The Gene: An Intimate History

“Freaks became norms, and norms became extinct. Monster by monster, evolution advanced.”

These lines illustrate the recursive relationship between mutations and “normal” species, invoking The Shifting Line Between Normalcy and Mutation. In crude terms, a normal species can be defined as a majority, but the majority itself starts off as a minority of one. The circular equation between “freaks” and “norms” shows the definitions of normalcy are contextual and shifting.

“The crucial driver of evolution, Darwin understood, was not nature’s sense of purpose, but her sense of humor.”

Mukherjee examines Darwin’s word for mutations—“sports”—to illustrate something fundamental about the great scientist’s understanding of nature. Darwin instinctually grasped that trying out mutations is nature’s way of being creative, playful, and funny. People may try to attach purpose and design to evolution, but it is a neutral process driven by nature’s love for experimentation.

“In the early 1850s, Mendel had tried a more audacious variation of his experiment, starting with white and grey field mice. He had bred mice in his room […] but the abbot, although generally tolerant of Mendel’s whims, had intervened: a monk coaxing mice to mate to understand heredity was a little too risqué, even for the Augustinians […] He drew the line at mice, but didn’t mind giving peas a chance.”

This passage is an example of Mukherjee’s use of humor to enliven the narrative. The permissive abbot drawing the line at a monk deliberately mating mice is a warm, humorous image that humanizes Mendel’s story for the reader.

“‘Modesty is a virtue,’ he would later write, ‘yet one gets further without it.’”

This line, attributed to Hugo de Vries, illustrates a running motif in the text: Scientists denied their share of glory because of their reticence, and scientists taking glory for themselves without offering due credit to lesser-known peers. A linear narrative of scientific achievement may suggest that every major scientific discovery is immediately feted, but the truth is science is filled with unsung heroes, such as Mendel, the subject of de Vries’s observation. Success in scientific fields owes itself as much to genius, as it does to ambition and lobbying. De Vries himself did not do much to bring Mendel to the world’s attention, deliberately ignoring his debt to Mendel when publishing his own research.

“When power is discovered, man always turns to it […] The science of heredity will soon provide power on a stupendous scale […] that power will be applied to control the composition of a nation.”

Writing decades before the excesses of Nazism, Bateson is shown as remarkably prescient about the dangers of genetic knowledge, speaking to The Ethics of Eugenics and Gene Editing in Policy and Medicine. This passage also highlights how scientific knowledge can be misused as a source of “power” instead of as a humane undertaking meant to better life for everyone, leading to atrocities like genocide under the Nazis when exploited by tyrannical regimes.

 “He walked through England and Scotland tabulating ‘beauty’—secretly ranking the women he met as ‘attractive,’ ‘indifferent’ or ‘repellent’ […] It seemed no human attribute could escape Galton’s sifting […] eye: ‘Keenness of Sight and Hearing, Color Sense, Judgement of Eye; Breathing Power.’”

Galton appears a ridiculous and very sexist figure in this passage, secretly assessing people for qualities as unquantifiable as “color sense”; yet, his intent and actions were anything but laughable. Behind the strange assessment was the desire to break down humans into the narrowest categories, discarding anyone short of his idea of perfection and revealing his own biases.

“It is difficult to describe what happened next—except to say that it is a moment that occurs uniquely in the history of refugees. A tiny bolt of understanding passed between them. The woman recognized my father—not the actual man, whom she had never met, but the form of the man: a boy returning home. In Calcutta—in Berlin, Peshawar, Delhi, Dhaka—men like this seem to turn up every day, appearing out of nowhere off the streets and walking unannounced into houses, stepping casually over thresholds into their past.”

This passage is an example of Mukherjee’s lyrical writing style, and also illustrates one of the book’s subtler themes: The shared experience of humanity. Throughout the book, Mukherjee stresses that all humans come from a relatively small pool of DNA, perhaps a single tribe in sub-Saharan Africa. The genetic similarity is mirrored in the universality of experience, with the unknown woman and Mukherjee’s father coming to an understanding because both know the gestures of displacement. Mukherjee further links his father’s gesture with the actions of returning refugees all over the world, whether in Berlin or Calcutta.

“‘Seek simplicity, but distrust it,’ Alfred North Whitehead, the mathematician and philosopher, once advised his students. Dobzhansky had sought simplicity—but he had also issued a strident moral warning against the oversimplification of the law of genetics.”

Whitehead’s oft-quoted maxim highlights the critical difference between seeking the simple elegance that underlines most physical and natural laws and using it to for a reductive understanding of lived reality. Dobzhansky, who was one of the most vocal scientific critics of Nazi eugenics, may have devised the simple, profound equation that genotype + environment determines phenotype, but he was also categoric that the principle should not be used to make distorted inferences about actual human beings, reflecting the importance of Heredity, Environment, and Chance Resisting Simple Determinism.

“The word genocide shares its root with gene—and for good reason: the Nazis used the vocabulary of genes and genetics to launch, justify, and sustain their agenda.”

The link between eugenics and the mass murder of the Jewish and Roma people is sometimes undermined, but Mukherjee shows the profound impact eugenics had on Nazi policy, invoking the problem of The Ethics of Eugenics and Gene Editing in Policy and Medicine. While deep antisemitism was the political impetus behind the genocide, its instrument was genetic elimination. Language itself asserts this connection, with “gene” and “genocide” sharing the same root: Gen, which means origin or birth. The Nazis wanted to root out “inferior” races from the very root.

“Junk science props up totalitarian regimes. And totalitarian regimes produce junk science.”

Mukherjee’s observation about Nazi Germany and Soviet Russia has relevance for the contemporary age as well, with extreme right-wing politicians stoking fears about population decline, the effect of vaccines on health and fertility, and women’s right to terminate pregnancies. The passage also speaks to The Ethics of Eugenics and Gene Editing in Policy and Medicine, as corrupt regimes can twist scientific advances for their own ends.

“In a conceptual sense, every virus is a professional gene carrier. Viruses have a simple structure: they are often no more than a set of genes wrapped inside a coat—a ‘piece of bad news wrapped in a protein coat,’ as Peter Medawar, the immunologist, had described them. When a virus enters a cell, it sheds its coat, and begins to use the cell as a factory to copy its genes, and manufacture new coats, resulting in millions of new viruses budding out of the cell.”

As this passage shows, Mukherjee uses figurative language to unpack scientific concepts for the general reader. The virus is presented as a single-minded infiltrator that has jettisoned all accessories so it can easily enter cells. Inside the cell, it gets right down to business, jumping into cells and copying its simple genetic material to create clones. Thankfully for scientists, the simple structure of the virus means it can be used as a vector to sneak in other cellular material inside cloning factories.

“Introns are not the exception in human genes; they are the rule. Human introns are often enormous-spanning several hundreds of thousands of bases of DNA. And genes themselves are separated from each other by long stretches of intervening DNA, called intergenic DNA […] To return to our analogy; these regions might be described as long ellipses scattered with occasional punctuation marks. The human genome can thus be visualized as:

This……is…………the……(…)…s…truc…ture……of……your……gen…om…e.”

This passage is an example of Mukherjee’s use of visual analogy to explain a concept or structure. The visual immediately helps the reader see that DNA is filled with stuffers and gaps, much as the universe is filled with vast stretches of seemingly empty space.

“There are codes beyond codes, like mountains beyond mountains.”

This sentence highlights Mukherjee’s use of visual imagery to make an abstract concept real: The mysteries of the genomic code are as endless as an endless horizon of mountains. The line also illustrates the fact that despite all that is known about human genes, most of it is completely unknown.

“The exclusively female origin of all the mitochondria in an embryo has an important consequence. All humans—male or female—must have inherited their mitochondria from their mothers, who inherited their mitochondria from their mothers, and so forth, in an unbroken line of female ancestry stretching indefinitely into the past […] Each of us can trace our mitochondrial lineage to a single human female who existed in Africa about two hundred thousand years ago […] I find the idea of such a founding mother endlessly mesmerizing. In human genetics, she is known by a beautiful name—Mitochondrial Eve.”

One of the subtler jokes running through the book is that while early theories centered the male as the dominant principle in heredity, science has proven the female is at least equally as relevant. The homunculus may have been a fallacy, but a “femunculus” is closer to truth. The Mitochondrial Eve also highlights the fact that all modern humans come from a relatively narrow gene pool, and thus, are one large tribe at the genetic level.

“As a consequence of this constant genetic bombardment, the human Y chromosome began to jettison information millions of years ago. […] As information was lost, the Y chromosome itself shrank—whittled down piece by piece by the mirthless cycle of mutation and gene loss. That the Y chromosome is the smallest of all chromosomes is not a coincidence: it is largely a victim of planned obsolescence […] Male readers of that last paragraph should take notice: we barely made it.”

Another example of Mukherjee’s subtle dig at the male-centered world-view which has long-dominated science, this passage shows how at the cellular level, maleness is as vulnerable as any other attribute. The lines also provide a comprehensive description of the Y chromosome. Scientists now theorize that the Y chromosome was almost made obsolete, before nature “saved” it by implanting it with a very critical genes, prolonging its relevance.

 “The existence of a transgender identity provides powerful evidence for this geno-developmental cascade. In an anatomical and physiological sense, sex identity is quite binary: just one gene governs sex identity, resulting in the striking anatomical and physiological dimorphism that we observe between males and females. But gender and gender identity are far from binary. Imagine a gene—call it TGY—that determines how the brain responds to SRY (or some other male hormone or signal). One child might inherit a TGY gene variant that is highly resistant to the action of SRY on the brain, resulting in a body that is anatomically male, but a brain that does not read or interpret that male signal. Such a brain might recognize itself as psychologically female; it might consider itself neither male or female, or imagine itself belonging to a third gender altogether.”

The critical insight of this passage is that gender identity—even when it differs from physiological sex—is influenced by genes. Through providing a genetic explanation for gender identity, Mukherjee provides an effective counter to arguments about gender dysphoria being “conditioning” or “confusion.”

“A note of caution: epigenetics is also on the verge of transforming into a dangerous idea. Epigenetic modifications of genes can potentially superpose historical and environmental information on cells and genomes—but this capacity is speculative, limited, idiosyncratic, and unpredictable […] Most epigenetic ‘memories’ are the consequence of ancient evolutionary pathways, and cannot be confused with our longing to affix desirable legacies on our children.”

This passage highlights the maxim against applying simple scientific concepts to lived reality. Many people misconstrue the concept of epigenetics as an ability to influence the fetus or the next generation, such as expectant mothers being pressurized to take supplements to prevent autism in the child. The truth is epigenetics is governed by its own laws, largely out of the active intervention of human beings.

“‘We of the craft are all crazy,’ Lord Byron, the high priest of crazies, wrote. ‘Some are affected by gaiety, others by melancholy, but all are more or less touched.’”

An example of Mukherjee’s use of allusion from the world of literature, this quote argues that the extremes of emotion that drive certain mental health conditions are also associated with increased creative output. Extraordinary writers like Byron himself, Sylvia Plath, and Anne Sexton all dealt with low phases. Given this contradictory fact, the very term “crazy” ought to be destigmatized and reevaluated, adding a poetic dimension to The Shifting Line Between Normalcy and Mutation.

“The largest ‘negative eugenics’ project in human history was not the systemic extermination of Jews in Nazi Germany or Austria in the 1930s. That ghastly distinction falls on India and China, where more than 10 million female children are missing from adulthood because of infanticide, abortion, and neglect of female children.”

Mukherjee uses the examples of India and China to show how even seemingly innocuous technologies, such as fetal ultrasounds, amniocentesis, and PGT, can be used to ghastly ends, such as the killing of girls in utero and at birth just because of their female sex. The use of sex-selection tools to identify and kill girls also shows that the worst crimes sometimes happen in ordinary, everyday settings.

“It is a peculiar modern fallacy to imagine that the definitive solution to illness is to change nature—i.e., genes—when the environment is often more malleable.”

With modern medicine focused on a “cure,” it often loses sight of the fact that illnesses can be managed more easily by changing the environment of the patient. The cure-focused approach ends up further stigmatizing illness, as it unintentionally implies that anything short of perfect, “normal” health is undesirable.

“History repeats itself, in part because the genome repeats itself. And the genome repeats itself, in part because history does […] 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.”

Mukherjee uses an extended simile to describe how both the constancy and variance of the human genome is reflected in the extremes of human behavior. More importantly, this means some humans are likely to repeat the crimes of the past, such as eugenics. Therefore, as technology evolves, society and culture must remain vigilant about protecting those at the margins, never forgetting that in nature, the marginal is also a norm.

“‘Show me that you can divide the notes of a song;

But first, show me that you can discern

Between what can be divided.

And what cannot.’

—An anonymous musical composition inspired by a classical Sanskrit poem.”

Mukherjee prefaces all the parts and chapters in the book with epigraphs from literature, science and popular culture to cast their contents in a fresh light. The epigraph from the Epilogue derives from a popular, anonymous song based on the philosophy of Advaita Vedanta, which argues that the part is indivisible from the whole, just as a song is indivisible from a note, and the soul is indivisible from divinity. In the context of the book, the song implies that while scientists introduce categories and distinctions to understand the world, human experience itself cannot be reduced to components.

“Illness might progressively vanish, so might identity. Grief might be diminished, but so might tenderness. Traumas might be erased but so might history. Infirmities might disappear, but so might vulnerability. Chance would become mitigated, but so, inevitably, would choice.”

These lines sum up a provocative thought experiment, questioning whether the end of physical suffering or extremes of emotion could fundamentally change what it means to be human. It also serves as a reminder that separating supposedly “desirable” traits from “undesirable” ones is often not as straightforward as it may seem.