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

It?s easy to make perfect decisions with perfect information. Medicine asks you to make perfect decisions with imperfect information.

Min Chiu Li, the researcher who had been expelled from the institute for treating women with placental tumors with methotrexate long after their tumors had visibly disappeared.

Nineteenth-century doctors often linked cancer to civilization: cancer, they imagined, was caused by the rush and whirl of modern life, which somehow incited pathological growth in the body. The link was correct, but the causality was not: civilization did not cause cancer, but by extending human life spans?civilization unveiled it.

Postwar U.S. was the world's leader in science and technology. The investment in science research was staggering.

Specificity refers to the ability of any medicine to discriminate between its intended target and its host. Killing a cancer cell in a test tube is not a particularly difficult task: the chemical world is packed with malevolent poisons that, even in infinitesimal quantities, can dispatch a cancer cell within minutes. The trouble lies in finding a selective poison?a drug that will kill cancer without annihilating the patient. Systemic therapy without specificity is an indiscriminate bomb. For an anticancer poison to become a useful drug, Meyer knew, it needed to be a fantastically nimble knife: sharp enough to kill cancer yet selective enough to spare the patient.

The chances in some cases are infinitesimal, but the potential is still there. This is about all that patients need to know and it is about all that patients want to know.

The job?s most inventive academic perk, perhaps, was his new title: the Curator of the Museum and the Inspector of the Dead.

The theory began to convulse out of these results, a theory so magnificent and powerful that it would explain decades of disparate observations in a single swoop: perhaps src, the cancer-causing gene, was endogenous to the cell. Retrovirologists had long believed that the virus had introduced an activated src into normal cells to transform them into malignant cells. But the src gene had not originated in the virus. It had originated from a precursor gene that existed in a cell?in all cells.

This isolation was key to Farber?s early success. Insulated from the spotlights of public scrutiny, he worked on a small, obscure piece of the puzzle. Leukemia was an orphan disease, abandoned by internists, who had no drugs to offer for it, and by surgeons, who could not possibly operate on blood.

We now know precise and quantitative answers to these questions. A number of studies have tried to quantify the level of genetic diversity of the human genome. The most recent estimates suggest that the vast proportion of genetic diversity (85 to 90 percent) occurs _within_ so-called races (i.e., within Asians or Africans) and only a minor proportion (7 percent) within racial groups (the geneticist Richard Lewontin had estimated a similar distribution as early as 1972). Some genes certainly vary sharply between racial or ethnic groups -- sickle-cell anemia is an Afro-Caribbean and Indian disease, and Tay-Sachs disease has a much higher frequency in Ashkenazi Jews -- but for the most part, the genetic diversity within any racial group dominates the diversity between racial groups -- not marginally, but by an enormous amount. The degree of interracial variability makes race a poor surrogate for nearly any feature: in a genetic sense, an African man from Nigeria is so different from another man from Namibia that it makes little sense to lump them into the same category.

Both Premarin (its named derived from pregnant mare urine) and DES were initially marketed as elixirs to cure menopause. But for Huggins, the existence of synthetic estrogens suggested a markedly different use; he could inject them to feminize the male body and stop the production of testosterone in patients with prostate cancer. He called the method chemical castration. And once again, he found striking responses. As with surgical castration, patients with aggressive prostate cancer chemically castrated with feminizing hormones responded briskly to the therapy, often with minimal side effects. (The most prominent complaint among men was the occurrence of menopause-like hot flashes.) Prostate cancer was not cured with these steroids; patients inevitably relapsed with cancer that had become resistant to hormone therapy. But the remissions, which often stretched into several months, proved that hormonal manipulations could choke the growth of a hormone-dependent cancer. To produce a cancer remission, one did not need a general cellular poison (such as cisplatin or nitrogen mustard).

By 1926, cancer had become the nation?s second most common killer, just behind heart disease.

Cancer is not a concentration camp, but it shares the quality of annihilation: it negates the possibility of life outside and beyond itself; it subsumes all living.

Could your medicine be a cell, not a pill? Could your medicine be an organ that's created outside the body? Could your medicine be an environment?

Freaks become norms, and norms become extinct. Monster by monster, evolution advanced

How many ?rules?, then, could Weinberg and Hanahan evoke to explain the core behavior of more than a hundred distinct types and subtypes of tumors? The question was audacious in its expansiveness; the answer even more audacious in its economy: six. ?We suggest that the vast catalog of cancer cell genotypes is a manifestation of six essential alterations in cell physiology that collectively dictate malignant growth.? 1. Self-sufficiency in growth signals: cancer cells acquire an autonomous drive to proliferate?pathological mitosis?by virtue of the activation of oncogenes such as ras or myc. 2. Insensitivity to growth-inhibitory (antigrowth) signals: cancer cells inactivate tumor-suppressor genes, such as retinoblastoma (Rb), that normally inhibit growth. 3. Evasion of programmed cell death (apoptosis): cancer cells suppress and inactivate genes and pathways that normally enable cells to die. 4. Limitless replicative potential: cancer cells activate specific gene pathways that render them immortal even after generations of growth. 5. Sustained angiogenesis: Cancer cells acquire the capacity to draw out their own supply of blood and blood vessels?tumor angiogenesis. 6. Tissue invasion and metastasis: cancer cells acquire the capacity to migrate to other organs, invade other tissues, and colonize these organs, resulting in their spread throughout the body.

I wanted to explore cancer not just biologically, but metaphorically. The idea that tuberculosis in the 19th century possessed the same kind of frightening and decaying quality was very interesting to me, and it seemed that one could explore the idea that every age defined its own illness.

In 2005, a man diagnosed with multiple myeloma asked me if he would be alive to watch his daughter graduate from high school in a few months. In 2009, bound to a wheelchair, he watched his daughter graduate from college. The wheelchair had nothing to do with his cancer. The man had fallen down while coaching his youngest son's baseball team.

In Paris, friend of Bequerel?s, a young physicist-chemist couple named Pierre and Marie Curie, began to scour the natural world for even more powerful chemical sources of X-rays. 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.

Is medicine a science?

Its false-positive and false-negative rates make it far from an ideal screening test. But the fatal flaw in mammography lies in that these rates are not absolute: they depend on age. For women above fifty-five, the incidence of breast cancer is high enough that even a relatively poor screening tool can detect an early baseline tumor and provide a survival benefit. For women between forty and fifty years, though, the incidence of breast cancer sinks to a point that a mass detected on a mammogram, more often than not, turns out to be a false positive. To use a visual analogy: a magnifying lens designed to make small script legible does perfectly well when the font size is ten or even six points. But then it hits a limit. At a certain size font, chances of reading a letter correctly become about the same as reading a letter incorrectly.

Modesty is a virtue, he would later write, yet one gets further without it.

Normalcy is the antithesis of evolution.

Probably the most important reason we are seeing more cancers than before is because the population is ageing overall. And cancer is an age-related disease.

Src was a prototypical kinase?although a kinase on hyperdrive. The protein made by the viral src gene was so potent and hyperactive that it reflexively phosphorylated anything and everything around it, including the antibody that Erikson had used to bind it. Src worked by unleashing a volley of phosphorylation?throwing on dozens of molecular switches. In src?s case, the activated series of proteins eventually impinged on proteins that controlled cell division. Src thus forcibly induced a cell to change its state from non-dividing to dividing, ultimately inducing accelerated mitosis, the hallmark of cancer.

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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