Training The Immune System To Fight Cancer Has 19th-Century Roots

Dec 28, 2015
Originally published on December 28, 2015 7:22 pm

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. 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.

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.

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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STEVE INSKEEP, HOST:

An idea for cancer treatment that helped Jimmy Carter is older than he is. The former president is 91. He announced recently that his advanced melanoma had been successfully treated. He credited an immunotherapy drug which does not directly kill cancer cells, instead boosting the patient's immune system to do the job. It is cutting-edge cancer treatment, although the idea behind it dates back more than a century. NPR's Rebecca Davis reports.

REBECCA DAVIS, BYLINE: In the late summer of 1890, surgeon William Coley prepared to examine a new patient. What he didn't know at the time was this young woman would change his life and the future of cancer research.

DAVID B. LEVINE: Her name was Elizabeth Dashiell, known as Bessie Dashiell.

DAVIS: Dr. David B. Levine is director of archives at the Hospital for Special Surgery in New York. He says 17-year-old Bessie had injured her hand. It seemed like a simple bump, but it kept getting worse and worse.

LEVINE: She had a lot of pain and nobody could diagnose what the problem was.

DAVIS: At first Dr. Coley thought Bessie must have an infection. But when he took a biopsy...

LEVINE: It turned out to be this cancer - a very malignant cancer, very advanced cancer.

DAVIS: A kind of cancer called sarcoma. Stephen Hall, author of "A Commotion In The Blood," says there wasn't very much Dr. Coley could do for Bessie.

STEPHEN HALL: You have to remember this is prior to radiation therapy, prior to chemotherapy. And he didn't typically treat cancer patients. He was a general surgeon.

DAVIS: So Dr. Coley did the only thing he could. He amputated.

HALL: Right arm just below the elbow.

DAVIS: Hoping, says David Levine, to stop the spread of the cancer.

LEVINE: Within a month, she had widespread metastasis of her cancer to her lungs, her liver and all over her body.

DAVIS: There was nothing to do but wait for the end. When the time came, Dr. Coley stayed by Bessie's side.

LEVINE: On Jan. 23, 1891, she died.

DAVIS: It was an ugly death and a painful one. Stephen Hall says it made a huge impression on Coley.

HALL: He's still a young surgeon. He's in his 20s. He sees this seemingly healthy young woman come in, and within the course of several months, her body is completely overtaken by this malignant disease. It really shocked him.

DAVIS: And it spurred him into action. There wasn't a lot known about cancer at the time, so Coley started digging through dozens upon dozens of old hospital records, looking for something that would help him understand this cruel and aggressive disease. Stephen Hall.

HALL: As a student, he had read Darwin. And one of the lessons he took away from Darwin was always pay attention to exceptions to the rule. When there's a biological exception to a rule, ask yourself why this has happened.

DAVIS: Coley discovered one of these biological exceptions. It was the case of a German immigrant named Fred Stein. Stein had been a cancer patient at the hospital eight years earlier. Doctors had removed a cancerous growth - a sarcoma - from his neck. But the tumor kept coming back. And then Stein contracted a serious bacterial infection of the skin. David Levine says his days were numbered.

LEVINE: Only Stein didn't die. His infection subsided. And along with that, his mass, which was large, disappeared. And he was discharged from New York Hospital.

DAVIS: Coley wondered if all these years later Stein could still be alive. It was the winter of 1891 when William Coley the surgeon became William Coley the detective. He headed for the tenements of the Lower East Side of Manhattan, knocking on door after door, asking for a man named Fred Stein with a distinctive scar across his neck. After several weeks of searching, Coley found him alive and cancer-free. But why? Why did Fred Stein's cancer go away and stay away after getting a bacterial infection?

LEVINE: Coley speculated that the strep infection could reverse cancer.

DAVIS: And if that were the case then what would happen if he tried to reproduce that effect on purpose, if he deliberately injected cancer patients with a bacteria? Coley decided to test his idea on the most seriously ill patients. He started with an Italian immigrant named Zola, a man who had, just like Bessie Dashiell, was suffering from sarcoma with life-threatening tumors riddling his throat. Coley armed himself with a good supply of the strep bacteria and his experiment began. Stephen Hall.

HALL: This process went on for months. You know, he would create little cuts and rub the bacteria in it. And there'd be a slight response but not really too much.

DAVIS: And then Coley got his hands on a much stronger strain of the bacteria. And this time, Zola got violently ill. The infection could easily have killed him.

HALL: But Coley then describes this tumor - in this case I think they described it as the size of an orange - almost within 24 hours beginning to decrease in size, sort of liquefy and kind of disintegrate. This was the phenomenon that seemed to occur very rarely, but nonetheless, when you saw it you were utterly astonished.

DAVIS: Zola completely recovered. And Coley knew he was onto 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 he was celebrated in America and abroad. But Bradley Coley Jr., William Coley's grandson, says the American medical establishment at the time was skeptical.

BRADLEY COLEY JR: It was a hard sell, especially when nobody knew how it worked, including my grandfather, by the way.

DAVIS: Because the immune system was still a mystery and the results couldn't be replicated with any consistency. Then, in the early 1900s, along came radiation. And this would be the treatment medicine embraced. William Coley remained committed to his toxins, but they were largely overshadowed.

COLEY: When he died, all interest in it stopped.

DAVIS: And quite possibly, that's where Coley's legacy could have ended, except for this - after his death in 1936, his daughter, Helen Coley Nauts, started looking through hundreds and hundreds of her father's cases. And she found he had had some extraordinary rates of success using Coley's toxins to make certain cancers go away. But she couldn't get anyone interested in studying her father's work, so she decided to do it herself. In 1953, with a modest grant, she started up the Cancer Research Institute, an organization that helped create a whole new field dedicated to understanding the immune system and its relationship to cancer, a dedication that has been key in making immunotherapy the promising treatment it is today. Rebecca Davis, NPR News. Transcript provided by NPR, Copyright NPR.