Siddhartha Mukherjee

Siddhartha
Mukherjee
1970

American Physician, Biological Scientist and Author, Awarded Pulitzer Prize for his book, The Emperor Of All Maladies: A Biography of Cancer

Author Quotes

The problem with racial discrimination, though, is not the inference of a person's race from their genetic characteristics. It is quite the opposite: it is the inference of a person's characteristics from their race. The question is not, can you, given an individual's skin color, hair texture, or language, infer something about their ancestry or origin. That is a question of biological systematics -- of lineage, taxonomy, of racial geography, of biological discrimination. Of course you can -- and genomics as vastly refined that inference. You can scan any individual genome and infer rather deep insights about a person's ancestry, or place of origin. But the vastly more controversial question is the converse: Given a racial identity -- African or Asian, say -- can you infer anything about an individual's characteristics: not just skin or hair color, but more complex features, such as intelligence, habits, personality, and aptitude?

There's a phrase in Shakespeare: he refers to it as the 'hidden imposthume', and this idea of a hidden swelling is seminal to cancer. But even in more contemporary writing it's called 'the big C'.

Two presentations, among all, stood out in their particularly chilling fervor. The first was an enthusiastic and precise exhibit by the Germans endorsing race hygiene?a grim premonition of times to come. Alfred

As early as the sixth century BC, ayurvedic practitioners in India had recognized the general symptoms of anemia.

But the pigs--seventy pounds of porcine weight that did not take kindly to weekly endoscopies--did not sprout any ulcers. And testing the theory on humans was ethically impossible: how could one justify infecting a human with a new, uncharacterized species of bacteria to prove that it caused gastritis and predisposed to cancer?

Cancer geneticists already knew two answers to this question. First proto-oncogenes need to be cultivated through mutations, and mutations are rare events. Second, tumor suppressor genes need to be inactivated, but typically two copies exist of each such tumor suppressor gene, and thus, two independent mutations are needed to inactivate a tumor suppressor, an even rare event. Vogelstein provided the third answer. Activating or inactivating any single gene, he postulated, produced only the first steps of a march toward carcinogenesis. Cancer?s march was long and slow and proceeded through many mutations in many genes over many iterations. In genetic terms, our cells were not sitting on the edge of the abyss of cancer. They were dragged toward that abyss in graded, discrete steps.

Carla had acute lymphoblastic leukemia. It is one of the most common forms of cancer in children, but rare in adults.

Every era casts illness in its own image. Society, like the ultimate psychosomatic patient, matches its medical afflictions to its psychological crises; when a disease touches such a visceral chord, it is often because that chord is already resonating.

He was willing to have faith in divine wisdom, but not in Halsted as divine wisdom. In God we trust, he brusquely told a journalist. All others [must] have data.

I had never expected medicine to be such a lawless, uncertain world. I wondered if the compulsive naming of parts, diseases, and chemical reactions? frenulum, otitis, glycolysis? was a mechanism invented by doctors to defend themselves against a largely unknowable sphere of knowledge. The profusion of facts obscured a deeper and more significant problem: the reconciliation between knowledge (certain, fixed, perfect, concrete) and clinical wisdom (uncertain, fluid, imperfect, abstract).

In 1940, after a prolonged and unsuccessful convalescence, Lasker?s mother died in Watertown. For Lasker, her mother?s death brought to a boil the fury and indignation that had been building within her for decades. She had found her mission. I am opposed to heart attacks and cancer, she would later tell a reporter, the way one is opposed to sin. Mary Lasker chose to eradicate diseases as some might eradicate sin?through evangelism. In people did not believe in the importance of a national strategy against diseases, she would convert them, using every means at her disposal.

In God we trust, he brusquely told a journalist. All others [must] have data.

In their respective papers, Temin and Baltimore proposed a radical new theory about the life cycle of retroviruses. Retroviruses, they postulated, exist as RNA outside cells. When these RNA viruses infect cells, they make a DNA copy of their genes and attach this copy to the cell?s genes. This DNA copy, called a provirus, makes RNA copies, and the virus is regenerated, phoenix-like, to form new viruses. The virus is thus constantly shuttling states, rising from the cellular genome and falling in again?RNA to DNA to RNA; RNA to DNA to RNA?ad infinitum.

It takes counterculture to counter culture ? and it was only inevitable, perhaps, that the sweeping political movements that gripped America in the 1960s and 1970s would shake the notions of general intelligence and IQ by their very roots. As the civil rights movement and feminism highlighted chronic political and social inequalities in America, it became evident that biological and psychological features were not just inborn but likely to be deeply influenced by context and environment. The dogma of a single form of intelligence was also challenged by scientific evidence.

Lung cancer incidence in men increased dramatically in the 1950s as a result of an increase in cigarette smoking during the early twentieth century. In women, a cohort that began to smoke in the 1950s, lung cancer incidence has yet to reach its peak.

Neither variant was morally or biologically superior; each was just more or less adapted to a particular environment.

Penicillin, that precious chemical that had to be milked to its last droplet during World War II (in 1939, the drug was re-extracted from the urine of patients who had been treated with it to conserve every last molecule), was by the early fifties being produced in thousand-gallon vats. In 1942, when Merck had shipped out its first batch of penicillin?a mere five and a half grams of the drug?that amount represented had been half of the entire stock of the antibiotic in America.

Second, proto-oncogenes and tumor suppressor genes typically lie at the hubs of cellular signaling pathways.

The approach required more persistence than imagination, but it produced remarkable results.

The Human Genome Project, the full sequence of the normal human genome, was completed in 2003. In its wake comes a far less publicized but vastly more complex project: fully sequencing the genomes of several human cancer cells. Once completed, this effort, called The Cancer Genome Atlas, will dwarf the human genome in its scope. The sequencing effort involves dozens of teams of researchers across the world. The initial list of cancers to be sequenced includes brain, lung, pancreatic, and ovarian cancer. The Human Genome Project will provide the normal genome, against which cancer?s abnormal genome can be juxtaposed and contrasted. The result, as Francis Collins, the leader of the Human Genome Project describes it, will be a ?colossal atlas? of cancer?a compendium of every gene mutated in the most common forms of cancer: ?When applied to the 50 most common types of cancer, this effort could ultimately prove to be the equivalent of more than 10,000 Human Genome Projects in terms of the sheer volume of DNA to be sequenced. The dream must therefore be matched with an ambitious but realistic assessment of the emerging scientific opportunities for waging a smarter war.? The only metaphor that can appropriately describe this project is geological. Rather than understand cancer gene by gene, The Cancer Genome Atlas will chart the entire territory of cancer: by sequencing the entire genome of several tumor types, every single mutated gene will be identified. It will represent the beginnings of the comprehensive ?map? so hauntingly presaged by Maggie Jencks in her last essay.

The question that confronts our current era is what happens when this power devolves to the individual. It is a question that requires us to balance the desires of the individual?to carve out a life of happiness and achievement, without undue suffering?with the desires of a society that, in the short term, may be interested only in driving down the burden of disease and the expense of disability.

These rhetorical and historical shifts in the concept of intelligence are worth noting, for we will return to them in a few paragraphs. General intelligence (g) originated as a statistical correlation between tests given under particular circumstances to particular individuals. It morphed into the notion of ?general intelligence? because of a hypothesis concerning the nature of human knowledge acquisition. And it was codified into ?IQ? to serve the particular exigencies of war. In a cultural sense, the definition of g was an exquisitely self-reinforcing phenomenon: those who possessed it, anointed as ?intelligent? and given the arbitration of the quality, had every incentive in the world to propagate its definition.

Unidentified flying objects, abominable snowmen, the Loch Ness monster and human cancer viruses. ?Medical World News, 1974, on four mysteries widely reported and publicized but never seen

As the saying ran, was one night with Venus, followed by a thousand nights with mercury.

But the story of leukemia--the story of cancer--isn't the story of doctors who struggle and survive, moving from institution to another. It is the story of patients who struggle and survive, moving from on embankment of illness to another. Resilience, inventiveness, and survivorship--qualities often ascribed to great physicians--are reflected qualities, emanating first from those who struggle with illness and only then mirrored by those who treat them. If the history of medicine is told through the stories of doctors, it is because their contributions stand in place of the more substantive heroism of their patients.

First Name
Siddhartha
Last Name
Mukherjee
Birth Date
1970
Bio

American Physician, Biological Scientist and Author, Awarded Pulitzer Prize for his book, The Emperor Of All Maladies: A Biography of Cancer