This red immune system cell, called a macrophage, is engulfing tuberculosis bacteria. (Zeiss Microscopy)
A novel immunotherapy drug is credited for successfully treating former President Jimmy Carter's advanced melanoma. Instead of killing cancer cells, these drugs boost the patient's immune system, which does the job instead.
Immunotherapy is cutting-edge cancer treatment, but the idea dates back more than 100 years, to a young surgeon who was willing to think outside the box.
His name was William Coley, and in the late summer of 1890 he was getting ready to examine a new patient at his practice in New York City. What he didn't know was that the young woman waiting to see him would change his life and the future of cancer research.
Her name was Elizabeth Dashiell, also known as Bessie, says Dr. David Levine, director of archives at the Hospital for Special Surgery in New York. Bessie was 17 and showed up complaining of a problem with her hand. It seemed like a minor injury, just a small bump where she'd hurt it, but it wasn't getting better, and she was in a lot of pain. She'd seen other doctors but nobody could diagnose the problem.
At first Coley thought Bessie must have an infection. But when he took a biopsy, it turned out to be a malignant, very advanced cancer called a sarcoma.
In those days there wasn't very much anyone could do for Bessie. This was before radiation and chemotherapy, so Coley did the only thing he could — he amputated Bessie's right arm just below the elbow in an attempt to stop the disease from spreading. Sadly, it didn't work, and within a month, according to David Levine, the cancer had spread "to her lungs, to her liver and all over her body."
Bessie's final days were wrenching and painful. Coley was with her when she died on Jan. 23, 1891.
Coley Discovers a Clue
Bessie's death made a huge impression on the young surgeon. "It really shocked him," says Stephen Hall, who wrote about Coley in his book A Commotion in the Blood: Life, Death and the Immune System.
Bessie's death also spurred Coley into action. There wasn't a lot known about cancer at the time, so Coley started digging through dozens upon dozens of old records at New York Hospital. He was looking for something that would help him understand this cruel and aggressive disease.
As a student, Coley had read Charles Darwin, and one of the lessons he took away from Darwin, Hall says, was to always pay attention when there's a biological exception to the rule. "To ask yourself: Why this has happened?"
Coley discovered one of these biological exceptions. It was the case of a German immigrant named Fred Stein. Stein had been a patient in New York Hospital eight years earlier. He had a tumor on his neck that doctors tried to remove several times. Unfortunately for Stein, the tumor kept coming back and doctors expected him to die from the disease.
Then Stein contracted a serious infection of the skin caused by the strep bacteria. "It looked like Stein's days were numbered," Levine says. But Stein didn't die. In fact, his tumor disappeared, and he was discharged. Coley wondered if all these years later, Stein could still be alive.
So in the winter of 1891, William Coley the surgeon became William Coley the detective. He headed for the tenements of the Lower East Side of Manhattan where the German immigrant community lived. He knocked on door after door asking for a man named Fred Stein who had a distinctive scar across his neck. After several weeks of searching, Coley found him alive and cancer-free.
Can an Infection Reverse Cancer?
So why did Stein's cancer go away and stay away after he got a bacterial infection? Coley speculated that the strep infection had reversed the cancer, and wondered what would happen if he tried to reproduce the effect by deliberately injecting cancer patients with bacteria.
He decided to test his idea on people who were the most seriously ill. His first subject was an Italian immigrant named Zola who, just like Bessie Dashiell, was suffering from sarcoma. Zola had tumors riddling his throat. He was so sick he could barely eat or speak or even breathe. For months Coley would try to make Zola sick from infection by creating little cuts and rubbing the strep bacteria into them, Hall says. There would be "a slight response but not too much."
Then Coley got his hands on a much stronger strain of the bacteria. This time, Zola became violently ill with an infection that could easily have killed him. But within 24 hours, Zola's orange-sized tumor began to liquefy and disintegrate. "This was a phenomenon that occurred rarely, but when you saw it you were utterly astonished," Hall says.
Zola completely recovered. Coley knew he was on to something. He kept experimenting and refining his use of bacteria. Eventually, he named the treatment Coley's toxins.
It was an exciting time. Coley was having tremendous success and his efforts were celebrated in America and abroad. But Bradley Coley Jr., William Coley's grandson, says the American medical establishment at the time was skeptical. Nobody knew how Coley's toxins worked, or why they worked sometimes and not others. Not even Coley could explain it.
That's largely because the immune system was still a mystery and would remain so for decades to come.
Coley's Discovery Almost Disappeared
When radiation therapy came along in the early 1900s, interest in Coley's toxins was completely overshadowed by this new therapy. When his grandfather died, Bradley Coley says, "All interest in [Coley's toxins] stopped."
And quite possibly, that's where Coley's legacy would have ended except for this: After Coley's death in 1936, his daughter, Helen Coley Nauts, started looking through her father's papers while doing research for his biography. She found about 1,000 files of patients her father had treated with Coley's toxins.
She spent years carefully analyzing these cases and could see that he had extraordinary rates of success in regressing some cancerous tumors. She couldn't get anyone interested in studying her father's work, so she decided to do it herself. With a small grant, in 1953 Helen Coley Nauts started the Cancer Research Institute, dedicated to understanding the immune system and its relationship to cancer.
In the more than 60 years since, researchers have expanded their understanding of the immune system dramatically and today, that understanding is paying off. Treatments that harness the power of the immune system are now available for a range of cancers such as stomach, lung, leukemia, melanoma and kidney.
Jedd Wolchok, chief of the melanoma and immunotherapeutics service at Memorial Sloan Kettering Cancer Center, says any treatment currently in use that exploits the power of the immune system to fight cancer has to "tip its hat" to the work William Coley began more than 100 years ago.
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