The Emperor of All Maladies

The story in brief

Siddhartha Mukherjee is an oncologist and cancer researcher at Columbia University. He began The Emperor of All Maladies as a journal during his training as a cancer specialist, in an attempt to answer a question from a patient who asked what she was fighting. The book, published in 2010, calls itself a biography of cancer. It won the Pulitzer Prize for General Nonfiction in 2011, and a documentary series based on it, presented by Ken Burns, was broadcast on PBS in 2015.

The book moves between Mukherjee’s own patients and a history that begins with an Egyptian medical text, attributed to Imhotep, which describes a bulging mass in the breast and concludes that there is no treatment. It follows the disease through the Greeks, who named it after the crab, karkinos; through nineteenth-century surgeons who attempted ever more extensive operations; through the twentieth-century development of radiation and chemotherapy; to the molecular understanding of cancer as a disease of genes, and the targeted drugs that followed.

The decisions that made it

In the 1890s the American surgeon William Halsted developed the radical mastectomy, which removed the breast, the underlying chest muscles and the lymph nodes. His reasoning was that cancer spread outward from its origin like ink, so removing more tissue would remove more cancer. The operation became standard for decades and became more radical still. Only in the 1970s did trials led by Bernard Fisher show that less extensive surgery, combined with other treatment, gave the same survival. Mukherjee shows how a theory, plausible at the time, became an orthodoxy that went untested for seventy years.

In 1947 Sidney Farber, a pathologist in Boston, gave children with leukaemia a drug called aminopterin, which blocked the vitamin folic acid. Some children went into temporary remission. It was the first evidence that a chemical could make cancer recede, and it began the era of chemotherapy.

From the 1960s, researchers at the National Cancer Institute decided to combine several drugs, at high doses, to cure childhood leukaemia. The approach was controversial and the treatment brutally toxic, but it produced lasting cures in many children, and it shaped a generation of oncologists’ belief that cancer could be beaten with enough force.

In 1971, after a campaign led by the philanthropist Mary Lasker and Sidney Farber, President Nixon signed the National Cancer Act, which became known as the war on cancer. Its supporters believed a cure was within reach with enough funding. Mukherjee shows the decision as partly visionary and partly premature. The basic biology of cancer was not yet understood, and the war’s early victories were fewer than its champions had promised.

In 1950 Richard Doll and Austin Bradford Hill in Britain, and Ernst Wynder and Evarts Graham in the United States, published studies linking smoking to lung cancer. The tobacco industry spent decades contesting the evidence. Mukherjee treats prevention, and the fight against tobacco, as one of the most consequential and least glamorous parts of the story.

Finally, research from the 1970s onwards found that cancer arises from mutations in specific genes that control cell growth. That understanding led to drugs aimed at the specific molecular faults of particular cancers. The first great success was imatinib, sold as Gleevec, developed with the oncologist Brian Druker and approved in 2001, which transformed chronic myeloid leukaemia from a fatal disease into a manageable one for most patients.

What the book sees in them

Mukherjee’s central theme is that cancer is inseparable from life. Cancer cells are our own cells, grown out of control through the same mechanisms of division and repair that keep us alive. That is why it has been so hard to defeat without harming the patient.

He also shows how medicine has been shaped by hope, conviction and the personalities of its leaders, as well as by evidence. Halsted, Farber and the champions of the war on cancer were brilliant and committed. They were also, at times, too sure. Mukherjee judges their decisions by what they could know at the time, and shows how often progress required someone to challenge an orthodoxy that had become comfortable. The site’s idea page Sunk Costs and the Escalation of Commitment explores why established commitments are so hard to give up.

Since it was published

Cancer treatment has changed substantially since 2010. Immunotherapies, which help the immune system attack cancer, have produced lasting responses in some patients with cancers that were previously untreatable, and the 2018 Nobel Prize in Physiology or Medicine was awarded to James Allison and Tasuku Honjo for discoveries behind them. Genome sequencing of tumours has become routine in many cancers, and new tools, including artificial intelligence, are being used in diagnosis and drug development. Mukherjee has continued to write on these subjects, in The Gene (2016) and The Song of the Cell (2022).

What it asks of someone deciding

The book asks how long your organisation has been doing something because it seemed right once. The radical mastectomy lasted seventy years without a proper test. Every field has practices that rest on theories no one has checked.

It asks how you balance urgency and evidence. Farber’s willingness to try, and the leukaemia researchers’ willingness to push, saved lives. The same boldness, applied without testing, harmed others. Knowing which situation one is in is the hard part.

And it asks what the least glamorous work is worth. Prevention saved more lives than many dramatic treatments, and received less attention. The most effective actions are not always the most visible.