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

But another truth should be foremost in mind: that what we call nature today is a kinder, gentler, more depauperate world than at any time since at least the late Paleozoic, some 300 million years ago. Nature is not a temple but a ruin. A beautiful ruin, but a ruin all the same.

By now the perpetually changing landscape of breast cancer was beginning to tire him out. Trials, tables, and charts had never been his forte; he was a surgeon, not a bookkeeper.

Cancer thus exploits the fundamental logic of evolution unlike any other illness. If we, as a species, are the ultimate product of Darwinian selection, then so, too, is this incredible disease that lurks inside us.

Down to their innate molecular core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves.

Genes cannot tell us how to categorize or comprehend human diversity; environments can, cultures can, geographies can, histories can. Our language sputters in its attempt to capture this slip. When a genetic variation is statistically the most common, we call it normal ? a word that implies not just superior statistical representation but qualitative or even moral superiority? When the variation is rare, it is termed a mutant ? a word that implies not just statistical uncommonness, but qualitative inferiority, or even moral repugnance. And so it goes, interposing linguistic discrimination on genetic variation, mixing biology and desire.

How many pathways are typically dysregulated in a cancer cell. Typically, Vogelstein found, between eleven and fifteen, with an average of thirteen. The mutational complexity on a gene-by-gene level was still enormous. Any one tumor bore scores of mutations pockmarked throughout the genome. But the same core pathways were characterisically dysregulated in any tumor type, even if the specific genes responsible for each broken pathway differed from one tumor to the next. Ras may be activated in one sample of bladder cancer; Mek in another; Erk in the third?but in each case, some vital piece of the Ras-Mek-Erk cascade was dysregulated.

If the history of medical genetics teaches us one lesson, it is to be wary of precisely such slips between biology and culture. Humans, we now know, are largely similar in genetic terms ? but with enough variation within us to represent true diversity. Or, perhaps more accurately, we are culturally or biologically inclined to magnify variations, even if they are minor in the larger scheme of the genome. Tests that are explicitly designed to capture variances in abilities will likely capture variances in abilities ? and these variations may well track along racial lines. But to call the score in such a test ?intelligence,? especially when the score is uniquely sensitive to the configuration of the test, is to insult the very quality it sets out to measure.

In 2010, about six hundred thousand Americans, and more than 7 million humans around the world, will die of cancer. In the United States, one in three women and one in two men will develop cancer during their lifetime. A quarter of all American deaths, and about 15 percent of all deaths worldwide, will be attributed to cancer. In some nations, cancer will surpass heart disease to become the most common cause of death.

In the 1990s, Barbara Bradfield was among the first women to be treated with a drug, Herceptin, that specifically attacks breast cancer cells. She is the longest survivor of that treatment, with no hint of her cancer remaining.

It felt?nearly twenty-five hundred years after Hippocrates had naively coined the overarching term karkinos?that modern oncology was hardly any more sophisticated in its taxonomy of cancer.

Leukemia is cancer of the white blood cells?cancer in one of its most explosive, violent incarnations. As one nurse on the wards often liked to remind her patients, with this disease even a paper cut is an emergency.

Most discoveries even today are a combination of serendipity and of searching.

On that pea-size blue planet glimmering on the horizon, this was a moment of reckoning. It was a stunning scientific and intellectual accomplishment, Time reported in July 1969, for a creature who, in the space of a few million years?an instant in evolutionary chronology?emerged from primeval forests to hurl himself at the stars?. It was, in any event, a shining reaffirmation of the optimistic premise that whatever man imagines he can bring to pass.

Radiation can be used to control or palliate metastatic tumors in selected cases, but is rarely curative in these circumstances.

Steve Harmon, thirty-six, had esophageal cancer growing at the inlet of his stomach. For six months, he had soldiered through chemotherapy as if caught in a mythical punishment cycle devised by the Greeks. He was debilitated by perhaps the severest forms of nausea that I had ever encountered in a patient, but he had to keep eating to avoid losing weight. As the tumor whittled him down week by week, he became fixated, absurdly, on the measurement of his weight down to a fraction of an ounce, as if gripped by the fear that he might vanish altogether by reaching zero. Meanwhile, a growing retinue of family members accompanied him to his clinic visits: three children who came with games and books and watched, unbearably, as their father shook with chills one morning; a brother who hovered suspiciously, then accusingly, as we shuffled and reshuffled medicines to keep Steve from throwing up; a wife who bravely shepherded the entire retinue through the whole affair as if it were a family trip gone horribly wrong. One morning, finding Steve alone on one of the reclining chairs of the infusion room, I asked him whether he would rather have the chemotherapy alone, in a private room. Was it, perhaps, too much for his family?for his children? He looked away with a flicker of irritation. I know what the statistics are. His voice was strained, as if tightening against a harness. Left to myself, I would not even try. I?m doing this because of the kids.

The crucial driver of evolution, Darwin understood, was not nature?s sense of purpose, but her sense of humor).

The largest negative eugenics project in human history was not the systemic extermination of Jews in Nazi Germany or Austria in the 1930s. That ghastly distinction falls on India and China, where more than 10 million female children are missing from adulthood because of infanticide, abortion, and neglect of female children.

The very effect of X-rays killing rapidly dividing cells?DNA damage?also created cancer-causing mutations in genes.

This was the tenth month of my fellowship in oncology - a two-year immersive medical program to train cancer specialists - and I felt as if I had gravitated to my lowest point. In those ten indescribably poignant and difficult months, dozens of patients in my care had died. I felt as if I was slowly becoming inured to the deaths and the desolation - vaccinated against the constant emotional brunt.

When you decide to test for ?future risk,? you are also, inevitably, asking yourself, what kind of future am I willing to risk?

But because of the systematic neglect of cancer research: There are not over two dozen funds in the U.S. devoted to fundamental cancer research. They range in capital from about $500 up to about $2,000,000, but their aggregate capitalization is certainly not much more than $5,000,000...The public willingly spends a third of that sum in an afternoon to match a major football game.

By the early 1940s, asking about a connection between tobacco and cancer was like asking about an association between sitting and cancer.

Cancer was not an unnatural group of different maladies.

Ehrlich hedged. The cancer cell, he explained, was a fundamentally different target from a bacterial cell. Specific affinity relied, paradoxically, not on affinity, but on its opposite?on difference. Ehrlich?s chemicals had successfully targeted bacteria because bacterial enzymes were so radically dissimilar to human enzymes. With cancer, it was the similarity of the cancer cell to the normal human cell that made it nearly impossible to target.

Genetic tests, as Eric Topol, the medical geneticist described it, are also moral tests. When you decide to test for ?future risk,? you are also, inevitably, asking yourself, what kind of future am I willing to risk? Three case studies illustrate the power and the peril of using genes to predict future risk.

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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