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Oncologist
July 17, 1970
American
&
Indian
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Author
&
Oncologist
July 17, 1970
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.
Siddhartha Mukherjee
In God we trust. All others [must] have data. - Bernard Fisher
Siddhartha Mukherjee
And this was to save rats, right? Or mice? You spent all this money to save mice the problem of developing tumors?
Siddhartha Mukherjee
When a disease insinuates itself so potently into the imagination of an era, it is often because it impinges on an anxiety latent within that imagination. AIDS loomed so large on the 1980s in part because this was a generation inherently haunted by its sexuality and freedom; SARS set off a panic about global spread and contagion at a time when globalism and social contagion were issues simmering nervously in the West. 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.
Siddhartha Mukherjee
It was Disney World fused with Cancerland.
Siddhartha Mukherjee
Labs, too, can become machines. In science, it is more often a pejorative description than a complimentary one: an efficient, thrumming, technically accomplished laboratory is like a robot orchestra that produces perfectly pitched tunes but no music.
Siddhartha Mukherjee
The cure of even one solid cancer in adults, Farber knew, would singularly revolutionize oncology. It would provide the most concrete proof that this was a winnable war.
Siddhartha Mukherjee
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.
Siddhartha Mukherjee
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.
Siddhartha Mukherjee
McKusick's belief in this paradigm-the focus on disability rather than abnormalcy-was actualized in the treatment of patients in his clinic. Patients with dwarfism, for instance, were treated by an interdisciplinary team of genetic counselors, neurologists, orthopedic surgeons, nurses, and psychiatrists trained to focus on specific disabilities of persons with short stature. Surgical interventions were reserved to correct specific deformities as they arose. The goal was not to restore "normalcy"-but vitality, joy, and function. McKusic had rediscovered the founding principles of modern genetics in the realm of human pathology. In humans as in wild flies, genetic variations abounded. Here too genetic variants, environments, and gene-environment interactions ultimately collaborated to cause phenotypes-except in this case, the "phenotype" in question was disease. Here too some genes had partial penetrance and widely variable expressivity. One gene could cause many diseases, and one disease could be caused by many genes. And here too "fitness" could not be judged in absolutes. Rather the lack of fitness-illness [italicized, sic] in colloquial terms- was defined by the relative mismatch between an organism and environment.
Siddhartha Mukherjee
Nothing is invented; nothing is extraneous. Cancer's life is a recapitulation of the body's life, its existence a pathological mirror of our own [. . .] this is not a metaphor. Down to their innate molecular core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves.
Siddhartha Mukherjee
A furious researcher stumbled out of one of the lab buildings and shouted, 'I'm a scientist working on the AIDS cure. Why are you here? You are making too much noise.' It was a statement that epitomized the vast and growing rift between scientists and patients.
Siddhartha Mukherjee
Only one person was conspicuously missing from the (American Society of Clinical Oncology, ASCO) party - Dennis Slamon. Having spent the afternoon planning the next phase of Herceptin trials with breast oncologists at ASCO, Slamon had jumped into his rundown Nissan and driven home.
Siddhartha Mukherjee
Scientists divide. We discriminate. It is the inevitable occupational hazard of our profession that we must break the world into its constituent parts -- genes, atoms, bytes -- before making it whole again. We know of no other mechanism to understand the world: to create the sum of its parts, we must begin by dividing it into the parts of the sum.
Siddhartha Mukherjee
It is hard to look at the tumor and not come away with the feeling that one has encountered a powerful monster in its infancy
Siddhartha Mukherjee
Emblematic of this era was the prolific Viennese surgeon Theodor Billroth. Born in 1821, Billroth studied music and surgery with almost equal verve. (The professions still often go hand in hand. Both push manual skill to its limit; both mature with practice and age; both depend on immediacy, precision, and opposable thumbs.)
Siddhartha Mukherjee
If the history of the last century taught us the dangers of empowering governments to determine genetic “fitness” (i.e., which person fits within the triangle, and who lives outside it), then 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. And operating silently in the background is a third set of actors: our genes themselves, which reproduce and create new variants oblivious of our desires and compulsions— but, either directly or indirectly, acutely or obliquely, influence our desires and compulsions. Speaking at the Sorbonne in 1975, the cultural historian Michel Foucault once proposed that “a technology of abnormal individuals appears precisely when a regular network of knowledge and power has been established.” Foucault was thinking about a “regular network” of humans. But it could just as easily be a network of genes.
Siddhartha Mukherjee
History repeats itself, in part because the genome repeats itself. And the genome repeats itself, in part because history does. The impulses, ambitions, fantasies, and desires that drive human history are, at least in part, encoded in the human genome. And human history has, in turn, selected genomes that carry these impulses, ambitions, fantasies, and desires. This self-fulfilling circle of logic is responsible for some of the most magnificent and evocative qualities in our species, but also some of the most reprehensible. It is far too much to ask ourselves to escape the orbit of this logic, but recognizing its inherent circularity, and being skeptical of its overreach, might protect the week from the will of the strong, and the 'mutant' from being annihilated by the 'normal'.
Siddhartha Mukherjee
Freaks become norms, and norms become extinct. Monster by monster, evolution advanced
Siddhartha Mukherjee
Natures and features last until the grave
Siddhartha Mukherjee
Intelligence...[is] not marathon rac[e]: there is no fixed criteria for success, no start or finish lines -- and running sideways or backwards, might secure victory.
Siddhartha Mukherjee
Without equality, he argued, eugenics would degenerate into yet another mechanism by which the powerful could control the weak.
Siddhartha Mukherjee
History repeats, but science reverberates.
Siddhartha Mukherjee
Without equality, he argued, eugenics would degenerate into yet another mechanism by which the powerful could control the weak.
Siddhartha Mukherjee
History repeats, but science reverberates.
Siddhartha Mukherjee
If we define "beauty" as having blue eyes (and only blue eyes), then we will, indeed, find a "gene for beauty." If we define "intelligence" as the performance on only one kind of test, then we will, indeed, find a "gene for intelligence." The genome is only a mirror for the breadth or narrowness of human imagination.
Siddhartha Mukherjee