Coley’s toxins and the birth of cancer immunotherapy

[from the cutting-room floor…] (Image source: Wikipedia)

Elizabeth Dashiell walked into the Memorial Hospital in New York with what she thought was probably a minor – albeit annoying – complaint. A small, painful nodule had formed on the back of her hand after she had jammed it between two seats on a train a couple of months earlier. Her doctor, a young surgeon by the name of William Coley, was perplexed. The lump had all the signs of an infection, but investigations finally led Coley to conclude that Bessie had sarcoma, a type of cancer.

The year was 1890 – a time when cancer was an almost guaranteed death sentence. On November 8, just five weeks after he had first seen his 17-year-old patient, Coley amputated Bessie’s right hand and forearm in an attempt to save her life. But even amputation proved futile, and Bessie died two and a half months later, riddled with tumours that had sprouted throughout her body.

Coley, just 28 at the time, was devastated by his patient’s rapid demise and resolved to find a way of preventing similar deaths in the future. Trawling through hospital medical records for clues to a possible cure, he stumbled upon the case of a German immigrant named Stein. Surgeons had repeatedly attempted to remove Stein’s neck cancer without success – the tumour stubbornly regrew each time. Until, that is, Stein succumbed to a severe post-operative skin infection. On this occasion, his tumour had shrunk and disappeared, leaving Stein cancer-free.

Coley suspected he had discovered something important and began deliberately injecting his patients’ tumours with bacteria – first live, and then killed – hoping to replicate Stein’s mysterious cure. Over the ensuing years, Coley tinkered with his formulation to find just the right combination of bacterial strains to produce a robust fever and tumour remission. He went on to treat hundreds of people with his ‘Coley’s toxins’, effectively curing a quarter of his sarcoma patients – a remarkable achievement for the time.

“Even though his work started over 100 years ago, he was really quite advanced [for his time],” says Stephen Hoption Cann, an immunologist from the University of British Columbia in Canada and chief medical officer at MBVax Bioscience, a small biotech firm in Vancouver.

Coley had figured out how to harness the body’s natural defence system to combat cancer. After his death in 1936, Coley’s toxins fell out of use. Patients required multiple doses, often of increasing strength, so “treating patients was a little more involved,” says Hoption Cann. With Coley no longer available to provide advice on how best to modify the dosage for each patient, and other simpler therapies, like chemotherapy and radiation therapy gaining favour, the idea of utilising the immune system to treat cancer was largely forgotten.

Coley’s work has belatedly earned him a distinguished place in medical history. Many now regard him as the father of cancer immunology, a field that has attracted increasing attention over recent years and was last year singled out as the ‘Breakthrough of the Year’ by the prestigious journal Science. Hoption Cann and others have been picking up where Coley left off, investigating treatments that kick-start the immune system to fight cancer.

To read more about current cancer immunotherapies, check out my feature in Cosmos Magazine, Is immunotherapy a cancer game changer? [paywall]