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The Gene: An Intimate History

Book by Siddhartha Mukherjee · 27 quotes · Gen, Genetics, Science

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The Gene: An Intimate History Quotes

“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.”

HumanityNatureDiversityVariationGeneticsMutationHuman Genome
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“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.”

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“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.”

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“The desire to categorize humans along racial lines, and the impulse to superpose attributes such as intelligence (or criminality, creativity, or violence) on those lines, illustrates a general theme concerning genetics and categorization. Like the English novel, or the face, say, the human genome can be lumped and split in a million different ways. But whether to split or lump, to categorize or synthesize, is a choice. ... The narrower the definition of the heritable feature or the trait, the more likely we will find a genetic locus for that trait, and the more likely we will find that the trait will segregate within some human sub-population.”

CategorizationCategorisationGenetic DeterminismRacial Categorisation
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“As with Dalton and the atom, neither Bateson nor Johannsen had any understanding of what a gene was. They could not fathom its material form, its physical or chemical structure, its location within the body or inside the cell, or even its mechanism of action. The word was created to mark a function; it was an abstraction. A gene was defined by what a gene does: it was a carrier of hereditary information. “Language is not only our servant,” Johannsen wrote, “[but] it may also be our master. It is desirable to create new terminology in all cases where new and revised conceptions are being developed. Therefore, I have proposed the word ‘gene.’ The ‘gene’ is nothing but a very applicable little word. It may be useful as an expression for the ‘unit factors’ . . . demonstrated by modern Mendelian researchers.” “The word ‘gene’ is completely free of any hypothesis,” Johannsen remarked. “It expresses only the evident fact that . . . many characteristics of the organism are specified . . . in unique, separate and thereby independent ways.”

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“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.”

InspirationalTechnologyBalanceGeneticsGenomicsDouble Edged SwordModern Genetics
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“...los lectores de la India y China quizá reconozcan, con cierta vergüenza y seriedad, que el mayor proyecto de -eugenesia negativa- de la historia de la humanidad no fue el del exterminio sistemático de los judíos en Alemania y Austria concebido en los años 30. Esta espantosa distinción la tienen India y China, donde faltan más de diez millones de mujeres debido al infanticidio, el aborto y el abandono de niñas.”

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“Biyolojide eskiden beri işlenegelen bir günah, özelliğin tanımıyla özelliğin kendisini birbirine karıştırmaktır. Örneğin ''güzellik'' tanımını mavi gözlü olma diye yaparsak, o zaman tabi ki de ''güzellik geni''ni bulabiliriz. ''Zeka''yı sırf belli bir testteki, sırf belli bir tip problemi çözme performansı olarak tanımlarsak, o zaman tabi ki ''zeka geni'' bulabiliriz. Genom kendi kurgularımızın genişliğinin veya darlığının bir aynasıdır yalnızca; Narkissos'un suda yansıyan yüzü.”

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“The universe seeks equilibriums; it prefers to disperse energy, disrupt organization, and maximize chaos. Life is designed to combat these forces. We slow down reactions, concentrate matter, and organize chemicals into compartments; we sort laundry on Wednesdays. "It sometimes seems as if curbing entropy is our quixotic purpose in the universe," James Gleick wrote. We live in the loopholes of natural laws, seeking extensions, exceptions and excuses. The laws of nature still mark the outer boundaries of permissibility - but life, in all its idiosyncratic, mad weirdness, flourishes by reading between the lines.”

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“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).”

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“Griffith, verilerini 'Journal of Hygiene' diye adını kimsenin duymamışlığı konusunda Mendel'i bile kıskandıracak bir dergide yayımladı. Süklüm püklüm bir tonla yazan Griffith, sanki genetik bilimi köklerinden sarstığı için özür diler gibiydi. Çalışmasında transformasyondan mikrobiyolojideki hoş bir ilginçlik gibi bahsediyor, ama kalıtımın kimyasal temelini keşfetmiş olabileceğine hiç değinmiyordu. Son on yılın en önemli biyokimya makalesinin en önemli sonucu, ağır metin yığının altında nazik bir öksürük gibi boğulup gitti.”

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“Genetik kod basittir: DNA'dan RNA inşa edilir, RNA'dan da protein inşa edilir. DNA'daki her baz üçlüsü, proteinde bir aminoasidi belirler. Oysa genomik kod karmaşıktır: Genin üzerinde, genin ne zaman ve nerede ifade edileceği ile ilgili bilgileri barındıran DNA parçaları vardır: Genlerin genom üzerindeki yerlerinin neye göre belirlenmiş olduğunu da bilmiyoruz. Genler arasındaki DNA bölgelerinin gen fizyolojisini nasıl düzenlediğini ve koordine ettiğini de bilmiyoruz. Dağların ötesinde dağların olması gibi, kodların ötesinde de kodlar vardır.”

GenGenom
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“Artık biliyoruz ki hücrelerin içinde viral genleri tanıyıp etkileşmelerini engelleyen kadim algılayıcıları var. Bu algılayıcılar viral geni saptadıktan sonra üstüne kimyasal işaretlerle ''kullanılmaz'' damgasını vuruyorlar. Demek ki genom kendini değiştirme işlemlerine uslu uslu boyun eğmiyordu. Sihirbazlar arasında eski bir söz vardır: Bir şeyi yok etmeyi öğrenmeden önce geri getirmeyi öğrensen iyi olur. Gen terapistleri bu dersi yeni baştan öğreniyorlardı. Bir geni hücrenin içine çaktırmadan yerleştirmek kolaydır. Asıl zorluk onu tekrar görünür kılmaktı.”

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“1980'lerden bu yana neredeyse otuz yıl boyunca, psikologlar ve genetikçiler aynı koşullarda büyütülmüş özdeş ikizlerin nasıl ıraksak gelişim yazgıları izlediklerini açıklayabilecek ince farkları belgelemeye ve ölçmeye çalıştılar. Fakat somut, ölçülebilir, sistematik farkları bulmak için yapılan tüm girişimler başarısız oldu: İkizler aynı ailede büyümelerine, aynı evde yaşamalarına, genelde aynı okula gitmelerine, neredeyse aynı yemekleri yemelerine, çoğu zaman aynı kitapları okumalarına, aynı arkadaş çevrelerine sahip olmalarına ve aynı kültürden beslenmelerine rağmen nasıl oluyorsa bariz biçimde birbirinden farklı oluyorlardı. Bu fark nereden kaynaklanıyordu? 20 yıl içinde yapılan 43 çalışma sonunda güçlü ve tutarlı bir yanıta ulaşıldı: ''sistematik olmayan, kendine özgü, tesadüfi olaylar''. Hastalıklar. Kazalar. Travmalar. Tetikleyiciler. Kaçırılmış bir tren; kayıp bir anahtar; kafayı kurcalayan bir düşünce. Moleküllerdeki oynamalar sonucu genlerde meydana gelen oynamalar; genlerdeki oynamalar sonucu biçimde meydana gelen oynamalar. Venedik'te bir kavisi dönerken kanala düşüp suya kapılmak. Aşka kapılmak. Hayatın tesadüfleri. Şans. Bu yanıt çileden çıkarıcı değil mi biraz? Onlarca yıllık araştırmaların ardından yazgıyı ortaya çıkaran şeyin sonuçta ... yazgı olduğunu mu söyleyeceğiz? Canlıları oldukları gibi yapan şey ... öyle olmalarıdır mı diyeceğiz? Bu formülasyonda çok aydınlatıcı bir güzellik var bence.”

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“Genler içinde bulundukları çevrelere programlanmış tepkiler gösterirler - yoksa korunan bir biçim olmazdı. Fakat aynı zamanda şansın kendine özgü kaprislerinin yapışması için de pay bırakırlar. Bu etkileşime ''yazgı'' diyoruz; kendimizin buna verdiği tepkimelere de ''seçim''. Konuşma yetisine sahip iki ayaklı ve dik yürüyen bir organizma, işte bu şekilde bir plan dahilinde, ama aynı zamanda planın dışına çıkmak üzere inşa edilir. Böyle bir organizmanın tek bir eşsiz varyantına ''birey'' deriz.”

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