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
Refining a Method
Coley tried inactivated microbes on four patients but obtained only modest fever-inducing effects and temporary changes in their tumors. The preparations likely were too weak. By the end of 1892, the French doctor G. H. Roger had published his observation that the virulence of the erysipelas bacterium, Streptococcus pyogenes, increased when it was grown in the presence of another, then called Bacillus prodigiosus, now Serratia marcescens, a mild pathogen involved in eye and urinary infections.
In January 1893 Coley administered for the first time one variant of what today are still called “Coley’s toxins.” It was a heat-sterilized, combined culture of S. pyogenes and S. marcescens bacteria administered by injection. The patient was a 16-year-old boy with a large inoperable abdominal tumor, a malignant sarcoma. After receiving increasing doses over 10 weeks, the boy developed symptoms mimicking those of a heavy erysipelas infection: chills, headache, fever, local redness and swelling at injection sites. The tumor shrank by 80 percent. Coley kept in touch with his patient, who remained cancer-free for more than 20 years.
Coley treated another five patients during 1893. No result was as promising as his first. Coley published the results of his experiments in the The American Journal of the Medical Sciences under the title “The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases” in 1893. The report stirred considerable excitement—for a while.
At the beginning of the 20th century radiation treatment came on the cancer therapy scene. This new procedure captured nearly the full attention of the oncology community due to its immediately visible effects. One could now, it seemed, x ray away tumors. Within the medical mainstream, interest in Coley’s methods faded.
Still, some physicians did try to test Coley’s treatment. Nicholas Senn of Rush Medical College in Chicago reported uniform failure of the method. William Keen, a surgeon in Philadelphia, failed to obtain a response in seven patients. A Dr. Caulkins of Watertown, New York, reported a large number of successes, as did Dr. Matagne from Belgium, who prepared his own fresh extracts. Matagne published his observations in lower-tier French and Belgian journals.
Two stubborn surgeons, S. L. Christian and L. A. Palmer, at the U.S. Marine Hospital in Stapleton, New York, reported a spectacular cure in 1928. Two years before, a U.S. Marine captain they described as “G. B.” developed bone sarcoma and endured an above-the-knee amputation. He was 31 years old. In 1926, G. B. received daily injections of “Coley’s fluid” from January 5 to February 20, until he seemed too weak to endure more. Treatments were started and stopped that spring and started again that summer, fall and winter, with daily injections totaling 20 weeks cumulatively. The patient was last examined on January 9, 1928. No evidence of disease was present.
Coley, throughout his 40-plus-year career, treated hundreds with multiple versions of his toxin. He never achieved a clear-cut, uniform result. Some patients responded. Among them, some were cured, but some were not. At a 1934 meeting, Coley discussed 44 cases of Ewing’s sarcoma. Twelve out of 44 patients had been treated with radiation by other physicians and none of these survived five years. But the remaining 32 patients had been treated with bacterial extract by Coley. Twelve of them remained disease free for more than five years. A five-year survival rate of zero after radiation and 38 percent after Coley’s treatments merited deeper scrutiny.
Helen Coley Nauts, Coley’s daughter, meticulously reexamined her father’s clinical cases after his death. This was not easy. Undoubtedly a man of determination, Coley was not a methodical scientist. His patient records were a mess, he treated different patients for different time periods and his bacterial extracts, over time, were inconsistently made. Coley Nauts counted 15 different preparations. Eleven of them, she concluded, were not potent enough to have a strong effect.
Coley Nauts determined that her father had treated several hundred patients by the time he died in 1936, many of whom had received radiation and sometimes surgery as well. To estimate the overall success of extracts, the analysis should be restricted to patients with inoperable cancer and treated by toxin alone. In another review from 1994, immunologist and oncology researcher Charles Starnes identified 170 such patients with adequate medical records (121 with some form of sarcoma, 43 with carcinoma and myeloma, and 6 with melanoma). The remission rate among them was 64 percent; the five-year survival rate was more than 44 percent.
According to the analyses of Coley Nauts and Starnes, treatment success correlated with length of therapy and the fevers induced by the toxins. Higher was better. This correlation was reported among several other observations but without emphasis or any explanation by the authors.
Only a few uncoordinated attempts to apply Coley’s ideas were pursued from mid-century on. Bacterial extracts used in the later studies, in the 1960s and 1970s, were commercial preparations called MBV (produced by Bayer) and Vaccineurin (produced by Südmedica of Munich). They were similar to, but not identical to, Coley’s extracts. The experimenters appeared to be hunting for anticancerous substances that could be applied a limited number of times to be effective, a traditional cancer therapy model embraced by pharmaceutical companies. Length of treatment and fever level were not adequately considered. A majority of the patients in the studies had been pretreated with chemotherapy, radiation therapy or both, measures that likely distorted the immune response that appears to be triggered by the bacterial extracts. Results were mixed: several remissions, even long-lasting ones, with several failures.
Well-controlled studies of bacterial-extract cancer treatment that incorporate all the lessons from the retrospective analysis of Coley’s and other treatments have not been pursued since. But medical case studies, cancer epidemiology and our more precise understanding of immunology make a strong case that they should.
Spontaneous regression or remission is the partial or complete disappearance of an untreated malignant tumor or a tumor treated with a therapy considered inadequate to exert significant influence. It sounds like fantasy, but about 1,000 case studies in the medical literature during the past century detail spontaneous regression from cancer. Surely more have occurred. And there’s a pattern to some of the cases.
A prior fever was recorded in 25 to 80 percent of documented cases of spontaneous regression of cancer. For instance, Diamond and Luhby in 1951 reported 26 spontaneous remissions in a cohort of 300 cases of childhood leukemia; 80 percent were accompanied by infection. Stephenson and colleagues in 1971 investigated 224 cases of spontaneous regression and reported that in 62 cases, or 28 percent, regression was preceded by either an infection or a persistent temperature elevation. In many cases, S. pyogenes, the pathogen that produced erysipelas, was involved.
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