When Medical Researchers Were Brave As Well As Brilliant
— Mayo’s role in the first tuberculosis drug

In the cold of November 1944 a veterinarian and researcher named William Feldman boarded a train and traveled cross-country from Rochester, Minnesota to New Brunswick, New Jersey, to Rutgers University. The tall, thin investigator knocked on the office door of Dr. Selman Waksman, who opened it to hear the simple request, “I’ve come to ask for some of your streptomycin so we can test it at Mayo Clinic.”

Very little of this drug existed. It had been isolated only four weeks earlier by Dr. Waksman’s assistant, Albert Schatz, who was losing sleep making up limited batches of it in his basement lab. It had not yet been tested by a medical facility. But Dr. Feldman was determined to have some of the compound. Dr. Waksman was aware of and had respect for the basic research that had been done at Mayo on an earlier compound thought to have some activity against TB. He agreed to mail a streptomycin sample to Rochester once Schatz had produced enough for the tests.

Back in Minnesota Dr. Feldman would conduct the first animal toxicology tests on it. Later he and H. Corwin Hinshaw, M.D., a Mayo pulmonary disease specialist, would perform the first clinical trials on tuberculosis patients from Mineral Springs Sanitarium in nearby Cannon Falls. The medical director there, Karl Pfuetze, M.D., supervised the tests and was a co-author on the original published findings. In those days almost every county had a sanitarium, where the afflicted would go for bed rest and fresh air, the only approach that seemed to help at all. Here’s how Dr. Hinshaw described tuberculosis in his unpublished journal:

“At the midpoint of the 20th century, tuberculosis was recognized by all as the ‘White Plague’ — undeniably the most dreaded enemy of the human race by any measure. Whether measured by prevalence, cost, social consequences, sheer misery or any yardstick, I believe that any observer of the time would consider the bacillus of tuberculosis as enemy number one of the human race.” (from The Forgotten Plague, Frank Ryan, 1993).

The impact of TB is hard to envision today. In addition to severe chest pains, coughing spasms, spitting up blood and severe weight loss and weakness, secondary infections could damage the voice box, the bowel, the digestive system and cause ulcers that ate through the skin on the body and the face. In some cases, patients could literally drown in their own blood. Some patients were disfigured. Estimates are that TB killed 100 million people in the last century alone.

Ultimately, lives were saved thanks to this research collaboration. The first TB patient treated successfully with streptomycin began treatments on November 20, 1944 at Mayo Clinic.

Streptomycin was not a universal miracle drug; it did not work for everyone or for all strains of TB. But it was the beginning of effective treatments of a disease that previously had meant almost certain death for thousands of people around the world. It was also one of the first major drugs that began the era of “chemotherapy” — treating disease directly with chemicals. Today “chemo” is associated with cancer treatments, but it began as a weapon against bacterial infections.

Drs. Feldman, Waksman and Hinshaw published their findings in 1944. Dr. Waksman — who was not a physician, but a soil microbiologist — was invited to speak to a Mayo grand rounds special event. He later won the Nobel Prize. Dr. Feldman ended up contracting tuberculosis himself and was confined to a sanitarium in Duluth and another in the Southwest. He was treated with the next drug developed, called PAS, that came from Sweden. He survived and returned to work.

All this happened 65 years ago during the last days of World War II and the immediate postwar era. Drs. Feldman and Hinshaw were innovators, interdisciplinary collaborators, who took basic research from bench to bedside and gave thousands hope for their lives in what was still a rather dark time in medicine. They risked their lives working with some of the most lethal strains of TB. Yet, there was no hesitation. The needs of the patients came first.

— Robert Nellis, December 2009