Coley’s toxins

William Coley (1862 - 1936) was an American doctor. After a medical degree from Harvard Medical School in 1888 Coley began working at New York Hospital, now Weill Cornell Medical Center, as a surgical intern.

In 1890, Coley began his first year of private practice at New York Hospital and met Elizabeth (Bessie) Dashiell, a 17-year-old patient. Dashiell visited Coley after suffering from a hand injury which he soon discovered to be an aggressive bone tumour. Treatment for sarcoma at the time was scarce; the most widely accepted form of treatment was a complete amputation of the affected limb. Despite receiving such a critical surgery as forearm amputation, Bessie died just ten weeks later due to widespread metastasis of the original cancer. Bessie's death had a profound effect on Coley's approach to practicing medicine.

After the death of Bessie Dashiell, Dr. Coley decided to review and research similar cases of sarcoma in the medical files at New York Hospital, where he found a case of interest involving a patient with an inoperable tumour in his neck. To the astonishment of the doctors in the hospital at the time, his globular cell sarcoma seemingly vanished after being diagnosed with a skin infection now known to be caused by the bacterium Streptococcus pyogenes.

Curious to discover the reason for the man's remission, Coley decided to search for the hospital's discharged patient, who he eventually found in Manhattan with no trace of cancer left in his body. Coley, inflicted with an inclination that this case of microbial infection may have some correlation to his remission, then began thoroughly reviewing similar cases of bacterial infections having positive effects on malignant tumours.

As Coley continued his investigation, he found forty-seven cases that suggested that infections may be linked to cancer regression and could become a possible method of cancer treatment in the future.

In 1891, he began his experiments on a patient named Zola, an Italian immigrant and drug-addict with a life-threatening tumour which he described as "the size of a small hen's egg" in Zola's right tonsil. Hoping to spawn a similar case of remission that he had been studying for the past year, Coley attempted to induce a response by Zola's immune system by injecting Streptococcus directly into his tumour. Five months and several trials of injection later, Zola finally developed a full-blown infection. The tumour once thought to be irreversible then began to dissolve, disappearing within two weeks. Zola recovered and lived another eight years, before eventually succumbing to a recurrence of the tumour.

Two years after Zola's initial treatment, Coley treated ten more of his own patients with the same live Streptococcus bacteria. Because of the unpredictable nature of infection, which killed patients on two separate occasions, Coley changed the bacterial ingredients of what would be coined Coley's toxins from the live Streptococcus bacteria, to two dead bacteria, Streptococcus pyogenes and Serratia marcescens.  

After studying and publishing the positive effects of injecting ten of his patients with his own personalized treatment formula, Coley received an abundance of attention and skepticism from doctors and researchers in the field of cancer. By 1901, the development of x-rays as a cancer treatment showed great promise. In particular, the therapy resulted in immediate tumour destruction and pain relief. Although Coley claimed successful treatment of hundreds of patients, the absence of proven benefit or reproducibility led to broader emphasis on surgery and on the newly developing field of radiation therapy. In 1962 the Food and Drug Administration required Coley's toxins to be labeled as a "new drug". This further reduced its use for cancer treatment.  

As is described in more detail on BCG, a bacterial immunotherapy-based treatment for non-muscle invasive bladder cancer (NMIBC) was developed in the 1960’s and approved by the FDA in 1976. BCG is also based on an intentional bacterial infection and is highly related to Coley's Toxins.

In addition, in Japan & Taiwan the product OK-432 is approved in the treatment of (paediatric) lymphangiomas and is based on the injection of sterilised Streptococcus pyogenes, one of the two bacteria Coley had previously used in his toxins. OK-432 has been extensively, and succesfully, tested as treatment for a variety of cancer types. 

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