Immunotherapy in the Twentieth Century: William Coley and Lloyd J. Old
Dr Clifford Pukel, a board certified medical oncologist and CEO of the Cancer Vaccine Cancer Immunotherapy (CVCI) foundation, discusses some important moments in the history of immunotherapy.
Five years after Dr Old passed he is now recognized as the founder of modern cancer immunology, with the joint American Association of Cancer Research (AACR)/CRI award in cancer immunology named after him. I believe future historians will find that his tremendous intellect and vision places him in the exalted company of men like Newton and Einstein.
The medical discipline of cancer immunology is, however, still in its discovery phase, and is struggling with an incomplete understanding of the fundamental laws (perhaps a code within a code) that guide the immune response to cancer. As a society we have long embraced the collective wisdom that people whose immune systems are healthy can better "fight" cancer, but until the last 20 years or so, there was little in the way of firm and compelling examples of achieving consistent results with cancer immunotherapy.
Now cancer immunotherapy has been rediscovered and with countless billions of dollars at stake (not to ignore the lives of millions); pharmaceutical companies are also spending a tremendous amount of money about the benefits of this "new" approach, and are taking out full page ads in major newspapers to promote its potential benefits. In a society that is already accused of narcissism, the ads encourage us to believe in the "the power of me" to treat a disease that like nearly everything else we believe in has become another example of every person's uniqueness and immeasurable value.
My own perspective as a medical oncologist who has signed the death certificates of too many patients who have failed the treatment I administered (and so I am a part of that failure), is to say: before we celebrate the next great thing in cancer treatment, that we pause and consider how modest our achievements are so far, and that more and more people die from cancer (if for no other reason than because there are more people living longer than ever). Until we accept a measure of scientific humility and plain ignorance as to what causes cancer and how the immune system (however imperfectly) controls cancer naturally, we will continue to be disappointed and frustrated by a lack of great progress in controlling this disease.
Dr Old, like Dr Coley, was too far ahead of everyone else and probably too modest, kind, and polite to be fully appreciated as a national treasure. Those of us who were lucky to be his students and disciples will continue to appreciate his sayings, including: "cancer is smart and the immune system is smart. They're both smart." So please keep in mind that, when we start to see another cycle of enthusiasm and excitement in cancer immunology followed by disappointment and pessimism, it is always the case that modern discoveries are just the beginning of a long story that will probably take another century or more to perfect, leading, ultimately, to the vaccination of our descendants against cancer, which we are already doing against virally-driven liver cancer caused by hepatitis B and cancers caused by human papillomavirus (HPV).8
Try to avoid being seduced by the hype, hope, and spin of Madison Avenue. My impression after 40 years of observation and study of cancer is that, as Dr Old said: "There is so marvelously much to do." But please allow me to also remind you that, as was so beautifully said by the philosopher Alfred North Whitehead: "Seek simplicity, but distrust it."
- Hall SS. A Commotion in the Blood: Life, Death, and the Immune System. New York: Henry Holt & Company; 1997.
- Levine DB. Anatomy of a Hospital: Hospital for Special Surgery 1863-2013. New York: Print Mattes, an imprint of Hospital for Special Surgery; 2013.
- Old LJ. Tumor necrosis factor. Scientific American. https://www.scientificamerican.com/article/tumor-necrosis-factor/. Published May 1998.
- Old LJ. Immunotherapy for cancer. Scientific American. https://www.scientificamerican.com/article/immunotherapy-for-cancer/. Published September 1, 1996.
- Grabstald H. Unproved methods of cancer treatment: Coley's mixed toxins. CA Cancer J Clin. 1965;15:139-40.
- Nauts HC, Swift WE, Coley BL. The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, M.D., reviewed in the light of modern research. Cancer Res. 1946;6:205-16.
- Karbach J, Neumann A, Brand K, et al. Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity. Clin Cancer Res. 2012;18(19):5449-59. doi: 10.1158/1078-0432.CCR-12-1116
- Goyal A, Murray JM. The impact of vaccination and antiviral therapy on hepatitis B and hepatitis D epidemiology. PLoS One. 2014;9(10):e110143. doi: 10.1371/journal.pone.0110143