by Justin Lee

Created on: February 22, 2009

In the early 1900s, Dr. William B. Coley, chief physician at the Bone Service of what is now Memorial Sloan Kettering Center, purposely infected his cancer patients with Streptococcus pyogenes and Serratia marcescens in order to elicit a fever response. The bacterial mixture he used was dubbed "Coley's Toxins" or the "Mixed Bacteria Vaccine," and many patients given this concoction experienced spontaneous tumor regression. Coley knew that fever induction was a key aspect of his treatment (a strong febrile reaction was the symptom most associated with tumor regression), and it is likely that concurrent immune and heat responses induced by fever played a large role in stifling tumor growth.

Despite its early success in the early 20th century, the thought of deliberately infecting a cancer patient as a method of treatment has become a medical farce. The largest reason for this shift was the development of sterile technique in hospitals. In accordance with sterile technique (an overall positive introduction), microbes put patients at risk for infection, so every effort was made to destroy them. Suggestions that bacterial infections of cancer patients might improve survival were harshly criticized as "a doctrine that would make surgery go backwards." Additionally, the introduction of antibiotics into medical practice in the 1900s made the immune system "redundant" in fighting bacterial infections, and antipyretics (anti-fever compounds) came into routine use to eliminate the discomforting symptoms of an immune response.

The rise of chemotherapy and radiation therapy sealed the downfall of Coley's toxins. These treatments could be more easily standardized than Coley's approach and the hope that these therapies would eventually lead to a cure for cancer was high. Such therapies run counter to fever-induced cancer (immuno)therapy, as they are highly immunosuppressive.

As a result of these changes, reports of spontaneous regression have become less commonplace, although when they do occur, an association with acute infections is often noted. A retrospective study by Ruckdeschel et al. found that patients who developed empyema (pus/infection) after lung cancer surgery had a significantly better five-year survival (50% vs. 18%).

Modern medicine hasn't completely discarded Coley's toxins. Instead, it has isolated the components of fever response that help control tumors. Western scientific reductionism has directed scientists to focus on separate development of various cancer immunotherapies and hyperthermia therapies. Researchers argue that this refocusing will allow oncologists to reap the benefits of cancer fever therapy without having to "crudely" infect a patient with microbes, but others have argued that this reductionism is counterproductive since a more holistic effect takes place when people develop a fever.

Specifically, these detractors have argued that fever is more than just a rise in body temperature (i.e. hyperthermia, mechanically achieved increase in temperature) and a revved up immune system. Human fevers are accompanied by diverse physiological changes: biochemical reaction rates increase 2 to 3-fold during febrile thermogenesis, leucocyte proliferation, maturation, and activation is enhanced, and a multitude of cytokine cascades are triggered. Coley supporters contend that scientists can't see the synergism at play if they only examine the effects of hyperthermia or a specific immunotherapy drug (e.g. interleukin-2) in isolation.

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