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Over 100 years ago, an American bone surgeon by the name of William Coley, was one of the first researchers to pioneer methods of stimulating the immune system as a core methodology in the treatment of cancer. He developed a naturally derived bacterial-based therapy that he investigated for the treatment of multiple types of cancer, that was later named “Coley’s Fluid.”
Years later, after a thorough review can be made of his preliminary clinical studies, it is no longer a question “if Coley’s Fluid worked on many cancers?” The results of his early trials at Memorial Sloan Kettering had phenomenal results rivaling the standard of care we have today for indications such as melanoma and sarcoma tumors. However the question remains, what happened to his research, and why are these treatments not available today in the United States?
Coley became a man on a mission after an upsetting death of a Sarcoma patient that he thought would be cured after surgery.1 After this patient’s death, Coley went through the files of Memorial Hospital (now Sloan Kettering) to find if anyone had ever survived a Sarcoma. He only found one patient who had survived and 7 years later brought this patient back in to figure out how he was alive. It turned out this patient contracted an erysipelas infection while he had the sarcoma. When the patient survived the infection the cancer was gone.2,3
Coley thought that if an accidental infection could cause the spontaneous remission of cancer then so should an intentional infection. Coley treated patients with this live bacteria reporting dramatic tumor regression but also some fatalities.4 Coley’s rationale was to change to a dead bacteria, making it safe so the immune response wouldn’t keep repeating itself. Remarkably, from 1891-1936, Dr. Coley had a higher success rate treating many cancers than we do today! 5
His daughter, Helen Coley Nauts, carried on his work and spent 16 years researching her father’s files. She made history by publishing his monographs at Memorial Hospital showing that he did in fact have a treatment that produced many complete and durable remissions. In 1953 she founded the Cancer Research Institute which carried on the work of Immunotherapy for Cancer for the last 66 years.6
In a paper written at MD Anderson by Dr. William Dekkar and Dr. Amar Safdar they state:
“This fortuitous combination of gram negative and gram positive bacteria possessed a wide array of immune-stimulatory properties allowing Dr. Coley to achieve long term cure rates unrivaled by medical science 73 years past his death.” 7
So why wasn’t Coley’s Fluid given more credit for treating cancer even with remarkable documented complete responses?
Looking back 100 years, a brilliant pathologist named James Ewing didn’t believe in Dr. Coley’s work and became his number 1 opponent.8 Ewing was the co-founder of The American Society of Control of Cancer which is now the American Cancer Society,9 and unlike William Coley, he had the backing of the conventional oncology community.10
In 1910, James Ewing was given $100,000 (Approximately $2.4 million today) to endow 20 beds and purchase radiation equipment.11 This was in collaboration with Memorial Hospital and it inspired Ewing to be a “fanatical supporter of radiation therapy.”12 While he was doing these studies, Coley was showing his results which proved to be more successful for overall survival than radiation. Ewing and his powerful group criticized Coley for not doing the treatment the same every time, injecting the fluid in different places and not keeping records the way they wanted.13 Ewing, known as The Chief of Cancer Pathology,14 also questioned if Coley’s patients had cancer at all. Later Ewing became Coley’s boss and outlawed the use of the fluids at memorial hospital.15
“James Ewing, perhaps the most famous cancer pathologist in the country, was a leading opponent of Coley's work. This was a particular problem for Coley because Ewing was Medical Director of Memorial Hospital, and for many years was Coley's boss. Their memos to one another reflect constant interpersonal animosity. Ewing himself had become a fanatical supporter of radiation therapy for the treatment of all bone tumors and repudiated any other theories for the treatment of cancer. Ewing therefore refused Coley permission to use his toxins at Memorial Hospital. This was ironic, because Coley had more experience than any other surgeon in the country in treating the small round blue cell sarcoma that still carries Ewing's name.” 16 (Ewing Sarcoma)
The banning of Coley’s fluid by Dr. Ewing came at a time when Coley was getting many complete responses without surgery. Coley would inject his fluid which would cause flu like symptoms and a fever. If his injection didn’t cause a fever he would raise the dose the next day. This was administered repeatedly without accumulated toxicity. Coley had many durable remissions even with cancers that are very complicated today.17
Take for instance that according to John Hopkins “Ewing sarcoma patients have a 5 year survival rate of between 15% to 30%.18 The treatment today includes radiation therapy. Coley had 11 of 52 non operable Ewing Sarcoma patients (21%) that lived 5 years.19 Ewings Sarcoma is known not to respond well to chemotherapy or checkpoint inhibitors.
Or take Inoperable Melanoma. Dr. Coley showed a 60% 5 year survival.20 The latest SEER government data from 2008-2014 showed a 23% 5 year survival for stage 4 melanoma.21 With the new checkpoint inhibitors the Melanoma 5 year survival is likely to go up but the fact is Dr. Coley had a better success rate treating this disease than the numbers posted from the latest numbers in the SEER database from 2008-2014.22
“Their memos to one another reflect constant interpersonal animosity”
Imagine what it would look like now if 100 years ago Dr. Coley and Dr. Ewing were able to get along. Two brilliant doctors who are today regarded as some of the biggest influences in cancer research. The problem was both men wanted to be right and the quest for being right led to the world not choosing to use immunotherapy in conjunction with radiation.
We are in a paradigm shift in cancer therapy. Although there are those that are still very righteous, many scientists and doctors are starting to realize that there can be something taken from all areas. Working together is a lot easier than working against each other. Being stuck to one ideology ( i.e. Only chemo, radiation and surgery) doesn’t serve anyone except the ones that MUST be “right”. (Or those who profit from it)
Immunotherapy as a cancer treatment was laughed at until the last few years by the establishment oncologists…but the results have been astounding! In the last 5 years, multiple trials have launched mixing things like radiation and immunotherapy.
“A new role for radiotherapy as a valuable partner of cancer immunotherapy is emerging. Preclinical evidence was recently confirmed by clinical objective responses reported in patients with different types of cancers at advanced stage of disease. The optimal immunotherapy to combine with radiotherapy remains to be defined. However, initial responses in the clinic have occurred with diverse immunotherapy approaches, which supports a general role of radiotherapy as a valid adjuvant.
Dose and fractionation are likely to be key variables in determining the effects of ionizing radiation on the immune system of the patients and/or in determining the success of radiotherapy when combined with different forms of immunotherapy. Similarly, the correct sequencing of radiotherapy and immunotherapy depends on the type of immunotherapy chosen.
In any event, radiation effects on the immune system have uncovered a novel application of this modality beyond that of a therapy that merely aims to accomplish local control of tumors, a paradigm shift from its current use in cancer. More than a century after the discovery of radium, ionizing radiation continues to surprise by revealing additional clinical effects and consequences.”
This paper talks about using different doses of radiation, at different times with immunotherapy. The methodology of how and when to use it with immunotherapy still needs to be figured out, but it’s great to see a top radiation oncologist and immunologist looking at this. It can also possibly mean less radiation and less immunotherapy which means less side effects.
So the lesson learned from Dr. James Ewing vs Dr. William Coley is that no person “won”. And in reality the world lost out. Just think if these two brilliant minds could have aligned realizing that their shared vision was to cure cancer. 100 years later we are finally studying the effects of immunotherapy and radiation combined. Pride and ego can get in the way of some amazing people. People that are still revered today but couldn’t get along 100 years ago while working at the same institution. An institution that has pioneered both of their work but wasn’t able to overcome the damage the battle caused until now.
We now know the lesson. It’s up to us as a society to learn from it.
CHIPSA has used immunotherapy for nearly 40 years. In 1996, the famed German physician Dr. Josef Issels came to Tijuana Mexico from Germany. Dr. Issels used Coley’s fluid and different immunotherapy treatments in Germany since the 1950’s. He would also use Coley’s fluid in conjunction with chemotherapy.
Issels brought the Coley’s treatment to Mexico. He had an interest in the effects of diet on cancer. In previous manuscripts Dr. Max Gerson mentioned that he was interested in working with Dr. Coley. This is something that Dr. Issels was open to. Issels was a doctor and scientist with an open mind; he spent the last two years of his life working at CHIPSA and sharing his knowledge. His family has also carries on his work today.
Now, 22 years later, Coley’s fluid is still an integral part of our treatment protocol. We see it as a “super adjuvant” as it works on multiple pathways that have now been discovered by mainstream science. In 2011, Bruce Buetler won a Nobel prize for discovering the TLR-4 pathway.24 In 2007 CPG was popularized when Coley’s Pharmaceutical sold 27% of their company to Pfizer for $164,000,000. CPG is a TLR 7, 8 and 9 therapeutic and was discovered as one of the drivers of Coley’s fluid.25 Basically, Coley’s fluid drives the innate immune system hard and allows the immune system to “wake up”. This increases the potential positive effects of treatments like IPT, Gerson Therapy, Apatone, and conventional approaches like chemotherapy and radiation.
1 Cancer Immunotherapy Principles and Practices
2 Dr William Coley and tumour regression: a place in history or in the future
3. 2 Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. Am J Med Sci
4 Coley WB. Treatment of inoperable malignant tumors with toxins of erysipelas and the bacillus prodigiosus. Trans Am Surg Assn
5 Bioimmunoadjuvants for the treatment of neoplastic and infectious disease: Coley's legacy revisited.
7 Bioimmunoadjuvants for the treatment of neoplastic and infectious disease: Coley's legacy revisited.
8 The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas
9 Brand RA. Biographical sketch: James Stephen Ewing, MD (1844-1943). Clin Orthop Relat Res. 2012 Mar
10 Brand RA. Biographical sketch: James Stephen Ewing, MD (1844-1943). Clin Orthop Relat Res. 2012 Mar
11 James B. Murphy James Ewing Biographical Memoir National Academy of Sciences Washington D.C.,1951
12 The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas
16 The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas
17 Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley's Toxin
19 Helen Coley Nauts Monographs of Coley’s toxins
20 Helen Coley Nauts Monographs of Coley’s toxins
22 Helen Coley Nauts Monographs of 896 patients
23 Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift