Pearce, Louise (1885–1959)

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Pearce, Louise (1885–1959)

American physician and pathologist who was part of the team that developed the drug tryparsamide to treat sleeping sickness. Born Louise Pearce in Winchester, Massachusetts, on March 5, 1885; died in New York, New York, on August 10, 1959; daughter of Susan Elizabeth Hoyt and Charles Ellis Pearce; graduated from Girl's Collegiate School, Los Angeles, California, 1903; Stanford University, A.B., 1907; attended Boston University; Johns Hopkins University,M.D., 1912; lived with Ida A.R. Wylie (1885–1959, a novelist); never married; no children.

Awards:

Order of the Belgian Crown (1921); honorary Doctor of Science, Wilson College (1947); honorary Doctor of Medical Science, Beaver College (1948); Elizabeth Blackwell Award (1951); Women's Medical College of Philadelphia citation (1952); honorary Doctor of Medical Science, Women's Medical College of Philadelphia (1952); King Leopold II Prize (1953); officer of the Royal Order of the Lion (1953).

Moved to California (c. 1890); Paul Ehrlich discovered salvarsan (1910); interned at Johns Hopkins Hospital (1912); named fellow of the Rockefeller Institute (1913); worked with Wade Hampton Brown on arsenic-based compounds (1913–19); tested tryparsamide, Belgian Congo (1920); investigated syphilis in rabbits (1920–28); appointed trustee, New York Infirmary for Women and Children (1921); appointed associate member of the Rockefeller Institute (1923); discovered the Brown-Pearce Carcinoma (1924); appointed to the General Advisory Council of the American Social Hygiene Association (1925); appointed visiting professor of syphilology at Peiping Union Medical College, China (1931); appointed to the National Research Council (1931); isolated the rabbit pox virus (1932); named member of the board of the Corporation of the Philadelphia Women's Medical College (1941); death of Wade Hampton Brown (1942); director of the Association of University Women (1945); became president of the Corporation of the Philadelphia Women's Medical College (1946); retired (1951).

Selected publications:

(with W.H. Brown) "Chemotherapy of trypanosoma and spirochaete infections. Biological series. I. The toxic action of N-phenylglycineamide-p-arsonic acid," in Journal of Experimental Medicine (Vol. 30, 1919); (with C.M. Van Allen) "Effects of operative interference with the endocrines on the growth and malignancy of a transplanted tumor of the rabbits," in Transactions of the Association of American Physicians (Vol. 38, 1923); (with A.E. Casey) "Studies in the blood cytology of the rabbit. I. Blood counts in normal rabbits," in Journal of Experimental Medicine (Vol. 51, 1930); "The treatment of human trypanosomiasis with tryparsamide: A Critical Review" (Rockefeller Institute for Medical Research, Monograph no. 23, 1930); "Experimental Syphilis of Oriental Origin: Clinical Reaction in the Rabbit," in Journal of Experimental Medicine (Vol. 67, 1938); "Hereditary osteopetrosis of the rabbit. II. X-ray, haematologic, and chemical observations," in Journal of Experimental Medicine (Vol. 88, 1948); "Hereditary distal foreleg curvature in the rabbit. II. Genetic and pathological aspects," in Journal of Experimental Medicine (Vol. 111, 1960).

Louise Pearce, one of the central participants in the development and testing of tryparsamide to treat sleeping sickness, was born in Winchester, Massachusetts, on March 5, 1885, the only daughter of Susan Elizabeth Hoyt and Charles Ellis Pearce, who ran a tobacco and cigar business. Soon after 1889, the family moved to Los Angeles, California, where Pearce attended the Girl's Collegiate School for three years.

In 1907, Pearce was awarded a bachelor's degree from Stanford University in Palo Alto, where she had studied histology and physiology. She spent two years as a medical student at Boston University, before transferring to the Johns Hopkins School of Medicine in 1909. In 1912, Pearce became a doctor of medicine and interned at the Johns Hopkins Hospital, where she was the first woman to be on the staff of the psychiatry department. Notes Marion Fay : "Many of her teachers and her classmates were, or were to be, outstanding figures in American medicine, and they greatly influenced her scientific career."

In 1913, Pearce was the first woman to be appointed as an assistant to Dr. Simon Flexner, the Rockefeller Institute's original director. Initially, her efforts were to go towards isolating the bacillus of scarlet fever, whooping cough, and measles. Instead, she was asked to do chemotherapeutic research with pathologist Wade Hampton Brown, testing arsenic-based compounds on the parasite which causes African trypanosomiasis or sleeping sickness.

During his explorations of Africa, Dr. David Livingstone was the first to report on the effects of the tsetse fly on European livestock. But it was Thomas Winterbottom, a Scottish physician who practiced in Sierra Leone during the late 18th century, who provided one of the earliest descriptions of the effects of the sleeping sickness on humans:

At the commencement of the disease, the patient has commonly a ravenous appetite, eating twice the quantity of food he was accustomed to take when in health, and becoming very fat. When the disease has continued some time, the appetite declines, and the patient gradually wastes away…. The disposition to sleep is so strong, scarcely to leave a sufficient respite for the taking of food; even the repeated application of a whip, a remedy which has been frequently used, is hardly sufficient to keep the poor wretch awake…. The disease, under every mode of treatment, usually proves fatal within three or four months.

In 1910, German chemist Paul Ehrlich discovered salvarsan arsphenamine, a natural compound containing arsenic. Ehrlich was known as the father of chemotherapy—the science of treating diseases with poisons which act against the infecting agent, but not against the patient. He used salvarsan to treat syphilis, but it had no effect on sleeping sickness.

Simon Flexner was determined to find an arsenic-based drug for the treatment of sleeping sickness, a disease all too common in equatorial Africa. The First World War interrupted supplies of salvarsan from Germany, therefore threatening a syphilis epidemic in the United States. Flexner assigned two biochemists employed by the Rockefeller Institute, W.A. Jacobs and Michael Heidelberger, to produce salvarsan. He also assigned Louise Pearce and Wade Hampton Brown to test the various arsenic-based compounds which might have an effect on sleeping sickness. The team investigated the effects of more than 243 arsenicals upon rabbits, mice, rats, and guinea pigs.

As John J. McKelvey noted, "the trouble with arsenic … was that it was devastating and nondiscriminating. It attacked the host and the parasite with equal vigor." Jacobs and Heidelberger adapted one of Ehrlich's arsenicals, and replaced its carboxyl group with amide, thus reducing its toxicity to tissue. After six years of extensive testing, Pearce and Brown discovered that the substance was successful in the treatment of rabbits with syphilis. The new drug was named tryparsamide, short for TRYPanosome-ARSenic-AMIDE. It also appeared to have a beneficial effects on animals with the trypanosoma parasitic protozoa transmitted by the tsetse fly, which causes sleeping sickness.

In May 1920, Louise Pearce was asked by the Rockefeller Institute to travel alone to the Belgian Congo (Republic of Congo), where thousands died each year from sleeping sickness. She was, as J.D. Fulton described, "of resolute character and endowed besides with great physical strength and vigor." In the Congo, she undertook field trials of the new drug on victims suffering from the disease. Pearce worked in Léopoldville, in a hospital laboratory put at her disposal by the Belgian colonial administration.

During the next several months, Pearce initiated a carefully planned treatment program for 77 patients in various phases of the illness. She employed graded doses of tryparsamide, which were administered intravenously, and closely monitored the results. Pearce found that the parasites were purged from the bloodstream within weeks, and that mental functions in the more serious cases returned to normal. The health of the majority of patients was restored, even those with advanced cases of sleeping sickness.

Tryparsamide owes its effectiveness to the fact that it reaches the cerebro-spinal fluid in concentrated form, and affects the trypanosomes in the central nervous system. Pearce's test results were spectacular, and the new experimental drug proved to be a tremendous improvement over atoxyl, also known as Bayer 205, a drug previously used on sleeping sickness victims. Atoxyl possessed trypanocidal action, but the drug proved useless in later stages of the disease.

In 1923, Dr. Eugène Jamot, who received 250 grams of tryparsamide from Pearce in New York, treated 14 patients in French Cameroon with single injections. As with earlier compounds such as atoxyl, which Albert Schweitzer described as "frightfully dangerous," Jamot anticipated that an overdose might cause blindness in his patients. It did not. Jamot's work confirmed Pearce's results. Several years later, however, one of Jamot's overzealous colleagues overdosed 700 patients, who all went blind. As well, it was discovered that over time certain strains of sleeping sickness developed a resistance to the drug.

Pearce's monograph, "The Treatment of Human Trypanosomiasis with Tryparsamide," became a formative work in the field. It reviewed ten years of clinical trials in the Congo, and delineated research done by other European scientists in Equatorial Africa and Cameroon. In another article published in 1925, Pearce reported on later clinical results in the Belgian Congo:

Van den Branden and Van Hoof, who have continued the observations and treatments in Léopoldville, reported in October, 1923, on the condition of 55 patients first treated three years previously…. Twenty of these patients were early cases … all were alive and in good health when last seen…. Thir ty-five patients were advanced cases of various types with pronounced lethargy. Three very advanced patients had died. Thirty-two patients were alive and well.

Writes Peyton Rous, Pearce "brought about one of the most shining and spectacular of the early purposeful achievements of the Institute, the conquest of sleeping sickness." The pathological, chemical, and clinical aspects of Pearce's work deeply impressed the Belgian government, which began widely employing tryparsamide in the Congo. In recognition of Pearce's work, the Belgian government rewarded her with the Order of the Crown of Belgium in 1921. In a commencement address at Bryn Mawr College in the same year, Dr. Simon Flexner held Pearce up as an example of the contributions which women were capable of making to science.

In 1923, Pearce was appointed an associate member of the Rockefeller Institute. She subsequently concentrated her research efforts on the biology and inheritance of disease, related in particular to syphilis and cancer. She continued to work in close association with Wade Hampton Brown. From 1920 to 1928, the pair investigated syphilis in rabbits, which closely mimics the syphilis found in humans. Their research proved of great value to immunologists, and in the development of treatments for human diseases. With Brown, she also discovered the Brown-Pearce Carcinoma, which is found in rabbits, and successfully transplanted the tissue from the carcinoma into other rabbits. For decades, the Brown-Pearce Carcinoma was the only available laboratory cancer tumor in the study of human disease and was employed by medical researchers around the globe.

In 1929, Pearce and Brown began a selective breeding program of rabbits. Together they studied birth defects and the rabbit's genetic susceptibility to infection. Their research project was threatened when the rabbit colony suffered three epidemics of rabbit pox. Eventually, Pearce isolated the virus which causes rabbit pox, a disease similar to human smallpox. In time, the rabbit colony outgrew its quarters at the Rockefeller Institute. In 1935, it was transferred to Princeton University.

By 1940, Pearce had isolated more than two dozen inherited diseases and deformities in rabbits, which had implications for the treatment of human disease. After Wade Brown's death in 1942, she continued this research alone. Eventually, Pearce terminated the breeding program and edited their results on osteopetrosis and achondroplasia for publication. Though she published several more papers after her retirement in 1951, the bulk of the remaining research would be destroyed upon her death. Several articles were also published posthumously.

Pearce was keenly interested in the medical education of women. She was an active and enthusiastic member of the American Association of University Women, as well as of its international counterpart. She became director of the Association of University Women in 1945, a position she held until 1951. She also served on the board of the Women's Medical College of Philadelphia beginning in 1941, and in 1946 she became president of the college.

Pearce's interests were many and varied, running the gamut from tropical medicine to bacteriology to cancer. She was a member of numerous professional bodies, including the American Society of Exploratory Pathology, the American Association of Cancer Research, the Pathology Society of Great Britain and Ireland, the Peiping Society of Natural History, and the Société belge de Médicine tropicale.

Pearce spent her entire career at the Rockefeller Institute, from 1913 to 1951. She maintained an active interest, however, in many areas of medicine, and served various other organizations. She was appointed a trustee of the New York Infirmary for Women and Children in 1921, and worked for the institution until 1928. In 1925, Pearce joined the General Advisory Council of the American Social Hygiene Association, remaining on the council until 1944. She was also appointed to the National Research Council in 1931. As well, Pearce maintained a six-year association with Princeton Hospital, beginning in 1940.

Little is known of Pearce's personal life. As George W. Corner noted:

Preeminently the professional physician-scientist, Dr. Pearce left few traces of her personality in the official record. Surviving friends recall her as a cordial and hospitable woman, who appreciated social amenities, and had a fondness for fine clothes, jewelry, books, and art. A vigorous individual, possessed of an incisive mind, Louise Pearce not only held her own in conservation with male colleagues, but also enlivened the rather sedate atmosphere of the Rockefeller Institute.

In 1951, Louise Pearce retired from the Rockefeller Institute. She spent the remaining years of her life at Trevenna Farm, in Skillman, New Jersey, where she shared a home with novelist Ida A.R. Wylie . Pearce loved to travel and spent considerable time in France and England. It was on a return voyage from Europe in 1959 that she fell ill aboard ship; she died shortly after her arrival in the United States, in a New York hospital, on August 10, 1959. She was 74. Ida Wylie died two months later.

Louise Pearce was the recipient of many honors and awards. In 1931, she served as a visiting professor with the Peiping (Beijing) Union Medical College in China. She was awarded numerous honorary degrees, from institutions such as Wilson College, Beaver College, and the Women's Medical College of Philadelphia. In 1953, the Belgian government awarded Pearce the King Leopold II Prize, and a check worth $10,000, in recognition of her contribution to finding a treatment for sleeping sickness 34 years earlier. As well, she and her colleagues were awarded the Royal Order of the Lion and their work chronicled in the ironically titled Man Against Tsetse. The two medals awarded by the Belgian government now hang along with Pearce's portrait in the president's office of the Women's Medical College of Philadelphia. Over the years, Pearce accumulated an incomparable collection of works on syphilis, from early manuscripts to the latest books. She bequeathed this extensive collection to Johns Hopkins University upon her death.

Louise Pearce conducted extensive studies on experimental syphilis. The discovery of the Brown-Pearce Carcinoma proved to be a significant contribution to our understanding of cancer. Her early work on the treatment of sleeping sickness is perhaps her best known, and the most clinically influential, of her research. But she was also deeply concerned about the education of women in medicine, and generously volunteered her time to many organizations. In sum, as J.D. Fulton put it: "She proved a good citizen of the world."