She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity (39 page)

Hirschhorn and his colleagues found that many of the genes on their list are unusually active in growth plate cells. Obviously, other parts of the body have to grow as well in order for people to become taller. But it's possible that the growth plates lead the parade. Mutations to the genes used by growth plate cells speed up or slow down the increase in limb bones. The rest of the parade has to adjust its speed to follow the leader.

Yet Hirschhorn knew that he would have to find other stories to tell about height. HMGA2, the first gene he and his colleagues discovered influencing height, remained the strongest common variant. It's active in embryonic cells, not in growth plates in children. And despite a lot of research by Hirschhorn and his graduate students, he still couldn't say why it's so important. “That one still boggles my mind,” Hirschhorn admitted.

It's possible that Hirschhorn will have to become a Scheherazade of the genome to tell all the stories about how the genes we inherit influence our height. In 2017, Jonathan Pritchard, the scientist who invented STRUCTURE, tried to predict how many genes scientists would ultimately find linked to height. Would Hirschhorn reach a thousand genes and be able to close down his shop? Pritchard thinks the answer is a definite no.

For their study, Pritchard and his colleagues took a closer look at a genome-wide association study that Hirschhorn and his colleagues published in 2014. In that study, Hirschhorn's team scanned 2.4 million genetic markers in a quarter of a million people. They looked for variants at each of the markers with a very strong link to height—so strong that they could confidently reject the possibility that the links were just coincidences.

That study gave Hirschhorn and his colleagues a list of about seven hundred strongly supported genes. But they also found many other ambiguous variants that didn't quite meet their strict standards. Those variants might have a weak effect on height, or they might simply have turned up in Hirschhorn's study by chance. Pritchard used new statistical techniques on those ambiguous variants, to see if he could separate the genetic wheat from the chaff.

He and his colleagues looked for people who carried two copies of each variant and checked their height. Then they looked at the height of people with only one copy of the variant, and that of people with no copies. In many cases, this comparison revealed a small but measurable effect. Two copies of a variant might make people shorter than average, while one copy made them a little taller, and no copies made them taller still. Pritchard and his colleagues then turned to an entirely different group of twenty thousand people to test these results. They found the same effects from the same variants.

What made this study startling was just how many of these variants Pritchard and his colleagues found. At 77 percent of the markers they studied—almost two million spots in people's DNA, in other words—they could detect an influence on height. The markers were not clumped around a few genes on one chromosome. They were instead spread out across all the chromosomes, encompassing the entire human genome.

These variants likely altered the sequence of many genes, changing the structure of their proteins. But they probably also changed the regions of DNA that act like switches to turn the genes on and off. Each of the nearly two million variants had, on average, an exquisitely tiny effect—adding or subtracting the width of a human hair. But collectively, this vast army of weak variants accounted for much more variation in height than the strongest genes that Hirschhorn and his colleagues put together in their catalog.

Traditionally, geneticists have called height polygenic—meaning “many genes.” Pritchard thinks a new word is called for:
omnigenic
.

If height really is omnigenic, as Pritchard believes, we may need to rethink the way our cells work. There may be a core group of genes lurking in growth plates that take the lead in determining how tall we get. But some of those genes also have other jobs. They work with other genes in other kinds of cells. You can think of our genes as a set of networks. There's a network of genes that work together in growth plate cells. And you can draw a line from some of those genes to other networks. Thanks to the way these networks are organized, it may take only a few steps to go from any given gene to any other gene in the human genome. With all these connections, a
mutation to a single gene can have wide-ranging effects. It can alter a gene that has nothing directly to do with height, but its influence can reach across the networks to affect the ones that do. In science's hunt for how we inherit height, scientists may have to expand their search to the entire genome.

I
N 1864
, when Francis Galton was forty-two, he posed for a photograph. He was now middle-aged and had grown a beard girdling his jaw. His forehead rose into a high, hairless dome. Galton leaned his left hand on a bookshelf next to a globe, the icon of the geographer. A chair stood next to him, a top hat sitting on the seat, the brim turned up like an open pot. The scrolled back of the chair reached almost to the level of Galton's hip. It served as accidental measuring tape, documenting his generous height. The photograph, in other words, is a typical picture of a tall Victorian gentleman: a mass of about 37 trillion nineteenth-century cells nurtured through years of divisions by
a wealthy British childhood.

Galton inherited that wealth, but not through his genes. His great-great-grandfather Joseph Farmer opened a small smithy in Birmingham in the early 1700s, where he made a modest living producing sword blades and gun parts. In 1717, Farmer took a big gamble that paid off for generations. Traveling to the American colonies, he set up forges and furnaces in Maryland, where he could smelt the iron from nearby mines. He shipped the metal back to his factories in Birmingham, where his workers could then craft them into more expensive goods. Thanks to the efforts of businessmen like Farmer, Maryland became one of the world's main iron suppliers in the eighteenth century. Farmer would brag about his “plantation” iron—a name it earned for a very simple and
lucrative reason:
Maryland's ironworks relied heavily on the labor of African slaves.

When Farmer died in 1741, his son James inherited the business, which by then specialized in gunlock springs and musket barrels. His family invested some of the profits in slave-trade companies in Lisbon, bringing them even greater riches. Five years later, James's sister married Francis Galton's great-grandfather Samuel. Samuel Galton had been a draper of modest means, but his new brother-in-law hired him as an assistant. It wasn't long before Samuel became a partner in the firm.

Guns and slavery grew even more intertwined in the Galton family fortune. By the 1750s, the Galtons were delivering more than twenty-five thousand guns a year to European traders, who sold the weapons to African states engaged in increasingly bloody battles. The warring states captured prisoners in the fights, and then sold them to European slave traders. Before long, they demanded to be paid for the slaves with more guns instead of gold.

Samuel Galton took sole control of the firm and began to supply arms to the British government, which used his muskets against American rebels. When Samuel Galton's son, Samuel John Galton, came of age, he joined the firm, and together the two Samuels grew their business for a few decades. When he died, Samuel had amassed 139,000 pounds. “His fortune had been
the fruit of God's blessing on his industry,” Galton's granddaughter later said.

The Galtons were a pious family of Quakers, but by the end of the 1700s, the wealth they made from war and slavery had largely turned the Society of Friends against them. In 1790, a faction of Quakers tried to bar the Galtons from their monthly meetings. Delegations of wealthy Quakers tried to persuade the Galtons to get into a different line of work. Samuel the elder agreed to stop taking profits from the family's gun business. But Samuel the younger refused. He wouldn't even admit he was doing anything wrong. In a letter read to the monthly meeting in Birmingham in 1796, he cast himself as a helpless prisoner of heredity.

“
The Trade devolved upon me as if it were an inheritance,” he declared. “My Engagements in the Business were not a matter of choice.”

The Quakers didn't buy that excuse. They barred him from their meetings for life. Eight years later, perhaps out of some delayed remorse, Samuel Galton abandoned the gun business to his son, Francis's father, and busied himself with opening a new bank. In 1815, Samuel Tertius Galton closed down the gun business for good. The Industrial Revolution had arrived in Birmingham, and the family bank's investments in factories and canals were proving profitable. By the time Francis Galton was born in 1822, the family fortune had swelled to 300,000 pounds.

As a child, Francis proved to be a prodigy, reciting passages of Shakespeare from memory and discussing the finer points of
The Iliad
. Despite their wealth, the Galtons always felt like outsiders, in part because no one in their family had completed a university education. They loaded their hopes for legitimacy on Francis's small shoulders. At age four, when Tertius asked his son what he hoped for most of all, Francis replied, “
Why, university honors, to be sure.”

They never came. At age eighteen, when Galton went to Cambridge, his father stocked his rooms with everything a young gentleman at university needed, from silver teaspoons to a steady supply of wine. Above his fireplace, Francis mounted crossed foils and pistols. In a small room next to his bedroom lived his three servants. Once he was settled in, Galton set out to study mathematics, aiming to take the honors examination known as the Tripos. To improve his concentration, he bought a “Gumption-Reviver,” a contraption that dripped water on his head and had to be refilled by a servant every fifteen minutes. He hired a tutor with a reputation for brilliance to teach him math.

Despite all his promise and spending, Galton received third-class honors on his first-year exams—the equivalent of a gentleman's C. In the hopes of improving his scores, Galton hired an even better math tutor, who accompanied him and four fellow students on a “reading party” in the Lake District. When it came time to take his first major exam, nicknamed Little Go, Galton made only second class.

In a letter to his father, Galton made light about the score, boasting about “going into the Little Go when I had not read over half my subjects
and coming out unplucked.” In truth, he was bitterly disappointed to watch his friends—who had studied with the same tutors at the same reading parties—get first honors. One of Galton's tutors urged him to give up his childhood hope. He should simply finish up Cambridge as most students did, and take a so-called poll degree.

Galton refused. Poll degrees were for the mediocre. Instead, he hired a new math tutor and went to Scotland for another reading party. This time the stress of studying gave Galton a nervous breakdown. “
A mill seemed to be working inside my head,” he later recalled. Looking back at the crisis he went through in the fall of 1842, Galton concluded he had pushed his brain too far. “It was as though I had tried to make a steam-engine perform more work than it was constructed for.”

For a few more months, Galton kept up the illusion of a top student. He wrangled a “certificate of degradation” from one of his tutors, which allowed him to put off his final honors examination for another year. He distracted himself from heart palpitations and dizzy spells with wine parties, poetry, and hockey. It was all a facade, one that collapsed when his father suddenly died. Galton left Cambridge with a poll degree and inherited his father's fortune. He was mediocre, yet rich beyond compare.

Galton's failure at Cambridge left him forever insecure about his own standing in the scientific world, always seeking to bask in the genius of others. He would later look back at his Cambridge years with gratitude that he had spent time with “
the highest intellects of their age.”

Their high intellects may well have inspired
Galton's obsession with heredity. He was struck by “the many obvious cases of heredity among the Cambridge men who were at the University about my own time.” The students who got the highest honors at Cambridge were exquisitely rare, and yet they generally seemed to have a father, a brother, or some other male relative who had gotten high honors as well. Galton didn't think that was a coincidence.

In later years, this observation mushroomed into a fervent conviction. In Galton's 1869 book,
Hereditary Genius
, he declared that human intellectual abilities “are derived by inheritance under exactly the same limitations as are the form and physical features of the whole organic world.”

Galton believed intelligence, like height, was deeply rooted in biology—so deep that it could be inherited. To persuade his readers, he needed a way to measure intelligence in relatives. But in the 1860s, no one knew how to do that. For a crude approximation, Galton got his hands on the scores of seventy-three boys who took the admission test to the Royal Military Academy at Sandhurst.

The scores, he was pleased to discover, roughly followed a bell curve, much like the one he found for height. Most of the boys scored close to average, while the curve tapered off in either direction—to what Galton would call stupidity and genius. He lingered lovingly over the scores of Cambridge students who earned honors in mathematics, drawing up a table in which fewer and fewer students managed to reach higher and higher scores. Yet Galton considered even the lowest-scoring Cambridge honors students to be brilliant in comparison to the majority of English people. “
The average mental grasp of even of what is called a well-educated audience, will be found to be ludicrously small when rigorously tested,” Galton declared. He never mentioned where he himself fit into that Cambridge continuum.

Galton then gathered evidence for heredity. He followed up on his intuition about his bright college mates at Cambridge, researching their genealogies and building a pedigree of the mind. Galton claimed his data showed that high-scoring students had high-scoring kin. He looked for other examples from history, investigating presidents and scientists and composers, more than a thousand men of talent all told. (Women barely counted in his argument.)

Height and intelligence would remain the twin guideposts for Galton. When thousands of visitors came to his Anthropometric Laboratory, he not only recorded their height but also timed their reactions and recorded the circumference of their heads—two traits Galton suspected were related to intelligence.

But when Galton developed eugenics, height and intelligence would take on very different roles in his thinking. When he dreamed about his hereditary utopia, it was intelligence that he wanted to breed. He pictured a nation of geniuses, not giants.

Galton's disciple Karl Pearson pursued more research on intelligence at the same time as he studied height. He asked teachers at hundreds of London schools to describe their students, picking the most apt words for each one from a list of adjectives such as
slow
and
quick
. When Pearson tallied up the replies and ranked them, he ended up with a bell curve.

To see if heredity played a part in the intelligence of the students, Pearson compared siblings. He found that the ability of siblings was correlated—the siblings of low-scoring students tended to score low as well; the quick ones tended to have quicker siblings. Pearson was impressed that the correlation of intelligence was much like the correlation for physical traits. We inherit the mental abilities of our parents, Pearson declared, “
even as we inherit their stature, forearm and span.”

Yet Pearson's argument for the inheritance of intelligence suffered from a fundamental weakness: For his measurements, he had to rely on the gut instincts of teachers. In the 1910s, Henry Goddard and other American psychologists replaced those subjective scores with Binet-based test results. And instead of studying hundreds of people, they tested millions.

To
Goddard's collaborator Lewis Terman, the army tests confirmed that intelligence was primarily the result of heredity. Among army recruits, immigrants scored lower on average than native-born soldiers. “
The immigrants who have recently come to us in such large numbers from Southern and Southeastern Europe are distinctly inferior mentally to the Nordic and Alpine Strains which we received from Scandinavia, Germany, Great Britain, and France,” Terman said. Intelligence, the tests made clear, was “chiefly a matter of native endowment,” and so “these are differences which the highest arts of pedagogy are powerless to neutralize.”

Terman was so convinced of the inheritance of intelligence that he ignored his own data. His test results showed that the longer immigrants lived in the United States, the higher they scored on intelligence tests. Terman and his colleagues built their tests from questions steeped in everyday American life, which required familiarity as well as intellect. Recruits were
shown a picture of a tennis game, to see if they noticed the net was missing. They were quizzed about the color of sapphires. They had to complete sentences such as “The Percheron is a kind of . . .” (Answer: Horse).

As it became clear that intelligence test scores could be influenced by people's cultural backgrounds, some psychologists tried to strip that background away. One psychologist, named Stanley Porteus, decided to avoid language altogether by testing people with mazes. He designed mazes of different levels of complexity and had them printed. Traveling across Australia, Asia, and Africa, he searched for people with little contact with the West who he could examine.
Porteus found that the so-called Bushmen of the Kalahari scored a mental age of seven. Yet his subjects were navigating their way through Porteus's printed mazes in the middle of a vast desert that they could navigate without a map, finding all the food and shelter they required.

When he presented his results in 1937, Porteus recognized that even a wordless maze test might be skewed by culture. “The Maze is by itself far from being a satisfactory measure of intelligence,” he said. In fact, the experience left him wondering what his tests were measuring. “All we can say of it is that the complex of qualities needed for its performance seem to be valuable in making adjustments to our kind of society,” Porteus said.

Other researchers have argued that intelligence isn't merely what it takes to survive in one society. They maintain it's
a deep-seated feature of the human brain. The neuroscientist Richard Haier, for example, has defined intelligence as “
a catch-all word that means the mental abilities most related to responding to everyday problems and navigating the environment.”