“Immunotherapy” is a big buzz word right now when it comes to cancer research and treatment. This promising form of therapy harnesses the power of our own immune systems to fight cancer. Many researchers and physicians feel that soon, immunotherapy will become the 4th pillar in effective cancer treatment, along with chemotherapy, radiation, and surgery.
However, while the concept appears to be quite new, it has actually been years — over a century — in the making.
The idea behind modern immunotherapy started with Dr. William Coley, who practiced medicine in New York between 1890 and 1936. Coley was known for being an exceptional surgeon, but it was his study of non-surgical immunotherapy that ultimately earned him the unofficial title, the “Father of Immunotherapy.”
Bessie’s Cancer Inspires Dr. Coley to Find an Answer
In 1890, 28-year-old Coley was a brand new surgeon in New York City. He was introduced to Elizabeth “Bessie” Dashiell, a 17-year-old girl with a questionable, sore bump on her hand. Bessie had gotten her hand caught between the seats of a passenger train car, and when the pain continued for over a month, she made an appointment with Dr. Coley.
Bessie’s case seemed pretty cut-and-dry; she probably had a mild infection at the site of the injury and it would be easily treatable. Coley, however, discovered that instead of an infection, Bessie had cancer — a sarcoma (bone tumor) that was growing very aggressively, much like mesothelioma tends to do.
Today, we would expect someone with a sarcoma to undergo a few rounds of chemotherapy, or maybe radiation. But in 1890, experts felt that amputation of the limb was the best way to attack the cancer growth. Bessie’s arm was amputated below the elbow in November 1890, but the radical surgery did nothing to help the rapid spread of tumors. By January 1891, Bessie was dead.
Watching such a young girl die so quickly had a profound effect on Coley. He became determined to find an answer — anything that would help him understand cancer and how to treat it more effectively. He knew there had to be a better way to save lives.
Coley Finds a Link Between Infection and Cancer Remission
Following Bessie’s death, Coley jumped into research. He combed through countless medical records at New York Hospital and eventually came across an interesting case from 8 years earlier that caught his attention:
A German immigrant named Fred Stein had come to the hospital with a cancer very similar to Bessie’s, except the tumor was growing on his neck. Doctors treated Stein’s cancer with surgery, but his outcome was quite different from Bessie’s — he lived and went in to total remission. The disease was gone.
What made Stein’s case so different from Bessie’s? After surgery, Stein developed erysipelas, a serious bacterial skin infection that caused a high fever. These were the days before antibiotics, and Stein nearly died, but his immune system eventually kicked in and he beat the infection. Doctors soon learned, however, that in addition to eradicating the infection, Stein’s tumor had completely disappeared.
Because this medical marvel had taken place 8 years earlier, Coley wanted to know if Stein had remained cancer-free. He knocked on every door in Manhattan’s Germany immigrant community until he found what he was looking for: Fred Stein, alive, without any signs of cancer.
Coley knew that he was on to something and that possibly, the infection had been the cause of the tumor’s regression. He focused his research on this concept and ultimately found approximately 47 cases that documented the beneficial effect of infections on tumors. For example, in 1725, Diedier noted that patients with syphilis developed very few malignant tumors. And in 1867, Busch, a German physician, found that when one of his patient’s developed erysipelas, a malignant tumor disappeared. In fact, many successful cases, Coley found, involved erysipelas in some way.
After meeting Stein and conducting thorough research, Coley knew what he needed to do next: Purposely infect a cancer patient with erysipelas.
Coley’s Experiments with “Toxin” Therapy
Coley’s first subject in 1891 was Zola, an Italian immigrant who had sarcoma and was incredibly sick. It was a struggle for Zola to simply eat, speak, or even breathe due to the tumors lining his throat.
In the beginning, Coley created small cuts on Zola’s body and then rubbed strep bacteria into them. When it became clear that approach was not working, Coley found a stronger strain of the bacteria that did its job — it gave Zola a horrible, life-threatening infection.
And this horrible, life-threatening infection? It saved his life.
Over the course of 24 hours, the large tumor on Zola’s neck began to disintegrate before Coley’s eyes. He made a complete recovery, left the hospital, and went on to live 26 more years before he died from a heart attack.
This success encouraged Coley to keep going with his research. Next, he treated 2 patients with long-bone sarcomas. There was some observable shrinkage of their tumors, but the dangerous infections took their lives. Because of this, he created what came to be known as Coley’s Toxin — a heat-killed streptococcal organism combined with a second organism called Serratia marcescens that would hopefully be less lethal when injected in patients.
Coley’s Toxin went on to save many lives. In 1899, Parke Davis & Company began to prepare Coley’s mixed bacterial toxins and they were widely used by physicians for the next 30 years. By the end of his career, Coley had treated almost 1,000 patients and written 150 papers on his findings.
Technology and Skepticism Overshadow Coley’s Accomplishments
While it would seem like the concept of immunotherapy would continue to improve and grow once Coley’s Toxin went mainstream, the opposite happened.
At the same time Coley was studying the effects of infection on cancerous tumors, a German physics professor, Wilhelm Conrad Roentgen, was inventing X-rays and radiation therapy. When it became known that radiation therapy could cure cancer, many people turned their focus toward radiation and away from Coley’s Toxin. Even Coley’s boss, famous cancer pathologist James Ewing, was a huge supporter of radiation therapy and refused to let Coley use his toxins at Memorial Hospital.
Ewing wasn’t the only skeptic when it came to Coley’s Toxin. Some researchers and physicians felt that his work was inconsistent. They pointed to poor patient follow-up, 13 different preparations of the toxins, and various methods of administration (intravenously, intramuscularly, directly into the tumor). Scientists like solid documentation, consistent methods, and flawless follow-up — none of which they felt Coley provided. Coley wasn’t even sure why his toxins worked, but he just knew that they did.
Coley’s Daughter Continues His Work
Coley died in 1936, and a couple years later, daughter Helen Coley Nauts, wanted to start researching and writing his biography. She had no idea that her father had developed an effective treatment for cancer, but it soon became very apparent as she went through his files. She studied his work for years and felt that while his methods had been inconsistent, it was clear that there was something there — something very important.
She struggled to convince researchers to study her father’s work, and eventually took matters into her own hands when she founded the New York City-based Cancer Research Institute (CRI) in 1953. Her goal was to raise money to fund research into the immune system and cancer.
Nauts’ hard work paid off and according to the CRI, she “rekindled the medical community’s interest in exploring the link between cancer and the immune system.” During the first 20 years of the CRI, the science of cancer immunology went into overdrive. She recruited some of the nation’s best, including prominent cancer immunologist Dr. Lloyd J. Old. Her commitment to the field of immunotherapy played a major role in the modern immunology science that we know today.
Immunotherapy today is much different than when Coley first began his work, but the idea is the same: harnessing the body’s immune system to fight cancer. Coley knew that it was possible to help to coax the human body in to attacking cancer, and the past decades of research and growth have proven that theory to be true.