Knowing nothing of this 2010 book when I picked it up (other than bells rung by its evocative title, likely from my hearing earlier this year about its recent adaptation into a documentary film), I didn’t expect author Siddhartha Mukherjee to frame his “Biography of Cancer” with a first-person recollection of his residency among the oncologists at Harvard Medical School in the first years of the twenty-first century — exactly when I too worked there, a bioinformatics programmer helping cell biologists work towards broadly similar cancer-eradication goals.
At the start of my read, I took this as amusing coincidence. By the end, after Mukherjee had wound through millennia of human medicine’s evolving knowledge about cancer, landing at the present day’s genetically driven experiments and targeted therapies, I couldn’t avoid feeling some disappointment at my past self for walking away from this world, ten years ago. With a stubbornness born of immaturity, I had treated the scientists’ talk of knockout genes and kinase inhibitors with incuriosity, even boredom. Feeling no interest in my work making web applications that displayed the results of these researchers’ experiments — provided to me as large, context-free comma-seprated-value files — I left to go work on video games instead.
While I hardly regret the person I became as a result, I can’t shake the feeling that I made an ill-informed decision just the same. The last sections of this book described the years of scientific breakthroughs immediately preceding the work I had, in a very small way, contributed to, giving me a clear and fascinating backgrounder I never had at the time. Reading it today makes a part of me want to travel back in time, shake my younger self by the lapels, and insist he at least try talking to the scientists, maybe? But, no, he would have been more into the video games even then, I’m sure. And so here we are.
The book’s summary of oncology’s state of the art comes after hundreds of pages describing all that came before, and as a reader I very much felt the vast stretches of time this story straddles. It took me a solid four weeks to work all the way through. Emperor carries the weight of a whole series of books, each focusing on a different era of cancer therapy, though rather like a game of Civilization the number of years that each spans shrinks on a logarithmic scale.
The story opens with the uncertainty of antiquity, beginning with the writings of the ancient Egyptian physician Imhotep, then reaching down past Galen’s black-bile theories and into the early modern period where microscope-weilding physicians first realize that all cancers, from solid tumors to liquid leukemias, involve runaway cell division. Then we read about the surgical revolutions that began in the late nineteenth century, epitomized by the radical mastectomy. Its practitioners named it “radical” not because of its extreme nature but because it saw cancer as something like an invasive plant — one it attempted to pull it out by the root (radix, in latin). Even if that meant tearing away not just the patient’s breast but the muscles beneath it, the lymph nodes nearby, and the skeletal structures that supported them all.
In hindsight, we know that these surgeries’ permanently disfiguring, debilitating effects needn’t have happened. The operations’ occasional successes matched those times when the cancer had been detected early, before it had metastasized — therefore removing any possible benefit from cutting away all that additional, perfectly healthy tissue. However, Mukherjee marks this time as a pivotal shift in humanity’s relationship with cancer: the first time medicine started to see cancer as fallible, something it could defeat, even it it required horribly extreme measures. This new attitude would allow the next century’s obsession with eliminating cancer to unfold.
From there, we travel with Sidney Farber and Mary Lasker through the cancer-driven clinical and political developments, respectively, of the middle twentieth century. The era containing Nixon’s “war on cancer” and the ultimately false hope that a single therapy might apply to all types of cancer, these years also saw the development of chemotherapy, and the decades of terrifying and often tragic medical trials that subjected patients to as much chemical poison, deadly radiation, and other tortures and depravations as they tolerate in order to destroy their cancers without killing them outright.
The Emperor of All Maladies does not flinch in recalling chemotherapy’s origins at Boston’s Children’s Hospital, how Farber’s first trial subjects were little children with leukemia, all admitted to the hospital with the expectation that they’d die quickly, as they always had. For the most part, they continued to do just that so despite Farber’s treatments — but often enough, the kids’ cancers would recede into remission, an astounding and unprecedented reaction to any kind of non-surgical therapy. The cancer would inevitably come roaring back with swiftly fatal fury within weeks, but even this brief delay proved enough to define a new course of therapudic research for decades, setting the stage for countless trials of various cytotoxic cocktails against equally various cancers. Surgical intervention continued along its own path, but sometimes research paired the bludgeon of chemotherapy with surgery’s scalpel, seeking ways to cut out the cancer without tearing the whole body asunder as in years past.
Beyond the fact of my own fleeting and tangential involvement with the science, I found Emperor most interesting to read when it arrives at oncology’s dawning realizations of the late 1980s. At long last, we begin to realize that cancer appears in the body not due to any invasive force, as long assumed, but due to cells simply doing their jobs, reading the instructions encoded within their genes — after those instructions have been subject to severely unlucky genetic misprints. Every cell capable of dividing is just a few highly specific mutations away from becoming or begetting a cancer cell, ready to follow its “go ahead and divide” instruction as soon as it can, without the “stop dividing” or “shut down and die” instructions that a healthy cell would have available to check it.
External actors, such as inflammatory carcinogens or gene-damaging radiation, can sharply tip the balance, but the fact remains that cancer ultimately comes from within. It struck me as a natural extension of Age is hiding in our bodies, the many-meaninged epigraph of Spring Chicken. So, too, does cancer hide within us, a coiled potential in every cell whose chance of exploding out only becomes greater as we age, our blown die-rolls accumulating along a frustratingly predictable probability-curve.
Despite this startling reality, it is only this latter part of the book — describing the science performed by Mukherjee’s own, current generation of oncology researchers and clinicians — that begins to cast something like real hope over the landscape of cancer medicine, after so many chapters recounting more than a hundred years of false leads and broken dreams within the science and those who helped fund it. It comes after the book’s fourth major section, describing the most subtle anti-cancer efforts of the 20th century, those of not of scarring, poisonous treatment but of screening and prevention (and, inevitably, the tobacco industry that got in the way of so much of it). With the clarity of genetic research, and the population-scaled controls offered by preventative practices, surgery and chemotherapy begin seeming less like scorched-earth weapons against a completely inscrutable foe, and more like something we can actually start aiming, for once.
It’s not like we’ve got cancer nailed, but at least we’re pretty sure that we’re looking in the right place for it. For the first time, those living with certain cancers can live out their lives keeping their cells’ bad behavior at bay via a daily pill. We don’t know how to repair genetically defective cells, but we can in some cases gently, continuously correct their messed-up marching orders. Mukherjee foresees a near future that never quite eradicates cancer, but which, with humans’ ever-increasing confidence in their own bioinformatics, shrinks it from a ubiquitous and terrible life-ender to a common nuisance, manageable for each patient through a personalized regimen defined by their particular genome.
The book takes a more confident tonal shift as soon as it enters this modern era of targeted, gene-aware therapy. I imagine this stems from the author, a twenty-first-century cancer scientist, speaking from firsthand knowledge rather than purely historical research. History still plays a major role in this facet of cancer’s biography, though, as the seeds of the disease’s genetic study came from a nineteenth-century case study of a Brazilian family who appeared to pass a very rare form of retinal cancer down through its generations. An utter mystery at first, this case remained in the background of medical research as knowledge of genetic mechanics slowly unfurled through the proceeding decades, and it would directly influence scientific breakthroughs a full century later. I would have loved to read a book focusing only on the science that this unlucky family unwittingly fueled! (I haven’t read it, but I am aware that The Immortal Life of Henrietta Lacks exists, and takes a very similar and much-celebrated tack. The library put both that book and Emperor on its late-summer suggested-reading shelf, side-by-side, and I chose what I chose. I won’t blame the book for delivering the sweeping history that it promised.)
I would have also liked to learn more about the ethical politics, often left unstated or implied, around the whole notion of clinical trials regarding terminal illnesses. I get the impression that the medical histories that Mukherjee worked from simply didn’t consider the patient’s point of view, for the most part. He does acknowledge this in a roundabout way by describing how the AIDS crisis of the early-to-mid 1980s created a new political movement comprising protestor-patients, fighting for the right of the terminally ill to submit themselves to medical trials that offer any hope at all of therapy in the face of otherwise certain death. This had an effect in other areas of medicine, including research of cancer drugs. But even as the medical establishment became more sympathetic to this movement, the need to adhere to the scientific method still created tension: one can’t properly prove a treatment’s efficacy simply by hitting every patient with everything one has. There must be control groups, and that often calls for a random selection of patients to receive placebos rather than the drug under study. How do doctors participating in trials feel, administering bogus no-op drugs to desperate patients, even if they know it makes for better science? How aware of all this are the patients themselves? I’d read a book on that, too.