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

I began wondering, can one really write a biography of an illness? But I found myself thinking of cancer as this character that has lived for 4,000 years, and I wanted to know what was its birth, what is its mind, its personality, its psyche?

If we, as a species, are the ultimate product of Darwinian selection, then so, too, is this incredible disease that lurks inside us.

In an essay titled A View From the Front Line, Jencks described her experience with cancer as like being woken up midflight on a jumbo jet and then thrown out with a parachute into a foreign landscape without a map: There you are, the future patient, quietly progressing with other passengers toward a distant destination when, astonishingly (Why me?) a large hole opens in the floor next to you. People in white coats appear, help you into a parachute and ? no time to think ? out you go. You descend. You hit the ground... But where is the enemy? What is the enemy? What is it up to?... No road. No compass. No map. No training. Is there something you should know and don't? The white coats are far, far away, strapping others into their parachutes. Occasionally they wave but, even if you ask them, they don't know the answers. They are up there in the Jumbo, involved with parachutes, not map-making.

In the glass-paneled sanatorium where patients walked for leisure, Alsop recalled, the windows were covered in heavy wire mesh to prevent the men and women confined in the wards from jumping off the banisters and committing suicide.

It is here that an insight enters our discussion?and it might sound peculiar at first: a test can only be interpreted sanely in the context of prior probabilities.

Like musicians, like mathematicians?like elite athletes?scientists peak early and dwindle fast. It isn?t creativity that fades, but stamina: science is an endurance sport. To produce that single illuminating experiment, a thousand non-illuminating experiments have to be sent into the trash; it is battle between nature and nerve. Avery

Mutations litter the chromosomes. In individual specimens of breast and colon cancer, between fifty to eighty genes are mutated; in pancreatic cancers, 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 genetic alterations 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. In

One swallow is a coincidence, but two swallows make summer.

Science begins with counting. To understand a phenomenon, a scientist must first describe it; to describe it objectively, he must first measure it.

Syphilis?the secret malady of eighteenth-century Europe?was a sensational illness, a

The discipline of medicine concerns the manipulation of knowledge under uncertainty.

The novelist Thomas Wolfe, recalling a lifelong struggle with illness, wrote in his last letter, I?ve made a long voyage and been to a strange country, and I?ve seen the dark man very close. I had not made the journey myself, and I had only seen the darkness reflected in the eyes of others. But surely, it was the most sublime moment of my clinical life to have watched that voyage in reverse, to encounter men and women returning from the strange country?to see them so very close, clambering back.

There is a duality in recognizing what an incredible disease it is - in terms of its origin, that it emerges out of a normal cell. It's a reminder of what a wonderful thing a normal cell is. In a very cold, scientific sense, I think a cancer cell is a kind of biological marvel.

To understand cancer as a whole, he reasoned, you needed to start at the bottom of its complexity, in its basement.

Writing anything as an expert is really poisonous to the writing process, because you lose the quality of discovery.

An emerging, though highly controversial, answer to this question is that cancer?s immortality, too, is borrowed from normal physiology. The human embryo and many of our adult organs possess a tiny population of stem cells that are capable of immortal regeneration. Stem cells are the body?s reservoir of renewal. The entirety of human blood, for instance, can arise from a single, highly potent blood-forming stem cell (call a hematopoietic stem cell), which typically lives buried inside the bone marrow. Under normal conditions, only a fraction of these blood-forming stem cells are active; the rest are deeply quiescent?asleep. But if blood is suddenly depleted, by injury or chemotherapy say, then the stem cells awaken and begin to divide with awe-inspiring fecundity, generating cells that generate thousands upon thousands of blood cells. In weeks, a single hematopoietic stem cell can replenish the entire human organism with new blood?and then, through yet unknown mechanisms, lull itself back to sleep.

But the activated ras pathway (Ras?>Mek?>Erk) does not merely cause accelerated cell division; the pathway also intersects with other pathways to enable several other ?behaviors? of cancer cells. At Children?s Hospital in Boston in the 1990s, the surgeon-scientist Judah Folkman demonstrated that certain activated signaling pathways within cancer cells, Ras among them, could also induce neighboring blood vessels to grow. A tumor could thus ?acquire? its own blood supply by insidiously inciting a network of blood vessels around itself and then growing, in grapelike clusters, around those vessels, a phenomenon that folkman called tumor angiogenesis.

By the time Virchow died in 1902, a new theory of cancer had slowly coalesced out of all these observations. Cancer was a disease of pathological hyperplasia in which cells acquired an autonomous will to divide. This aberrant, uncontrolled cell division created masses of tissue (tumors) that invaded organs and destroyed normal tissues. These tumors could also spread from one site to another, causing outcroppings of the disease?called metastasis?in distant sites, such as the bones, the brain, or the lungs. Cancer came in diverse forms?breast, stomach, skin, and cervical cancer, leukemias and lymphomas. But all these diseases were deeply connected at the cellular level. In every case, cells had acquired the same characteristic: uncontrollable pathological cell division.

Cancer, perhaps, is an ultimate perversion of genetics?a genome that becomes pathologically obsessed with replicating itself.

Etymologically, patient means sufferer. It is not suffering as such that is most deeply feared but suffering that degrades. ?Susan Sontag, Illness as Metaphor

Great science emerges out of great contradiction.

I believe the biggest breakthroughs on cancer could come from brilliant researchers based in India.

In 1788, the Chimney Sweepers Act was passed in Parliament, preventing master sweeps from employing children under eight (children over eight were allowed to be apprenticed).

In August 1867, a thirteen-year-old boy who had severely cut his arm while operating a machine at a fair in Glasgow was admitted to Lister?s infirmary. The boy?s wound was open and smeared with grime?a setup for gangrene. But rather than amputating the arm, Lister tried a salve of carbolic acid, hoping to keep the arm alive and uninfected. The wound teetered on the edge of a terrifying infection, threatening to become an abscess. But Lister persisted, intensifying his application of carbolic acid paste. For a few weeks, the whole effort seemed hopeless. But then, like a fire running to the end of a rope, the wound began to dry up. A month later, when the poultices were removed, the skin had completely healed underneath.

In the laboratory, we call this the six-degrees-of-separation-from-cancer rule: you can ask any biological question, no matter how seemingly distant?what makes the heart fail, or why worms age, or even how birds learn songs?and you will end up, in fewer than six genetic steps, connecting with a proto-oncogene or tumor suppressor.

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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