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

Our encounter with cancer has rounded us off; it has smoothed and polished us like river rocks.

Scientists divide. We discriminate. It is the inevitable occupational hazard of our profession that we must break the world into its constituent parts -- genes, atoms, bytes -- before making it whole again. We know of no other mechanism to understand the world: to create the sum of its parts, we must begin by dividing it into the parts of the sum.

The (cancer) cells, technically speaking, are immortals. The woman from whose body they were once taken has been dead for thirty years

The greatest clinicians who I know seem to have a sixth sense for biases. They understand, almost instinctively, when prior bits of scattered knowledge apply to their patients?but, more important, when they don?t apply to their patients.

The point is this: if you cannot separate the phenotype of mental illness from creative impulses, then you cannot separate the genotype of mental illness and creative impulse.

There was no detectable association between gliomas and cell phone use overall. Prevention experts, and phone-addicted teenagers, may have rejoiced?but only briefly.

Turned into a horrific mistake. Lucy Willis had observed that folic acid, if administered to nutrient-deprived patients, could restore the normal genesis of blood. Farber wondered whether administering folic acid to children with leukemia might also restore normalcy to their blood. Following that tenuous trail, he obtained some synthetic folic acid, recruited a cohort of leukemic children, and started injecting folic acid into them. In the months that passed, Farber found that folic acid, far from stopping the progression of leukemia, actually accelerated it. In one patient, the white cell count nearly doubled. In another, the leukemia cells exploded into the bloodstream and sent fingerlings of malignant cells to infiltrate the skin. Farber stopped the experiment in a hurry.

Yet, old sins have long shadows, and carcinogenic sins especially so. The lag time between tobacco exposure and lung cancer is nearly three decades, and the lung cancer epidemic in America will have an afterlife long after smoking incidence has dropped. Among men, the age-adjusted incidence of lung adenocarcinoma, having peaked at 102 per 100,000 in 1984, dropped to 77 in 2002. Among women, though, the epidemic still runs unabated. The stratospheric rise of smoking among women in Rose Cipollone?s generation is still playing itself out in the killing fields of lung cancer.

And this was to save rats, right? Or mice? You spent all this money to save mice the problem of developing tumors?

But the MSA has not signaled the death of the industry in a more global sense; beleaguered in America, the Marlboro Man has simply sought out new Marlboro countries. With their markets and profits dwindling and their legal costs mounting, cigarette manufacturers have increasingly targeted developing countries as new markets, and the number of smokers in many of these nations has risen accordingly. Tobacco smoking is now a major preventable cause of death in both India and China. Richard peto, an epidemiologist at Oxford and a close collaborator of Richard Doll?s (until Doll?s death in 2005), recently estimated that the number of smoking-related deaths among adults in India would rise to 1 million per year in the 2010s and continue to rise in the next decade. In China, lung cancer is already the leading cause of death, attributable to smoking in men.

Cancer changes your life, a patient wrote after her mastectomy. It alters your habits.? Everything becomes magnified.

Cancer's life is a recapitulation of the body's life, its existence a pathological mirror of our own. Susan Sontag warned against overburdening an illness with metaphors. But this is not a metaphor. Down to their innate molecular core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves.

Every drug, the sixteenth-century physician Paracelsus once opined, is a poison in disguise. Cancer chemotherapy, consumed by its fiery obsession to obliterate the cancer cell, found its roots in the obverse logic: every poison might be a drug in disguise.

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.

I had a novice's hunger for history, but also a novice's inability to envision it.

In 1870, the per capita consumption in America was less than one cigarette per year. A mere thirty years later, Americans were consuming 3.5 billion cigarettes and 6 billion cigars every year. By 1953, the average annual consumption of cigarettes had reached thirty-five hundred per person. On average, an adult American smoked ten cigarettes every day, an average Englishman twelve, a Scotsman nearly twenty.

In Georgian England, sweeps and climbing-boys were regarded as general cesspools of disease?dirty, consumptive, syphilitic, pox-ridden?and a ragged, ill-looking sore, easily attributed to some sexually transmitted illness, was usually treated with a toxic mercury-based chemical and otherwise shrugged off. (Syphilis, as the saying ran, was one night with Venus, followed by a thousand nights with mercury.)

In the neighboring town of Carlisle, Lister had observed sewage disposers cleanse their waste with a cheap, sweet-smelling liquid containing carbolic acid. Lister began to apply carbolic acid paste to wounds after surgery. (That he was applying a sewage cleanser to his patients appears not to have struck him as even the slightest bit unusual.)

It remains an astonishing, disturbing fact that in America - a nation where nearly every new drug is subjected to rigorous scrutiny as a potential carcinogen, and even the bare hint of a substance's link to cancer ignites a firestorm of public hysteria and media anxiety - one of the most potent and common carcinogens known to humans can be freely bought and sold at every corner store for a few dollars.

Low fiber, red meat rich diets increase the risks of colon cancer, and obesity is linked to breast cancer, but much more about these links remain unknown, especially in molecular terms.

Negative genes, such as Rb, suppress cell division. In normal cells, these anti-oncogenes, or tumor suppressor genes, provide the brakes to cellular proliferation, shutting down cell division when the cell receives appropriate signals. In cancer cells, these brakes have been inactivated by mutations. In cells with missing brakes, to use Bishop?s analogy again, the stop signals for mitosis can no longer be registered. Again, the cell divides and keeps dividing, defying all signals to stop. Both abnormalities, activated proto-oncogenes and inactivated tumor suppressors (jammed accelerators and missing brakes), represent the core molecular defects in the cancer cell. Bishop, Knudson, and Varmus did not know how many such defects were ultimately needed to cause human cancers. But a confluence of them, they postulated, caused cancer.

Patients tell stories to describe illness; doctors tell stories to understand it. Science tells its own story to explain diseases.

Scientists often study the past as obsessively as historians because few other professions depend so acutely on it. Every experiment is a conversation with a prior experiment, every new theory a refutation of the old.

The Apollo mission and the Manhattan Project, the two models driving this War on Cancer were both technological achievements that stood on the shoulders of long and deep scientific discoveries (atomic physics, fluid mechanics, and thermodynamics). In contrast, even a cursory understanding of the process that made cells become malignant was missing. Seizing on the Laskerites? favorite metaphor, Sol Spiegelman, the Columbia University cancer scientist, argued, an all-out effort at this time would be like trying to land a man on the moon without knowing Newton?s laws of gravity. James Watson, who had discovered the structure of DNA, unloosed a verbal rampage against the Senate bill. Doing ?relevant? research is not necessarily doing ?good? research, Watson would later write. In particular we must reject the notion that we will be lucky?. Instead we will be witnessing a massive expansion of well-intentioned mediocrity.

The history of Medicine is replete with examples of cures obtained years, decades, and even centuries before the mechanism of action was understood for these cures.

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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