The Gene: An Intimate History

by Siddhartha Mukherjee

Human beings are ultimately nothing but carriers—passageways—for genes. They ride us into the ground like racehorses from generation to generation. Genes don’t think about what constitutes good or evil. They don’t care whether we are happy or unhappy. We’re just means to an end for them. The only thing they think about is what is most efficient for them. —Haruki Murakami, 1Q84

Martin Neimöller, the German theologian, summarized the slippery march of evil in his often-quoted statement: First they came for the Socialists, and I did not speak out— Because I was not a Socialist. Then they came for the Trade Unionists, and I did not speak out— Because I was not a Trade Unionist. Then they came for the Jews, and I did not speak out— Because I was not a Jew. Then they came for me—and there was no one left to speak out for me.

Science [would be] ruined if—like sports—it were to put competition above everything else. —Benoit Mandelbrot

Stripped to its bare essence, a medicinal chemical—a drug—is nothing more than a molecule that enables a therapeutic change in human physiology.

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Our ability to read out this sequence of our own genome has the makings of a philosophical paradox. Can an intelligent being comprehend the instructions to make itself? —John Sulston

For modern humans, that number has reached one: each of us can trace our mitochondrial lineage to a single human female who existed in Africa about two hundred thousand years ago. She is the common mother of our species. We do not know what she looked like, although her closest modern-day relatives are women of the San tribe from Botswana or Namibia. I find the idea of such a founding mother endlessly mesmerizing. In human genetics, she is known by a beautiful name—Mitochondrial Eve.

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. These men (or women) have something akin to a Swyer syndrome of identity: their chromosomal and anatomical gender is male (or female), but their chromosomal/anatomical state does not generate a synonymous signal in their brains. In rats, notably, such a syndrome can be caused by changing a single gene in the brains of female embryos or exposing embryos to a drug that blocks the signaling of “femaleness” to the brain. Female mice engineered with this altered gene or treated with this drug have all the anatomical and physiological features of femaleness, but perform the activities associated with male mice, including mounti...

But the twin studies provided incontrovertible evidence that genes influenced homosexuality more strongly than, say, genes influenced the propensity for type 1 diabetes (the concordance rate among twins is only 30 percent), and almost as strongly as genes influence height (a concordance of about 55 percent).

Bailey had profoundly changed the conversation around sexual identity away from the 1960s rhetoric of “choice” and “personal preference” toward biology, genetics, and inheritance. If we did not think of variations in height or the development of dyslexia or type 1 diabetes as choices, then we could not think of sexual identity as a choice.

But myc is also one of the most potent cancer-causing genes known in biology; it is also activated in leukemias and lymphomas, and in pancreatic, gastric, and uterine cancer.