Esmond R. Long and Florence B. Seibert
Esmond Long. Courtesy the Historical Society of Pennsylvania (HSP), Philadelphia Record Photo Morgue Collection (v07).
In the 1930s Esmond R. Long (1890–1979) and Florence B. Seibert (1898–1991) developed a better diagnostic test for the deadly lung infection tuberculosis (TB)—the PPD test, which is still the standard test in use today.
Long was the son of a chemistry professor at Northwestern University, just outside Chicago. In 1911 he received his A.B. degree in chemistry from the University of Chicago. Thanks to his family background, he had very broad cultural interests—in literature, languages, and history—and was also a fine athlete. His seemingly golden path to a productive and happy life went off course in his second year of medical school at the University of Chicago. During a tennis match he coughed up several mouthfuls of blood. When he performed the microscopic inspection of his own sputum, he determined that he was in fact infected with TB bacteria. In the United States, until the advent of Selman Waksman’s streptomycin during World War II, TB was feared as the killer of young, otherwise healthy, adults. The bacteria usually attack the lungs, but TB bacteria can attack any part of the body. If not treated properly, it can be fatal. To this day it is a major killer worldwide, in part due to the bacteria’s evolving resistance to a variety of antibiotics.
Long spent the next five years undergoing the various therapies for TB being practiced at the time—dry-air treatments in Arizona, a modified exercise regimen, a year of bed rest in Seattle, and a high-cholesterol diet. As a medical student, he was permitted in the later days of his convalescence in Seattle and in Saranac Lake, New York, to treat other patients and to do laboratory analyses and research. The early detection of TB became a major goal for him.
Florence B. Seibert. Courtesy University of Pennsylvania Archives.
Long was allowed to return to the University of Chicago, and in 1918 received his Ph.D. in pathology—to be precise, what was then known as “chemical” pathology, in contrast to simply focusing on the shapes of pathogens and diseased tissues. While teaching pathology at the university, he continued to work to finish the requirements for the M.D., receiving it in 1926. Meanwhile, he became associated with the Sprague Memorial Institute in Chicago, an institution devoted to improving the health of Chicagoans. There Long performed studies on TB with a brilliant younger colleague, Florence Seibert, who was already making her mark in medical research.
Seibert was born in Easton, Pennsylvania. When she was three years old, she contracted polio. The disease left her partially disabled, and she had difficulty walking for the rest of her life. Even as an adult she stood four feet nine inches tall and weighed less than 100 pounds. As a child she learned to play the violin, a talent she maintained throughout her long life. As a teenager she became interested in science, reading biographies of famous scientists for pleasure.
After high school Seibert attended Goucher College in Baltimore, Maryland. She studied science hoping to be a doctor; going to the Johns Hopkins School of Medicine was her dream. But when she graduated from college in 1918, she took a temporary job in a chemistry lab at a paper mill in New Jersey, just to earn money for medical school. Back then women usually faced discrimination when hunting for scientific jobs, but World War I had taken many male scientists away to the battlefields, opening a window of opportunity for women scientists like Seibert. In addition, one of her professors had become a director of research at the mill and helped her get the job.
Seibert soon decided she liked chemical research more than medicine, partly because the duties of a chemist did not require her to be on her feet as much as the duties of a doctor. She went on to earn a Ph.D. in biochemistry from Yale University in 1923 and did postdoctoral research at the University of Chicago. While she was in Chicago, she learned to drive a car with hand controls for the accelerator, clutch, and brakes. Seibert found freedom and independence in her hand-controlled car, which she called “a new pair of legs.”
Next Seibert went to work at the Sprague Memorial Institute, where she eventually met Long. In her first year there she received the University of Chicago’s Howard Taylor Ricketts Prize for work she began at Yale and continued in Chicago. In those days patients often came down with short but intense fevers after receiving distilled water intravenously. Seibert discovered that although distilling the water killed bacteria and other microbes in the water, it often did not destroy the toxins that the bacteria had produced before they were killed. Sometimes spray from the water boiling in the distillation flask carried the toxins into the receiving flask, contaminating the distilled water. These toxins were causing the severe fevers. Seibert invented a new spray-catching trap for the still that kept the toxins from contaminating the distilled water.
At the institute Seibert began working with Long on TB studies. When Long became professor of pathology at the University of Pennsylvania and director of laboratories at its Phipps Institute for TB in 1932, he invited his talented collaborator to come with him to Philadelphia, and she became an assistant professor at the University of Pennsylvania. Their objective was to improve an existing test for diagnosing TB called the tuberculin skin test. In the test a small amount of a substance called tuberculin, which is made by the TB bacteria, is injected underneath a patient’s skin. Tuberculin was discovered back in the 1890s. It is an antigen, which is a substance that will trigger an immune response by the body in the form of what are called antibodies. If a person has been exposed to and infected by the TB bacteria, but does not necessarily show the symptoms of the disease, he or she will already have developed an immune response and formed TB antibodies. When the body is injected with the antigen tuberculin, these antibodies rush to the spot of the injection to attack the tuberculin, and within a few days they form a hard red bump. That red bump indicates that someone has been infected by the TB bacteria. If the person does not develop a red bump on the skin, then he or she has not been infected with the TB bacteria and antibodies have never been formed.
The test as it existed in the early 1930s, however, was unreliable owing to impurities in the tuberculin. Back in Chicago, Long and Seibert had discovered that the active agent in tuberculin was a protein. It now became Seibert’s goal to separate the protein from the other substances in the tuberculin and purify it. It took almost a decade of work to develop the purification process. Finally, she developed a technique that used filters made from porous clay and cotton that had been treated with nitric acid. The purified tuberculin protein that Seibert developed is now known as purified protein derivative, or PPD, and is still used in TB skin tests today.
Seibert spent most of the rest of her career at the University of Pennsylvania. Despite her scientific achievements she remained at the rank of associate professor for nearly 20 years before being named a full professor. She became a specialist in the field of protein separation. As in the case of tuberculin, sometimes proteins need to be separated from each other or from other substances in order to study them individually. Seibert was one of the first U.S. scientists to master two important protein-separation techniques, ultracentrifugation and electrophoresis. In retirement she pursued an investigation of the role of bacteria in cancer.
While Seibert received several honors in her lifetime, including the Garvan Medal of the American Chemical Society, Long held many significant posts and received many honors. He became in turn director of the Phipps Institute, chairman of the Division of Medical Sciences of the National Research Council, an important figure in maintaining the health of troops and civilian populations during and after World War II, and editor of the International Journal of Leprosy. Leprosy was the disease that captured his research attention in the latter part of his career.
A woman of her generation, Seibert remained eternally grateful to Long for having recognized her abilities: “Science has a lot of big men in it. And big men are quick to give opportunities to women as well as to men if they see the kind of ability a scientific problem calls for and a willingness to put into it the kind of work it needs.”