The Emperor of All Maladies: A Biography of Cancer
Siddhartha Mukherjee, a young oncologist and cancer researcher, has managed the seemingly impossible. He has produced a monumental literary work, written in his off-hours over a six year period that started in the summer of 2004, while at the same time working, both clinically and in the laboratory, as an assistant professor of medicine at Columbia University and as a staff physician at that university’s medical center. The mixture of scientific inquiry with medical practice reflects what he tells us when he says “clinical medicine moves me viscerally. But I am a lab rat… drawn to the basic biology of cancer.” He is, of course, even more than that. He is a former Rhodes Scholar whose literary education shines through with an erudition that makes the book a delight to read. Without the touches of literary allusion and the personalized narratives that tell the stories of individual patients, doctors and researchers, the average reader (though an intelligent one who should have a proclivity toward serious reading) would most likely grow impatient with Mukherjee’s lucid but intricate explanations of cancer science.
From this, it should be apparent that The Emperor of All Maladies can be read at different levels. It has a great deal of science in it, tracing the ebb and flow of cancer research and therapy in their many permutations over several centuries, with special emphasis on the cellular science that has come on so strongly in recent years. This means it is well suited for biologists and medical students at all levels – undergraduate, graduate and post-graduate – as a vastly informative overview of their fields of professional interest. At the same time, the book has a more general appeal: “the book is written,” Mukherjee tells us, “entirely for a layperson to understand.” It should be noted, though, that he adds that “I wanted to treat this audience with the utmost seriousness.” This places a certain expectation on readers, who owe him the same seriousness he gives them. It would be fatuous to recommend the book to those who read only for light entertainment.
Perhaps it is more accurate to call this a biography of cancer research and therapy than of cancer itself. It is impossible to tell the story of the science, however, without inevitably revealing the enormous suffering and mortality from the disease. Thus, the nearly 600 pages convey a mixture of tragedy and exaltation. The tragedy is always there, and is heightened when we find that some of the therapies themselves have been horribly disfiguring or have been calculated to take the patient to the brink of death before bringing him back. One of these was the “radical mastectomy” that started in 1891 and ended in 1981 (when it was found to have no benefit over much more humane alternatives), long prevailing as the conventional wisdom among surgeons, for whom, as Mukherjee says, it “fossilized into dogma.” It was a “procedure in which surgeons removed the breast, the pectoral muscles, the axillary modes, the chest wall, and occasionally the ribs, parts of the sternum, the clavicle, and the lymph nodes inside the chest.” The thinking was that breast cancer spreads (“metastasizes”) from the breast directly to the adjacent organs, and that those organs should be removed to increase the chance of defeating or preventing metastasis. As with so many “wrong turns” during the centuries of cancer research, this was shown to be faulty. It became known that the spread could just as well be to distant organs. We look back with pathos when we think of the many people who, desperately clinging to any chance for extended life, eagerly sought the surgery.
A reader can hardly become so preoccupied with the tragedy, however, that he fails to see the exaltation. In his Prologue, Mukharjee says the book will be an account of “inventiveness, resilience, and perseverance.” He speaks of “an incandescent century of biological discovery – spanning from Mendel’s discovery of genes in 1860 to Monod’s identification of the RNA copy of genes in the late 1950s.” Then “the cloning of ras and retinoblastoma – oncogene and anti-oncogene – was a transformative moment in cancer genetics. In the decade between 1983 and 1993, a horde of other oncogenes and anti-oncogenes (tumor suppressor genes) were swiftly identified….” But even these passages are insufficient to reveal more than a fragment of the tapestry of on-going scientific research and therapeutic refinement that has long been carried on by thousands of brilliant minds, sometimes working alone and sometimes in large-scale institutional collaboration with others. This, along with the work being done in physics, chemistry, electronics, robotics and an array of other areas, marks what is arguably the proudest achievement of the human race. Those of us who are more ordinary and who take life as it appears in our everyday experience can hardly fathom a mental world that reaches so far into the unseen. The nano world of the most minute particles of life and of physical existence, the macrocosmic inspection of spiral nebulae, and the exploitation of the invisible world of rays, waves and particles of all kinds that permeate the space within and around us – each of these and more show how far the human intellect has taken us beyond the mundane.
Readers find out a great deal about cancer from the book, but are necessarily left with an awareness that there is much remaining to be understood. We are told that cancer is not just one disease, but many, all of which “share a fundamental feature: the abnormal growth of cells.” It is surprising to find that it starts from a single cell (out of the ten trillion in the human body, or out of the 300 billion-plus blood cells created by the human body every day), and that with most cancers there is not just one cellular mutation, but a piling of one upon another. Most recently, it has been found that “cancer-inducing signals move through cells,” so that cancer “is really a pathway disease.”
The science has many features. Mukherjee recounts a process that reminds us of the alpine rivulets that come flowing down to form larger streams in the pristine mountain country near Vail, Colorado. “Science is often described as an iterative and cumulative process, a puzzle solved piece by piece, with each piece contributing a few hazy pixels of a much larger picture,” but sometimes taking a major leap forward when “a truly powerful new theory” causes “an entire field of observations… to crystallize into a perfect whole.” The new theories, in a process of “creative destruction,” often strew the path with “shattered theories.” A reader may be surprised to find how vast the effort has been to discover therapies through trial and error (now aided enormously by computers): thousands of plants and animals have been experimented upon. These have included, among many others, sea urchins, pea plants, fruit flies, slime mold, red-eyed flies, chickens, the ubiquitous mice of laboratory fame – and even human organ samples. Nevertheless, as an indication of what remains to be done, “thousands of chemicals proposed as carcinogens remain untested.” Randomized trials were devised in the 1940s; physics and probability theories are used to create computer models; meta-analysis brings together the findings from assorted trials; longitudinal studies track outcomes over extended periods of time; and new technologies are developed to allow the investigation to press into areas previously inaccessible. The mapping of the human genome has extended into the mapping of the cancer genome, and beyond that is reaching into formulating a “full catalog of mutations” for particular types of cancer, such as in 2009 for “ovarian cancer, pancreatic cancer, melanoma, lung cancer, and several forms of leukemia.” Despite all this, Mukherjee remains aware that science has still not arrived at a full understanding of the causal mechanisms at work.
We could call it a “side effect” of Mukherjee’s narrative that it uncovers, for those who are interested in noticing it, a “sociology” of cancer (or, more broadly, of any scientific) research. We are reminded again and again of how any such enterprise is a human endeavor, conducted by people, and thus subject to all of the strengths and weaknesses, brilliance, foibles and venality, that mark any human effort. It is relevant that when Mukherjee wrote of “inventiveness, resilience, and perseverance,” as we quoted above, he went on to speak, too, of “hubris, arrogance, paternalism, misperception, false hope, and hype.”
Here are examples of the human interplay – the “sociology,” so to speak: There is self-sacrifice, as when in 1984 the researcher Barry Marshall deliberately swallowed a “turbid bacterial culture” full of toxic bacteria, became “violently ill, with nausea, vomiting, night sweats, and chills,” and after recovering submitted a paper for publication demonstrating that the type of bacteria he had swallowed was “indisputably the cause of gastric inflammation.” Great strides have been taken in the research by “outcasts from their fields,” while at the same time “there is hardly a cancer center in which there are not collaborative groups.” There is serendipity, with the accidental discovery of cancer-fighting chemicals, as when German planes blew up an American ship in 1943 “stockpiled with seventy tons of mustard gas stowed away for possible use,” with the ensuing disaster leading to an awareness that mustard gas had “the capacity to decimate white blood cells” and thus was useful in fighting cancers of the lymph glands. We see the power of money, as when “the tobacco industry uses its wealth to influence politicians to create a favorable environment to promote smoking.” There is, too, the importance of profit and loss, as when Genentech’s management decided to “focus on simpler and more profitable drugs” in preference to jeopardizing the company’s finances by pouring money into research of a certain protein drug that was promising but much more problematical. In recent years, there has been the power of activist lobbies, which we have seen in the “AIDs activism” that has pressed for speeding drugs into use, bypassing the usual lengthy experimental phase. There have been “rivalries for power and information,” which find expression in the burying of competing theories and therapies, the ignoring of disfavored hypotheses, sharp competition treating research as a race between contenders, and a desire for exclusivity such as when the OncoMouse in 1988 became “the first animal patented in history.” Necessarily in so complex an effort, there have been intellectual divides, leading to “interminable institutional scuffles” and “bitterly opposed camps.”
A subject worth studying (and that no doubt has been the subject of much interest) is the role of “medical culture.” It is significant that Mukherjee tells us that when radical mastectomy fell from favor, “an entire culture of surgery collapsed with it.” People and organizational structures come to identify with certain ways of thinking or of doing things, and cling to them as a belief-system and way of life. More broadly, there are differences in culture in general: Mukherjee speaks of how a “cure-obsessed America” saw a slower development of palliative care, as exemplified by the creation of hospices, than in Europe, where beginning in the late 1940s there was a “movement to restore sanity and sanctity to the end-of-life care of cancer patients.” Similarly, there have been evolving notions regarding such things as human experimentation and the need for consent from patients. The book recounts how in the 1940s “consent to run a clinical trial for a drug… was not typically required.” Even when the trial was conducted on children, “parents were [only] occasionally cursorily informed” and the “children were almost never informed or consulted.” Ideology can play a part: we see this when in the 1970s, “political feminism was birthing medical feminism.” A result was some women’s “refusing to submit to radical mastectomy.” (This was before that kind of surgery was shown not to have the benefit it was thought to have.) It can’t be surprising, then, that “political correctness” [i.e., the dominant opinion-creating culture’s insistence on conformity to prescribed thoughts and speech] comes into play. Thus, AIDs (the acronym for “acquired immune deficiency syndrome”) was originally called GRID (for “gay-related immune disease”). Even Mukherjee himself succumbs to political correctness at a few points in the narrative, distorting his otherwise great good sense.
There is, of course, much more that can be pointed to in such a sociological review. It would be worthwhile to mention the importance of new technologies, each allowing science to peer deeper than it has before; how researchers today are “standing on the shoulders” of generations of minds that have preceded them; and how important it has been to mobilize resources through public campaigns and political support. But we must end the list somewhere. Mukherjee focuses on the science and therapies, but readers of a less scientific bent may find the sociological factors one of the more fascinating aspects of the book.
Dwight D. Murphey