Coley's Toxins and the Origins of Immunotherapy

Stuff You Missed in History Class

This episode explores the pioneering work of William B. Coley in developing early immunotherapy using bacterial infections to treat cancer,

Key takeaways

• Coley's discovery was inspired by a patient whose sarcoma disappeared after contracting erysipelas, leading him to intentionally induce the infection as treatment.
• His method, known as Coley's toxins, involved injecting live or killed bacteria to stimulate the immune system against cancer.

Main topics

• William B. Coley's medical career and personal motivation
• The historical link between bacterial infection and tumor regression

Notable quotes

"Among these cases was a small, round-celled sarcoma... the tumor began to soften and decrease rapidly in size."

Conclusion

William B. Coley's bold experiments with bacterial infections marked one of

Transcript preview

Speaker 3 (0:00) This Speaker 4 (0:00) is an iHeart Podcast. Speaker 3 (0:02) Guaranteed human. Speaker 4 (0:05) Welcome to Stuff You Missed in History Class, a production of iHeart Radio. Speaker 1 (0:16) Hello and welcome to the podcast. I'm Tracy V. Wilson. And I'm Holly Frey. I don't usually watch the news on television, but I do at my parents' house because my parents watch it. And I was visiting them recently and saw some news coverage of a clinical trial of a vaccine that is meant to help prevent recurrences of melanoma in people who have melanoma. And one of the things that came up in this news segment was a move to describe these kinds of therapies as immunotherapy rather than as vaccines because of the anti-vaccine movements and its impacts on things like funding for mRNA research. And as I was being frustrated about that, I thought, hey, don't you have something about immunotherapy on your shortlist for episodes? And I did. Over the course of working on this episode, though, it shifted. from an overall history of immunotherapy to focus on one specific part of that history. And that's the work of William B. Coley, who started using a bacterial infection to treat cancers in the late 19th century, which was one of the earliest uses of an immunotherapy. So we're going to start here with a little bit of Speaker 4 (1:37) background. Immunotherapy can be defined as anything that modifies the immune system in some way, generally activating or suppressing it. Sometimes prophylactic vaccines are included under the broad definition of immunotherapy, so some histories of immunotherapy start with variolation. That is using material from smallpox sores to stimulate the immune system to create antibodies, leading to a typically milder case of smallpox and lifelong immunity to it. The practice of variolation dates back hundreds of years at least, and it is something that we have talked about in our episodes on Edward Jenner and the eradication of smallpox. As I was researching this, Speaker 1 (2:22) there seemed to be some... Not exactly debate, but kind of a lack of consistency about whether people considered things like the smallpox vaccine, the flu shot, that kind of thing to fall under the umbrella of immunotherapy or not, or whether it's only the therapeutic vaccines, not the more preventive ones that are considered immunotherapy. I can't answer that question conclusively. I do not work in that field. But today... The term immunotherapy is most often used in the context of cancer treatment, activating a person's own immune system to recognize and fight cancer cells. One of the first attempts to intentionally do this, although it's not necessarily what the doctors involved understood that they were doing, started in the 19th century. Two different doctors in Germany documented patients whose malignant tumors shrank or disappeared completely after they contracted a bacterial skin infection known as erysipelas. Sometimes these infections were contracted during surgery that attempted to treat the cancers, and that was one of the many risks of surgery before Joseph Lister developed his antiseptic system for infectious control. Speaker 4 (3:45) These doctors were Friedrich Felicin and Wilhelm Busch, and they each tried to investigate whether this was a coincidence. In 1868, Busch intentionally infected a cancer patient with erysipelas using another patient's bedsheets, and he reported that the patient's tumor shrank. By 1882, Felicin had identified and isolated the bacteria that caused erysipelas. At the time, it was called Streptococcus erysipelas, but now it is known as Streptococcus pyogenes. That is the same bacterial strain that causes strep throat, scarlet fever, and other illnesses and infections. Felicin injected these bacteria directly into his patients' tumors. In 1887, German surgeon Paul von Bruns also published a paper describing a patient whose tumor shrunk after being injected with streptococcus bacteria. Speaker 1 (4:44) William B. Coley was not aware of this work when he started working as a doctor. He was born in Connecticut on January 12, 1862. He went to college at Yale. and then after spending some time teaching in Oregon, he went to Harvard Medical School. Medical education in the United States was not nearly as formalized or extensive as it is today, and he was able to enter a three-year medical program as a second-year student, thanks to having spent some time accompanying his physician uncle on his rounds. I like how it's kind of like Speaker 4 (5:19) the way you could get college credit for certain high school courses, but it really didn't correlate, except this is dealing with people's lives and bodies. Speaker 1 (5:27) Yeah, it doesn't seem like he spent all that much time with his uncle, but it was considered enough to skip a Speaker 4 (5:34) whole year of med school. Coley spent the summer between his two years of medical school working as an acting junior surgeon at New York Hospital. He had friends who worked there, and he was filling in for one of the surgeons on staff who was out on leave. Coley started a surgical internship at the hospital after graduating from Harvard in 1888, and he became a house surgeon there in 1889. Not long after that, he was also appointed to the staff of the Hospital for the Ruptured and Crippled, later known as the Hospital for Special Surgery. That is an orthopedic and rheumatologic hospital that still exists today. Speaker 1 (6:14) In 1890, Coley treated 17-year-old Elizabeth Daschle, known as Bessie, who had injured her hand while on a train trip and was still having pain more than a month later. She had seen other doctors and tried various treatments and was eventually referred to Coley. After some investigation and eventually a biopsy, Coley diagnosed her with a periosteal sarcoma. The standard course of treatment for this was an amputation, with the hope that the cancer had not already spread beyond the amputation site. Coley amputated Daschle's arm below the elbow, but soon there were more tumors in other parts of her body. She died on January 23, 1891, at the age of 18, only about 10 weeks after Coley first examined her. Speaker 4 (7:07) Bessie Daschle's death had a profound effect on William Coley. As Tracy said, she was only 18, and she had been healthy and active, so the rapid progression of her illness and her death seemed particularly shocking and tragic. Coley was also only 28 himself, and he was in his first year of working as a surgeon. It really bothered him that amputation was the only thing that he had been able to offer her as a treatment option, and that such a life-altering surgery had not even worked. He wanted to find some more. effective treatments, and he started poring over the records at New York Hospital, studying the cases of past cancer patients. He went through all the details of about 90 cancer patients who had undergone surgery at the hospital in the previous 15 years. One Speaker 1 (8:00) record stood out, and that was a patient of his colleague, Dr. William T. Bull. In Coley's words, quote, among these cases was a small, round-celled sarcoma of the neck, four times recurrent. At the fifth operation in 1884, Dr. Bull found the tumor to involve the deep structures so extensively that it was impossible to remove it, and he gave up the attempt. The case was regarded as absolutely hopeless when, shortly after the operation, the man developed a very severe attack of accidental erysipelas in the face and neck, followed two weeks later by a second attack. Within a few days after the beginning of the first attack, the tumor began to soften and decrease rapidly in size. The history stated that when the patient left the hospital, his tumors had entirely disappeared. And the hospital didn't Speaker 4 (8:55) have any further record of this patient after he left, so Coley tracked him down, going door-to-door in the German immigrant community where he was likely to have lived. Coley, quote, finally found him alive and well, with no evidence of any local or general recurrences in the spring of 1891, seven years later. He was examined both by Dr. Bull and myself. Speaker 1 (9:21) Coley started looking through historical medical literature, and he found other reports of patients whose tumors shrank or disappeared after some kind of infection. Like Felicin and Bush, Coley decided to see if he could replicate this effect. On May 2, 1891, he started trying to induce erysipelas in a patient who had an inoperable sarcoma of the tonsil and neck. The tumors were so large that this patient could not eat solid food and could only swallow very small amounts of liquid. Coley exposed Speaker 4 (9:55) this patient to bacteria that had been cultured in a lab. But for months, he was not able to induce a case of erysipelas, no matter how the cultures were prepared or what method he used to expose the patient to them. Finally, in October, he tried a culture that a colleague brought him from Robert Koch's laboratory in Germany. This injection made the patient very ill, but in Coley's words, quote, at the end of two weeks, the neck tumor had disappeared and the tonsil tumor had decreased in size. The patient remained well for eight years and then died in Italy of a local recurrence. Speaker 1 (10:35) We'll talk about how Coley started trying to replicate these results after a sponsor break. Speaker 3 (10:43) What would change if you stopped letting money stress run your life, sis? I'm Mandy Money, host of Brown Ambition, the podcast. And right now I'm taking you through my six part money reboot series. This is your chance to hit reset, break the debt cycle, get honest about where your money's going, build a savings plan that actually sticks and start making financial choices that support the life you want, not just the bills you have. Because wealth building is not about being perfect. 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