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

Should I refuse my dinner because I don?t understand the digestive system?

The art of medicine is long, Hippocrates tells us, and life is short; opportunity fleeting; the experiment perilous; judgment flawed.

The idea of preventive medicine is faintly un-American. It means, first, recognizing that the enemy is us.

The radical mastectomy is rarely, if ever, performed by surgeons today.

Third, the relentless cycle of mutation, selection, and survival creates a cancer cell that has acquired several additional properties besides uncontrolled growth.

Viewed thus, the cancer genome is at first glance a depressing place. Mutations litter the chromosomes. In individual specimens of breast and colon cancer, between fifty to eighty genes are mutated; in pancreatic cancer about fifty to sixty. Even brain cancers, which often develop at earlier ages and hence may be expected to accumulate fewer mutations, possess about forty to fifty mutated genes. Only a few cancers are notable exceptions to this rule, possessing relatively few mutations across the genome. One of these is an old culprit, acute lymphoblastic leukemia: only five or ten mutations cross its otherwise pristine genomic landscape. Indeed, the relative paucity of genetic aberrancy in this leukemia may be one reason that this tumor is so easily felled by cytotoxic chemotherapy. Scientists speculate that genetically simple tumors (i.e., those carrying few mutations) might inherently be more susceptible to drugs, and thus intrinsically more curable. If so, the strange discrepancy between the success of high-dose chemotherapy in curing leukemia and its failure to cure most other cancers has a deep biological explanation. The search for a ?universal cure? for cancer was predicated on a tumor that, genetically speaking, is far from universal.

At 4:17 p.m. EDT on July 20, 1969, a fifteen-ton spacecraft moved silently through the cold, thin atmosphere above the moon and landed on a rocky basalt crater on the lunar surface. A vast barren landscape?a magnificent desolation?stretched out around the spacecraft. It suddenly struck me, one of the two astronauts would recall, that that tiny pea, pretty and blue, was the earth. I put up my thumb and shut one eye, and my thumb blotted out the planet.

But these two traditional Achilles? heels of cancer?local growth and rapid cell division?can only be targeted to a point. Surgery and radiation are intrinsically localized strategies, and they fail when cancer cells spread beyond the limits of what can be surgically removed or irradiated. More surgery thus does not lead to more cures, as the radical surgeons discovered to their despair in the 1950s. Targeting cellular growth also hits a biological ceiling because normal cells must grow as well. Growth may be the hallmark of cancer, but it is equally the hallmark of life. A poison directed at cellular growth, such as vincristine or cisplatin, eventually attacks normal growth, and cells that grow most rapidly in the body begin to bear the collateral cost of chemotherapy. Hair falls out. Blood involutes. The lining of the skin and gut sloughs off. More drugs produce more toxicity without producing cures, as the radical chemotherapists discovered to their despair in the 1980s.

Cancer is a flaw in our growth, but this flaw is deeply entrenched in ourselves.

Children with cancer, as one surgeon noted, were typically tucked in the farthest recesses of the hospital wards. They were on their deathbeds anyway, the pediatricians argued; wouldn?t it be kinder and gentler, some insisted, to just let them die in peace?

Facebook users have higher levels of total narcissism, exhibitionism, and leadership than Facebook nonusers, the study?s authors wrote. In fact, it could be argued that Facebook specifically gratifies the narcissistic individual?s need to engage in self-promoting and superficial behavior.

History repeats, but science reverberates.

I think the cardinal rule of learning to write is learning to read first. I learned to write by learning to read.

In 1982, Weinberg, Barbacid, and Wigler independently published their discoveries and compared their results. It was a powerful, unexpected convergence: all three labs had isolated the same fragment of DNA, containing a gene called ras, from their respective cancer cells. Like src, ras was also a gene present in all cells. But like src again, the ras gene in normal cells was functionally different from the ras present in cancer cells. In normal cells, the ras gene encoded a tightly regulated protein that turned ?on? and ?off? like a carefully modulated switch. In cancer cells, the gene was mutated, just as Varmus and Bishop had predicted. Mutated ras encoded a berserk, perpetually hyperactive protein permanently locked ?on.? This mutant protein produced an unquenchable signal for a cell to divide?and to keep dividing. It was the long-sought ?native? human oncogene, captured in flesh and blood out of a cancer cell. ?Once we had cloned a cancer gene,? Weinberg wrote, ?the world would be at our feet.? New insights into carcinogenesis, and new therapeutic inroads would instantly follow. ?It was? as Weinberg would later write, all ?a wonderful pipedream.?

In late 1970, faced with the daily brunt of negative publicity, tobacco makers voluntarily withdrew cigarette advertising from broadcast media (thus nullifying the need for a proportional representation of antitobacco commercials). The last cigarette commercial was broadcast on television on January 1, 1971. At 11:59 p.m., on the first night of the New Year, the Virginia Slims slogan You?ve come a long way, baby flashed momentarily on TV screens, then vanished forever. Talman had already died in 1968 of lung cancer that had metastisized to his liver, bones, and brain.

Indeed, cancer?s emergence in the world is the product of a double negative: it becomes common only when all other killers themselves have been killed.

It was, I suspected, not the first time that a patient had consoled a doctor about the ineffectuality of his discipline.

Medicine, I said, begins with storytelling. Patients tell stories to describe illness; doctors tell stories to understand it. Science tells its own story to explain diseases.

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

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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