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Siddhartha Mukherjee

Siddhartha Mukherjee Quotes

Physician

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“But what *is* "natural"? I wonder. On one hand: variation, mutation, change, inconstancy, divisibility, flux. And on the other: constancy, permanence, indivisibility, fidelity. Bhed. Abhed. It should hardly surprise us that DNA, the molecule of contradictions, encodes an organism of contradictions. We seek constancy in heredity—and find its opposite: variation. Mutants are necessary to maintain the essence of our selves. Our genome has negotiated a fragile balance between counterpoised forces, pairing strand with opposing strand, mixing past and future, pitting memory against desire. It is the most human of all things that we possess. Its stewardship may be the ultimate test of knowledge and discernment for our species.”

“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? /I/ Genes can certainly tell us about race, but can race tell us anything about genes? /i/ To answer this question, we need to measure how genetic variation is distributed across various racial categories. Is there more diversity _within_ races or _between_ races? Does knowing that someone is of African versus European descent, say, allow us to refine our understanding of their genetic traits, or their personal, physical, or intellectual attributes in a meaningful manner? Or is there so much variation within Africans and Europeans that _intraracial_ diversity dominates the comparison, thereby making the category "African" or "European" moot? 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 Nigria is so "different" from another man from Namibia that it makes little sense to lump them into the same category.”

“Ants have a powerful caste system. A colony typically contains ants that carry out radically different roles and have markedly different body structures and behaviors. These roles, Reinberg learned, are often determined not by genes but by signals from the physical and social environment. 'Sibling ants, in their larval stage, become segregated into the different types based on environmental signals,' he said. 'Their genomes are nearly identical, but the way the genes are used—turned on or off, and kept on or off—must determine what an ant "becomes." It seemed like a perfect system to study epigenetics. And so Shelley and I caught a flight to Arizona to see Jürgen Liebig, the ant biologist, in his lab.' The collaboration between Reinberg, Berger, and Liebig has been explosively successful—the sort of scientific story ('two epigeneticists walk into a bar and meet an entomologist') that works its way into a legend. Carpenter ants, one of the species studied by the team, have elaborate social structures, with queens (bullet-size, fertile, winged), majors (bean-size soldiers who guard the colony but rarely leave it), and minors (nimble, grain-size, perpetually moving foragers). In a recent, revelatory study, researchers in Berger’s lab injected a single dose of a histone-altering chemical into the brains of major ants. Remarkably, their identities changed; caste was recast. The major ants wandered away from the colony and began to forage for food. The guards turned into scouts. Yet the caste switch could occur only if the chemical was injected during a vulnerable period in the ants’ development. [...] The impact of the histone-altering experiment sank in as I left Reinberg’s lab and dodged into the subway. [...] All of an ant’s possible selves are inscribed in its genome. Epigenetic signals conceal some of these selves and reveal others, coiling some, uncoiling others. The ant chooses a life between its genes and its epigenes—inhabiting one self among its incipient selves.”

“When scientists underestimate complexity, they fall prey to the perils of unintended consequences. The parables of such scientific overreach are well-known: foreign animals, introduced to control pests, become pests in their own right; the raising of smokestacks, meant to alleviate urban pollution, releases particulate effluents higher in the air and exacerbates pollution; stimulating blood formation, meant to prevent heart attacks, thickens the blood and results in an increased risk of blood clots in the heart. But when nonscientists overestimate [italicized, sic] complexity- 'No one can possibly crack this [italicized, sic] code" - they fall into the trap of unanticipated consequences. In the early 1950s , a common trope among some biologists was that the genetic code would be so context dependent- so utterly determined by a particular cell in a particular organism and so horribly convoluted- that deciphering it would be impossible. The truth turned out to be quite the opposite: just one molecule carries the code, and just one code pervades the biological world. If we know the code, we can intentionally alter it in organisms, and ultimately in humans. Similarly, in the 1960s, many doubted that gene-cloning technologies could so easily shuttle genes between species. by 1980, making a mammalian protein in a bacterial cell, or a bacterial protein in a mammalian cell, was not just feasible, it was in Berg's words, rather "ridiculously simple." Species were specious. "Being natural" was often "just a pose.”

“Most notably, perhaps, children with Down syndrome have an extraordinary sweetness of temperament, as if in inheriting an extra chromosome they had acquired a concomitant loss of cruelty and malice (if there is any doubt that genotypes can influence temperament or personality, then a single encounter with a Down child can lay that idea to rest).”