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{{short description|American surgeon and cancer researcher}}
Dr. '''William Coley''' (1862–1936) was an American bone surgeon and [[cancer]] researcher, pioneer of [[cancer immunotherapy]]. He developed a treatment based on provoking an [[immune response]] to [[bacteria]].
{{for|the Ohio politician|Bill Coley}}
{{Infobox person
| name = William Bradley Coley
| image = William Coley 1892.jpg
| caption =
| birth_name =
| birth_date = {{Birth date|1862|1|12}}
| birth_place = [[Westfield, Connecticut]], U.S.
| death_date = {{Death date and age|1936|4|16|1862|1|12}}
| death_place = [[New York City]], U.S.
| nationality =
| other_names =
| known_for = [[Cancer immunotherapy]]
| education = [[Yale University]], [[Harvard Medical School]], [[Weill Cornell Medical Center]]
| employer =
| occupation = [[Surgeon]]
| title =
| height =
| term =
| predecessor =
| successor =
| party =
| boards =
| spouse =
| partner =
| children =
| parents = Horace Bradley Coley<br>Clarina B. Wakeman
| relatives =
}}
'''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]], specifically causing infection as a way to fight cancer, a practice used as far back as 1550 BC.<ref>{{cite journal |last1=Thomas Jessy |title=Immunity over inability: The spontaneous regression of cancer |journal=[[Journal of Natural Science, Biology, and Medicine]] |date=2011 |volume=2 |issue=1 |pages=43–49 |doi=10.4103/0976-9668.82318 |pmid=22470233 |pmc=3312698 |doi-access=free }}</ref> His work was not proven effective in his lifetime, and today [[Coley's toxins]] are known to be both ineffective and potentially harmful. Coley is nevertheless recognized as the ''Father of Cancer Immunotherapy'' for his contributions to the science.<ref name=acs/>


==Early life and career==
==Overview==
===Education===
Dr. William Coley began his career as a bone surgeon at [[New York Cancer Hospital]] (which later became part of the [[Memorial Sloan-Kettering Cancer Center]]); 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]] infection, now known as [[Streptococcus pyogenes]].<ref name="Coley">{{cite journal |author=Coley WB |title=The Treatment of Malignant Tumors by Repeated Innoculations of Erysipelas: With a Report of Ten Original Cases. |journal= American Journal of the Medical Sciences |volume=10 |pages=487-511 |year=1893}}</ref> 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]], [[Louis Pasteur]], and [[Emil von Behring]], had recorded observations of erysipelas infection coinciding with cancer regression.
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.<ref name="McCarthy">{{cite journal|last1=McCarthy|first1=Edward|title=The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas|journal=The Iowa Orthopaedic Journal|date=2006|volume=26|pages=154–158|pmid=16789469|pmc=1888599}}</ref>


===Early sarcoma patients===
Coley’s first intentional erysipelas infection was performed on a patient named Mr. Zola on May 3, 1981, who had tonsil and [[throat cancer]]. Mr. Zola came down with erysipelas and his condition improved tremendously. Mr. Zola lived for another eight and a half years.<ref name="Coley">{{cite journal |author=Coley WB |title=Contributions to the Knowledge of Sarcoma. |journal= Annals of Surgery |volume=14 |pages=199-220 |year=1891}}</ref><ref name="Coley">{{cite journal |author=Coley WB |title=The Treatment of Malignant Tumors by Repeated Innoculations of Erysipelas: With a Report of Ten Original Cases. |journal= American Journal of the Medical Sciences |volume=10 |pages=487-511 |year=1893}}</ref>
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]].<ref>{{cite journal|last1=Levine|first1=David B.|title=The Hospital for the Ruptured and Crippled: William Bradley Coley, Third Surgeon-in-Chief 1925–1933|journal=HSS Journal|date=2008|volume=4|issue=1|pages=1–9|pmid=18751855|pmc=2504278|doi=10.1007/s11420-007-9063-2}}</ref> 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.<ref name="McCarthy"/>


===A clinician-scientist at work===
Coley was convinced that he could effectively use bacteria to treat cancer and created a mixture of killed bacterial infusions called [[Coley’s Toxins]]. 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. <ref name="Coley">{{cite journal |author=Coley WB |title=The treatment of malignant tumors by repeated inoculations. |journal=The American Journal of Medical Sciences |volume=105 |pages=487-511 |year=1893}}</ref> The cancerous cells would then slough off.
After the death of Bessie Dashiell, 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]]''.<ref name="Coley">{{cite journal |last1=Coley |first1=William |title=The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases |journal= American Journal of the Medical Sciences |volume=105 |issue=6 |pages=487–511 |year=1893 |url=https://babel.hathitrust.org/cgi/pt?id=uc1.c027395420&seq=511 }}</ref> Curious to discover the reason for the man's remission, Coley decided to search for the hospital's discharged patient, whom he eventually found in Manhattan with no trace of cancer left in his body.<ref name="Coley"/>


==Developing Coley's toxins==
His clinical tests achieved a number of [[remissions]], in patients with severe or terminal [[tumors]]. His work was however marginalized, by the advent of [[radiology]] and radiation treatment.
{{Main|Coley's toxins}}
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.<ref name=acs>{{cite web |url=http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/coley-toxins |title=Coley Toxins |publisher=[[American Cancer Society]] |accessdate=April 14, 2014 |date=1 November 2008}}</ref> 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<ref>{{cite journal|last1=Kienle|first1=Gunver|title=Fever in Cancer Treatment: Coley's Therapy and Epidemiologic Observations|journal=Global Advances in Health and Medicine|date=1 March 2012|volume=1|issue=1|pages=92–100|pmid=24278806|pmc=3833486|doi=10.7453/gahmj.2012.1.1.016}}</ref>


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.<ref>[https://theconversation.com/viruses-are-highly-evolved-infectious-agents-perfect-to-go-after-cancer-42867 theconversation.com]</ref><ref name=acs/>
The infusions of killed bacteria are now known as Coley's Toxins. They are currently not available to patients suffering from cancer. One reformulation of Coley's Toxins persists under the name [[Coley Fluid]].[http://www.mbvax.com/pdf/Coley%20Fluid%20-%20Mechanism%20and%20Studies.pdf]


===Emergence and popularity of radiation therapy===
==Clinical trials==
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.<ref name="McCarthy" />
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]] directly into inoperable tumors. This met with much success, even after [[metastasis]].{{Fact|date=March 2008}} 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.<ref name="Busch">{{cite journal |author=Busch W |title=Aus dersitzung der medicinichen. |journal=Berliner Klinische Wochenschrift |volume=5 |pages=137 |year=1867}}</ref> Later, Coley decided to use a mixture of dead [[Streptococcus pyogenes]] and dead [[Serratia marcescens]] bacteria. According to [[Stephen Hoption Cann]] of the [[University of British Columbia]], "He had successes you simply couldn't hope for today, curing even extensive metastatic disease."<ref name=newscientist>{{cite web
| url=http://www.newscientist.com/article/mg17623675.700.html
| title=Dr Coley's Famous Fever
| last=Pain
| first=Stephanie
| publisher=''[[New Scientist]]''
| date=[[2 November]] [[2002]]
}}</ref>


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 (pathologist)|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.<ref name="McCarthy"/>
On January 24, 1893, the first patient to receive [[Coley Vaccine]] 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.<ref name="Coley">{{cite journal |author=Coley WB |title=The Treatment of Malignant Tumors by Repeated Innoculations of Erysipelas: With a Report of Ten Original Cases. |journal= American Journal of the Medical Sciences |volume=10 |pages=487-511 |year=1893}}</ref>


===Commercialization and current use of Coley's Toxins===
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]].


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.<ref>{{cite book|last1=Coley|first1=William|title=Neoplasms of Bone|date=1949|publisher=Medical Book Department of Harper & Brothers|location=New York|pages=565–570}}</ref> 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.<ref>{{cite journal|last1=Chang AE|first1=Shu S.|title=Current status of adoptive immunotherapy of cancer|journal=Critical Reviews in Oncology/Hematology|date=1996|volume=22|issue=3|pages=213–228|doi=10.1016/1040-8428(96)00194-1|pmid=8793276}}</ref>
===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 successfully treated hundreds of patients, his superiors decided to put the emphasis on the newly invented [[radiation therapy]]. At the time, it was thought that radiation therapy could be improved into an effective cure for cancer.


== Effectiveness ==
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 x-ray therapy was localized, temporary and not curative. Others disagreed and cited the dangerous and unpredictable effects, predominantly the fever caused by the bacteria, that the vaccine had upon individuals weakened by cancer. Furthermore the creation of the vaccine had to be made to a patient's exact needs, making the [[Coley's Toxins|Coley Vaccine]] more labour intensive, time consuming and expensive.


There is no good evidence that Coley's toxins have any benefit in cancer treatment, and their use as an adjunct or replacement for established treatment risks serious harm.<ref name=acs/><ref name=cruk>{{cite web |url=https://about-cancer.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/complementary-alternative-therapies/individual-therapies/coleys-toxins-cancer-treatment |title=What is Coley's toxins treatment for cancer? |publisher=[[Cancer Research UK]] |date=22 August 2012 |archive-url=https://web.archive.org/web/20191217170042/https://about-cancer.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/complementary-alternative-therapies/individual-therapies/coleys-toxins-cancer-treatment |archive-date=17 December 2019}}</ref> 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.<ref name=cruk/>
==Conclusions==


==Legacy==
Coley died in 1936, and his treatment method more or less died with him. There is only now a renewed interest in his ideas. MBVax manufactures MBVax Coley Fluid for clinical trials.[http://www.mbvax.com/][http://www.redorbit.com/news/health/1308556/avax_to_present_results_of_phase_iii_study_of_mvaxr/index.html] Drug makers including Pfizer and Sanofi-Aventis also have a renewed interest in modern versions of Coley's Toxins. [http://www.nytimes.com/2005/10/05/business/05toll.html?_r=1&scp=2&sq=william%20B%20coley&st=cse]


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 been pretreated with chemotherapy, radiation therapy, or both, which likely distorted what appeared to be an immune response to the Coley Vaccine.<ref name="Hobohm">Hobohm, Uwe (January - February 2009). "Healing Heat: Harnessing Infection to Fight Cancer" ''American Scientist'' '''97''' (1): 34-41.</ref> The recently formed non-profit Global Cures Foundation<ref>[http://www.global-cures.org/promising_therapies Global Cures Foundation] - Promising Therapies</ref> plans to fund research trials of Coley's Toxins in the near future.
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.<ref name="Hobohm">{{cite journal | author = Hobohm Uwe | year = 2009 | title = Healing Heat: Harnessing Infection to Fight Cancer | journal = American Scientist | volume = 97 | issue = 1| pages = 34–41 | doi=10.1511/2009.76.34}}</ref>


===Creation of the Cancer Research Institute===
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.
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.<ref>{{cite web|title=CRI History|url=https://cancerresearch.org/about-cri/cri-history|website=Cancer Research Institute|accessdate=21 April 2018}}</ref>


===Cancer Immunotherapy===
==References==
While Coley's own efforts to stimulate the immune system to fight cancer showed marginal results, the field of [[cancer immunotherapy]] is now a burgeoning field within medicine. Multiple approaches exist, including reprogramming T-cells to specifically attack cancerous cells and blocking checkpoints so the immune system can more effectively attack cancerous cells. Coley is regarded as a key early influence in this field.
{{reflist}}


===Death===
== Further reading ==
* Hall, Steven S. (1997) ''A Commotion in the Blood''. New York, New York: Henry Holt and Company. ISBN 0-8050-5841-9
* Hess, David J. (1997) ''Can Bacteria Cause Cancer? Politics and Evaluation of Alternative Medicine''. New York, New York: NYU Press.
* Hobohm, Uwe (January - February 2009). "Healing Heat: Harnessing Infection to Fight Cancer" ''American Scientist'' '''97''' (1): 34-41.[http://www.americanscientist.org/issues/feature/2009/1/healing-heat]
* Starnes, C. (1992) "Coley's Toxins in Perspective" ''Nature'' '''357''' :11-12.


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.<ref>{{cite news |title=Eminent Authority on Cancer and Abdominal Surgery, 74, Won Many Honors |url=https://www.nytimes.com/1936/04/17/archives/rites-tomorrow-fordr-w-b-coley-eminent-authority-on-cancer-and.html |work=[[The New York Times]] |date=April 17, 1936 |accessdate=2010-11-22 }}</ref>
==See Also==

==See also==
* [[William B. Coley Award]]
* [[William B. Coley Award]]
* [[Timeline of immunology]]


==External links==
==References==
{{reflist|30em}}


== Further reading ==
* [http://www.cancerresearch.org/ Cancer Research Institute] founded by William Coley's daughter Helen Coley Nauts
* {{cite journal | author = Decker WK, Safdar S | year = 2009 | title = Bioimmunoadjuvants for the treatment of neoplastic and infectious diseases: Coley's legacy revisited | journal = Cytokine & Growth Factor Reviews | volume = 20 | issue = 4| pages = 271–81 | doi=10.1016/j.cytogfr.2009.07.004| pmid = 19656718 }}
* [http://www.coleypharma.com/ Coley Pharmaceutical Group]
* Donald HM. (2003) "Coley" ''Spontaneous Regression: Cancer and the Immune System'' Philadelphia: Xlibris{{Self-published inline|certain=yes|date=January 2018}}. [https://web.archive.org/web/20110714055913/http://www.mbvax.com/pdf/Book_Excerpt.pdf]
* [http://www.mbvax.com/ MBVax Bioscience Inc]
* Hall, Steven S. (1997) ''A Commotion in the Blood''. New York: Henry Holt and Company. {{ISBN|0-8050-5841-9}}
* Hess, David J. (1997) ''Can Bacteria Cause Cancer? Politics and Evaluation of Alternative Medicine''. New York: NYU Press.
* {{cite journal | author = Hobohm Uwe | year = 2009 | title = Healing Heat: Harnessing Infection to Fight Cancer | url = http://www.americanscientist.org/issues/feature/2009/1/healing–heat | journal = American Scientist | volume = 97 | issue = 1| pages = 34–41 | doi=10.1511/2009.76.34}}
* Hoption Cann SA, van Netten JP, van Netten C. (2003) "Dr William Coley and tumour regression: a place in history or in the future" ''Postgraduate Medical Journal'' '''79''' (938): 672–680 [https://web.archive.org/web/20110419180641/http://www.mbvax.com/pdf/Hoption_Cann_2003.pdf] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742910/pdf/v079p00672.pdf] [https://web.archive.org/web/20211022122033/http://health.toodoc.com/pdf/7861.pdf]
* Hoption Cann SA, Gunn HD, van Netten JP, van Netten C. (2004) "Spontaneous regression of pancreatic cancer" ''Case Reports and Clinical Practice Review'' 293–296 [https://web.archive.org/web/20090126231825/http://mbvax.com/pdf/Pancreas.pdf] [https://web.archive.org/web/20211022122019/http://health.toodoc.com/pdf/17043.pdf]
* {{cite journal | author = McCarthy Edward F., MD | year = 2006 | title = The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas | journal = Iowa Orthopedic Journal | volume = 26 | pages = 154–158 | pmc=1888599 | pmid=16789469}}
* {{cite journal | author = Starnes C | year = 1992 | title = Coley's Toxins in Perspective | journal = Nature | volume = 357 | issue = 6373| pages = 11–12 | doi=10.1038/357011a0| pmid = 1574121 | bibcode = 1992Natur.357...11S | s2cid = 4265230 }}

==External links==
* [http://www.cancerresearch.org/ Cancer Research Institute (CRI)] founded by William Coley's daughter [[Helen Coley Nauts]]
* [https://www.forbes.com/forbes/2009/0302/074_cancer_miracles.html/ "Cancer Miracles"] ''Forbes''
* [http://www.cancerresearch.org/pressroom/2009/02/16/forbes-cancer-miracles-a-CRI-success.html CRI Response to Forbes' "Cancer Miracles"] Editorial by Cancer Research Institute executive director Jill O'Donnell-Tormey, Ph.D.
* [https://web.archive.org/web/20080323144256/http://www.coleypharma.com/ Coley Pharmaceutical Group]
* [https://web.archive.org/web/20071214072909/http://www.mbvax.com/ MBVax Bioscience Inc]
* {{cite web
* {{cite web
| url=http://www.damninteresting.com/?p=871
| url=http://www.damninteresting.com/?p=871
| title=Coley’s Cancer-Killing Concoction
| title=Coley's Cancer-Killing Concoction
| last=Castle
| last=Castle
| first=Matt
| first=Matt
| publisher=DamnInteresting.com
| publisher=DamnInteresting.com
| date=[[July 13]] [[2007]]
| date=July 13, 2007
}}
}}

{{Authority control}}

{{DEFAULTSORT:Coley, William}}
{{DEFAULTSORT:Coley, William}}
[[Category:American physicians]]
[[Category:American cancer researchers]]
[[Category:19th-century American surgeons]]
[[Category:1862 births]]
[[Category:1862 births]]
[[Category:1936 deaths]]
[[Category:1936 deaths]]
[[Category:Oncologists]]
[[Category:Alternative cancer treatment advocates]]
[[Category:Immunologists]]
[[Category:American immunologists]]
[[Category:Physicians of Hospital for Special Surgery]]
[[Category:Scientists from New York (state)]]
[[Category:Yale College alumni]]
[[Category:Harvard Medical School alumni]]
[[Category:20th-century American surgeons]]

Latest revision as of 17:00, 24 November 2024

For the Ohio politician, see Bill Coley.
William Bradley Coley
Born(1862-01-12)January 12, 1862
Westfield, Connecticut, U.S.
DiedApril 16, 1936(1936-04-16) (aged 74)
New York City, U.S.
EducationYale University, Harvard Medical School, Weill Cornell Medical Center
OccupationSurgeon
Known forCancer immunotherapy
Parent(s)Horace Bradley Coley
Clarina B. Wakeman

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, specifically causing infection as a way to fight cancer, a practice used as far back as 1550 BC.[1] His work was not proven effective in his lifetime, and today Coley's toxins are known to be both ineffective and potentially harmful. Coley is nevertheless recognized as the Father of Cancer Immunotherapy for his contributions to the science.[2]

Early life and career

[edit]

Education

[edit]

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.[3]

Early sarcoma patients

[edit]

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.[4] 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.[3]

A clinician-scientist at work

[edit]

After the death of Bessie Dashiell, 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.[5] Curious to discover the reason for the man's remission, Coley decided to search for the hospital's discharged patient, whom he eventually found in Manhattan with no trace of cancer left in his body.[5]

Developing Coley's toxins

[edit]
Main article: Coley's toxins

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.[2] 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[6]

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.[7][2]

Emergence and popularity of radiation therapy

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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.[3]

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.[3]

Commercialization and current use of Coley's Toxins

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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.[8] 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.[9]

Effectiveness

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There is no good evidence that Coley's toxins have any benefit in cancer treatment, and their use as an adjunct or replacement for established treatment risks serious harm.[2][10] 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.[10]

Legacy

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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.[11]

Creation of the Cancer Research Institute

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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.[12]

Cancer Immunotherapy

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While Coley's own efforts to stimulate the immune system to fight cancer showed marginal results, the field of cancer immunotherapy is now a burgeoning field within medicine. Multiple approaches exist, including reprogramming T-cells to specifically attack cancerous cells and blocking checkpoints so the immune system can more effectively attack cancerous cells. Coley is regarded as a key early influence in this field.

Death

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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.[13]

See also

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References

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  1. ^ Thomas Jessy (2011). "Immunity over inability: The spontaneous regression of cancer". Journal of Natural Science, Biology, and Medicine. 2 (1): 43–49. doi:10.4103/0976-9668.82318. PMC 3312698. PMID 22470233.
  2. ^ a b c d "Coley Toxins". American Cancer Society. 1 November 2008. Retrieved April 14, 2014.
  3. ^ a b c d 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.
  4. ^ Levine, David B. (2008). "The Hospital for the Ruptured and Crippled: William Bradley Coley, Third Surgeon-in-Chief 1925–1933". HSS Journal. 4 (1): 1–9. doi:10.1007/s11420-007-9063-2. PMC 2504278. PMID 18751855.
  5. ^ a b 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. 105 (6): 487–511.
  6. ^ 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.
  7. ^ theconversation.com
  8. ^ Coley, William (1949). Neoplasms of Bone. New York: Medical Book Department of Harper & Brothers. pp. 565–570.
  9. ^ 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.
  10. ^ a b "What is Coley's toxins treatment for cancer?". Cancer Research UK. 22 August 2012. Archived from the original on 17 December 2019.
  11. ^ Hobohm Uwe (2009). "Healing Heat: Harnessing Infection to Fight Cancer". American Scientist. 97 (1): 34–41. doi:10.1511/2009.76.34.
  12. ^ "CRI History". Cancer Research Institute. Retrieved 21 April 2018.
  13. ^ "Eminent Authority on Cancer and Abdominal Surgery, 74, Won Many Honors". The New York Times. April 17, 1936. Retrieved 2010-11-22.

Further reading

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