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The strange case of Coley’s Toxins

Highlands Journal

10-19-17

In the early 1890s, there was a young surgeon named William Coley who worked at Memorial Hospital in New York City. He developed a way to destroy cancerous tumors by injecting patients with a mixture of toxic bacteria. Met with consternation more than 100 hundred years ago, his “outside the box” approach would set the framework for what would become modern immunotherapy. His treatments were commonly referred to as Coley’s Toxins.

Coley had become intrigued by an assortment of odd cancer stories that were referenced in the medical literature of that day. Stories such as patients once riddled with inoperable tumors suddenly finding themselves cancer-free after contracting erysipelas, a potentially fatal ailment in those days. Coley discovered 47 similar cases and became fascinated by what he perceived to be a link between these cases.

He enthusiastically proceed directly to human trials in May of 1891. An Italian immigrant named Zola would become his first test subject. Zola’s last shot at survival was in the hands of a 29-year-old bone surgeon who believed he had found a cure for cancer. Coley filled a syringe with living Streptococcus Pyogenes, which was known to induce erysipelas attacks. He injected the solution directly into Zola’s tumor. It took repeated injections over five months, finally, about an hour after one of the injections, Zola broke out into sweaty chills, and his body temperature soared to 105 degrees.

Two days into the throes of erysipelas, the tumor began to shrink. In less than two weeks, the tumor had disappeared. Due to the infection caused by injecting Zola with the toxins, his immune system had responded and attacked the tumor. According to reports, Zola lived for eight more years before the tumor returned and took his life while living in Italy.

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.

Coley’s approach was actually used by many doctors in the years around the turn of the century and after, including by the Mayo brothers (of the Mayo Clinic in Minnesota) and orthopedic surgeon Henry W. Meyerding. Meyerding used the toxins in conjunction with surgery for patients with bone cancer, achieving survival rates far higher than with surgery alone.

Coley dedicated the next 40 years of his life to perfecting his unorthodox cancer treatment. A major obstacle to Coley was that the toxin results were inconsistent. More than a dozen formulations were produced at one point. Some mixtures more effective, some were less so. In addition to this, each patient reacted differently to the treatments and the toxins themselves were, at times, fatal.

Coley would not be without controversy. He became both a revered cancer surgeon and an oft-criticized doctor who stubbornly defended both his treatment and his reputation until his death in 1936. More than 100 years after his first success, cancer researchers are still traveling the path Coley blazed long ago.

One of the major battles Coley fought, and seemingly lost, was in his own hospital. Around the same time that Coley’s Toxins became the talk of the town, radiation therapy was also an emerging cancer treatment. The nation’s preeminent cancer pathologist, James Ewing, was staunchly in favor of treating patients with the promising new radiation method. Ewing was also Coley’s boss and his biggest opponent. Ewing forbade Coley from using his toxin inside Memorial Hospital. A large blow to the surgeon’s work. Another problem with the toxins and Coley’s research was that he could not explain why they worked. Or did not work, as the case may have been. Despite this, Coley continued to firmly believe that microorganisms were what caused cancer and that the toxins, in some cases, killed those cancer causing agents that were at work in the body. He held this belief until the day he died.

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. 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.

Today, immunotherapy is a rapidly ascending field of cancer research because scientists are finally figuring out the immune system’s quirks, and the pharmaceutical industry is getting into the game. “Immunotherapy is probably the hottest area of cancer research right now,” says Jill O’Donnell-Tormey, CEO and director of scientific affairs at the Cancer Research Institute.

She notes that biotech firms are investing heavily in immunotherapy research, and about 40 percent of the roughly 6,000 cancer clinical trials taking place in the United States today include some form of immunotherapy.

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