Siddhartha Mukherjee


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Annotated by:
Miksanek, Tony

Primary Category: Literature / Nonfiction

Genre: Essay

Summary:

This thoughtful essay from the author of The Emperor of All Maladies expounds on information, uncertainty, and imperfection in the medical setting. The author recalls witnessing a difficult operation when he was a medical student. The attending surgeon admonished the operating room team, "Medicine asks you to make perfect decisions with imperfect information" (p.5). This essay is constructed around that idea as the author shares three personal principles that have guided him throughout his medical career.
     Law One: A strong intuition is much more powerful than a weak test. (p. 22)
     Law Two: "Normals" teach us rules; "outliers" teach us laws. (p. 38)
     Law Three: For every perfect medical experiment, there is a perfect human bias. (p.54)

He views the medical world as a "lawless, uncertain" place and stresses that biomedicine is a "softer science" than chemistry or physics. Clinical wisdom, in his opinion, is imperfect, fluid, and abstract whereas the knowledge base of other basic sciences is concrete, fixed, and certain. He laments, "My medical education had taught me plenty of facts, but little about the spaces that live between facts" (p. 6).

His own "laws" of medicine are actually laws of imperfection. Clinical diagnosis can be thought of as a "probability game" where human bias creeps into the process. And ultimately common sense trumps pure statistical reasoning. Woven into the discussion are considerations on a variety of topics - children with autism, Heisenberg's uncertainty principle, genomics, radical masectomy, and randomized, double-blind studies. Nods to Lewis Thomas (The Lives of a Cell: Notes of a Biology Watcher), Thomas Bayes (Bayes' Theorem), and Johannes Kepler (Kepler's Laws of planetary motion) fit in nicely with the thrust of the treatise.


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Primary Category: Literature / Nonfiction

Genre: Treatise

Summary:

This is a huge and wonderful book about cancer, the collection of diseases that sickens people all over the globe and kills many of them. An epigraph to the book states, “A quarter of all American deaths, and about 15 percent of all deaths worldwide, will be attributed to cancer,” but the book also describes medical advances that now heal, prevent, or palliate most forms of cancer.

Mukherjee, a cancer physician and researcher, has several strong themes. He sees cancer as an affliction with a long history, a story worthy of a biography; indeed recent discoveries show it to be rooted in our genes (although external factors such as viruses, asbestos, and tobacco smoke can cause genetic disruption). The story of cancer implies a surrounding triangle, the stories of sick people, treating physicians, and biological researchers, all of which Mukherjee artfully weaves across 472 pages. Cancer has Rohrschach blot qualities: depending on time, place, and role in life, humans have perceived different attributes of cancer. As the book ends, however, there is a coalescence of scientific understanding that is satisfying—although there is certainly more to be learned and we are all still vulnerable to genetic errors and, of course, we are intractably mortal.

Another strand is the nature of stories themselves, their twists and turns, presumed early solutions, and personal and social values embedded in them. Mukherjee threads throughout the book the case of a contemporary kindergarten teacher, Carla Reed, who has a leukemia. He bookends his text with ancient Persian Queen Atossa with (presumably) breast cancer. Reed, healed by the end of the book, was Mukherjee’s patient; Atossa was described by Herodotus: both suffered emotional turmoil because of their disease.  Mukherjee understands the affective dimensions of disease for patients and caregivers alike; literature represents these in various ways, and he quotes in his chapter epigraphs and in his prose many writers who describe human experience deeply: Aleksandr Solzhenitsyn, Susan Sontag, Charles Dickens, Thomas Mann, William Carlos Williams, Carlo Levi, and Italo Calvino, to name a few.

The primary story, however, is the interplay of cancer and a large cast of observers, investigators, doctors, scientists, activists, and government officials. Sidney Farber and Mary Lasker dominate the first 100 pages with their two-decade war against cancer. While surgery—historically dramatic and disfiguring—had been a mainstay for treatment of cancer, Farber pursued a biochemical route, which elaborated into chemotherapy, the second major approach of the late 20th century.

Mukherjee also explains ancient views, Hippocrates’, Galen’s humors, Vasealius’ anatomy, Hunter’s stages, Lister’s antisepsis, and Röntgen’s X-rays, which became the third major approach. By 1980, however, the American “War on Cancer” had not been won.

Further advances in cellular biology and genetics would be needed to make targeted molecular therapy possible.  Mukherjee tells this complicated story clearly and engagingly, showing the human investigators to be personable and dogged in their pursuits.  

Another important approach is prevention. The biostatistical work of Doll and Hill, for example, showed the links between tobacco and lung cancer. Screening, such as Pap smears and mammograms, also saved lives, but the basic cellular understanding still eluded investigators.

The final 150 pages explain the search for and discovery of genetic factors, specifically oncogenes. Harold Varmus and J. Michael Bishop were the leaders, winning a Nobel Prize in 1989. Bert Vogelstein, Judah Folkman, Robert Weinberg and Douglas Hanahan took the work further, opening the doors for such drugs as Herceptin, Gleevec, and Avastin. 

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