The Emperor of All Maladies – CANCER

Some books make you wonder, “Where has this book been all this time?” This was such a book for me. Beyond being generally well written, engaging, and informative, certain points caught my attention more than others. I will explore these topics under separate headings.

Here are my recollections from a deeply passionate book by Pulitzer Prize-winning medical oncologist Dr. Siddhartha Mukherjee, The Emperor of All Maladies / A Biography of Cancer.

Sidney Farber's upbringing

Although this part may occupy only half a page in the book, it was a detail that fascinated me. Dr. Sydney Farber, the father of modern chemotherapy, grew up in an environment ruled by discipline. Farber was an American pediatric pathologist. He is regarded as the father of modern chemotherapy for his work using folic acid antagonists to fight leukemia, which led to the development of other chemotherapies against cancers.  

In Farber's childhood home, only Hebrew was allowed upstairs, while German and English were spoken downstairs. His father brought him textbooks and asked him to study them and present a detailed report. I think this demanding environment, where failure was not an option, was the driving force behind his achievements in cancer.

To explain this, I first need to clarify what is known in English as the “Comfort zone”, the comfort zone. We can describe the comfort zone as a set of behaviors that do not cause psychological discomfort. If you are shy, meeting new people means stepping outside your comfort zone. This is not limited to difficulty opening yourself to new behaviors; sometimes giving up a familiar behavior also means leaving the comfort zone, such as a retired officer still shaving every day despite no longer being required to. What does this concept have to do with our topic?

The proportion of people who study medicine and become doctors in America is low. It imports more doctors from other countries. One reason is that medical education is expensive in America but free in countries like ours, Türkiye. Yet I want to draw attention to a different reason. America is a country where people can enjoy adequate finances and considerable opportunities without higher education, whereas in Türkiye people choose medical school more to secure their economic future. In other words, we study medicine largely because of the opportunities it offers. If we become a developed country one day, will we too become a country that imports doctors, scientists, and engineers rather than training them? Everyone would agree that we need engineers, doctors, and scientists to advance as a world. Yet increasing opportunities are making us lazy.

Complaining alone is not useful; we need to find solutions to our problems. This book seemed to offer me a solution. It pointed to a truth that had always been in front of me but that I struggled to see. Of course, I am not saying we should raise our children like robots. But let us avoid the mistake of offering children limitless opportunities because of the pain of having grown up with deprivation. These are the thoughts Farber's upbringing prompted in me.

The importance of data and randomness in statistics

In a world of increasing scientific advances, yet with so much still unknown, we can understand the importance of collecting and analyzing data by looking at how far Halsted and his followers went in radical mastectomy (extensive breast cancer surgery), believing in the sanctity of their scalpels without objective data. Of course, it would be arrogant to look retrospectively, viewing the past through today's lens rather than judging it under the conditions of its time. Randomness in statistics was not yet used even in laboratory studies. Doctors selected their own patients for trials, choosing those more likely to recover, creating subjectivity in experiments. Considering this, and the helplessness created by insufficient treatment knowledge, it is not surprising that doctors clung to the only remedy they had. Nevertheless, surgeons' refusal in the 1960s to participate in trials conducted in light of new statistical methods was unscientific, reflecting unnecessary and excessive confidence in themselves and their methods.

"God is the only one we trust; everyone else must lay out their data." ~ Bernard Fisher

These facts lead to an important conclusion: every patient's data must be recorded very carefully, including not only tests we can interpret today but also other data we hope to interpret in the future. Avoiding unnecessary tests, choosing discriminating tests, and reaching diagnosis and treatment by the shortest route are, of course, essential qualities in a doctor. By tests we hope to interpret in the future, we do not mean ordering every test on the computer, but targeted tests to investigate findings whose relationship to the disease is uncertain. This can be achieved through communication among health authorities both within the country and internationally.

Politics in scientific progress

In the book, we see that Farber's enthusiasm and determination to work become insufficient at one point. Mary Lasker comes to his aid. Besides being a successful entrepreneur with strong political connections, illnesses experienced by her or her loved ones throughout her life, including the Spanish flu pandemic that gripped the world, led her to become a health activist, guide, and guardian angel after the age of 40. Thanks to her, an all-out war against cancer could be launched. She influenced politicians and secured large cancer budgets. It would be disrespectful to overlook Farber's success with the Jimmy Fund, but we cannot fail to note that Lasker was on a different level.

Science has generally not been a profitable short-term investment. For this reason, HER2 drugs, later regarded as one of biotechnology's first major victories, were considered unlikely to make a profit by Genentech, which reduced their funding for a time. Companies and enterprises naturally consider their own profits. We cannot blame them for that. But the application in which I am writing this, and the internet that allows me to distribute it, exist because scientists watered the tree of science with discoveries, allowing it gradually to grow and bear fruit. We must always provide adequate research funding so that this tree does not dry up and can continue bearing fruit even years later. As we learned from Lasker, we can do this by raising public awareness and enabling people to demand these things themselves. This is why I attach great importance to health literacy, and try to read, write, and share day and night. If people make their demands heard sufficiently, politicians will eventually have to respond. This is why social grouping and organization are essential. Science cannot be considered separately from politics because it needs resources.

Will you still discharge me if I cannot recover?

This was one of the book's most striking headings for me. Siddhartha describes an elderly woman with cancer who came to his clinic with her daughter. With age, mother and daughter roles reverse, and the responsibility this brings awakens an instinct in the daughter, a doctor, to find the best treatment and strongest drug for her mother. But there was a problem. Her mother's tests showed that her liver had not yet failed but was close to doing so, while her kidneys were also functioning at their limit. Rather than using strong drugs for an incurable disease and exposing the patient to other problems, Siddhartha thought palliative treatment would be better. But her daughter disagreed: "We came here for treatment, not to listen to the kind of advice given to elderly people in a nursing home!". A few weeks later, Siddhartha learned that the woman had found another doctor, presumably one who agreed to powerful treatment. It remains unknown whether she died from cancer or from treatment.

Fortunately, Cicely Saunders, a nurse in England who later studied medicine, came to these patients' aid. Saunders developed this idea in the almost abandoned cancer wards where she worked. Hopeless cancer cases lay in windowless rooms, their voices unheard, abandoned to die in a corner. Saunders's response to this scene was to revive palliative medicine as a field. For doctors, palliative care signaled that the battle against cancer had been lost; for Saunders, it meant something very different. She summarized doctors' reactions in these words: "Resistance to the idea of providing palliative care was so strong that, when we told doctors to redirect their efforts from saving the patient to restoring the patient's comfort and dignity, they would avert their eyes. ...Doctors were allergic to the smell of death. Death meant failure and defeat. It actually meant their own death, the death of medicine, the death of oncology."

School lessons or this book?

An activity we enjoy when choosing it freely may not be as enjoyable under external pressures such as exams or grades. Instead of pure curiosity and aspects that directly interest us, what the other person (teacher, etc.) considers important now enters the picture. The pure love of learning between the person and their subject of curiosity is replaced by concern for personal benefit. The situation is generally similar for teachers. Some decorate lessons with stories and events to awaken a love of learning, while others focus only on the subject. I do not mean a teacher concentrating only on what will appear in the exam. Teachers who explain a subject engagingly from different angles can emphasize points important for exams, while a purely information-focused teacher may concentrate on details irrelevant to exams and perhaps unnecessary for life. The point is that presenting certain subjects from different perspectives can stimulate curiosity and enjoyment of learning in one case, yet evoke only a simple “hmm, that is another piece of information” response in another.

For example, Helicobacter pylori and its relationship to various diseases felt completely different when learned in school compared with reading about it in the book. We know that the scientists who discovered Helicobacter pylori swallowed a bacterial culture to prove it and won the Nobel Prize. This was not an incorrect statement, but hearing it this way did not affect me. Yet at the time, the prevailing belief was that no bacteria could survive in acid. Meanwhile, statistical studies had shown that chronic gastritis caused cancer. The cause of gastritis was not fully understood; stress was thought to cause it...

Two doctors, Robin Warren and Barry Marshall, set out together to investigate gastritis. During microscopic examinations, Warren discovered a pale-blue layer on the pits forming in the stomach. Looking more closely, he saw spiral organisms. But he could not isolate them in the laboratory. The belief that no bacteria could grow in the stomach's highly acidic environment was then as unquestionable as the belief in a flat world had once been. Believing in himself, Warren continued his work with determination: what he saw could not be a dream. Yet he could not grow the bacteria in culture and repeatedly found himself throwing away empty culture dishes. One weekend, by chance, the hospital was so busy that he forgot to empty the cultures. Because incubation had lasted longer than usual, he entered the laboratory to find bacterial colonies growing in the dish. He had finally obtained the bacteria and named them Helicobakter pylori (after their spiral structure and location in the stomach's pylorus), but this did not yet prove that the bacterium caused gastritis. None of the pigs in the experiments developed ulcers either. Facing the prospect of his experiments being halted and project support withdrawn, he was driven to a difficult decision: he would perform the unethical human experiment on himself. Later, in Medical Journal of Australia, he would describe himself in the published article as “a volunteer swallowed a pure culture consisting of the organism itself”. This account in the book filled me once again with respect and admiration for colleagues and scientists who contributed greatly to medicine and humanity. These days, we experience these feelings with the BioNTech/Pfizer coronavirus vaccine developed in Germany by Uğur Şahin, Özlem Türeci, and their team, now beginning to be used in 6 countries worldwide.

I felt the same about methotrexate, used in cancer patients, in biochemistry. In biochemistry classes we examined only its mechanism of action. In the book, learning the historical development of these anticancer drugs, part of Farber's journey beginning with antifolates, and viewing them from the perspective of their time as a “paradigm shifter” or “game changer”, felt like personally experiencing the wars described in history lessons. The Philadelphia chromosome mutation felt the same. As mentioned under science and politics, HER2 drugs, a treatment for HER2-positive breast cancers, were nearly abandoned because they were thought unprofitable. Yet determined scientists now allow these patients to live no differently from healthy people. This did not feel the same as learning about the disease in class.

I am not disparaging current medical education systems. Of course, I think they do not use their potential well. But instead of constantly demanding things from a system designed to train us and test our readiness, perhaps we should do our part and awaken our own curiosity. Reading / researching historical stories may be the most positive way to stimulate curiosity, motivation, and professional enthusiasm.

Carcinogens – fighting them: the smoking exception

The real force that turned smoking into a battle for freedom was the tobacco lobby. This book helped me understand that very well.

I am not saying freedom is unimportant. It is unquestionably important. Although China's authoritarian regime used strict quarantines (such as closing an entire city or region over even a single case) to prevent spread and, despite being where the pandemic began, has now become a place with almost no cases, I would never want to live under an authoritarian regime like China's. What has really changed is that smoking no longer represents freedom in our eyes.

We cannot blame only manufacturers for the spread of smoking. It became widespread as a brief escape for soldiers from the bleak atmosphere of World Wars 1 and 2. But after the wars, as scientists gradually recognized its harms, tobacco companies, concerned only with profits, obstructed efforts to raise public awareness. For years, these companies attracted doctors to their side through advertising (such as doctor posters for cigarettes in the 1950s), while trying to obstruct research by doctors opposing them. Research on smoking was also very difficult then because almost nobody was left who did not smoke. Researchers had no control group. By funding experiments in mice, tobacco companies presented themselves as angels investigating smoking's harms, then skillfully shifted the goalposts by saying the results showed no proven effect in humans. These efforts could not prevent the results of genuine scientific studies and legal regulations, but delayed them for decades...

As Siddhartha also says, the FDA applies very strict measures to every drug entering the market, yet being so permissive about cigarettes is absurd. Examples like this show why we must insist on raising public awareness and the importance of social organization in such matters.

Endgame – The end of the game

At the end of the book, the author describes this cat-and-mouse chase with cancer through a dialogue from Lewis Carrol's novel “Through the Looking-Glass”.

"But in our country," Alice says, breathless, "when you run for a long time, as we have just done, you generally get somewhere." "What a slow country yours must be!" the Queen replies. "Here, you must run as hard as you can just to stay in the same place. If you want to get somewhere, you must run at least twice as fast!"

Although new cancer treatments are constantly being found, cancer cells continually respond to these treatments with new mutations, and resistance is acquired. As the Red Queen says, "This is a race in which we must keep running even to stay where we are." Because cancer will not wait for us.