Tonight... on Biography

I also recently plowed through Siddhartha Mukherjee’s “The Emperor of All Maladies: A Biography of Cancer”.

This is an imposing book. The text runs to 470 pages, and there are no less than 60 pages of back-notes. It’s quite a lengthy read.

On the other hand, the reviews I’d read were all effusively positive, calling it touchingly personal, citing its approachability, and even using the phrase “page-turner”.

I generally agree with that assessment. It’s very engaging and readable, deftly melding the author’s first-person experiences in his oncology residency with interesting stories of man’s early history with this disease. It goes on to add more depth to cancer’s more familiar recent narrative and solid insight into the current state of the art. Although the later chapters tend to rely a bit more on technical jargon, Mukherjee keeps things moving so that the reader doesn’t lose interest.

Part of the reason why he undertook this work was because as a neophyte oncologist, he was so buried in the tactical concerns of fighting the disease that he was unable to answer his patients’ more strategic-level questions about where we are in the overall battle and whether the increased attention of recent years has translated to improvements in prevention, treatment, and outcomes.

Throughout its long course, the book hits on most major forms of cancer—lung, breast, leukemia, Hodgkin’s Disease—and several obscure ones. For a time it follows the search for a single root cause, touching on carcinogenic chemicals like Asbestos and cigarette smoke as well as the cancers precipitated by viral infections like HPV.

But if I had to single out the primary theme of the book, however, it would have to be the hubris of physicians throughout the ages in misunderstanding and underestimating cancer, as well as overestimating their ability to cure it with a single, massive intervention.

In Rome, Claudius Galen attributed the disease to an overabundance of an unknown and unobserved liquid called “black bile”, setting our understanding of cancer on a wrong track for the following 1500 years.

Next up were the surgeons, whose simplistic answer to recurrent breast cancer was to cut deeper and deeper, until the standard preventative practice was to remove the entire breast, the lymph nodes, the muscles of the chest, the clavicle, several ribs, and part of the lung. Better to cut too much than too little, right?

As surgery began to give way to chemotherapy in the 1950s, the next group of oncologists fell for the same old “more is better” fallacy, prescribing massive doses of multiple drugs, eventually concluding that the best policy was to completely destroy the patient’s ability to generate new blood cells, then rebuild it by transplanting new stem cells (either one’s own, harvested before treatment, or transfused from a donor).

Even today, with the mapping of the human genome and gene therapy providing an historical breakthrough in cancer treatment, geneticists have once again fallen into the same mental trap as Galen did 2000 years ago, of thinking that this new technology would spell the end of cancer. Cancer is an incredibly deft, diverse, adaptive, and opportunistic disease, and its defeat is just not going to be that simple.

Despite all these unfortunate missteps, each generation of treatment has produced significant improvements in outcomes. Surgery, chemotherapy, radiation, gene therapy, targeted drugs, and combinations of these can each be the right treatment for the right patient.

And Mukherjee’s book does do a wonderful job depicting some of the fortuitous coincidences that led to the discovery of these new treatments. For example, who knew that a humble jar of Marmite was the key that unlocked the broad spectrum of chemotherapy drugs that have saved so many lives?

Aside from the knowledge that cancer was the result of uncontrolled growth, it wasn’t until the past twenty years that we actually began to understand exactly how and why cancer works at a cellular and genetic level. Before 1970, oncologists could only develop treatments by trial and error. But armed with our new understanding of what cancer is, researchers can now identify cancer’s specific biochemical vulnerabilities and start developing therapies such as Herceptin that precisely target those weaknesses.

In the end, the reader comes away from the book with a much better understanding of why cancer is so difficult to combat, and that each person’s instance of cancer is so unique that it requires an entirely individual treatment.

As a Pan-Mass Challenge rider, I was proud to discover how central Sidney Farber, the Dana-Farber Cancer Institute, and the Jimmy Fund have been. They take center stage in much of Mukherjee’s narrative, as does Mass General, MIT, and the American Cancer Society.

Before I picked up the book, I saw Dr. Mukherjee at an author talk he gave at the BPL. I took the opportunity to ask him whether the recent discovery that the human genome is not identical in every cell had any implications for gene therapy.

Between his response and my readings, it was clear that it isn’t the human genome that matters so much as the characteristic modifications cancer makes to it. By designing drugs that recognize and respond to the unique cancerous fingerprint of a particular genetic alteration, it is possible to starve tumors or at least deactivate their growth. The challenge right now is to catalog those fingerprints and discover drugs that match them.

It’s probably true that you need some curiosity about cancer or medicine to get through this book. But those with sufficient interest will find it informative, entertaining, and very readable.