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Since the early days of Pennsylvania's settlement, the arrival of summer meant the appearance of typhoid, smallpox, cholera, and other diseases. In the summer of 1793, a yellow-fever epidemic killed nearly 7 percent of Philadelphia's population in three months. Cholera again ravaged the Delaware valley in August 1832. Smallpox struck statewide in 1860, and in 1899 typhoid fever devastated Harrisburg. Pennsylvanians also feared a mysterious and sinister summer disease that left its victims paralyzed. Befuddled doctors called the disease "acute paralysis," and attributed it to excessive chilling, overheating, trauma, stress or other diseases. Though it mainly struck children, polio could affect adults-as it did in an 1894 Vermont epidemic. Because its symptoms were very similar to other diseases, doctors rarely knew of its presence until the onset of paralysis.

Dr. Florence Siebert sitting at desk in the Phipps Institute Children's Clinic,...

In the summer of 1900, poliomyelitis entered the quiet town of Easton, Pa. One of the children struck was a bright three-year-old girl named Florence Barbara Seibert. Her affliction led her to wonder what caused her and so many other children of Easton to fall ill. Many of her peers played on a large sand hill near the Delaware River. Very near this spot was a stable where flies congregated. Could these flies be the communicators of polio, she wondered? Flies, in fact, do not to carry the disease, but Seibert's inquisitiveness would lead to a long career devoted to analyzing the causes and characteristics of humankind's most debilitating diseases.

After graduating from Easton High School as valedictorian in 1914, Seibert entered Goucher College in Towson, Md., where she became fascinated by the mysteries of human biology. There, Professor Jesse Minor encouraged her to "go on and study more basic science to prepare yourself to solve bigger and broader problems." A year later, Seibert enrolled in a biochemistry program at Yale University, where scientists T.B. Osborne and H.B. Vickery introduced her to the vexing problem of pyrogens.

"Cow Pock-or-the Wonderful Effects of the New Inoculation!" an 1802 cartoon...

Vaccinations had been around since the 1790s, when Edward Jenner first transferred the disease-causing organism into the bloodstream via an opening in the skin. But Jenner's method of vaccination soon fell out of favor. In the 1800s, scientists experimented with liquid mediums to reduce the potency of the original disease-causing agent and slow the agent's movement throughout the body. They wanted these mediums to be sterile, inert solutions, but try as they might, the solutions often became contaminated by bacteria, which afflicted patients with fevers of indeterminate intensity and length. Even distilled water, the purest of pure solutions, sometimes caused fevers.

Whittling away at the reasons that a solution would become fever-generating or "pyrogenic," Seibert hypothesized that at some point in the distilling process, bacteria was introduced to the solution. She then set out to develop a way to prevent contamination. In 1923, Seibert reported on her pyrogen-free process in the American Journal of Physiology. Soon thereafter, the Food and Drug Administration, the National Institutes of Health, and fourteen pharmaceutical firms all adopted her process for testing and producing pyrogen-free solutions. After receiving her doctorate from Yale, Seibert continued her research at the University of Chicago, then moved to the University of Pennsylvania's Phipps Institute to study one of the nation's most loathsome diseases: tuberculosis.

The Phipps Institute, 7th and Lombard Streets, Philadelphia, PA, circa 1915.

Called the "white plague" or "consumption," tuberculosis in the 1800s killed more young adults than any other disease and was the largest cause of cardiovascular disease among adults. In the early 1900s, it was still a major killer in Philadelphia. Funded by Philadelphia-born businessman and philanthropist Henry Phipps (1839-1930), a one-time partner of Andrew Carnegie, the Phipps Institute was located in Philadelphia's oldest African-American neighborhood, at 7th and Lombard streets, to serve one of the city's poorest and most afflicted populations. There, the Institute's staff ministered to those infected with TB while researchers developed improved methods for diagnosing tuberculosis. Attached to the research staff, Siebert began working on a better material for tuberculosis skin tests.

Back in the 1880s, German scientist Robert Koch had discovered that injecting a small amount of a substance called tuberculin-a sterile liquid containing proteins taken from cultures of the tubercle bacilli-caused a mild skin reaction in patients infected with tuberculosis. This enabled doctors to determine whether someone was infected with the disease. Prior to the advent of antibiotics, treatment usually meant time in a sanitarium. But Koch's tuberculin solution, still in use in the 1920s, produced inconsistent results, so a better skin test was vital for the control and eradication of this terrible disease. Funded by the National Tuberculosis Association, Seibert worked for years to develop a more reliable skin test. In 1934, she and the Phipps Institute announced the development of Purified Protein Derivative, or PPD, a tuberculin much purer than Koch's "old tuberculin."

"Doing Cure in Kiosk, 16 below," White Haven Sanitarium, White Haven, PA, circa...

The PPD process soon became the standard method for making test tuberculin. In 1940, Seibert began designing an even more refined standard of tuberculin purity. For a year she labored in freezing culture rooms at the Sharp and Dohme pharmaceutical company's labs in Glenolden, Pa. In 1941, the Federal government accepted her 107 grams of highly pure PPD. Adopted as the national and international standard of quality, it became known as PPD-Standard. By devising a quality tuberculin, Seibert gave doctors a better chance of diagnosing tuberculosis, thus preventing the spread of the disease in susceptible populations. Since 1953, when nearly 20,000 Americans died from tuberculosis, the combination of tuberculosis screening and strong antibiotic treatment has reduced the national total of tuberculosis deaths to a record low 646 in 2005.

After the World War II, Seibert turned her attention to the relationship between bacilli and cancer. Although some scientists claimed that bacteria were merely "ubiquitous contaminants" found among cancer cells, Seibert believed atypical bacilli caused high cancer rates. Her somewhat controversial assertion inspired debate that continues today. After moving to Florida, Seibert joined the staff of the Bay Pines V.A. Research Center in St. Petersburg to further study the relationship between bacteria and cancer.

To this day, the combination of PPD tuberculin testing and a strong antibiotic regimen can effectively cure most forms of tuberculosis. New antibiotic resistant strains of the disease, emerging throughout the world, however, now present new challenges for epidemiologists. In 1990, Seibert was inducted into the National Women's Hall of Fame, where she joined founder of the Philadelphia Clinical Laboratory, Mary Engle Pennington and the sex chromosome researcher, Bryn Mawr biologist Nettie Stevens. Seibert died on August 23, 1991.

Beyond the Marker