FEATURE ARTICLE
Healing Heat: Harnessing Infection to Fight Cancer
Modern immunology plus historic experiments suggest a better way to gear up the human immune system to battle malignant disease
Uwe Hobohm
Toxin Therapy
Elisabeth Dashiell was 17 years old when she entered New York Hospital in the autumn of 1890 with severe pain in her hand but no sign of infection. Her newly trained surgeon, William B. Coley, saw no improvement after a period of observation. In November 1890, a biopsy revealed round-cell sarcoma, a relatively rare form of cancer originating in soft tissue and bone.
Shortly after the biopsy, Dashiell’s arm was amputated below her elbow, but her cancer still spread ferociously. In December a tumor was detected in her right breast; within days, nodules appeared in her left breast. By January a huge tumor swelled in her abdomen and her heart began to fail. On January 23, 1891, Dashiell died.
Medicine back then offered little more than amputation and morphine to cancer patients such as Dashiell. Shocked by his ineffectiveness, Coley dove into hospital records and the medical literature for clues to how to help more. He found about 90 sarcoma case reports. About half contained follow-up histories. The one that grabbed him most involved Fred Stein.
Stein, a German immigrant, had been diagnosed with cheek sarcoma in 1884. Despite four operations, his cancer kept recurring. He was considered a hopeless case. However, in late 1884 Stein developed high fever from erysipelas, a postoperative skin disease common in that era. To the great surprise of his physicians, his tumor disappeared. Stein was discharged from the hospital in February 1885.
Five months after Elisabeth Dashiell died, Coley tracked Stein to New York City’s Lower East Side. Photographed and examined, Stein showed no trace of residual cancer six years after his puzzling recovery. That drove Coley to dig deeper for records of similar cases. The young doctor, who had studied some German at Yale University, likely encountered a report published more than two decades earlier, in 1868, in the journal Berliner Klinische Wochenschrift.
The German physician W. Busch reported that he had observed a patient’s tumor “re-absorbed” after a high fever. Unconstrained by modern ethics rules, Busch tested for some connection himself. That summer, by coincidence, a patient with a mild erysipelas infection that followed an injury and a 19-year-old girl with a huge sarcoma of the neck entered Busch’s clinic at around the same time. Over five months, the sarcoma had grown to the size of a child’s head. The young woman’s breathing was threatened; she could not completely close one eye.
Before antibiotics, erysipelas was one of the leading causes of death from postoperative infections in hospitals. Still, Busch burned a small piece of skin over the girl’s tumor and attached a cotton pad taken from the erysipelas patient onto her wound. The surrounding skin developed signs of erysipelas and the patient developed a high fever—104 degrees Fahrenheit. Her tumor, which had been tight and dense, softened and shrank rapidly. Within two weeks it reached the size of a small apple. She could close her eyes and breathe freely. Unfortunately, the young lady developed circulatory problems, and steps had to be taken to strengthen her weak condition. With the disappearance of the skin inflammation, the tumor reached its prior size. How she fared after leaving the clinic is not known.
In his literature search, Coley found more than 40 cases of disappearance of malignancies during an erysipelas attack. He came across another medical pioneer, Friedrich Fehleisen, also in Germany, who was the first to use cultured bacteria in related experiments. After successes and failures, Fehleisen discontinued the work. Still, Coley decided to try for himself.
In April 1891 an Italian immigrant, Mr. Zola, presented at New York Hospital with a large sarcoma tumor in his neck and an egg-sized metastasis in his right tonsil. He had been operated on twice before but was in hopeless condition. He could hardly speak or swallow and was unable to eat solid food. His life expectancy was, at the very most, a few months. He had nothing to lose by undergoing an experimental treatment.
Since erysipelas was so hazardous, the hospital was reluctant to host Coley’s experiment, so it was performed in a private apartment. Colleagues at the College of Physicians and Surgeons, now part of Columbia University, prepared the bacteria. Three applications were delivered over three weeks, with minor success. Zola’s temperature rose only slightly, and he showed no sign of full-blown infection. Coley tried a fresh preparation and a larger dose. Within hours, Zola developed severe chills, headache and vomiting. His temperature did not reach what one could expect from a full-blown erysipelas infection; it did not exceed 102 degrees Fahrenheit. Both tumors diminished in size. About one month after the treatment began, Zola could eat again.
Via a friend, Coley obtained fresh and potent bacteria culture from the leading German bacteriologist, Robert Koch. That fall, he again treated Zola, whose temperature that time rose above 104 degrees, with nausea, vomiting and severe pain. The infection almost killed him, but within two weeks, the neck tumor was not observable. The tonsil tumor stopped growing. Zola was in excellent health when Coley saw him four years later.
During the following two years Coley attempted to infect 12 patients who had inoperable cancer. He failed to induce a full-blown infection in four and succeeded in eight. All eight responded. Six had partial tumor remissions. Two showed full remission. But two patients died from infection. So Coley abandoned living cultures and turned toward what today we would call a bacterial extract.
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