William Coley
Encyclopedia
William Bradley Coley was an American bone surgeon and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 researcher, pioneer of cancer immunotherapy
Cancer immunotherapy
Cancer immunotherapy is the use of the immune system to reject cancer. The main premise is stimulating the patient's immune system to attack the malignant tumor cells that are responsible for the disease...

. He developed a treatment based on provoking an immune response to bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

. In 1968 a protein related to his work was identified and called tumor necrosis factor
Tumor necrosis factor
Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction...

 alpha.

Biography

He was born on January 12, 1862 in Westfield, Connecticut to Horace Bradley Coley and Clarina B. Wakeman.

He began his career as a bone surgeon at New York Cancer Hospital
New York Cancer Hospital
The New York Cancer Hospital in New York City was a cancer treatment and research institution founded in 1884 . The hospital was located at 455 Central Park West between 105th St and 106th St...

 (which later became part of the Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Memorial Sloan–Kettering Cancer Center is a cancer treatment and research institution founded in 1884 as the New York Cancer Hospital...

); however, he became more interested in cancer treatment when one of his early patients died from bone cancer. While going through hospital records, Coley found a sarcoma case study of one patient named Fred Stein, whose tumor disappeared following a high fever from erysipelas
Erysipelas
Erysipelas is an acute streptococcus bacterial infection of the deep epidermis with lymphatic spread.-Risk factors:...

 infection, now known as Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...

. This sparked Coley’s interest and drove him to find what few examples of similar cancer treatment had been previously recorded. He discovered that other medical pioneers including Robert Koch
Robert Koch
Heinrich Hermann Robert Koch was a German physician. He became famous for isolating Bacillus anthracis , the Tuberculosis bacillus and the Vibrio cholerae and for his development of Koch's postulates....

, Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...

, and Emil von Behring, had recorded observations of erysipelas infection coinciding with cancer regression.

Coley’s first intentional erysipelas infection was performed on a patient named Mr. Zola on May 3, 1891, who had tonsil and throat cancer
Head and neck cancer
Head and neck cancer refers to a group of biologically similar cancers that start in the upper aerodigestive tract, including the lip, oral cavity , nasal cavity , paranasal sinuses, pharynx, and larynx. 90% of head and neck cancers are squamous cell carcinomas , originating from the mucosal lining...

. Mr. Zola came down with erysipelas and his condition improved tremendously. Mr. Zola lived for another eight and a half years.

Coley was convinced that he could effectively use bacteria to treat cancer and created a mixture of killed bacterial infusions since known as Coley's Toxins
Coley's Toxins
Coley's toxins is a mixture consisting of killed bacteria of species Streptococcus pyogenes and Serratia marcescens, named after William Coley, a surgical oncologist who developed the mixture in the late 19th century as a treatment for cancer.- History :Observations of...

 or Coley's vaccine. The infusion was administered by injection in increasing doses to induce a fever. Once stimulated, he observed, the immune system could be capable of tackling cancerous cells along with the infection. The cancerous cells would then slough off.

Clinical trials

Coley developed the theory that it was the infections which had helped patients in the past to recover from their cancer. So he began to treat patients by injecting a brew of Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...

 directly into inoperable tumors. This met with much success, even after metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. The treatment was most effective when it provoked a fever and a full-blown infection. This observations coincided with similar observations in 1867 by the German physician W. Busch when his patient's tumor became smaller after a high fever. Later, Coley decided to use a mixture of dead Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...

 and dead Serratia marcescens
Serratia marcescens
Serratia marcescens is a species of Gram-negative, rod-shaped bacterium in the family Enterobacteriaceae. A human pathogen, S. marcescens is involved in nosocomial infections, particularly catheter-associated bacteremia, urinary tract infections and wound infections, and is responsible for 1.4% of...

 bacteria. According to Stephen Hoption Cann of the University of British Columbia
University of British Columbia
The University of British Columbia is a public research university. UBC’s two main campuses are situated in Vancouver and in Kelowna in the Okanagan Valley...

, "He had successes you simply couldn't hope for today, curing even extensive metastatic disease."

On January 24, 1893, the first patient to receive Coley vaccine (aka Coley's toxins) was John Ficken, a sixteen-year-old boy with a massive abdominal tumor. Every few days, Coley injected his vaccine directly into the tumor mass and produced the symptoms of an infectious disease, but did not produce the disease itself. On each injection, there was a dramatic rise in body temperature and chills. The tumour gradually diminished in size. By May 1893, after four months of intensive treatment, the tumour was a fifth its original size. By August, the remains of the growth were barely perceptible.

The boy received no further anticancer treatment and remained in good health until he died of a heart attack 26 years later. Coley published his results and by the turn of the century 42 physicians from Europe and North America had reported cases of cancer that had been successfully treated with Coley vaccine.

Radiation therapy vs. Coley vaccine

By 1901, the development of x-rays as a cancer treatment showed great promise. In particular, the therapy resulted in immediate tumor 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
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

. This decision was borne out by the eventual successful treatment of millions of people worldwide with radiation therapy.

Coley arranged for a wealthy friend to provide funds to purchase two x-ray machines for his use. However, after several years of experience, Coley came to the conclusion that the effect of that primitive x-ray therapy in the untrained hands of experimenters was localized, temporary and not curative. The scientific majority disagreed, most notably his contemporary James Ewing
James Ewing
James Stephen Ewing was an American pathologist. He was the first Professor of pathology at Cornell University and became famous with the discovery of a form of malignant bone tumor that later became known as Ewing's sarcoma.-Life:James Ewing, was born in 1866 to a prominent family of Pittsburgh....

. His contemporary critics cited the dangerous and unpredictable effects, predominantly the fever caused by the bacteria, that the vaccine had upon individuals weakened by cancer. Furthermore the vaccine had to be made to a patient's exact needs, making it more labour-intensive, time-consuming and expensive.

Coley died on April 16, 1936.

Legacy

Coley's Toxins are currently available in several countries. One reformulation of Coley's Toxins is called Coley Fluid.

Drug makers including Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...

 and Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...

 also have a renewed interest in modern versions of Coley's Toxins; Pfizer has acquired the Coley Pharmaceutical Group, set up in 1997

The historical results of Coley vaccine therapy are difficult to compare with modern results. Coley's studies were not well controlled and factors such as length of treatment and fever level were not adequately documented. Many of his patients had also received radiation and sometimes surgery. According to the analyses of Coley Nauts and Starnes, treatment success correlated with length of therapy and the fevers induced by the toxins. The recently formed non-profit Global Cures Foundation plans to fund research trials of Coley's Toxins in the near future.

There were, however, many different formulations of Coley Vaccine. These varied greatly in effectiveness, and there were many different treatment protocols that also varied greatly in effectiveness.

Further reading


External links

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