Saturday, June 02, 2018

In an Age of Gene Editing and Surrogacy, What Does Heredity Mean?

CreditMark Pernice
By Jennifer Raff
SHE HAS HER MOTHER’S LAUGH 
The Powers, Perversions, and Potential of Heredity
By Carl Zimmer
656 pp. Dutton. $30.
“The greatest scare of all, the one that made the world suddenly unfamiliar, swept over me while I was sitting with my wife, Grace, in the comfort of an obstetrician’s office.” In trying to map out his family tree in order to identify potential health risks to his unborn child, Carl Zimmer realized just how little he knew about his ancestors. “I had willingly become a conduit for heredity, allowing the biological past to make its way into the future. And yet I had no idea of what I was passing on.”
Parents will relate to this. We invest as much care in our young ones as we possibly can, but many of us also pass along to them the black box of our genomes. We usually have little understanding and virtually no control over that inheritance. As Zimmer’s healthy daughters grew up, his thoughts moved from their specific genetic legacies to a broader wonder about heredity itself and how we understand it.
In his extraordinary new book, “She Has Her Mother’s Laugh,” Zimmer (who writes the Matter column for The New York Times) uses history to offer a rigorous introduction to the basic principles of genetics, and molecular and developmental biology. To the Romans, heredity was a tool for passing on the assets of long-dead ancestors — they were concerned with what it meant to be an heir. In the Middle Ages the concept shifted and connoted instead the connection between the present and a noble past. Prominent families came to use visual depictions of these connections — pedigrees — to announce their proximity to greatness. Bloodlines were ways to pass on property and power, but also indicators of both inherent virtue and vice. It was only much later, as scientists like Gregor Mendel began to figure out how genetics works, that we would begin to understand which traits get passed on and why.
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“She Has Her Mother’s Laugh” challenges our conventional wisdom about heredity, especially as we enter the new realms of surrogate pregnancy and gene editing. One of the most astonishing insights is that mothers don’t just pass traits to their children — they receive them as well. I read Zimmer’s book (occasionally out loud) while feeding my baby son. Like Zimmer, I had genetic counseling and my partner and I experienced the same anxieties as he did. But unlike Zimmer, I was able to assuage our fears using a drop of my own blood. That’s because my baby’s DNA, floating freely in my bloodstream, could be tested for hundreds of genetic disorders at an early point in my pregnancy. We took great comfort in the test, without realizing all of its implications. The baby wasn’t just sharing his genetic secrets during the pregnancy. Fetal cells can persist for years after birth; as I sit and write these sentences, I may very well be a chimera: a mixture of some of my son’s cells and my own. This microchimerism may even have eventual effects on my health, although it isn’t fully understood. And he may carry some of my immune cells, too.
How does this sharing affect our current conception of heredity? And what about the other inherited elements that influence our development — like culture, microbes and (to a limited extent) the epigenetic factors that affect the expression of our genes? Zimmer cautions that we should not ignore their influence, arguing that “we cannot understand the natural world with a simplistic notion of genetic heredity.”
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The popular notion of “a gene for” a trait is largely a misconception. The Mendelian laws of inheritance — what most people study in school today — are not just “exquisitely fragile” but “regularly broken.” Most complex traits, such as height or intelligence, arise out of the intricate, combined action of hundreds of genes and depend strongly on the environmental conditions under which an individual develops. And failing to understand that has had dire results: “At the dawn of the 20th century, scientists came to limit the word heredity to genes. Before long, this narrow definition spread its influence far beyond genetic laboratories. It hangs like a cloud over our most personal experiences of heredity, even if we can’t stop trying to smuggle the old traditions of heredity into the new language of genes.”
To illustrate this point, Zimmer highlights the story of Emma Wolverton, a woman condemned as mentally defective and institutionalized. In the early 20th century she became a focal point for a movement trying to use Mendelian principles to improve humanity. Charles Davenport and Henry Goddard, a geneticist and a psychologist respectively, believed that the pedigrees of “feeble-minded children” would reveal the genetic basis of intelligence — something they believed would “conform perfectly to the Mendelian law.” According to their research, Emma was the fruit of six generations of “feeble-mindedness and crime” descending from a “feeble-minded tavern girl” during the Revolutionary War. In contrast, they claimed, the children the tavern girl’s partner had with his good Quaker wife were all virtuous and respectable citizens.
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On the foundation of this “natural experiment” Goddard and Davenport advocated for what they called the “salvation of the race through heredity.” You know this movement as eugenics, a term first coined by Charles Darwin’s cousin, Francis Galton. Goddard helped to popularize eugenics in the United States in a best-selling but inaccurate book about Emma (in which he gave her the pseudonym Deborah Kallikak), using a largely fictitious genealogy to cement intelligence and virtue in the public mind as Mendelian traits. The book was wildly influential in the movement and beloved by Nazi scientists. Ideas built on a wrongheaded understanding of heredity had devastating consequences.
Now that genetic ancestry testing is recreationally available, exploring heredity has become synonymous with a journey of self-discovery. For many people DNA offers a chance to identify and reconnect with ancestral homelands and understand familial histories. For others, it serves much the same function as pedigrees did for the nobility of medieval Europe; a way to claim great ancestors, whether they be nobles, poets or (in my own case) a vaudeville harpist. Regardless of their questionable accuracy, these stories seduce us with the notion that as we inherited genes from our ancestors, something of their greatness might live on in us.
Zimmer takes this journey far beyond what is available to most people. He had his entire genome sequenced and consulted a team of experts on the results. This intense self-exploration becomes a portal for discussing what genetic ancestry testing can — and can’t — tell us about our own histories, our evolution and the larger picture of human genetic variation.
“She Has Her Mother’s Laugh” particularly shines when it comes to engaging with the notion of race, a topic once again pushed to the forefront of public discourse. In recent years, we have seen the publication of numerous popular books purporting to tackle the “forbidden” issue of the biological basis of race. Many have been riddled with scientific errors, uninformed by history or lacking in nuance and clarity when discussing interpretations of patterns of human genetic variation. Zimmer’s book is a refreshing antidote. He details the history of scientific racism and explains the meaning (and lack of meaning) of genetic differences between people and populations in a way that is both accurate and accessible to nonscientists.
This book is Zimmer at his best: obliterating misconceptions about science with gentle prose. He brings the reader on his journey of discovery as he visits laboratory after laboratory, peering at mutant mosquitoes and talking to scientists about traces of Neanderthal ancestry within his own genome. Any fan of his previous books or his journalism will appreciate this work. But so, too, will parents wishing to understand the magnitude of the legacy they’re bequeathing to their children, people who want to grasp their history through genetic ancestry testing and those seeking a fuller context for the discussions about race and genetics so prevalent today.
Jennifer Raff is a geneticist who writes a science column for The Guardian.
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