beyond reason
DR. WILLIAM COLEY: THE “FATHER OF IMMUNOTHERAPYA�?
Immunotherapy is based on the concept that a patient’s immune system can be stimulated or enhanced to attack cancer. Dr. William B. Coley (1862-1936), a bone sarcoma surgeon was the first to study immunotherapy as a potential cancer treatment. For 40 years Coley injected streptococcal bacteria into cancer patients (primarily those with inoperable bone and soft-tissue sarcomas) in order to stimulate the immune system.
- 면역항암치료는 환자의 면역시스템을 자극하여 암세포를 공격한다는 개념
- 뼈육종 수술의사였던 윌리엄 콜리가 처음 시작함. 40년동안 콜리는 연쇄상구균 박테리아를 말기 육종암 환자에게 면역시스템을 자극하기 위하여 주사함.
Coley was not an “alternative doctor” working in the shadows, but rather was the Chief of the Bone Sarcoma Unit at Memorial Hospital in New York, America’s first cancer hospital. As a result of his innovative work, Coley became known as the “Father of Immunotherapy.” Nonetheless, during his life, Coley was often criticized because his methods of treatment and patient follow-up were not consistent, and many colleagues could not believe his impressive results.
- 콜리는 대체의학 의사가 아니라 뉴욕 메모리얼 병원에서 뼈육종 수술 chief였음.
- 그의 획기적인 치료법의 결과덕분에 콜리는 '면역항암치료의 아버지'로 알려짐.
Cancer and Infection
William Coley was born in 1862, went to college at Yale, graduated from Harvard Medical School in 1888, and thereafter joined the staff of Memorial Hospital. Soon after beginning his professional career, Coley learned about a patient who had had an inoperable malignant tumor in his neck that disappeared after he developed erysipelas (a bacterial skin infection). Coley searched for this patient and when he found him discovered that he had evidence of cancer.
- 콜리는 뉴욕 메모리얼 병원에서 근무하던 중 단독(박테리아의 피부감염)후에 말기암 환자가 회복되는 것을 관찰함.
Coley was intrigued and researched the medical/scientific literature for other patients who had cancer remission due to a concurrent bacterial infection. He found a number of sources, case histories, and citations including those from the well known physician Sir James Paget. In all, Coley was able to find over 40 cases in the literature documenting the beneficial effect of infections on tumors.
- 콜리는 박테리아 감염으로 회복된 암환자의 의학적/과학적 문헌을 조사
- 제임스 파젯의사의 40케이스 연구를 발견.
In 1891, Coley injected his first patient with streptococcal organisms and noticed the shrinkage of a malignant tumor. He treated other patients and two died from infection. Thereafter, Coley continued his treatments using a less virulent heat-killed streptococcal organism combined with a second organism (Serratia marcescens). This combination became known as Coley’s Toxin. By 1893, he had tried his toxin on ten patients, most of whom did well. By the end of his career, he had treated almost 1,000 cases. Other doctors used his modality to treat their own patients.
- 1891년 콜리는 첫번째 환자에게 연쇄상구균을 주사하고 암세포 크기가 줄어드는 것을 관찰함.
- 다른 두 환자는 감염때문에 사망함. 그래서 콜리는 열을 가하여 죽인 약한 연쇄상구균과 Serratia marcescens을 섞어서 주입함. 이 조합을 coley's toxin이라고 함.
- 1893년 10명의 환자에게 주사하여 좋은 결과를 보임. 이후 1천케이스를 시행하고 다른 의사들도 그의 치료법을 사용함.
Results
According to a 1965 article that was published in A Cancer Journal for Clinicians (1):
“In 1952, a bibliography of the literature, and, in 1953, a report on 30 inoperable cases which had been treated by Coley’s mixed toxins and had survived thereafter for periods of from 1 to 47 years (20 cases had a survival of over 20 years) were published.
- 1953년 희망이 없는 말기암환자 39케이스를 대상으로 coley mixed toxin을 주사하여 1-47년까지 생존함.
- 20케이스는 20년을 생존했다고 발표함.
The report is said to be based on a comparative analysis of over 1,200 cases treated with Coley’s toxins, and 300 cases in which intercurrent infections played a part. Over 270 cases were said to have shown complete regression of the tumor, but the 30 inoperable cases were selected for the report because the diagnoses had been confirmed by microscopic examination, and some information on their subsequent history was available. Of the 30 tumors, 7 were classified as carcinoma, 19 as various types of sarcoma, 2 as malignant melanoma, and 2 as giant cell tumors.”
- 이 보고서는 coley toxin 주사를 맞은 1200케이스를 비교분석하면서 300케이스는 intercurrent 감염이라고 함. 270케이스는 암크기가 완전히 사라졌음. 그중 30명의 환자는 조직검사로 확인하여 7명은 carcinoma, 19명은 sarcoma, 2명은 melanoma 2명은 giant cell tumor였음.
A complete response rate of 22% (270 out of 1200) was impressive by the standards of the 1960’s and today. But, despite these results, the article states that the, “American Cancer Society has found no evidence that treatment with Coley’s mixed toxins results in any objective benefit in the treatment of cancer in human beings.” It is difficult to reconcile this conclusion with the results cited in the same article. Perhaps the results were simply not believed as they were authored by Mrs. Helen Coley Nauts, Executive Director of the New York Cancer Research Institute. Mrs. Nauts was the daughter of William Coley.
- 완전 회복비율은 22%(1200명중 270명) 당시와 현재의 치료율 관점에서 매우 인상적인 결과였음.
Helen Coley Nauts
Helen Coley Nauts was not a dilettante, but a distinguished cancer researcher in her own right. According to her obituary:
“Helen Coley Nauts, D.Sc. (Hon.), Pioneering Force for Cancer Immunology. Dies at 93 Helen Coley Nauts, founder of the Cancer Research Institute and the only other woman after Dr. Marie Curie to win the National Institute of Social Sciences’ Gold Medal for Distinguished Service to Humanity, died of natural causes on the morning of January 2, 2001. She was 93. She was one of the leading scholars in the field of cancer immunology,” according to Dr. Lloyd J. Old, Director of the Ludwig Institute for Cancer Research and pioneer in the field. Her research has led to wide recognition of the seminal importance of the work of her father, Dr. William B. Coley, and his use of bacterial vaccines in the treatment of cancer. As a consequence of her tireless effort, William B. Coley is now generally acknowledged as the “Father of Cancer Immunotherapy.”
Acceptance by the Medical Community
Coley’s work was alternately embraced and reviled by the medical community. His early work at the turn of the last century was during the advent of radiation therapy and the majority of cancer practitioners sided with radiation as the treatment of choice (in combination with surgery).
- 콜리의 치료법은 의학계로부터 호응과 비난을 동시에 받음.
Many of the professional criticisms focused on Coley’s alleged poor record-keeping and follow-up, his use of at least thirteen different preparations of the toxins, and different methods of administration (i.e. intravenously, intramuscularly, or intra-tumor). Perhaps because of his variable use of the toxins, many doctors could not replicate his results.
- 많은 의사들이 콜리의 주장에 문제점을 지적. 혈관내 주사, 근육내 주사, 종양내 주사를 했는지.. 등등..
Since Dr. Coley’s death, the field of immunology has developed into a sophisticated specialty. Scientists are studying the effect on tumors of tumor necrosis factor (TNF), interferons, streptokinase and many other cytokines, all related to the immune system.
- 콜리가 사망한 후 면역분야에서 과학자들은 TNF, 인터페론, 스트렙토키나아제와 많은 사이토카인의 효과를 연구함.
In fact, Bacille Calmette-Guérin (BCG) a vaccine against tuberculosis prepared from a strain of weakened live bovine tuberculosis bacillus is now accepted as the most effective intravesical agent for the treatment and prophylaxis of superficial bladder cancer. It also prevents bladder tumor recurrence and progression, increases the disease-free interval, and prolongs survival. Even the American Cancer Society has changed his position on Dr. Coley. Its website now states, “Scientific evidence suggests Coley toxins or other mixed bacterial vaccines (MBVs) may have a role in treating cancer when combined with other treatments.”
Status Today
In 1963, Coley’s Toxins were assigned “new drug” status by the Food and Drug Administration (FDA), making it illegal in the U.S. to prescribe this kind of therapy outside of clinical trials. Because the constituent ingredients of Coley’s Toxins are naturally occurring and thus not patentable, no clinical trials have been financed in recent years. However, one company has stated that it is working towards conducting clinical trials in Canada and the United States.(2) Reportedly, there are clinics both in the U.S., Europe and Mexico who still use Coley’s Toxins in cancer as an adjuvant or immune boosting therapy.
- 1963년 coley's toxin은 FDA로부터 신약으로 인정됨.
Today, Dr. Coley’s reputation in medicine is becoming more firmly established. According to a recent review that appeared in the Iowa Orthopedic Journal (3):
“William Coley’s intuitions were correct: Stimulating the immune system may be effective in treating cancer. He was a model of the clinician-scientist, treating patients and using his practice to initiate research and build theories. But he was a man before his time, and he met with severe criticism. Despite this criticism, however, Coley stuck with his ideas, and today we are recognizing their potential value.”
'윌리엄 콜리의 직관은 옳았다. 면역시스템의 자극은 암치료에 효과적이다. 그는 임상-과학자의 규범이었고 ...
Citations
(1) Grabstald, h. Unproven Methods of cancer Treatment: Coley’s Mixed Toxins. CA Cancer J Clin. 1965 May-Jun;15:139-40
(2) MBVax Bioscience
(3) McCarthy EF, The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J. 2006;26:154-8.
A comprehensive review of the medical literature concerning Coley’s Toxins was performed by the M.D. Anderson Cancer Center which summarizes the results of 30 human studies performed with this modality. Biologic/Organic/Pharmacologic Therapies: Coley Toxins Detailed Scientific Review