It was in 1884 that a migrant house-painter in New York with a recurrent, aggressive cancer behind his ear — a four-inch ‘ugly, ominous bunch of grapes’ — underwent a fourth surgery to attempt to save his life, but the cancer was so large and invasive that the wound could not even be closed after the procedure. Left with an open crater in his neck and a virtual death sentence, the unfortunate man developed a raging skin infection that itself might have ended his life precipitously in those days before antibiotics. Instead, he survived the infection and a second one, and — to the astonishment of his surgeons — the cancerous ulcer healed and the malignancy disappeared.
This strange occurrence might have been relegated to some forgotten file of medical miracles had it not been noticed by a young surgeon devastated by the death several years later of one of his own patients with a similar cancer. Searching the “literature” of that time, William S Coley was struck by the juxtaposition of infection and cancer cure in the immigrant. He began a lifelong quest for a bacterial substance he believed would cure what was thought to be incurable. While he never learned that it wasn’t the organisms but the substances the body produced to fight them that had demolished the house-painter’s sarcoma, his work — and that of a phalanx of brilliant investigators since then — has pushed the boundaries of scientific knowledge of the human immune system to a level of complexity extraordinary enough to challenge even the most scientifically sophisticated. It is to his very great credit that Stephen S. Hall, in his book, A Commotion in the Blood — Life, Death, And The Immune System, has been able to construct a clear, engaging, carefully documented chronicle of the investigations and discoveries that have begun to delineate the science underpinning such miracles, and to do so even-handedly and with great empathy for the scientists, patients and doctors involved.
As recently as the early 1970s, standard medical texts contained almost nothing about Coley or others who utilized ingenuity and innovation to try to attack cancer immunologically in the face of a paucity of scientific information about the human immune system; those same texts contained little about the genetic or molecular biology of immunity. But the potential and the perils of delving into the body’s immune regulators to find those that could be stimulated to search out and destroy cancer exploded into international consciousness in 1975, when Fortune Magazine proclaimed a “Cancer Breakthrough” on its cover and reported that NIH scientist Dr Steven A Rosenberg’s work with two such immune substances had produced results “unheard of in cancer drugs.” (They were interleukin-2 and LAK cells; the former stimulates growth and development of one important group of the body’s infection-fighting cells, and was accidentally discovered during a search for a virus that might cause leukaemia; the latter are cells fished out of a pool of mouse lymphocytes that were found to kill cancer in the test tube).
In the last 20 years, new genetics corporations have emerged, sunk into bankruptcy, and been supplanted by others as first the promise, and later the profound problems, of using interleukin-2, tumour necrosis factor, interferon and other substances wrestled from the body’s immune armamentarium rocked the medical community and jolted research machines into high gear. Reputations and fortunes have been risked and sometimes lost in pursuit of a cure for cancer. Tantalizing fragments of the immune puzzle have been pieced together, and there have been impressive cures of some advanced melanomas, sarcomas and other cancers. But the financial costs have been mind-boggling, and an even more painful price has been paid in adverse effects of the immune modulators themselves on cancer patients — debilitation, long stays in intensive care units, sometimes death.
Stephen Hall, has scrupulously documented the gains and the price. He has searched the archives, interviewed scores of scientists, sat with people who have survived their cancers and talked with those who have subsequently died. He opens windows for readers into the laboratories where this highly exacting, tedious work is done and notes the fits and quirks of the sometimes haphazard process of discovery. He makes it possible to begin to grasp the order and timing of the immunologic discoveries of the last two decades and helps to make sense of what even medical professionals have found to be an overwhelming accumulation of information — and he does so with cleverness and patience and clarity. While the efficacy of immune regulators as cancer fighters remains problematic, impressive spin-offs have contributed substantially to human welfare. Substances have been identified and produced, such as the interferon used to treat hepatitis B and C and multiple sclerosis; erythropoietin (a stimulator of red blood cell development), which treats some previously untreatable anaemias; and stimulating factors that promote the growth of new white blood cells to help fight infection in people whose white blood cells have been destroyed. Stephen Hall’s book is fascinating and, in a sense, compelling.
On behalf of courageous people with cancer who have put their lives and well-being on the line to contribute to this research, and for physicians and scientists who have struggled to develop the technology to sustain their creative imaginings, the rest of us ought to read it and understand how difficult the task has been and how profound the challenges are that remain.