Summary of Coley's Toxins and the Origins of Immunotherapy

Overview of Coley’s Toxins and the Origins of Immunotherapy

This episode of Stuff You Missed in History Class traces the early history of immunotherapy through the work of Dr. William B. Coley, a late-19th-century surgeon who experimented with using bacterial infections and bacterial toxins to treat cancer. The episode explains how observations that some tumors shrank after infection led Coley to develop “Coley’s toxins,” an early and controversial cancer treatment that helped lay groundwork for modern cancer immunotherapy.

Key Historical Background

What counts as immunotherapy?

• Immunotherapy broadly means treatments that modify the immune system.
• Depending on the definition, it can include:
  • Preventive vaccines
  • Therapeutic cancer treatments
  • Immune-suppressing treatments
• In modern usage, the term is most often associated with cancer therapy, where the immune system is activated to attack tumors.

Early observations before Coley

• In 19th-century Germany, doctors observed that some cancer patients’ tumors shrank after they developed erysipelas, a serious bacterial skin infection.
• Doctors including Friedrich Fehleisen and Wilhelm Busch documented these cases and tried intentionally reproducing the effect.
• Fehleisen later identified the bacterium as what is now known as Streptococcus pyogenes.

William B. Coley’s Path to the Discovery

Personal and professional background

• William B. Coley was born in Connecticut in 1862.
• He studied at Yale, then attended Harvard Medical School.
• He trained and worked as a surgeon in New York, including at what later became Memorial Sloan Kettering.

The death of Bessie Dashiell

• Coley treated Elizabeth “Bessie” Dashiell, a 17-year-old patient with a sarcoma.
• Despite amputation, the cancer spread and she died in 1891 at only 18.
• Her death deeply affected Coley and pushed him to search for better treatments.

Coley’s Toxins: How the Treatment Developed

Finding the clue

• While reviewing hospital records, Coley found cases where cancer tumors had shrunk after erysipelas infections.
• He tracked down one patient whose tumor had disappeared after such an infection and confirmed he was still alive years later.

The first experiments

• Coley tried to deliberately trigger erysipelas in cancer patients with inoperable sarcomas.
• The results were mixed:
  • Some patients did not respond.
  • Others showed dramatic tumor shrinkage or disappearance.
• He later concluded that the toxins produced by the bacteria, not just the infection itself, were likely responsible.

The mixed-toxin approach

• Coley began using killed bacterial cultures and filtered toxins rather than live infections.
• He combined toxins from:
  • Streptococcus erysipelas (now Streptococcus pyogenes)
  • Bacillus prodigiosus (now Serratia marcescens)
• Coley and collaborators, including Dr. Martha Tracy, worked to standardize the doses.

Results, Beliefs, and Controversy

Reported effects

• Coley documented cases where tumors:
  • Lost blood supply and became paler
  • Softened and shrank
  • In some cases disappeared entirely
• He treated around 1,000 patients over several decades and published about 150 papers.

Coley’s theory

• Coley believed cancers had a microbial origin, meaning some organism caused them.
• He thought the toxins helped restore the body’s lost resistance, allowing tumors to regress.
• This theory was incorrect, though parts of his work foreshadowed later immune-based cancer treatments.

Scientific criticism

• Many doctors were skeptical because:
  • The treatment was risky
  • Results were inconsistent
  • Some patients clearly did not improve
  • Replication attempts often failed
• The treatment was also overshadowed by newer technologies like:
  • X-rays in 1895
  • Radium in 1898
• Coley also had a contentious relationship with James Ewing, a major cancer researcher who favored radiation therapy.

Legacy and Modern Relevance

Influence on cancer immunology

• Even though Coley’s methods were not widely adopted, his work is now seen as an important precursor to modern cancer immunotherapy.
• The episode highlights later research by Lloyd J. Old and others showing that BCG could stimulate immune responses against tumors.
• That research eventually led to:
  • Discovery of tumor necrosis factor (TNF)
  • The use of BCG in treating certain bladder cancers
• BCG bladder therapy was approved by the FDA in 1990 and is still used today.

Why Coley’s toxins faded

• The treatment was hard to manufacture consistently
• It was difficult to standardize
• Regulatory changes increased oversight of biologic products
• Later FDA classification made it an investigational drug
• The American Cancer Society once listed it among unproven cancer therapies, which added stigma

Later reevaluation

• Coley’s daughter, Helen Coley-Knotts, spent decades studying his work and helped found the Cancer Research Institute in 1953.
• The Cancer Research Institute still honors his legacy with the Coley Award for work in tumor immunology.
• A limited modern trial in 2007 suggested the toxins could provoke fever and immune activity, but producing them remains difficult and newer therapies have largely surpassed them.

Main Takeaways

• Coley’s work was one of the earliest intentional uses of immunotherapy in cancer treatment.
• His approach showed that activating the immune system could sometimes shrink tumors, even though his explanation was wrong.
• His legacy lives on in the broader field of cancer immunology, including treatments like BCG for bladder cancer and newer immune-based therapies.
• The episode frames Coley as a pioneering but imperfect figure whose experiments helped open a major new direction in medicine.