Siddhartha Mukherjee


American Physician, Biological Scientist and Author, Awarded Pulitzer Prize for his book, The Emperor Of All Maladies: A Biography of Cancer

Author Quotes

Never underestimate the power of? stupidity.

Pierre and Marie (then Maria Sklodowska, a penniless Polish immigrant living in a garret in Paris) had met at the Sorbonne and been drawn to each other because of a common interest in magnetism.

Something akin to this process, a few researchers believe, is constantly occurring in cancer?at at least in leukemia. In the mid-1990s, John dick, a Canadian biologist working in Toronto, postulated that a small population of cells in human leukemias also possess this infinite self-renewing behavior. These cancer stem cells act as the persistent reservoir of cancer?generating and regenerating cancer infinitely. When chemotherapy kills the bulk of cancer cells, a small remnant population of these stem cells, thought to be intrinsically more resistant to death, regenerate and renew cancer, thus precipitating the common relapses of cancer after chemotherapy. Indeed, cancer stem cells have acquired the behavior of normal stem cells by activated the same genes and pathways that make normal stem cells immortal?except, unlike normal stem cells, they cannot be lulled back into physiological sleep. Cancer, then, is quite literally trying to emulate a regenerating organ?or perhaps, more disturbingly, the regenerating organism. Its quest for immortality mirrors our own quest, a quest buried in our embryos and in the renewal of our organs. Someday, if cancer succeeds, it will produce a far more perfect being than its host?imbued with both immortality and the drive to proliferate. One might argue that the leukemia cells growing in my laboratory derived from the woman who died three decades earlier have already achieved this form of perfection.

The biochemist Arthur Kornberg once joked that the discipline of modern biology in its early days often operated like the man in the proverbial story who is frantically searching for his keys under a streetlamp. When a passerby asks the man whether he lost his keys at that spot, the man says that he lost them at home?but he is looking for the keys under the lamp because the light there is the brightest.

The intravenous chemotherapy that we would give Carla, no matter how potent, simply couldn?t break into the cisterns and ventricles that bathed her brain. The blood-brain barrier essentially made the brain into a sanctuary (an unfortunate word, implying that your own body could be abetting the cancer) for the leukemia cells. To send drugs directly into that sanctuary, the medicines would need to be injected directly into Carla?s spinal fluid, through a series of spinal taps.

The result, as the journalist Elizabeth Drew noted in the Atlantic Monthly, was an unabashed act to protect private industry from government regulation. Politicians were far more protective of the narrow interests of tobacco than of the broad interest of public health. Tobacco makers need not have bothered inventing protective filters, Drew wrote drily: Congress had turned out to be the best filter yet.

This book is the story of the birth, growth, and future of one of the most powerful and dangerous ideas in the history of science: the gene, the fundamental unit of heredity, and the basic unit of all biological information. I

We have not slain our enemy, the cancer cell, or figuratively torn the limbs from his body, Varmus said. In our adventures, we have only seen our monster more clearly and described his scales and fangs in new ways?ways that reveal a cancer cell to be, like Grendel, a distorted version of our normal selves.

Basic research leads to new knowledge. It provides scientific capital. It creates the fund from which the practical applications of knowledge must be drawn? basic research is the pacemaker of technological progress. In the nineteenth century, Yankee mechanical ingenuity, building largely upon the basic discoveries of European scientists, could greatly advance the technical arts. Now the situation is different. ?A nation which depends upon others for its new basic scientific knowledge will be slow in its industrial progress and weak in its competitive position in world trade, regardless of its mechanical skill.?

But Vannevar Bush was not convinced. In a deeply influential report to President Truman entitled Science and the Endless Frontier, first published in 1945, Bush had laid out a view of postwar research that had turned his own model of wartime research on its head: ?Basic research,? Bush wrote, ?is performed without thought of practical ends. It results in general knowledge and an understanding of nature and its laws. This general knowledge provides the means of answering a large number of important practical problems, though it may not give a complete specific answer to any one of them?

Cancer is a tremendous opportunity to have your face pressed right up against the glass of your mortality. But what patients see through the glass is not a world outside cancer, but a world taken over by it?cancer reflected endlessly around them like a hall of mirrors.

Civilization does not cause cancer, but by extending the human life span, exposed the cancer.

First, [Pinkel] reasoned that while combinations of drugs were necessary to induce remissions, combinations were insufficient in themselves. Perhaps one needed combinations of combinations?six, or seven, or even eight different chemical poisons mixed and matched together for maximum effect. Second, since the nervous system relapses had likely occurred because even these highly potent chemicals could not breach the blood-brain barrier, perhaps one needed to instill chemotherapy directly into the nervous system by injecting it into the fluid that bathes the spinal cord. Third, perhaps even that instillation was not enough. Since X-rays could penetrate the brain regardless of the blood-brain barrier, perhaps one needed to add high-dose radiation to the skull to kill residual cells in the brain. And finally, as Min Chiu Li had seen with choriocarcinoma, perhaps one needed to continue chemotherapy not just for weeks and months as Frei and Freireich had done, but for month after month, stretching into two or even three years.

Hodgkin had just returned from his second visit to Paris, where he had learned to prepare and dissect cadaveric specimens. He was promptly recruited to collect specimens for Guy?s new museum. The job?s most inventive academic perk, perhaps, was his new title: the Curator of the Museum and the Inspector of the Dead. Hodgkin

I think the way we think about cancer, the way we treat cancer, has dramatically changed in the last century. There is an enormous amount of options that a physician can provide today, right down from curing patients, treating patients or providing patients with psychic solace or pain relief.

In 1997, the NCI director, Richard Klausner, responding to reports that cancer mortality had remained disappointingly static through the nineties, argued that the medical realities of one decade had little bearing on the realities of the next. ?There are far more good historians than there are good prophets,? Klausner wrote. ?It is extraordinarily difficult to predict scientific discovery, which is often propelled by seminal insights coming from unexpected directions. The classic example?Fleming?s discovery of penicillin on moldy bread and the monumental impact of that accidental finding?could not easily have been predicted, nor could the sudden demise of iron-lung technology when evolving techniques in virology allowed the growth of poliovirus and the preparation of vaccine. Any extrapolation of history into the future presupposes an environment of static discovery?an oxymoron.

In Lewis Carroll?s Through the Looking-Glass, the Red Queen tells Alice that the world keeps shifting so quickly under her feet that she has to keep running just to keep her position. This is our predicament with cancer: we are forced to keep running merely to keep still.

Indeed, like many of his epidemiologist peers, Graham was becoming exasperated with the exaggerated scrutiny of the word cause. That word, he believed, had outlived its original utily and turned into a liability. In 1884, the microbiologist Robert Koch had stipulated that for an agent to be defined as the cause of a disease, it would need to fulfill at least three criteria. The causal agent had to be present in diseased animals; it had to be isolated from diseased animals; and it had to be capable of transmitting the disease when introduced into a secondary host. But Koch?s postulates had arisen, crucially from the study of infectious diseases and infectious agents; they could not simply be repurposed for many noninfectious diseases. In lung cancer, for instance, it would be absurd to imagine a carcinogen being isolated from a cancerous lung after months, or years, of the original exposure.

It would take biologists decades to fully decipher the mechanism that lay behind these effects, but the spectrum of damaged tissues?skin, lips, blood, gums, and nails?already provided an important clue: radium was attacking DNA. DNA is an immutable molecule, exquisitely resistant to most chemical reactions, for its job is to maintain the stability of genetic information. But X-rays can shatter strands of DNA or generate toxic chemicals that corrode DNA. Cells respond to this damage by dying or, more often, by ceasing to divide. X-rays thus preferentially kill the most rapidly proliferating cells in the body, cells in the skin, nails, gums, blood.

Memories sharpen the past; it is reality that decays.

New drugs appeared at an astonishing rate: by 1950, more than half the medicines in common medical use had been unknown merely a decade earlier. Perhaps even more significant than these miracle drugs, shifts in public health and hygiene had also drastically altered the national physiognomy of illness. Typhoid fever, a contagion whose deadly swirl could decimate entire districts in weeks, melted away as the putrid water supplies of several cities were cleansed by massive municipal efforts. Even tuberculosis, the infamous white plague of the nineteenth century, was vanishing, its incidence plummeting by more than half between 1910 and 1940, largely due to better sanitation and public hygiene efforts. The life expectancy of Americans rose from forty-seven to sixty-eight in half a century, a greater leap in longevity than had been achieved over several previous centuries.

Portions of this interview first appeared in OncNurse magazine in February 2011. We are grateful to Christin Melton for her questions.

Soot is a mixture of chemicals that would eventually be found to contain several carcinogens.

The campaign against cancer, Farber learned, was much like a political campaign: it needed icons, mascots, images, slogans?the strategies of advertising as much as the tools of science. For any illness to rise to political prominence, it needed to be marketed, just as a political campaign needed marketing. A disease needed to be transformed politically before it could be transformed scientifically.

The Italian memoirist Primo Levi, who survived a concentration camp and then navigated his way through a blasted Germany to his native Turin, often remarked that among the most fatal qualities of the camp was its ability to erase the idea of a life outside and beyond itself. A person?s past and his present were annihilated as a matter of course?to be in the camps was to abnegate history, identity, and personality?but it was the erasure of the future that was the most chilling. With that annihilation, Levi wrote, came a moral and spiritual death that perpetuated the status quo of imprisonment. If no life existed beyond the camp, then the distorted logic by which the camp operated became life as usual.

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American Physician, Biological Scientist and Author, Awarded Pulitzer Prize for his book, The Emperor Of All Maladies: A Biography of Cancer