was first outlined by Ball. A local paper, the Honolulu Advertiser would also identify this oversight in a 1925 article: Hawai’ian Girl Heroine.
Many years later it would take the work of two activist scholars, Dr. Katharine Takara who discovered Ball’s work in the university’s archives in 1977, and Stan Ali, a retired federal worker, who read about the young Negro chemist in Charles Dutton’s book on leprosy: The Samaritans of Molokai (1932), to get Ball the “proper credit” for the life-changing and life-saving technic that she developed. [Ref 4]
On February 29, 2000, the State of Hawaii recognized its first “Alice Ball Day.” On the same day, the University of Hawaii honored its first female graduate and pioneering chemist with a bronze plaque mounted at the base of the lone chaulmoogra tree on campus. In January 2007, the Board of Regents of the University of Hawaii posthumously honored Alice’s work and memory with its Regent Medal of Distinction. The awards ceremony was held on April 14, 2007.
The CDC reports that about 150 to 250 persons in the United States and about 250,000 around the world are diagnosed with Hansen’s disease each year. In the past, Hansen’s disease was feared as a highly contagious, devastating disease. It is now considered a disease that is hard to spread and it’s easily treatable once recognized.
The work of Alice Augusta Ball allowed those suffering from Hansen’s disease to lead normal lives and for others, it reduced the suffering and negative effects of the disease. Ball’s development of an injectable form of chaulmoogra oil showed that Hansen’s disease was no longer hopeless but treatable. This resulted in increased funding for research that would later lead to the development of the sulfones and other effective treatments for Hansen’s disease.
“Truth never damages a cause that is just.” Mahatma Gandhi
- History of Leprosy, Stanford University, http://web.stanford.edu/class/humbio103/ParaSites2005/Leprosy/history.htm
- A History Of Leprosy, The Debilitating Disease Of Separation, May 13, 2015, by Lecia Bushak, http://www.medicaldaily.com/history-leprosy-debilitating-disease-separation-photo
- Alice A. Augusta Ball Young Chemist Gave Hope to Millions, by Paul Wermager and Carl Heltzel in ChemMatters, February 2007, http://patriotssch4u1.pbworks.com/w/file/fetch/58207153/Alice%20Ball.pdf
- Wonder Women: 25 Innovators, Inventors, and Trailblazers who Changed History, by Sam Maggs, Quirks Books, Philadelphia, PA, 2016