William Bradley Coley (January 12, 1862 – April 16, 1936) was an American bone surgeon and cancer researcher best known for his early contributions to the study of cancer immunotherapy. Although his work was not proven effective in his lifetime, modern discoveries and research in immunology have led to a greater appreciation for his work in cancer immunotherapy and his targeted therapy, Coley's toxins. Today, Coley is recognized as the Father of Cancer Immunotherapy for his contributions to the science.
William Bradley Coley
|Born||January 12, 1862|
Westfield, Connecticut, U.S.
|Died||April 16, 1936 (aged 74)|
New York City, NY, U.S.
|Education||Yale University, Harvard Medical School, Weill Cornell Medical Center|
|Known for||Cancer immunotherapy|
|Parent(s)||Horace Bradley Coley|
Clarina B. Wakeman
Early life and careerEdit
William Coley was born on January 12, 1862, in Saugatuck, a neighborhood of Westport, Connecticut. His parents were Horace Bradley Coley and Clarina B. Wakeman. He received his bachelor's degree in Classics from Yale University and his medical degree from Harvard Medical School in 1888. After his schooling, Coley began working at New York Hospital, now Weill Cornell Medical Center, as a surgical intern.
Early sarcoma patientsEdit
In 1890, Coley began his first year of private practice at New York Hospital and met Elizabeth (Bessie) Dashiell, a 17-year-old patient who would later go on to inspire Coley to search for better methods of treating sarcoma. Dashiell visited Coley after suffering from a hand injury which he soon discovered to be an aggressive bone tumor. 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. Coley was distressed that even modern medicine's customary procedure still could not save the life of one of his first patients. Coley then decided to take the search for new possible treatments into his own hands, soon becoming one of the medical community's model clinician-scientists.
A clinician-scientist at workEdit
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, a German immigrant named Fred Stein, with an inoperable tumor in his neck. To the astonishment of the doctors in the hospital at the time, Stein's round cell sarcoma seemingly vanished after being diagnosed with erysipelas, 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 Stein's case of post-procedural erysipelas may have some correlation to his remission, then began thoroughly reviewing similar cases of bacterial infections having positive effects on malignant tumors. He found that his suspicion was not a newfound thought in oncology. In 1853, Sir James Paget alluded to the fact that he himself had reason to believe that an infection may cause tumor regression. Coley had even found cases that aligned almost exactly with the Fred Stein's malignant tumor. In 1866, German physician Wilhelm Busch found similar evidence that his own patient had experienced a significant regression in his malignant tumor after contracting a post-operative infection, erysipelas. As Coley continued his investigation, he found forty-seven cases that suggested that infections may, in fact, be linked to cancer regression and could become a possible method of cancer treatment in the future.
Developing Coley's toxinsEdit
After months of research devoted to finding the connection between cancerous patients developing infections and their own remission, Coley decided to pursue his notion that such recoveries, considered miraculous at the time, were provoked by an immune response in the body's immune system. In 1891, he began his experiments on a patient named Zola, an Italian immigrant and drug-addict with a life-threatening tumor 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, a bacterium known to induce erysipelas attacks, directly into his tumor. Five months and several trials of injection later, Zola finally developed full-blown erysipelas infection. The tumor 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 of his 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. The formula change to the use of dead bacteria drastically reduced the risk of death in patients; however, Coley's toxins still remained controversial in the medical community.
Professional reception of Coley's toxinsEdit
After studying and publishing the 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. Published as an 1893 case series titled "The treatment of malignant tumors by repeated inoculations of Erysipelas, with a report of ten original cases", several medical organizations lacked confidence that his study, labeled as inconsistent and poorly documented, proved real results. The American Cancer Society released a review of the study in which it questions its credibility at such an early stage, stating that "more research would be needed to determine what benefit, if any, this therapy might have for people with cancer." In 1894, the American Medical Association published an editorial with a similar stance, calling question to the "entire failure" of the injections and labeling it as an "alleged remedy." Several physicians at the time had trouble accepting Coley's toxins method when the field itself was struggling to understand what the best plan of action for treating cancer was. James Ewing, a famed cancer pathologist at the time, was one of Coley's biggest critics. A leader in the field of oncology at the time, Ewing was a supporter of the newer method of treatment, radiation therapy, which soon became America's standard method of cancer treatment.
Emergence and popularity of radiation therapyEdit
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. This decision was borne by the eventual successful treatment of millions of people worldwide with radiation therapy.
Coley had 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. 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. Thus, the Coley's vaccine soon became obsolete due to the adoption of radiation technology in cancer treatment.
Commercialization and current use of Coley's ToxinsEdit
From its creation in 1893, to 1962 with the introduction of the Kefauver Harris Amendment, Coley's toxins were being used to treat several types of cancers around the world. In the United States, it was exclusively sourced by Parke-Davis, America's oldest and largest drug maker at the time. The passing of the 1962 Kefauver Harris Amendment, however, required Coley's toxins to be labeled as a "new drug" by the Food and Drug Administration. It was this final blow to Coley's life work that drastically reduced the use of the concoction for cancer treatment. Since its changed status under the FDA, it has only been able to be prescribed through experimental clinical trials, which have continuously produced mixed results.
Coley published the results of his work as a case series, making it difficult to interpret them with confidence. According to the American Cancer Society, "More research would be needed to determine what benefit, if any, this therapy might have for people with cancer". Cancer Research UK say that "available scientific evidence does not currently support claims that Coley's toxins can treat or prevent cancer". According to Cancer Research UK's current statement regarding Coley's toxins, people with cancer who participate in the Coley's immunotherapy alongside conventional cancer treatments, or who use it as a substitute for those treatments, risk seriously harming their health.
The historical results of Coley's vaccine therapy are difficult to compare with modern results because Coley's studies were not well controlled or adequately documented. Many of his patients had also received other treatments, like radiation or surgery, simultaneously with his vaccine. According to the analyses of Coley Nauts and Starnes, treatment success correlated with length of therapy and the fevers induced by the toxins. However, the very nature of his contributions not only as a physician but as a medical researcher are still being used in the medical community to this day.
Acceptance from the medical communityEdit
In 1935, both The Journal of the American Medical Association (JAMA) and renowned cancer surgeon Ernest Amory Codman reversed their positions on the validity of Coley's Toxin in cancer treatment, suggesting that "the combined toxins of erysipelas and prodigiosus "undoubtedly" may sometimes play a significant role in preventing or retarding malignant recurrence or metastases."
Creation of the Cancer Research InstituteEdit
Coley's daughter, Helen Coley Nauts (1907–2001), established the nonprofit Cancer Research Institute in 1953 to study her father's work in efforts to "advocate for a cancer research path that investigates harnessing the body’s immune system rather than one that seeks chemicals and radiation to attack the disease." The organization has since become a leader in funding research in immunology and tumor immunology at universities and hospitals worldwide.
Modern Use of Coley's ToxinsEdit
Four years later, in 2009, Coley's theory that the immune systems in humans functioned in a cycle was demonstrated by a research team led by Associate Professor Brendon Coventry, which could possibly have significant ramifications for cancer treatment in the future.
William Coley died on April 16, 1936, at the age of 74 in the Hospital for the Ruptured and Crippled (now called the Hospital for Special Surgery) in New York City. He was survived by his wife and two children who continuously worked after his death to preserve Coley's legacy in the field of cancer research.
- "Coley Toxins". American Cancer Society. 1 November 2008. Retrieved April 14, 2014.
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- McCarthy, Edward (2006). "The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas". The Iowa Orthopaedic Journal. 26: 154–158. PMC 1888599. PMID 16789469.
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- Coley WB (1893). "The Treatment of Malignant Tumors by Repeated Inoculations of Erysipelas: With a Report of Ten Original Cases". American Journal of the Medical Sciences. 10: 487–511.
- Coley, William (1893). "The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases". American Journal of the Medical Sciences (10): 487–511.
- Hobohm, U (Oct 2001). "Fever and cancer in perspective". Cancer Immunology, Immunotherapy. 50 (8): 391–396. doi:10.1007/s002620100216. PMID 11726133. S2CID 109998.
- Willard, Huntington; Ginsburg, Geoffrey (2009). Genomic and Personalized Medicine. Elsevier. pp. 573–575.
- That erysipelas could cause cancerous tumors to regress was known at least as early as the 1860s. See:
- Tanner, Thomas Hawkes (1863). "A clinical report on cancer of the female sexual organs". The British and Foreign Medico-chirurgical Review,... 32: 151–153. On p. 152, Tanner noted that the French surgeon Alfred-Armand-Louis-Marie Velpeau had been unusually successful in treating cancers: "... the only difference [that] he [viz, Tanner] can discover "between M. Velpeau's cases and those of other surgeons is this, that a much larger number of them suffered from erysipelas after the operation of excision than commonly happens."
- Collins, Maurice Henry (1864). On the Diagnosis and Treatment of Cancer and the Tumours Analogous to It. London, England: John Churchill and Sons. pp. 150–152. From p. 150: "With regard to the effect of erysipelas, a strange notion has existed in the minds of several independent observers.... It is that erysipelas is antagonistic to cancer; when a patient recovers from a severe attack of erysipelas after removal of the cancerous part, she is more safe from relapse." Collins then cites cases of "Mr. Tanner" and "Mr. Smyly".
- The German surgeon Wilhelm Busch observed cases in which erysipelas caused regression of tumors:
- (Editorial staff) (4 June 1866). "Niederrheinische Gesellschaft für Natur- und Heilkunde in Bonn. Aus der Sitzung der medicinischen Section vom 14. März 1866" [Lower Rhine Society for Science and Medicine in Bonn. From the session of the medical section on 14 March 1866]. Berliner klinische Wochenschrift (Berlin Clinical Weekly Journal) (in German). 3 (23): 245–246. From p. 245: "Prof. Busch bespricht den Einfluss, welchen heftige Erysipele zuweilen auf organisirte Neubilden ausüben." (Prof. Busch discussed the influence which severe erysipelas sometimes exerts on organized new formations [i.e., new malignancies in the lymphatic glands].)
- (Editorial staff) (23 March 1868). "Niederrheinische Gesellschaft für Natur- und Heilkunde in Bonn. Aus der Sitzung der medicinischen Section vom 13. November 1867" [Lower Rhine Society for Science and Medicine in Bonn. From the session of the medical section on 13 November 1867]. Berliner klinische Wochenschrift (Berlin Clinical Weekly Journal) (in German). 5 (12): 137–138. From p. 137: "Prof. Busch theilt eine neue Beobachtung über den Einfluss mit, welchen heftige Erysipele auf die Rückbildung von Geschwülsten haben, die hauptsächlich aus zelligen Wucherungen bestehen. In der Sitzung vom 14. März 1866 hatte er die ihm zu Gebote stehende Beobachtungen besprochen, bei welchen zufällig entstandene Erysipele eine Resorption der zelligen Massen ohne Eiterung hervorgebracht hatten." (Prof. Busch reported a new observation of the influence which severe erysipelas has on the regression of tumors, which mainly arise from cellular proliferation. In the session of 14 March 1866, he had discussed the observations that were at his disposal, in which cases erysipelas that had arisen incidentally had brought about a resorption of the cellular masses without suppuration.)
- Volkmann, Richard (1869). "Erysipelas, Rose, Rothlauf". In Pitha, Franz von; Billroth, Theodor (eds.). Handbuch der allgemeinen und speciellen Chirurgie ... (in German). Vol. 1, pt. 2. Erlangen, (Germany): Enke. pp. 128–186. From pp. 173–174: "§. 177. Zum Schluss muss ich noch dem höchst eigenthümlichen Einfluss erwähnen, den intercurrente Erysipele zuweilen auf die rasche Resorption entzündlich gewucherter oder indurirter Gewebe und selbst eigentlicher Geschwülste haben." (§. 177. In conclusion, I must mention the most strange influence that intercurrent erysipelas sometimes has on the sudden resorption of tissues that proliferated by inflammation or hardened and even of actual tumors.)
- Lücke, Albert (1869). Handbuch der allgemeinen und speciellen Chirurgie .. : Die Lehre von den Geschwülsten in anatomischer und klinischer Beziehung [Handbook of General and Special Surgery ... : The science of tumors in their anatomical and clinical aspects] (in German). Vol. 2, pt. 1. Erlangen, (Germany): Ferdinand Enke. p. 31. From p. 31: "Auch Erysipelas in den verschiedensten Formen und Graden kann von der gesunden Haut ausgehend in den Geschwülsten Eiterung, Zerfall und Verjauchung erzeugen." (Also erysipelas in its most varied forms and degrees can cause – from the healthy skin to the tumor – suppuration, disaggregation, and putrefaction.)
- Fehleisen, Friedrich (1883). Die Aetiologie des Erysipels (in German). Berlin, Germany: Theodor Fischer. p. 20. From p. 20: "Die ersten Angaben über die Heilwirkung des Erysipels stammen aus dem 17. Jahrhundert.... ganz unbestreitbar ist endlich die Thatsache, dass manche Geschwülste durch ein Erysipel zum Verschwinden gebracht worden sind." (The first indications about the healing effects of erysipelas come from the 17th century.... finally quite indisputable is the fact that some tumors have been made to vanish by erysipelas.)
- Bainbridge, William Seaman (1914). The Cancer Problem. New York, New York, USA: Macmillan Co. pp. 333–334.
- Kienle, Gunver (1 March 2012). "Fever in Cancer Treatment: Coley's Therapy and Epidemiologic Observations". Global Advances in Health and Medicine. 1 (1): 92–100. doi:10.7453/gahmj.2012.1.1.016. PMC 3833486. PMID 24278806.
- "Coley Toxins". American Cancer Society. Retrieved 1 March 2018.
- Coley, William (1949). Neoplasms of Bone. New York: Medical Book Department of Harper & Brothers. pp. 565–570.
- Chang AE, Shu S. (1996). "Current status of adoptive immunotherapy of cancer". Critical Reviews in Oncology/Hematology. 22 (3): 213–228. doi:10.1016/1040-8428(96)00194-1. PMID 8793276.
- "What is Coley's toxins treatment for cancer?". Cancer Research UK. 22 August 2012. Retrieved April 14, 2014.
- Hobohm Uwe (2009). "Healing Heat: Harnessing Infection to Fight Cancer". American Scientist. 97 (1): 34–41. doi:10.1511/2009.76.34.
- "Erysipelas and Prodigiosus Toxins (Coley)". Journal of the American Medical Association. 103 (14): 1067–1069. October 6, 1964. doi:10.1001/jama.1934.02750400038015.
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- The New York Times: article on Pfizer and Coley Pharmaceutical Group, 5 October 2005
- news-medical.net: "Pfizer to acquire Coley Pharmaceutical Group", 19 November 2007
- "A Matter of Time | Australasian Science Magazine".
- Coventry BJ, Ashdown ML, Quinn MA, Markovic SN, Yatomi-Clarke SL, Robinson AP, "CRP identifies homeostatic immune oscillations in cancer patients: potential treatment targeting tool?" Journal of Translational Medicine, 2009, 7: 102. Review.
- "Immunotherapy in the Twentieth Century: William Coley and Lloyd J. Old, CancerTherapyAdvisor.com, 15 March 2017
- "Eminent Authority on Cancer and Abdominal Surgery, 74, Won Many Honors". The New York Times. April 17, 1936. Retrieved 2010-11-22.
Dr. Coley died early yesterday morning in the Hospital for Ruptured and ... known as the Mixed Toxins of erysipelas and bacillus or Coley's Toxin. was found ...
- Decker WK, Safdar S (2009). "Bioimmunoadjuvants for the treatment of neoplastic and infectious diseases: Coley's legacy revisited". Cytokine & Growth Factor Reviews. 20 (4): 271–81. doi:10.1016/j.cytogfr.2009.07.004. PMID 19656718.
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- Starnes C (1992). "Coley's Toxins in Perspective". Nature. 357 (6373): 11–12. Bibcode:1992Natur.357...11S. doi:10.1038/357011a0. PMID 1574121. S2CID 4265230.
- Cancer Research Institute (CRI) founded by William Coley's daughter Helen Coley Nauts
- "Cancer Miracles" Forbes
- CRI Response to Forbes' "Cancer Miracles" Editorial by Cancer Research Institute executive director Jill O'Donnell-Tormey, Ph.D.
- Coley Pharmaceutical Group
- MBVax Bioscience Inc
- Castle, Matt (July 13, 2007). "Coley's Cancer-Killing Concoction". DamnInteresting.com.