Just two days into the throes of erysipelas, the man’s tumor began to liquefy and shrink; within two weeks, it completely disappeared. Zola’s immune system had turned its weaponry against the tumor after a call to action from a feverish infection. According to follow-up reports, Zola remained well for eight more years before dying from a recurrence of the tumor in his native Italy.
Coley wasn’t the first to observe this compelling quirk of the immune system that gave Zola and others extra years on their lives, if not complete remission. The earliest mention of cancer-fighting infections dates to a citation from 1550 B.C. and is attributed to Egyptian physician Imhotep, who called for treating the wound with cloth coated in a poultice that would almost certainly lead to infection, and then cutting into the tumor. Coley, however, was the first to study and test the efficacy of what would come to be known as immunotherapy, coaxing the human immune system to fight cancer.
After his success with Zola in that New York apartment, Coley dedicated the next 40 years of his life to perfecting his unorthodox cancer treatment. In the process, he would become both a nationally revered cancer surgeon and an embattled figure who stubbornly defended both his treatment and his reputation until his death in 1936. Now, more than 100 years after his first fateful success, cancer researchers are still traveling the path Coley blazed long ago.
Rise and Fall
In the two years following Zola’s treatment, Coley treated 10 more patients with live bacteria, but his approach proved to be highly unpredictable. Sometimes he couldn’t induce an infection; other times, patients had strong reactions but saw no cancer-fighting effect. On two consecutive occasions, the erysipelas infection killed the patients. So Coley changed course and crafted a vaccine with two dead bacteria, S. pyogenes and Serratia marcescens. Research at the time indicated the latter increased the virulence of the former when combined with each other, allowing the injections to induce the feverish effects while drastically reducing the risk of death. This reimagined mixture became known as Coley’s Toxin.
The pharmaceutical firm Parke-Davis & Co. made various formulations of Coley’s Toxin available to all physicians from 1899 to 1951, and at least 42 physicians from Europe and North America reported success stories in patients treated with the toxin, specifically for bone and soft-tissue sarcomas. In a 1945 study of the toxins’ efficacy, among 312 inoperable cases of cancer, 190 were considered regressions after treatment — a cure rate of about 60 percent. Coley went on to treat nearly 1,000 patients with his toxin and published more than 150 papers on the subject.
Coley’s research had one major, damning flaw: He couldn’t explain why his toxins worked.
The widespread use of his treatment and his prolific publishing record made Coley a leading cancer expert in the eyes of the public. And Coley was justly regarded for his success as a cancer surgeon — he retired from New York Memorial Hospital in 1933 as chief of the bone tumor service. (His son Bradley was appointed his successor.) In 1935 Coley was inducted as an honorary fellow into the Royal College of Surgeons of England, becoming just the fifth American to receive that honor. But where his toxin was concerned, Coley was a target for criticism in the medical community, and with good reason: His breakthrough was built upon a shaky foundation.
Coley may have been an audacious clinician whose work helped hundreds of patients, but a scientist, he was not. He knew how to treat his patients, but he was never trained in laboratory work, and his toxin research didn’t meet the increasingly stringent scientific standards of the era. Physicians chided Coley for poorly controlled and documented experiments. For example, he injected the toxin into multiple locations in test patients without properly noting the location of each injection.
Despite his best efforts, the toxin was still inconsistent at best: Thirteen different formulations of his toxin were produced at one point, with some mixtures more effective than others. Furthermore, each patient reacted unpredictably to the toxins, and the toxins still were sometimes fatal.
But even if Coley had been more meticulous, he was still battling a medical establishment that firmly believed any cancer cure that didn’t require surgery meant the “disease” was misdiagnosed as cancer. Plus, many doctors had a justifiably hard time reconciling the Hippocratic oath with the idea of inducing a potentially fatal infection in already-suffering patients.
Early in the 20th century, radiation therapy was also an emerging cancer treatment, and the nation’s preeminent cancer pathologist, James Ewing, staunchly favored treating patients with this promising new method. Ewing also happened to be Coley’s boss and biggest opponent — never a good combination. Ewing forbade Coley from using his toxin inside Memorial Hospital.
Coley’s research had one major, damning flaw: He couldn’t explain why his toxins worked. They just did (sometimes). Until the day he died, Coley tenaciously held to the belief that microorganisms caused cancer — a theory long dismissed by the medical establishment — and that his toxin somehow killed those cancer-causing organisms in the body.
He must not have been alone in this conviction. More than 15 years after Coley’s death — not of cancer, incidentally, or an ironic erysipelas infection, but of chronic diverticulitis — Parke-Davis continued to make Coley’s Toxin, even as chemotherapy and radiation rose to the forefront of cancer treatment. By 1962, however, the U.S. Food and Drug Administration refused to acknowledge the toxin as a proven drug and made it illegal to use to treat cancer. Still, the legacy of Coley’s Toxin would not be forgotten.
Over the next several decades, researchers stuck their toes into the murky and temperamental waters of immunotherapy. Since the 1960s, the medical community has gone back and forth as to whether the immune system could be made to launch an anti-tumor offensive. It’s only relatively recently that researchers have finally confirmed that, yes, our immune system is indeed programmed to fight cancer.