The Emperor of All Maladies: A Biography of Cancer is 2010 book by Columbia University cancer physician and assistant professor of medicine Dr. Siddhartha Mukherjee. This book is a magesterial work summarizing the history of cancer research over the past 2000 years, focussing in particular on the last ~100-150 years. I had read the book a few years ago, and it is one of my favorite works of popular science. (It was one of the books on my Book Bucket Challenge list.)
Recently, however, I came across on Amazon Prime Video the 2015 documentary of this book produced by Ken Burns and directed by Barak Goodman. This overview, while of the documentary, will also simultaneously be a reasonable approximation to an overview of the book, since they go over a lot of similar ground. This three-part, six-hour(!) documentary is divided into three parts, which cover three chronological periods of cancer research, while also simultaneously exploring three phenomenologically different aspects of looking at the research.
Part I, called Magic Bullets, looks at the history of the research upto the 1970s, with the main focus being the treatment approaches of surgery, and early chemotherapy and radiation therapy. The surgical approach towards cancer treatment was spearheaded by Dr. William Halstead, who also pioneered the use of aseptic techniques for surgery. Halstead’s approach to treating breast cancer, based on the [incorrect] idea that cancer spread radially outwards from a single point of origin, involved performing radical mastectomies, excising larger and larger areas in an attempt to catch the entire spread of cancer. Dr. Sidney Farber pioneered the use of chemical treatments for cancer, with the use of aminopterin for treating childhood lukemia, making him one of the leading experts on cancer. Farber, along with the health activist and philanthropist Mary Lasker, also pushed for widespread public awareness for cancer, resulting in them raising substantial amounts of money from private individuals, and governmental sources, to push research and treatments for cancer. Dr. Emil Frei and Dr. Emil Freireich pioneered the use of combination drugs for chemotherapy, so as to be able to target cancer which might not be treatable by a single drug by itself. All of these approaches, while showing promise, and success in select types of cancers, hit a wall at a point, beause they were symptomatic treatments without any understanding of the root cause of cancer.
Part II, called The Blind Men and the Elephant, covers the research in last quarter of the 20th century, with is primary focus on chemotherapy, and the growing realization of the need to understand the root causes of cancer, including the mechanism through which it arises, as well as the need to understand what the causative factors behind cancer might be. There were three competing theories, a viral theory, an environmental theory, and a genetic theory, each of which had evidence going for them for specific types of cancer, but none of which resulted in a comprehensive theory which could explain all types and occurences of cancer. However, great progress was made in terms of identifying certain strong direct carcinogens like cigarettes. Drs. Michael Bishop and Harold Varmus discovered the first human oncogenes, genes which cause cancer1. Another major development around this time was the growing involvement of biotech and pharma companies, which had the resources for large scale clinical trials, resulting in the development of drugs like Herceptin and Gleevac, which were potent weapons in the war on cancer.
In part III, called Finding the Acchiles Heel, the focus is mainly on the research of the 21st century, till the time of the making of the documentary. This part tells the tale of the greater and more detailed understanding we now have of cancer, as well as the development of targeted therapies, and immunological therapies, which look like the most promising approaches to cancer, due to their specificity. The most major cost of all previous approaches to treatment was the damage in the form of the healthy cells, or tissues which were collateral in the attack of chemotherapy or raditation on the cancer. These new therapies offer a hope of precise targeting of cancer to prevent collateral damage. The completion of the Human Genome Project, which created the first map of the human genome, along with other large consortia like the Cancer Genome Atlas have led to vast strides in the understanding of the root causes of cancer. Another major change was the development of palliative care as a discipline, to let people for whom the cures were not viable options, choose their last days with dignity, should they choose to not undertake punshing treatment regimes in an attempt to try to treat their cancer.
Over the course of these six hours, the documentary runs takes a whirlwind tour through this history of cancer research bringing us up to speed with the current state of research of this disease. Aside from the few names I have mentioned above as some of the most important, the documentary talks about many many other researchers and clinicians who have made invaluable contributions to the understanding and treatment of this disease.
In addition to the great trove of historical information, there were three points regarding the narrative that are also worth noting:
The eternal conflicts of the researchers and doctors trying to balance new discovery with the patient cost of untested treatements comes into stark view. The dilemma of what the right course of action would be becomes almost a trolley problem in cases like the Gleevac and Herceptin trials, where patients demanded access these medicines before the clinical trials were completed. Is it right for a doctor to give a patient a medicine which has not been tested? Or is it right for a doctor to withold a possible (though untested) remedy from patients who would die without it? This issue comes squarely into view particularly in the context of the recent passage of the Right to Try Law in the US.
The whole movie intertwines the historical narrative of discovery with the very, very real human cost of both the disesase, as well as the treatments which were implemented without sufficient understanding of the disease. Stories of real people who faced, and many more who are still facing this scourge with indomitable courage, bring into sharp focus the real nature of this disease in the form of its very real human cost.
And the last point that is impossible to not notice, particularly in light of the current political and social landscape is the observation of the demographics of the researchers and clinicians featured in this documentary. As we progress through each part of the documentary, we see a progressive increase in the number of women and non-white scientists and doctors that feature. That diversity in the sciences has long been a problem, and is now showing signs of improvement becomes clearly obvious as we note the demographies of the people featured in this documentary as it progresses over the decades in the three parts.
All in all, this is a fascinating, engaging, and informative narrative, beautifully told. I would absolutely recommend both the book and the documentary to anyone who is interested in this subject.
An poingnant post-script is that the narrator of this documentary, Edward Hermann, was himself sufferring from terminal brain cancer at the time of its production, and this was to be his last project.
Personal note: I am currently a postdoctoral scholar at the University of California, San Francisco, where Bishop and Varmus discovered oncogenes, and where Bishop is still an Emeritus Faculty. ↩