Shortly after Dr Coley began his medical practice, he encountered an unusually virulent bone sarcoma in a young woman. She had hurt her hand on a cross country trip in the summer of 1890, complained of worsening pain, and when finally cancer was diagnosed, Coley amputated her arm, feeling the young woman faced a decent prognosis. Only weeks later, other tumors began to appear all over her body, and she died several months later after great suffering. Coley was profoundly affected by her death, and by his inability to provide any sort of effective treatment against the disease that ravaged her so brutally before his eyes. This young woman, Bessie Dashiell, was a close friend of John D. Rockefeller Jr., and it is said that Rockefeller’s involvement in cancer philanthropy stems from his grief over Bessie’s death.
Coley resolved to review all the sarcoma records from the previous 15 years. He wanted to learn more about this disease. All the cases he came across were grim, until he discovered the 7 year old case of a German immigrant who came in with advanced sarcoma. After multiple operations to unsuccessfully remove the tumors, the case came to be viewed as hopeless. As the patient lay for months in the hospital with a large open wound, he twice contracted erysipelas, a virulent and often fatal skin infection that was a common hospital occurrence in those days. He recovered from the fevers. Amazingly, his large wound closed up and healed, any remaining sarcomatous tissue was absorbed, and he went home in good health. Coley resolved to find this man and searched through New York’s lower East Side tenements until he found him. The man was still well; there were no signs of cancer anywhere.
Coley received permission from his superiors to treat what were deemed inoperable cases of sarcoma with an artificially-induced erysipelas infection. He at first had difficulties getting his patient infected, but when he finally succeeded, the patient experienced a very dramatic recovery. (He died of a recurrence some eight years later.) As the experimentation proceeded with other patients, Coley became dissatisfied with this method -- it was difficult to induce the infection, and once started, it sometimes killed the patient. He hit upon mixing the attenuated strains of Streptococcus pyogenes (the cause of erysipelas) with another bacterium that lives in the human gut, today called Serratia marcescens. The fluid derived from the bacterial culture was then injected into the patient, into and around the tumors. Coley gradually titrated the doses until he got a good response -- fever, rash, chills, shakes and other symptoms today referred to as the "cytokine flu."
The first patient treated by Coley with his new toxin mix was a young boy with a huge abdominal tumor. After a number of weeks, the patient finally responded with a strong reaction, and the tumor began to shrink. When sent home a month later, only a little remained. The boy grew up and eventually died of a heart attack 26 years later.
Coley usually continued the administration of the toxins for a period of time, aiming for a strong response. (It is assumed today that the therapy should continue even after the response is experienced, for about 6 months altogether.) And in some successful cases, the treatment was carried on for several years. This approach was far more successful than anything else then available: it is estimated that he helped up to 40% of patients, with perhaps 10% cured. These results compare favorably to even today’s methods in some cancers. The toxins were said to be successful with sarcomas (including lymphosarcomas, as lymphomas were once known), and some current experts have conjectured that their beneficial effect may extend to all cancers that originate in mesodermal tissue (including kidney and ovarian cancer).
Coley was not alone in noticing that an infectious disease sometimes resulted in the sudden recovery from cancer. A few similar cases were described, in connection with erysipelas, tuberculosis, syphilis, malaria and gangrene. (And there have been reports of mumps and measles causing a regression of lymphoma.) Some European doctors reported similar encouraging results as did Coley. Coley’s treatment was at first received with guarded optimism in the medical community, but was soon rejected by many physicians who were either unable to reproduce Coley’s successes or regarded the treatment with distrust. The controversy fed further skepticism. Some doctors, however, did continue to use it until WWII, most notably the Mayo clinic. (It is a matter of some controversy whether the heat-killed or the filtered toxins were more effective.)
Why was his treatment not successfully assimilated into the practice of medicine? The literature lists the following reasons: 1) There were several preparations in use, and they were of very uneven quality. Coley was able to get high quality toxins through his connections. But many physicians relied on inferior and variable commercial preparations. The toxins were never standardized, and neither was their administration. 2) The effect did not fit into the immunology of the day, and so was often dismissed because current science did not provide any framework for understanding it. This framework did not emerge until the last third of the century. 3) Shortly after the toxins came into use, the country became infatuated with x-rays and radium, and the entire thrust of cancer treatment veered in that direction. It is mindboggling to read of the extent that this "magical" substance came to be viewed as panacea -- people drank radium water, rubbed radium creams into their skins, and expected radium to cure dread diseases like cancer. As commercial radium interests linked with the leadership at Memorial Hospital, Dr Coley’s treatment lost luster in comparison. 4) The administration of the toxins was an imprecise art that took many weeks or months. Many surgeons had neither the patience to learn it nor the required hospital beds for the extended time that was often needed. 5) Dr James Ewing who came to run the Memorial Hospital and was a big promoter of radiation, took a dislike to the toxins and had a hand in harming their reputation. Many times in the history of medicine, a wonderful new discovery has been attacked as worthless by the physicians of the day who are unwilling to advance someone else’s insight. 6) And finally, it seems that once a treatment becomes embroiled in controversy, even rather clear data in its support are not enough to convince, while a historically favored treatment continues to be favored despite lack of evidence of any benefits.
In 1934, Coley attended a symposium on Ewing’s sarcoma. Although retired, he was invited because of his unique expertise and success with this type of cancer. He compared the data then available (this was before clinical trials came into existence), and showed that of the patients treated with the toxins, some survived for 5 years, whereas of those treated by radiation alone, none survived. Of the inoperable cases, 24 were treated at Memorial with radiation alone, and 22 patients were treated with toxins, either alone or together with radiation. Of those 24 treated by radiation alone, 21 were dead, and 3 too recent to evaluate. Of the 22 patients treated with toxins, 12 survived 5 years. Despite these and other similar results, Dr. Ewing urged his colleagues to use radiation not only for bone cancer, but for all cases of unexplained bone pain! (This at a time when it was already known that radiation harms the bone marrow.)
Some physicians did suggest a trial after the conference, and it seems that the new director of Sloan Kettering, Dr Cornelius Rhoads, once planned such a trial. But it was never carried out. The toxins continued to be manufactured until the 50s, then were discontinued, and the American Cancer Society put Coley’s toxins on their infamous blacklist (they were removed in the 70s). Further research became difficult, as the FDA refused to grandfather them. It seems a preparation close to the toxins was sold OTC in Germany as a fever inducer until 1991, at the cost of about $2. At present, there are several alternative clinics that use the toxins: the CHIPSA hospital in Mexico (which is doing a study of the toxins for melanoma and uterine cancer), the Waisbren Clinic in Milwaukee (they use a preparation similar to the toxins which was originally developed to boost the immune systems of burn victims), and several other clinics. Most notably, Chinese physicians recently noted an amazing cure of a boy with cancer who got a bad infection from his biopsy. They became interested in Coley’s work, named a hospital after him, and are doing new research. And certain German cancer clinics have used the bacterial toxins to bring about hyperthermia.
After Coley’s death, his daughter Helen Coley Nauts reviewed his records, notes and results and published several papers, including one on the results of the 86 documented cases of lymphoma. She also founded the Cancer Research Institute which promotes immune therapies for cancer. A researcher between the wars recognized that endotoxins in the cell walls of Serratia had a profound anti-tumor effect, and named these lipopolysaccharides or LPS. (Some eighty years after Coley, scientists have discovered that such endotoxins produce a powerful immune reaction that floods the body with substances such as interferon, tumor necrosis factor and many other cytokines that can mobilize against the cancer. Pain-killing endorphins are also among the released substances.) And there have been a few studies implying that lipopolysaccharides derived from cells walls of plants can also provide a powerful immune boost.
Since the fifties, there have been several attempts to test the toxins. None of these studies were truly rigorous; each had some problems. But they all reported promising results. In the 50s, tests on mice showed that most anti-tumor activity is to be credited to Serratia but the Strep bacteria acted to increase its effect. The toxins reliably killed transplanted tumors in mice. In the 60s, a controlled study showed 9 patients on the vaccine responding vs 1 in the control group. There were several striking regressions. In the 80s, one study showed stabilization of disease and improvement in the quality of life in some serious cases. Another study on follicular lymphoma compared chemo alone with chemo plus toxins. Chemo alone achieved 44% CR while chemo plus toxins achieved an impressive 85% complete response. Initially, the survival of the toxin group was better, but eventually both mortality curves met. The Waisbren clinic published its results with some very advanced patients (including lymphoma). There were several notable regressions. And in the 90s, a small German study reported several remarkable regressions of melanoma after the toxin treatment. Also, the Chinese have recently reported positive results with liver cancers.
Despite the overall beneficial results obtained from the toxins, and the need of patients like us, most commentators on this frustrating history think that they will never be properly tested because the money cannot be raised to fund the commercial development of a non-patentable, cheap and easy to make substance.
In doing the research for this article, I utilized the excellent, very detailed and comprehensive information on Dr Coley in the recent book called A Commotion in the Blood, by Stephen S. Hall (1997). This book describes the history of immunological approaches to cancer. After reading the Coley chapters, I was stricken with terrible grief -- not only for Dr Coley who tried so hard on our behalf and was rejected, but grief for all of us. We have a type of cancer that may have been curable, at least occasionally, a hundred years ago. And today, still without any definite prospects for a cure, we have no access to this treatment, and no hope that researchers will undertake such a project, despite their recognition of its value.
I wonder if a community trial could be organized, comprised of low-grade lymphoma patient volunteers. If it can be done for AIDS, why not for cancer? Also we need follow-up data from China and from Germany. One online resource mentioned that a trial was to have been undertaken in 1996 in Holland. No IND for Coley's is necessary, provided the toxins are delivered and produced in the same state. Depending on state laws, physicians have the right to dispense non-experimental vaccines in the best interest of their patients, as long as the vaccines are not sold for profit or commercial enterprise. The formula is available from the U. of Texas - CAM.
U. of Texas notes: "Available evidence suggests that Coley toxins are not harmful or dangerous to humans or animals suffering from various types of neoplasms, provided the toxins are administered properly as to dosage, site, and the usual aseptic precautions. The following patients should not be given the toxins because they will not respond: patients with severe hepatic insufficiency due to metastatic disease or other pathology, patients who have had severe heart conditions, or patients who are almost moribund." (Side effects: fever, nausea, headache, back pain and, occasionally, cold sores, some short-lived fatigue after treatment, as well as soreness at the injection site).
Ralph Moss has an article on Coley's on
his site but it requires Adobe Acrobat Reader:
www.ralphmoss.com/alt1.html
Cancer Research Institute, founded by Helen Coley Nauts, has two files of
interest:
www.cancerresearch.org/crigenrl.html
www.cancerresearch.org/crifound.html
Researched and written by Vera Bradova © 1998
Updated 11-15-1998
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