The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code
401
The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code
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Overview
In The Disappearing Spoon, bestselling author Sam Kean unlocked the mysteries of the periodic table. In The Violinist's Thumb, he explores the wonders of the magical building block of life: DNA.
There are genes to explain crazy cat ladies, why other people have no fingerprints, and why some people survive nuclear bombs. Genes illuminate everything from JFK's bronze skin (it wasn't a tan) to Einstein's genius. They prove that Neanderthals and humans bred thousands of years more recently than any of us would feel comfortable thinking. They can even allow some people, because of the exceptional flexibility of their thumbs and fingers, to become truly singular violinists.
Kean's vibrant storytelling once again makes science entertaining, explaining human history and whimsy while showing how DNA will influence our species' future.
Product Details
| ISBN-13: | 9780316182331 |
|---|---|
| Publisher: | Little, Brown and Company |
| Publication date: | 07/16/2013 |
| Pages: | 401 |
| Sales rank: | 121,504 |
| Product dimensions: | 5.80(w) x 8.04(h) x 1.17(d) |
About the Author
The Disappearing Spoon was a runner-up for the Royal Society of London's book of the year for 2010, and The Violinist's Thumb and The Tale of the Dueling Neurosurgeons were nominated for the PEN/E.O. Wilson Literary Science Writing Award in 2013 and 2015, as well as the AAAS/Subaru SB&F prize.
His work has appeared in the Best American Nature and Science Writing, the New Yorker, the Atlantic, the New York Times Magazine, Psychology Today, Slate, Mental Floss, and other publications, and he has been featured on NPR's "Radiolab," "All Things Considered," and "Fresh Air."
Read an Excerpt
The Violinist's Thumb
And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic CodeBy Sam Kean
Little, Brown and Company
Copyright © 2012 Sam KeanAll right reserved.
ISBN: 9780316182317
PART I
A, C, G, T, and You
How to Read a Genetic Score
1
Genes, Freaks, DNA
How Do Living Things Pass Down Traits to Their Children?
Chills and flames, frost and inferno, fire and ice. The two scientists who made the first great discoveries in genetics had a lot in common—not least the fact that both died obscure, mostly unmourned and happily forgotten by many. But whereas one’s legacy perished in fire, the other’s succumbed to ice.
The blaze came during the winter of 1884, at a monastery in what’s now the Czech Republic. The friars spent a January day emptying out the office of their deceased abbot, Gregor Mendel, ruthlessly purging his files, consigning everything to a bonfire in the courtyard. Though a warm and capable man, late in life Mendel had become something of an embarrassment to the monastery, the cause for government inquiries, newspaper gossip, even a showdown with a local sheriff. (Mendel won.) No relatives came by to pick up Mendel’s things, and the monks burned his papers for the same reason you’d cauterize a wound—to sterilize, and stanch embarrassment. No record survives of what they looked like, but among those documents were sheaves of papers, or perhaps a lab notebook with a plain cover, probably coated in dust from disuse. The yellowed pages would have been full of sketches of pea plants and tables of numbers (Mendel adored numbers), and they probably didn’t kick up any more smoke and ash than other papers when incinerated. But the burning of those papers—burned on the exact spot where Mendel had kept his greenhouse years before—destroyed the only original record of the discovery of the gene.
The chills came during that same winter of 1884—as they had for many winters before, and would for too few winters after. Johannes Friedrich Miescher, a middling professor of physiology in Switzerland, was studying salmon, and among his other projects he was indulging a long-standing obsession with a substance—a cottony gray paste—he’d extracted from salmon sperm years before. To keep the delicate sperm from perishing in the open air, Miescher had to throw the windows open to the cold and refrigerate his lab the old-fashioned way, exposing himself day in and day out to the Swiss winter. Getting any work done required superhuman focus, and that was the one asset even people who thought little of Miescher would admit he had. (Earlier in his career, friends had to drag him from his lab bench one afternoon to attend his wedding; the ceremony had slipped his mind.) Despite being so driven, Miescher had pathetically little to show for it—his lifetime scientific output was meager. Still, he kept the windows open and kept shivering year after year, though he knew it was slowly killing him. And he still never got to the bottom of that milky gray substance, DNA.
DNA and genes, genes and DNA. Nowadays the words have become synonymous. The mind rushes to link them, like Gilbert and Sullivan or Watson and Crick. So it seems fitting that Miescher and Mendel discovered DNA and genes almost simultaneously in the 1860s, two monastic men just four hundred miles apart in the German-speaking span of middle Europe. It seems more than fitting; it seems fated.
But to understand what DNA and genes really are, we have to decouple the two words. They’re not identical and never have been. DNA is a thing—a chemical that sticks to your fingers. Genes have a physical nature, too; in fact, they’re made of long stretches of DNA. But in some ways genes are better viewed as conceptual, not material. A gene is really information—more like a story, with DNA as the language the story is written in. DNA and genes combine to form larger structures called chromosomes, DNA-rich volumes that house most of the genes in living things. Chromosomes in turn reside in the cell nucleus, a library with instructions that run our entire bodies.
All these structures play important roles in genetics and heredity, but despite the near-simultaneous discovery of each in the 1800s, no one connected DNA and genes for almost a century, and both discoverers died uncelebrated. How biologists finally yoked genes and DNA together is the first epic story in the science of inheritance, and even today, efforts to refine the relationship between genes and DNA drive genetics forward.
Mendel and Miescher began their work at a time when folk theories—some uproarious or bizarre, some quite ingenious, in their way—dominated most people’s thinking about heredity, and for centuries these folk theories had colored their views about why we inherit different traits.
Everyone knew on some level of course that children resemble parents. Red hair, baldness, lunacy, receding chins, even extra thumbs, could all be traced up and down a genealogical tree. And fairy tales—those codifiers of the collective unconscious—often turned on some wretch being a “true” prince(ss) with a royal bloodline, a biological core that neither rags nor an amphibian frame could sully.
That’s mostly common sense. But the mechanism of heredity—how exactly traits got passed from generation to generation—baffled even the most intelligent thinkers, and the vagaries of this process led to many of the wilder theories that circulated before and even during the 1800s. One ubiquitous folk theory, “maternal impressions,” held that if a pregnant woman saw something ghoulish or suffered intense emotions, the experience would scar her child. One woman who never satisfied an intense prenatal craving for strawberries gave birth to a baby covered with red, strawberry-shaped splotches. The same could happen with bacon. Another woman bashed her head on a sack of coal, and her child had half, but only half, a head of black hair. More direly, doctors in the 1600s reported that a woman in Naples, after being startled by sea monsters, bore a son covered in scales, who ate fish exclusively and gave off fishy odors. Bishops told cautionary tales of a woman who seduced her actor husband backstage in full costume. He was playing Mephistopheles; they had a child with hooves and horns. A beggar with one arm spooked a woman into having a one-armed child. Pregnant women who pulled off crowded streets to pee in churchyards invariably produced bed wetters. Carrying fireplace logs about in your apron, next to the bulging tummy, would produce a grotesquely well-hung lad. About the only recorded happy case of maternal impressions involved a patriotic woman in Paris in the 1790s whose son had a birthmark on his chest shaped like a Phrygian cap—those elfish hats with a flop of material on top. Phrygian caps were symbols of freedom to the new French republic, and the delighted government awarded her a lifetime pension.
Much of this folklore intersected with religious belief, and people naturally interpreted serious birth defects—cyclopean eyes, external hearts, full coats of body hair—as back-of-the-Bible warnings about sin, wrath, and divine justice. One example from the 1680s involved a cruel bailiff in Scotland named Bell, who arrested two female religious dissenters, lashed them to poles near the shore, and let the tide swallow them. Bell added insult by taunting the women, then drowned the younger, more stubborn one with his own hands. Later, when asked about the murders, Bell always laughed, joking that the women must be having a high time now, scuttling around among the crabs. The joke was on Bell: after he married, his children were born with a severe defect that twisted their forearms into two awful pincers. These crab claws proved highly heritable to their children and grandchildren, too. It didn’t take a biblical scholar to see that the iniquity of the father had been visited upon the children, unto the third and fourth generations. (And beyond: cases popped up in Scotland as late as 1900.)
If maternal impressions stressed environmental influences, other theories of inheritance had strong congenital flavors. One, preformationism, grew out of the medieval alchemists’ quest to create a homunculus, a miniature, even microscopic, human being. Homunculi were the biological philosopher’s stone, and creating one showed that an alchemist possessed the power of gods. (The process of creation was somewhat less dignified. One recipe called for fermenting sperm, horse dung, and urine in a pumpkin for six weeks.) By the late 1600s, some protoscientists had stolen the idea of the homunculus and were arguing that one must live inside each female egg cell. This neatly did away with the question of how living embryos arose from seemingly dead blobs of matter. Under preformationist theory, such spontaneous generation wasn’t necessary: homuncular babies were indeed preformed and merely needed a trigger, like sperm, to grow. This idea had only one problem: as critics pointed out, it introduced an infinite regress, since a woman necessarily had to have all her future children, as well as their children, and their children, stuffed inside her, like Russian matryoshka nesting dolls. Indeed, adherents of “ovism” could only deduce that God had crammed the entire human race into Eve’s ovaries on day one. (Or rather, day six of Genesis.) “Spermists” had it even worse—Adam must have had humanity entire sardined into his even tinier sperms. Yet after the first microscopes appeared, a few spermists tricked themselves into seeing tiny humans bobbing around in puddles of semen. Both ovism and spermism gained credence in part because they explained original sin: we all resided inside Adam or Eve during their banishment from Eden and therefore all share the taint. But spermism also introduced theological quandaries—for what happened to the endless number of unbaptized souls that perished every time a man ejaculated?
However poetic or deliciously bawdy these theories were, biologists in Miescher’s day scoffed at them as old wives’ tales. These men wanted to banish wild anecdotes and vague “life forces” from science and ground all heredity and development in chemistry instead.
Miescher hadn’t originally planned to join this movement to demystify life. As a young man he had trained to practice the family trade, medicine, in his native Switzerland. But a boyhood typhoid infection had left him hard of hearing and unable to use a stethoscope or hear an invalid’s bedside bellyaching. Miescher’s father, a prominent gynecologist, suggested a career in research instead. So in 1868 the young Miescher moved into a lab run by the biochemist Felix Hoppe-Seyler, in Tübingen, Germany. Though headquartered in an impressive medieval castle, Hoppe-Seyler’s lab occupied the royal laundry room in the basement; he found Miescher space next door, in the old kitchen.
Hoppe-Seyler wanted to catalog the chemicals present in human blood cells. He had already investigated red blood cells, so he assigned white ones to Miescher—a fortuitous decision for his new assistant, since white blood cells (unlike red ones) contain a tiny internal capsule called a nucleus. At the time, most scientists ignored the nucleus—it had no known function—and quite reasonably concentrated on the cytoplasm instead, the slurry that makes up most of a cell’s volume. But the chance to analyze something unknown appealed to Miescher.
To study the nucleus, Miescher needed a steady supply of white blood cells, so he approached a local hospital. According to legend, the hospital catered to veterans who’d endured gruesome battlefield amputations and other mishaps. Regardless, the clinic did house many chronic patients, and each day a hospital orderly collected pus-soaked bandages and delivered the yellowed rags to Miescher. The pus often degraded into slime in the open air, and Miescher had to smell each suppurated-on cloth and throw out the putrid ones (most of them). But the remaining “fresh” pus was swimming with white blood cells.
Eager to impress—and, in truth, doubtful of his own talents—Miescher threw himself into studying the nucleus, as if sheer labor would make up for any shortcomings. A colleague later described him as “driven by a demon,” and Miescher exposed himself daily to all manner of chemicals in his work. But without this focus, he probably wouldn’t have discovered what he did, since the key substance inside the nucleus proved elusive. Miescher first washed his pus in warm alcohol, then acid extract from a pig’s stomach, to dissolve away the cell membranes. This allowed him to isolate a gray paste. Assuming it was protein, he ran tests to identify it. But the paste resisted protein digestion and, unlike any known protein, wouldn’t dissolve in salt water, boiling vinegar, or dilute hydrochloric acid. So he tried elementary analysis, charring it until it decomposed. He got the expected elements, carbon, hydrogen, oxygen, and nitrogen, but also discovered 3 percent phosphorus, an element proteins lack. Convinced he’d found something unique, he named the substance “nuclein”—what later scientists called deoxyribonucleic acid, or DNA.
Miescher polished off the work in a year, and in autumn 1869 stopped by the royal laundry to show Hoppe-Seyler. Far from rejoicing, the older scientist screwed up his brow and expressed his doubts that the nucleus contained any sort of special, nonproteinaceous substance. Miescher had made a mistake, surely. Miescher protested, but Hoppe-Seyler insisted on repeating the young man’s experiments—step by step, bandage by bandage—before allowing him to publish. Hoppe-Seyler’s condescension couldn’t have helped Miescher’s confidence (he never worked so quickly again). And even after two years of labor vindicated Miescher, Hoppe-Seyler insisted on writing a patronizing editorial to accompany Miescher’s paper, in which he backhandedly praised Miescher for “enhanc[ing] our understanding… of pus.” Nevertheless Miescher did get credit, in 1871, for discovering DNA.
Some parallel discoveries quickly illuminated more about Miescher’s molecule. Most important, a German protégé of Hoppe-Seyler’s determined that nuclein contained multiple types of smaller constituent molecules. These included phosphates and sugars (the eponymous “deoxyribose” sugars), as well as four ringed chemicals now called nucleic “bases”—adenine, cytosine, guanine, and thymine. Still, no one knew how these parts fit together, and this jumble made DNA seem strangely heterogeneous and incomprehensible.
(Scientists now know how all these parts contribute to DNA. The molecule forms a double helix, which looks like a ladder twisted into a corkscrew. The supports of the ladder are strands made of alternating phosphates and sugars. The ladder’s rungs—the most important part—are each made of two nucleic bases, and these bases pair up in specific ways: adenine, A, always bonds with thymine, T; cytosine, C, always bonds with guanine, G. [To remember this, notice that the curvaceous letters C and G pair-bond, as do angular A and T.])
Meanwhile DNA’s reputation was bolstered by other discoveries. Scientists in the later 1800s determined that whenever cells divide in two, they carefully divvy up their chromosomes. This hinted that chromosomes were important for something, because otherwise cells wouldn’t bother. Another group of scientists determined that chromosomes are passed whole and intact from parent to child. Yet another German chemist then discovered that chromosomes were mostly made up of none other than DNA. From this constellation of findings—it took a little imagination to sketch in the lines and see a bigger picture—a small number of scientists realized that DNA might play a direct role in heredity. Nuclein was intriguing people.
Miescher lucked out, frankly, when nuclein became a respectable object of inquiry; his career had stalled otherwise. After his stint in Tübingen, he moved home to Basel, but his new institute refused him his own lab—he got one corner in a common room and had to carry out chemical analyses in an old hallway. (The castle kitchen was looking pretty good suddenly.) His new job also required teaching. Miescher had an aloof, even frosty demeanor—he was someone never at ease around people—and although he labored over lectures, he proved a pedagogical disaster: students remember him as “insecure, restless… myopic… difficult to understand, [and] fidgety.” We like to think of scientific heroes as electric personalities, but Miescher lacked even rudimentary charisma.
Given his atrocious teaching, which further eroded his self-esteem, Miescher rededicated himself to research. Upholding what one observer called his “fetish of examining objectionable fluids,” Miescher transferred his DNA allegiance from pus to semen. The sperm in semen were basically nuclein-tipped missiles and provided loads of DNA without much extraneous cytoplasm. Miescher also had a convenient source of sperm in the hordes of salmon that clogged the river Rhine near his university every autumn and winter. During spawning season, salmon testes grow like tumors, swelling twenty times larger than normal and often topping a pound each. To collect salmon, Miescher could practically dangle a fishing line from his office window, and by squeezing their “ripe” testes through cheesecloth, he isolated millions of bewildered little swimmers. The downside was that salmon sperm deteriorates at anything close to comfortable temperatures. So Miescher had to arrive at his bench in the chilly early hours before dawn, prop the windows open, and drop the temperature to around 35°F before working. And because of a stingy budget, when his laboratory glassware broke, he sometimes had to pilfer his ever-loving wife’s fine china to finish experiments.
From this work, as well as his colleagues’ work with other cells, Miescher concluded that all cell nuclei contain DNA. In fact he proposed redefining cell nuclei—which come in a variety of sizes and shapes—strictly as containers for DNA. Though he wasn’t greedy about his reputation, this might have been a last stab at glory for Miescher. DNA might still have turned out to be relatively unimportant, and in that case, he would have at least figured out what the mysterious nucleus did. But it wasn’t to be. Though we now know Miescher was largely right in defining the nucleus, other scientists balked at his admittedly premature suggestion; there just wasn’t enough proof. And even if they bought that, they wouldn’t grant Miescher’s next, more self-serving claim: that DNA influenced heredity. It didn’t help that Miescher had no idea how DNA did so. Like many scientists then, he doubted that sperm injected anything into eggs, partly because he assumed (echoes of the homunculus here) that eggs already contained the full complement of parts needed for life. Rather, he imagined that sperm nuclein acted as a sort of chemical defibrillator and jump-started eggs. Unfortunately Miescher had little time to explore or defend such ideas. He still had to lecture, and the Swiss government piled “thankless and tedious” tasks onto him, like preparing reports on nutrition in prisons and elementary schools. The years of working through Swiss winters with the windows open also did a number on his health, and he contracted tuberculosis. He ended up giving up DNA work altogether.
Meanwhile other scientists’ doubts about DNA began to solidify, in their minds, into hard opposition. Most damning, scientists discovered that there was more to chromosomes than phosphate-sugar backbones and A-C-G-T bases. Chromosomes also contained protein nuggets, which seemed more likely candidates to explain chemical heredity. That’s because proteins were composed of twenty different subunits (called amino acids). Each of these subunits could serve as one “letter” for writing chemical instructions, and there seemed to be enough variety among these letters to explain the dazzling diversity of life itself. The A, C, G, and T of DNA seemed dull and simplistic in comparison, a four-letter pidgin alphabet with limited expressive power. As a result, most scientists decided that DNA stored phosphorus for cells, nothing more.
Sadly, even Miescher came to doubt that DNA contained enough alphabetical variety. He too began tinkering with protein inheritance, and developed a theory where proteins encoded information by sticking out molecular arms and branches at different angles—a kind of chemical semaphore. It still wasn’t clear how sperm passed this information to eggs, though, and Miescher’s confusion deepened. He turned back to DNA late in life and argued that it might assist with heredity still. But progress proved slow, partly because he had to spend more and more time in tuberculosis sanitariums in the Alps. Before he got to the bottom of anything, he contracted pneumonia in 1895, and succumbed soon after.
Later work continued to undermine Miescher by reinforcing the belief that even if chromosomes control inheritance, the proteins in chromosomes, not the DNA, contained the actual information. After Miescher’s death, his uncle, a fellow scientist, gathered Miescher’s correspondence and papers into a “collected works,” like some belle-lettrist. The uncle prefaced the book by claiming that “Miescher and his work will not diminish; on the contrary, it will grow and his discoveries and thoughts will be seeds for a fruitful future.” Kind words, but it must have seemed a fond hope: Miescher’s obituaries barely mentioned his work on nuclein; and DNA, like Miescher himself, seemed decidedly minor.
At least Miescher died known, where he was known, for science. Gregor Mendel made a name for himself during his lifetime only through scandal.
By his own admission, Mendel became an Augustinian friar not because of any pious impulse but because his order would pay his bills, including college tuition. The son of peasants, Mendel had been able to afford his elementary school only because his uncle had founded it; he attended high school only after his sister sacrificed part of her dowry. But with the church footing the bill, Mendel attended the University of Vienna and studied science, learning experimental design from Christian Doppler himself, of the eponymous effect. (Though only after Doppler rejected Mendel’s initial application, perhaps because of Mendel’s habit of having nervous breakdowns during tests.)
The abbot at St. Thomas, Mendel’s monastery, encouraged Mendel’s interest in science and statistics, partly for mercenary reasons: the abbot thought scientific farming could produce better sheep, fruit trees, and grapevines and help the monastery crawl out of debt. But Mendel had time to explore other interests, too, and over the years he charted sunspots, tracked tornadoes, kept an apiary buzzing with bees (although one strain he bred was so nasty-tempered and vindictive it had to be destroyed), and cofounded the Austrian Meteorological Society.
In the early 1860s, just before Miescher moved from medical school into research, Mendel began some deceptively simple experiments on pea plants in the St. Thomas nursery. Beyond enjoying their taste and wanting a ready supply, he chose peas because they simplified experiments. Neither bees nor wind could pollinate his pea blossoms, so he could control which plants mated with which. He appreciated the binary, either/or nature of pea plants, too: plants had tall or short stalks, green or yellow pods, wrinkled or smooth peas, nothing in between. In fact, Mendel’s first important conclusion from his work was that some binary traits “dominated” others. For example, crossing purebred green-pead plants with purebred yellow-pead plants produced only yellow-pead offspring: yellow dominated. Importantly, however, the green trait hadn’t disappeared. When Mendel mated those second-generation yellow-pead plants with each other, a few furtive green peas popped up—one latent, “recessive” green for every three dominant yellows. The 3:1 ratio held for other traits, too.
Equally important, Mendel concluded that having one dominant or recessive trait didn’t affect whether another, separate trait was dominant or recessive—each trait was independent. For example, even though tall dominated short, a recessive-short plant could still have dominant-yellow peas. Or a tall plant could have recessive-green peas. In fact, every one of the seven traits he studied—like smooth peas (dominant) versus wrinkled peas (recessive), or purple blossoms (dominant) versus white blossoms (recessive)—was inherited independently of the other traits.
This focus on separate, independent traits allowed Mendel to succeed where other heredity-minded horticulturists had failed. Had Mendel tried to describe, all at once, the overall resemblance of a plant to its parents, he would have had too many traits to consider. The plants would have seemed a confusing collage of Mom and Dad. (Charles Darwin, who also grew and experimented with pea plants, failed to understand their heredity partly for this reason.) But by narrowing his scope to one trait at a time, Mendel could see that each trait must be controlled by a separate factor. Mendel never used the word, but he identified the discrete, inheritable factors we call genes today. Mendel’s peas were the Newton’s apple of biology.
Beyond his qualitative discoveries, Mendel put genetics on solid quantitative footing. He adored the statistical manipulations of meteorology, the translating of daily barometer and thermometer readings into aggregate climate data. He approached breeding the same way, abstracting from individual plants into general laws of inheritance. In fact, rumors have persisted for almost a century now that Mendel got carried away here, letting his love of perfect data tempt him into fraud.
If you flip a dime a thousand times, you’ll get approximately five hundred FDRs and five hundred torches; but you’re unlikely to get exactly five hundred of either, because each flip is independent and random. Similarly, because of random deviations, experimental data always stray a tad higher or lower than theory predicts. Mendel should therefore have gotten only approximately a 3:1 ratio of tall to short plants (or whatever other trait he measured). Mendel, however, claimed some almost platonically perfect 3:1s among his thousands of pea plants, a claim that has raised suspicions among modern geneticists. One latter-day fact checker calculated the odds at less than one in ten thousand that Mendel—otherwise a pedant for numerical accuracy in ledgers and meteorological experiments—came by his results honestly. Many historians have defended Mendel over the years or argued that he manipulated his data only unconsciously, since standards for recording data differed back then. (One sympathizer even invented, based on no evidence, an overzealous gardening assistant who knew what numbers Mendel wanted and furtively discarded plants to please his master.) Mendel’s original lab notes were burned after his death, so we can’t check if he cooked the books. Honestly, though, if Mendel did cheat, it’s almost more remarkable: it means he intuited the correct answer—the golden 3:1 ratio of genetics—before having any real proof. The purportedly fraudulent data may simply have been the monk’s way of tidying up the vagaries of real-world experiments, to make his data more convincing, so that others could see what he somehow knew by revelation.
Regardless, no one in Mendel’s lifetime suspected he’d pulled a fast one—partly because no one was paying attention. He read a paper on pea heredity at a conference in 1865, and as one historian noted, “his audience dealt with him in the way that all audiences do when presented with more mathematics than they have a taste for: there was no discussion, and no questions were asked.” He almost shouldn’t have bothered, but Mendel published his results in 1866. Again, silence.
Mendel kept working for a few years, but his chance to burnish his scientific reputation largely evaporated in 1868, when his monastery elected him abbot. Never having governed anything before, Mendel had a lot to learn, and the day-to-day headaches of running St. Thomas cut into his free time for horticulture. Moreover, the perks of being in charge, like rich foods and cigars (Mendel smoked up to twenty cigars per day and grew so stout that his resting pulse sometimes topped 120), slowed him down, limiting his enjoyment of the gardens and greenhouses. One later visitor did remember Abbot Mendel taking him on a stroll through the gardens and pointing out with delight the blossoms and ripe pears; but at the first mention of his own experiments in the garden, Mendel changed the subject, almost embarrassed. (Asked how he managed to grow nothing but tall pea plants, Mendel demurred: “It is just a little trick, but there is a long story connected with it, which would take too long to tell.”)
Mendel’s scientific career also atrophied because he wasted an increasing number of hours squabbling about political issues, especially separation of church and state. (Although it’s not obvious from his scientific work, Mendel could be fiery—a contrast to the chill of Miescher.) Almost alone among his fellow Catholic abbots, Mendel supported liberal politics, but the liberals ruling Austria in 1874 double-crossed him and revoked the tax-exempt status of monasteries. The government demanded seventy-three hundred gulden per year from St. Thomas in payment, 10 percent of the monastery’s assessed value, and although Mendel, outraged and betrayed, paid some of the sum, he refused to pony up the rest. In response, the government seized property from St. Thomas’s farms. It even dispatched a sheriff to seize assets from inside St. Thomas itself. Mendel met his adversary in full clerical habit outside the front gate, where he stared him down and dared him to extract the key from his pocket. The sheriff left empty-handed.
Overall, though, Mendel made little headway getting the new law repealed. He even turned into something of a crank, demanding interest for lost income and writing long letters to legislators on arcane points of ecclesiastical taxation. One lawyer sighed that Mendel was “full of suspicion, [seeing] himself surrounded by nothing but enemies, traitors, and intriguers.” The “Mendel affair” did make the erstwhile scientist famous, or notorious, in Vienna. It also convinced his successor at St. Thomas that Mendel’s papers should be burned when he died, to end the dispute and save face for the monastery. The notes describing the pea experiments would become collateral casualties.
Mendel died in 1884, not long after the church-state imbroglio; his nurse found him stiff and upright on his sofa, his heart and kidneys having failed. We know this because Mendel feared being buried alive and had demanded a precautionary autopsy. But in one sense, Mendel’s fretting over a premature burial proved prophetic. Just eleven scientists cited his now-classic paper on inheritance in the thirty-five years after his death. And those that did (mostly agricultural scientists) saw his experiments as mildly interesting lessons for breeding peas, not universal statements on heredity. Scientists had indeed buried Mendel’s theories too soon.
But all the while, biologists were discovering things about cells that, if they’d only known, supported Mendel’s ideas. Most important, they found distinct ratios of traits among offspring, and determined that chromosomes passed hereditary information around in discrete chunks, like the discrete traits Mendel identified. So when three biologists hunting through footnotes around 1900 all came across the pea paper independently and realized how closely it mirrored their own work, they grew determined to resurrect the monk.
Mendel allegedly once vowed to a colleague, “My time will come,” and boy, did it. After 1900 “Mendelism” expanded so quickly, with so much ideological fervor pumping it up, that it began to rival Charles Darwin’s natural selection as the preeminent theory in biology. Many geneticists in fact saw Darwinism and Mendelism as flatly incompatible—and a few even relished the prospect of banishing Darwin to the same historical obscurity that Friedrich Miescher knew so well.
2
The Near Death of Darwin
Why Did Geneticists Try to Kill Natural Selection?
This was not how a Nobel laureate should have to spend his time. In late 1933, shortly after winning science’s highest honor, Thomas Hunt Morgan got a message from his longtime assistant Calvin Bridges, whose libido had landed him in hot water. Again.
A “confidence woman” from Harlem had met Bridges on a cross-country train a few weeks before. She quickly convinced him not only that she was a regal princess from India, but that her fabulously wealthy maharaja of a father just happened to have opened—coincidence of all coincidences—a science institute on the subcontinent in the very field that Bridges (and Morgan) worked in, fruit fly genetics. Since her father needed a man to head the institute, she offered Bridges the job. Bridges, a real Casanova, would likely have shacked up with the woman anyway, and the job prospect made her irresistible. He was so smitten he began offering his colleagues jobs in India and didn’t seem to notice Her Highness’s habit of running up extraordinary bills whenever they went carousing. In fact, when out of earshot, the supposed princess claimed to be Mrs. Bridges and charged everything she could to him. When the truth emerged, she tried to extort more cash by threatening to sue him “for transporting her across state lines for immoral purposes.” Panicked and distraught—despite his adult activities, Bridges was quite childlike—he turned to Morgan.
Morgan no doubt consulted with his other trusted assistant, Alfred Sturtevant. Like Bridges, Sturtevant had worked with Morgan for decades, and the trio had shared in some of the most important discoveries in genetics history. Sturtevant and Morgan both scowled in private over Bridges’s dalliances and escapades, but their loyalty trumped any other consideration here. They decided that Morgan should throw his weight around. In short order, he threatened to expose the woman to the police, and kept up the pressure until Miss Princess disappeared on the next train. Morgan then hid Bridges away until the situation blew over.
When he’d hired Bridges as a factotum years before, Morgan could never have expected he’d someday be acting as a goodfella for him. Then again, Morgan could never have expected how most everything in his life had turned out. After laboring away in anonymity, he had now become a grand panjandrum of genetics. After working in comically cramped quarters in Manhattan, he now oversaw a spacious lab in California. After lavishing so much attention and affection on his “fly boys” over the years, he was now fending off charges from former assistants that he’d stolen credit for others’ ideas. And after fighting so hard for so long against the overreach of ambitious scientific theories, he’d now surrendered to, and even helped expand, the two most ambitious theories in all biology.
Morgan’s younger self might well have despised his older self for this last thing. Morgan had begun his career at a curious time in science history, around 1900, when a most uncivil civil war broke out between Mendel’s genetics and Darwin’s natural selection: things got so nasty, most biologists felt that one theory or the other would have to be exterminated. In this war Morgan had tried to stay Switzerland, refusing at first to accept either theory. Both relied too much on speculation, he felt, and Morgan had an almost reactionary distrust of speculation. If he couldn’t see proof for a theory in front of his corneas, he wanted to banish it from science. Indeed, if scientific advances often require a brilliant theorist to emerge and explain his vision with perfect clarity, the opposite was true for Morgan, who was cussedly stubborn and notoriously muddled in his reasoning—anything but literally visible proof bemused him.
And yet that very confusion makes him the perfect guide to follow along behind during the War of the Roses interlude when Darwinists and Mendelists despised each other. Morgan mistrusted genetics and natural selection equally at first, but his patient experiments on fruit flies teased out the half-truths of each. He eventually succeeded—or rather, he and his talented team of assistants succeeded—in weaving genetics and evolution together into the grand tapestry of modern biology.
The decline of Darwinism, now known as the “eclipse” of Darwinism, began in the late 1800s and began for quite rational reasons. Above all, while biologists gave Darwin credit for proving that evolution happened, they disparaged his mechanism for evolution—natural selection, the survival of the fittest—as woefully inadequate for bringing about the changes he claimed.
Critics harped especially on their belief that natural selection merely executed the unfit; it seemed to illuminate nothing about where new or advantageous traits come from. As one wit said, natural selection accounted for the survival, but not the arrival, of the fittest. Darwin had compounded the problem by insisting that natural selection worked excruciatingly slowly, on tiny differences among individuals. No one else believed that such minute variations could have any practical long-term difference—they believed in evolution by jerks and jumps. Even Darwin’s bulldog Thomas Henry Huxley recalled trying, “much to Mr. Darwin’s disgust,” to convince Darwin that species sometimes advanced by jumps. Darwin wouldn’t budge—he accepted only infinitesimal steps.
Additional arguments against natural selection gathered strength after Darwin died in 1882. As statisticians had demonstrated, most traits for species formed a bell curve: . Most people stood an average height, for example, and the number of tall or short people dropped smoothly to small numbers on both sides. Traits in animals like speed (or strength or smarts) also formed bell curves, with a large number of average creatures. Obviously natural selection would weed out the slowpokes and idiots when predators snatched them. For evolution to occur, though, most scientists argued that the average had to shift; your average creature had to become faster or stronger or smarter. Otherwise the species largely remained the same. But killing off the slowest creatures wouldn’t suddenly make those that escaped any faster—and the escapees would continue having mediocre children as a result. What’s more, most scientists assumed that the speed of any rare fast creature would be diluted when it bred with slower ones, producing more mediocrities. According to this logic, species got stuck in ruts of average traits, and the nudge of natural selection couldn’t improve them. True evolution, then—men from monkeys—had to proceed by jumps.
Beyond its apparent statistical problems, Darwinism had something else working against it: emotion. People loathed natural selection. Pitiless death seemed paramount, with superior types always crushing the weak. Intellectuals like playwright George Bernard Shaw even felt betrayed by Darwin. Shaw had adored Darwin at first for smiting religious dogmas. But the more Shaw heard, the less he liked natural selection. And “when its whole significance dawns on you,” Shaw later lamented, “your heart sinks into a heap of sand within you. There is a hideous fatalism about it, a ghastly and damnable reduction of beauty and intelligence.” Nature governed by such rules, he said, would be “a universal struggle for hogwash.”
The triplicate rediscovery of Mendel in 1900 further galvanized the anti-Darwinists by providing a scientific alternative—and soon an outright rival. Mendel’s work emphasized not murder and starvation but growth and generation. Moreover, Mendel’s peas showed signs of jerkiness—tall or short stalks, yellow or green peas, nothing in between. Already by 1902 the English biologist William Bateson had helped a doctor identify the first known gene in humans (for an alarming but largely benign disorder, alkaptonuria, which can turn children’s urine black). Bateson soon rebranded Mendelism “genetics” and became Mendel’s bulldog in Europe, tirelessly championing the monk’s work, even taking up chess and cigars simply because Mendel loved both. Others supported Bateson’s creepy zealotry, however, because Darwinism violated the progressive ethos of the young century. Already by 1904, German scientist Eberhard Dennert could cackle, “We are standing at the death-bed of Darwinism, and making ready to send the friends of the patient a little money, to ensure a decent burial.” (A sentiment fit for a creationist today.) To be sure, a minority of biologists defended Darwin’s vision of gradual evolution against the Dennerts and Batesons of the world, and defended it fiercely—one historian commented on both sides’ “remarkable degree of bitchiness.” But these stubborn few could not prevent the eclipse of Darwinism from growing ever darker.
Still, while Mendel’s work galvanized the anti-Darwinists, it never quite united them. By the early 1900s, scientists had discovered various important facts about genes and chromosomes, facts that still undergird genetics today. They determined that all creatures have genes; that genes can change, or mutate; that all chromosomes in cells come in pairs; and that all creatures inherit equal numbers of chromosomes from Mom and Dad. But there was no overarching sense of how these discoveries meshed; the individual pixels never resolved into a coherent picture. Instead a baffling array of half theories emerged, like “chromosome theory,” “mutation theory,” “gene theory,” and so on. Each championed one narrow aspect of heredity, and each drew distinctions that seem merely confusing today: some scientists believed (wrongly) that genes didn’t reside on chromosomes; others that each chromosome harbored just one gene; still others that chromosomes played no role in heredity at all. It’s whiggishly unfair to say, but reading these overlapping theories can be downright frustrating today. You want to scream at the scientists, like a dimwit on Wheel of Fortune or something, “Think! It’s all right there!” But each fiefdom discounted discoveries by rivals, and they squabbled against each other almost as much as against Darwinism.
As these revolutionaries and counterrevolutionaries bitched it out in Europe, the scientist who eventually ended the Darwin-genetics row was working in anonymity in America. Though he mistrusted both Darwinists and geneticists—too much bloviating about theory all around—Thomas Hunt Morgan had developed an interest in heredity after visiting a botanist in Holland in 1900. Hugo de Vries had been one of the trio who rediscovered Mendel that year, and de Vries’s fame in Europe rivaled Darwin’s, partly because de Vries had developed a rival theory for the origin of species. De Vriesian “mutation theory” argued that species went through rare but intense mutation periods, during which the parents produced “sports,” offspring with markedly different traits. De Vries developed mutation theory after spotting some anomalous evening primroses in an abandoned potato field near Amsterdam. Some of these sport primroses sported smoother leaves, longer stems, or bigger yellow flowers with more petals. And crucially, primrose sports wouldn’t mate with the old, normal primroses; they seemed to have jumped past them and become a new species. Darwin had rejected evolutionary jumps because he believed that if one sport emerged, it would have to breed with normal individuals, diluting its good qualities. De Vries’s mutation period removed this objection at a stroke: many sports emerged at once, and they could breed only with each other.
The primrose results scored themselves into Morgan’s brain. That de Vries had no clue how or why mutations appeared mattered not a lick. At last Morgan saw proof of new species emerging, not speculation. After landing a post at Columbia University in New York, Morgan decided to study mutation periods in animals. He began experiments on mice, guinea pigs, and pigeons, but when he discovered how slowly they bred, he took a colleague’s suggestion and tried Drosophila, fruit flies.
Like many New Yorkers then, fruit flies had recently immigrated, in their case arriving on boats with the first banana crops in the 1870s. These exotic yellow fruits, usually wrapped in foil, had sold for ten cents per, and guards in New York stood watch over banana trees to prevent eager mobs from stealing the fruit. But by 1907 bananas and flies were common enough in New York that Morgan’s assistant could catch a whole horde for research simply by slicing up a banana and leaving it on a windowsill to rot.
Fruit flies proved perfect for Morgan’s work. They bred quickly—one generation every twelve days—and survived on food cheaper than peanuts. They also tolerated claustrophobic Manhattan real estate. Morgan’s lab—the “fly room,” 613 Schermerhorn Hall at Columbia—measured sixteen feet by twenty-three feet and had to accommodate eight desks. But a thousand fruit flies lived happily in a one-quart milk bottle, and Morgan’s shelves were soon lined with the dozens of bottles that (legend has it) his assistants “borrowed” from the student cafeteria and local stoops.
Morgan set himself up at the fly room’s central desk. Cockroaches scuttled through his drawers, nibbling rotten fruit, and the room was a cacophony of buzzing, but Morgan stood unperturbed in the middle of all, peering through a jeweler’s loupe, scrutinizing bottle after bottle for de Vries’s mutants. When a bottle produced no interesting specimens, Morgan might squash them with his thumb and smear their guts wherever, often in lab notebooks. Unfortunately for general sanitation, Morgan had many, many flies to smush: although the Drosophila bred and bred and bred, he found no sign of sports.
Meanwhile Morgan got lucky in a different arena. In autumn 1909, he filled in for a colleague on sabbatical and taught the only introductory course of his Columbia career. And during that semester he made, one observer noted, “his greatest discovery,” two brilliant assistants. Alfred Sturtevant heard about Morgan’s class through a brother who taught Latin and Greek at Columbia, and although just a sophomore, Sturtevant impressed Morgan by writing an independent research paper on horses and the inheritance of coat color. (Morgan hailed from Kentucky, and his father and uncle had been famous horse thieves behind Union lines during the Civil War, leading a band known as Morgan’s Raiders. Morgan scorned his Confederate past, but he knew his horses.) From that moment on, Sturtevant was Morgan’s golden boy and eventually earned a coveted desk in the fly room. Sturtevant cultivated a cultured air, reading widely in literature and doing trickier British crossword puzzles—although, amid the fly room’s squalor, someone also once discovered a mummified mouse in his desk. Sturtevant did have one deficiency as a scientist, red-green color blindness. He’d tended horses on the family fruit farm in Alabama largely because he proved useless during harvest, struggling to spot red strawberries on green bushes.
The other undergrad, Calvin Bridges, made up for Sturtevant’s poor eyesight, and his stuffiness. At first Morgan merely took pity on Bridges, an orphan, by giving him a job washing filth from milk bottles. But Bridges eavesdropped on Morgan’s discussions of his work, and when Bridges began spotting interesting flies with his bare eyes (even through the dirty glass bottles), Morgan hired him as a researcher. It was basically the only job Bridges ever had. A sensuous and handsome man with bouffant hair, Bridges practiced free love avant la lettre. He eventually abandoned his wife and children, got a vasectomy, and started brewing moonshine in his new bachelor lair in Manhattan. He proceeded to hit on—or flat-out proposition—anything in a skirt, including colleagues’ wives. His naive charm seduced many, but even after the fly room became legendary, no other university would blacken its reputation by employing Bridges as anything but a measly assistant.
Meeting Bridges and Sturtevant must have cheered Morgan, because his experiments had all but flopped until then. Unable to find any natural mutants, he’d exposed flies to excess heat and cold and injected acids, salts, bases, and other potential mutagens into their genitals (not easy to find). Still nothing. On the verge of giving up, in January 1910 he finally spotted a fly with a strange trident shape tattooed on its thorax. Not exactly a de Vriesian über-fly, but something. In March two more mutants appeared, one with ragged moles near its wings that made it appear to have “hairy armpits,” another with an olive (instead of the normal amber) body color. In May 1910 the most dramatic mutant yet appeared, a fly with white (instead of red) eyes.
Anxious for a breakthrough—perhaps this was a mutation period—Morgan tediously isolated white-eyes. He uncapped the milk bottle, balanced another one upside down on top of it like mating ketchup bottles, and shined a light through the top to coax white-eyes upward. Of course, hundreds of other flies joined white-eyes in the top bottle, so Morgan had to quickly cap both, get a new milk bottle, and repeat the process over and over, slowly dwindling the number with each step, praying to God white-eyes didn’t escape meantime. When he finally, finally segregated the bug, he mated it with red-eyed females. Then he bred the descendants with each other in various ways. The results were complex, but one result especially excited Morgan: after crossing some red-eyed descendants with each other, he discovered among the offspring a 3:1 ratio of red to white eyes.
The year before, in 1909, Morgan had heard the Danish botanist Wilhelm Johannsen lecture about Mendelian ratios at Columbia. Johannsen used the occasion to promote his newly minted word, gene, a proposed unit of inheritance. Johannsen and others freely admitted that genes were convenient fictions, linguistic placeholders for, well, something. But they insisted that their ignorance about the biochemical details of genes shouldn’t invalidate the usefulness of the gene concept for studying inheritance (similar to how psychologists today can study euphoria or depression without understanding the brain in detail). Morgan found the lecture too speculative, but his experimental results—3:1—promptly lowered his prejudice to Mendel.
This was quite a volte-face for Morgan, but it was just the start. The eye-color ratios convinced him that gene theory wasn’t bunk. But where were genes actually located? Perhaps on chromosomes, but fruit flies had hundreds of inheritable traits and only four chromosomes. Assuming one trait per chromosome, as many scientists did, there weren’t enough to go around. Morgan didn’t want to get dragged into debates on so-called chromosome theory, but a subsequent discovery left him no choice: because when he scrutinized his white-eyed flies, he discovered that every last mutant was male. Scientists already knew that one chromosome determined the gender of flies. (As in mammals, female flies have two X chromosomes, males one.) Now the white-eye gene was linked to that chromosome as well—putting two traits on it. Soon the fly boys found other genes—stubby wings, yellow bodies—also linked exclusively to males. The conclusion was inescapable: they’d proved that multiple genes rode around together on one chromosome.
That Morgan had proved this practically against his own will mattered little; he began to champion chromosome theory anyway.Overthrowing old beliefs like this became a habit with Morgan, simultaneously his most admirable and most maddening trait. Although he encouraged theoretical discussions in the fly room, Morgan considered new theories cheap and facile—worth little until cross-examined in the lab. He didn’t seem to grasp that scientists need theories as guides, to decide what’s relevant and what’s not, to frame their results and prevent muddled thinking. Even undergraduates like Bridges and Sturtevant—and especially a student who joined the fly room later, the abrasively brilliant and brilliantly abrasive Hermann Muller—grew hair-rippingly frustrated with Morgan in the many quarrels they had over genes and heredity. And then, just as exasperating, when someone did wrestle Morgan into a headlock and convince him he was wrong, Morgan would ditch his old ideas and with no embarrassment whatsoever absorb the new ones as obvious.
To Morgan, this quasi plagiarism was no big deal. Everyone was working toward the same goal (right, fellas?), and only experiments mattered anyway. And to his credit, his about-faces proved that Morgan listened to his assistants, a contrast to the condescending relationship most European scientists had with their help. For this reason Bridges and Sturtevant always publicly professed their loyalty to Morgan. But visitors sometimes picked up on sibling rivalries among the assistants, and secret smoldering. Morgan didn’t mean to connive or manipulate; credit for ideas just meant that little to him.
Nevertheless ideas kept ambushing Morgan, ideas he hated. Because not long after the unified gene-chromosome theory emerged, it nearly unraveled, and only a radical idea could salvage it. Again, Morgan had determined that multiple genes clustered together on one chromosome. And he knew from other scientists’ work that parents pass whole chromosomes on to their children. All the genetic traits on each chromosome should therefore always be inherited together—they should always be linked. To take a hypothetical example, if one chromosome’s set of genes call for green bristles and sawtooth wings and fat antennae, any fly with one trait should exhibit all three. Such clusters of traits do exist in flies, but to their dismay, Morgan’s team discovered that certain linked traits could sometimes become unlinked—green bristles and sawtooth wings, which should always appear together, would somehow show up separately, in different flies. Unlinkings weren’t common—linked traits might separate 2 percent of the time, or 4 percent—but they were so persistent they might have undone the entire theory, if Morgan hadn’t indulged in a rare flight of fancy.
He remembered reading a paper by a Belgian biologist-priest who had used a microscope to study how sperm and eggs form. One key fact of biology—it comes up over and over—is that all chromosomes come in pairs, pairs of nearly identical twins. (Humans have forty-six chromosomes, arranged in twenty-three pairs.) When sperm and eggs form, these near-twin chromosomes all line up in the middle of the parent cell. During division one twin gets pulled one way, the other the other way, and two separate cells are born.
However, the priest-biologist noticed that, just before the divvying up, twin chromosomes sometimes interacted, coiling their tips around each other. He didn’t know why. Morgan suggested that perhaps the tips broke off during this crossing over and swapped places. This explained why linked traits sometimes separated: the chromosome had broken somewhere between the two genes, dislocating them. What’s more, Morgan speculated—he was on a roll—that traits separating 4 percent of the time probably sat farther apart on chromosomes than those separating 2 percent of the time, since the extra distance between the first pair would make breaking along that stretch more likely.
Morgan’s shrewd guess turned out correct, and with Sturtevant and Bridges adding their own insights over the next few years, the fly boys began to sketch out a new model of heredity—the model that made Morgan’s team so historically important. It said that all traits were controlled by genes, and that these genes resided on chromosomes in fixed spots, strung along like pearls on a necklace. Because creatures inherit one copy of each chromosome from each parent, chromosomes therefore pass genetic traits from parent to child. Crossing over (and mutation) changes chromosomes a little, which helps make each creature unique. Nevertheless chromosomes (and genes) stay mostly intact, which explains why traits run in families. Voilà: the first overarching sense of how heredity works.
In truth, little of this theory originated in Morgan’s lab, as biologists worldwide had discovered various pieces. But Morgan’s team finally linked these vaguely connected ideas, and fruit flies provided overwhelming experimental proof. No one could deny that sex chromosome linkage occurred, for instance, when Morgan had ten thousand mutants buzzing on a shelf, nary a female among them.
Of course, while Morgan won acclaim for uniting these theories, he’d done nothing to reconcile them with Darwinian natural selection. That reconciliation also arose from work inside the fly room, but once again Morgan ended up “borrowing” the idea from assistants, including one who didn’t accept this as docilely as Bridges and Sturtevant did.
Hermann Muller began poking around the fly room in 1910, though only occasionally. Because he supported his elderly mother, Muller lived a haphazard life, working as a factotum in hotels and banks, tutoring immigrants in English at night, bolting down sandwiches on the subway between jobs. Somehow Muller found time to befriend writer Theodore Dreiser in Greenwich Village, immerse himself in socialist politics, and commute two hundred miles to Cornell University to finish a master’s degree. But no matter how frazzled he got, Muller used his one free day, Thursday, to drop in on Morgan and the fly boys and bandy about ideas on genetics. Intellectually nimble, Muller starred in these bull sessions, and Morgan granted him a desk in the fly room after he graduated from Cornell in 1912. The problem was, Morgan declined to pay Muller, so Muller’s schedule didn’t let up. He soon had a mental breakdown.
From then on, and for decades afterward, Muller seethed over his status in the fly room. He seethed that Morgan openly favored the bourgeois Sturtevant and shunted menial tasks like preparing bananas onto the blue-collar, proletariat Bridges. He seethed that both Bridges and Sturtevant got paid to experiment on his, Muller’s, ideas, while he scrambled around the five boroughs for pocket change. He seethed that Morgan treated the fly room like a clubhouse and sometimes made Muller’s friends work down the hall. Muller seethed above all that Morgan was oblivious to his contributions. This was partly because Muller proved slow in doing the thing Morgan most valued—actually carrying out the clever experiments he (Muller) dreamed up. Indeed, Muller probably couldn’t have found a worse mentor than Morgan. For all his socialist leanings, Muller got pretty attached to his own intellectual property, and felt the free and communal nature of the fly room both exploited and ignored his talent. Nor was Muller exactly up for Mr. Congeniality. He harped on Morgan, Bridges, and Sturtevant with tactless criticism, and got almost personally offended by anything but pristine logic. Morgan’s breezy dismissal of evolution by natural selection especially irked Muller, who considered it the foundation of biology.
Despite the personality clashes he caused, Muller pushed the fly group to greater work. In fact, while Morgan contributed little to the emerging theory of inheritance after 1911, Muller, Bridges, and Sturtevant kept making fundamental discoveries. Unfortunately, it’s hard to sort out nowadays who discovered what, and not just because of the constant idea swapping. Morgan and Muller often scribbled thoughts down on unorganized scraps, and Morgan purged his file cabinet every five years, perhaps out of necessity in his cramped lab. Muller hoarded documents, but many years later, yet another colleague he’d managed to alienate threw out Muller’s files while Muller was working abroad. Morgan also (like Mendel’s fellow friars) destroyed Bridges’s files when the free lover died of heart problems in 1938. Turns out Bridges was a bedpost notcher, and when Morgan found a detailed catalog of fornication, he thought it prudent to burn all the papers and protect everyone in genetics.
But historians can assign credit for some things. All the fly boys helped determine which clusters of traits got inherited together. More important, they discovered that four distinct clusters existed in flies—exactly the number of chromosome pairs. This was a huge boost for chromosome theory because it showed that every chromosome harbored multiple genes.
Sturtevant built on this notion of gene and chromosome linkage. Morgan had guessed that genes separating 2 percent of the time must sit closer together on chromosomes than genes separating 4 percent of the time. Ruminating one evening, Sturtevant realized he could translate those percentages into actual distances. Specifically, genes separating 2 percent of the time must sit twice as close together as the other pair; similar logic held for other percent linkages. Sturtevant blew off his undergraduate homework that night, and by dawn this nineteen-year-old had sketched the first map of a chromosome. When Muller saw the map, he “literally jumped with excitement”—then pointed out ways to improve it.
Bridges discovered “nondisjunction”—the occasional failure of chromosomes to separate cleanly after crossing over and twisting arms. (The excess of genetic material that results can cause problems like Down syndrome.) And beyond individual discoveries, Bridges, a born tinkerer, industrialized the fly room. Instead of tediously separating flies by turning bottle after bottle upside down, Bridges invented an atomizer to puff wee doses of ether over flies and stun them. He also replaced loupes with binocular microscopes; handed out white porcelain plates and fine-tipped paintbrushes so that people could see and manipulate flies more easily; eliminated rotting bananas for a nutritious slurry of molasses and cornmeal; and built climate-controlled cabinets so that flies, which become sluggish in cold, could breed summer and winter. He even built a fly morgue to dispose of corpses with dignity. Morgan didn’t always appreciate these contributions—he continued to squish flies wherever they landed, despite the morgue. But Bridges knew that mutants popped up so rarely, and when they did, his biological factory allowed each one to thrive and produce millions of descendants.
Muller contributed insights and ideas, dissolving apparent contradictions and undergirding lean-to theories with firm logic. And although he had to argue with Morgan until his tongue bled, he finally made the senior scientist see how genes, mutations, and natural selection work together. As Muller (among others) outlined it: Genes give creatures traits, so mutations to genes change traits, making creatures different in color, height, speed, or whatever. But contra de Vries—who saw mutations as large things, producing sports and instant species—most mutations simply tweak creatures. Natural selection then allows the better-adapted of these creatures to survive and reproduce more often. Crossing over comes into play because it shuffles genes around between chromosomes and therefore puts new versions of genes together, giving natural selection still more variety to work on. (Crossing over is so important that some scientists today think that sperm and eggs refuse to form unless chromosomes cross a minimum number of times.)
Muller also helped expand scientists’ very ideas about what genes could do. Most significantly, he argued that traits like the ones Mendel had studied—binary traits, controlled by one gene—weren’t the only story. Many important traits are controlled by multiple genes, even dozens of genes. These traits will therefore show gradations, depending on which exact genes a creature inherits. Certain genes can also turn the volume up or down on other genes, crescendos and decrescendos that produce still finer gradations. Crucially, however, because genes are discrete and particulate, a beneficial mutation will not be diluted between generations. The gene stays whole and intact, so superior parents can breed with inferior types and still pass the gene along.
To Muller, Darwinism and Mendelism reinforced each other beautifully. And when Muller finally convinced Morgan of this, Morgan became a Darwinian. It’s easy to chuckle over this—yet another Morgan conversion—and in later writings, Morgan still emphasizes genetics as more important than natural selection. However, Morgan’s endorsement was important in a larger sense. Grandiloquent theories (including Darwin’s) dominated biology at the time, and Morgan had helped keep the field grounded, always demanding hard evidence. So other biologists knew that if some theory convinced even Thomas Hunt Morgan, it had something going for it. What’s more, even Muller recognized Morgan’s personal influence. “We should not forget,” Muller once admitted, “the guiding personality of Morgan, who infected all the others by his own example—his indefatigable activity, his deliberation, his jolliness, and courage.” In the end, Morgan’s bonhomie did what Muller’s brilliant sniping couldn’t: convinced geneticists to reexamine their prejudice against Darwin, and take the proposed synthesis of Darwin and Mendel, natural selection and genetics, seriously.
Many other scientists did indeed take up the work of Morgan’s team in the 1920s, spreading the unassuming fruit fly to labs around the world. It soon became the standard animal in genetics, allowing scientists everywhere to compare discoveries on equal terms. Building on such work, a generation of mathematically minded biologists in the 1930s and 1940s began investigating how mutations spread in natural populations, outside the lab. They demonstrated that if a gene gave some creatures even a small survival advantage, that boost could, if compounded long enough, push species in new directions. What’s more, most changes would take place in tiny steps, exactly as Darwin had insisted. If the fly boys’ work finally showed how to link Mendel with Darwin, these later biologists made the case as rigorous as a Euclidean proof. Darwin had once moaned how “repugnant” math was to him, how he struggled with most anything beyond taking simple measurements. In truth, mathematics buttressed Darwin’s theory and ensured his reputation would never lapse again.
And in this way the so-called eclipse of Darwinism in the early 1900s proved exactly that: a period of darkness and confusion, but a period that ultimately passed.Beyond the scientific gains, the diffusion of fruit flies around the world inspired another legacy, a direct outgrowth of Morgan’s “jolliness.” Throughout genetics, the names of most genes are ugly abbreviations, and they stand for monstrous freak words that maybe six people worldwide understand. So when discussing, say, the alox12b gene, there’s often no point in spelling out its name (arachidonate 12-lipoxygenase, 12R type), since doing so confuses rather than clarifies, methinks. (To save everyone a migraine, from now on I’ll just state gene acronyms and pretend they stand for nothing.) In contrast, whereas gene names are intimidatingly complex, chromosome names are stupefyingly banal. Planets are named after gods, chemical elements after myths, heroes, and great cities. Chromosomes were named with all the creativity of shoe sizes. Chromosome one is the longest, chromosome two the second longest, and (yawn) so on. Human chromosome twenty-one is actually shorter than chromosome twenty-two, but by the time scientists figured this out, chromosome twenty-one was famous, since having an extra number twenty-one causes Down syndrome. And really, with such boring names, there was no point in fighting over them and bothering to change.
Fruit fly scientists, God bless ’em, are the big exception. Morgan’s team always picked sensibly descriptive names for mutant genes like speck, beaded, rudimentary, white, and abnormal. And this tradition continues today, as the names of most fruit fly genes eschew jargon and even shade whimsical. Different fruit fly genes include groucho, smurf, fear of intimacy, lost in space, smellblind, faint sausage, tribble (the multiplying fuzzballs on Star Trek), and tinman (which if mutated prevents fruit flies from growing a heart). A mutated armadillo gene gives fruit flies a plated exoskeleton. The turnip gene makes flies stupid. Tudor leaves males (as with Henry VIII) childless. Cleopatra can kill flies when it interacts with another gene, asp. Cheap date leaves flies exceptionally tipsy after a sip of alcohol. Fruit fly sex especially seems to inspire clever names. Ken and barbie mutants have no genitalia. Male coitus interruptus mutants spend just ten minutes having sex (the norm is twenty), while stuck mutants cannot physically disengage after coitus. As for females, dissatisfaction mutants never have sex at all—they spend all their energy shooing suitors away by snapping their wings. And thankfully, this whimsy with names has inspired the occasional zinger in other areas of genetics. A gene that gives mammals extra nipples earned the name scaramanga, after the James Bond villain with too many. A gene that removes blood cells from circulation in fish became the tasteful vlad tepes, after Vlad the Impaler, the historical inspiration for Dracula. The backronym for the “POK erythroid myeloid ontogenic” gene in mice—pokemon—nearly provoked a lawsuit, since the pokemon gene (now known, sigh, as zbtb7) contributes to the spread of cancer, and the lawyers for the Pokémon media empire didn’t want their cute little pocket monsters confused with tumors. But my winner for the best, and freakiest, gene name goes to the flour beetle’s medea, after the ancient Greek mother who committed infanticide. Medea encodes a protein with the curious property that it’s both a poison and its own antidote. So if a mother has this gene but doesn’t pass it to an embryo, her body exterminates the fetus—nothing she can do about it. If the fetus has the gene, s/he creates the antidote and lives. (Medea is a “selfish genetic element,” a gene that demands its own propagation above all, even to the detriment of a creature as a whole.) If you can get beyond the horror, it’s a name worthy of the Columbia fruit fly tradition, and it’s fitting that the most important clinical work on medea—which could lead to very smart insecticides—came after scientists introduced it into Drosophila for further study.
But long before these cute names emerged, and even before fruit flies had colonized genetics labs worldwide, the original fly group at Columbia had disbanded. Morgan moved to the California Institute of Technology in 1928 and took Bridges and Sturtevant with him to his new digs in sunny Pasadena. Five years later Morgan became the first geneticist to win the Nobel Prize, “for establishing,” one historian noted, “the very principles of genetics he had set out to refute.” The Nobel committee has an arbitrary rule that three people at most can share a Nobel, so the committee awarded it to Morgan alone, rather than—as it should have—splitting it between him, Bridges, Sturtevant, and Muller. Some historians argue that Sturtevant did work important enough to win his own Nobel but that his devotion to Morgan and willingness to relinquish credit for ideas diminished his chances. Perhaps in tacit acknowledgment of this, Morgan shared his prize money from the Nobel with Sturtevant and Bridges, setting up college funds for their children. He shared nothing with Muller.
Muller had fled Columbia for Texas by then. He started in 1915 as a professor at Rice University (whose biology department was chaired by Julian Huxley, grandson of Darwin’s bulldog) and eventually landed at the University of Texas. Although Morgan’s warm recommendation had gotten him the Rice job, Muller actively promoted a rivalry between his Lone Star and Morgan’s Empire State groups, and whenever the Texas group made a significant advance, which they trumpeted as a “home run,” they preened. In one breakthrough, biologist Theophilus Painter discovered the first chromosomes—inside fruit fly spit glands
—that were large enough to inspect visually, allowing scientists to study the physical basis of genes. But as important as Painter’s work was, Muller hit the grand slam in 1927 when he discovered that pulsing flies with radiation would increase their mutation rate by 150 times. Not only did this have health implications, but scientists no longer had to sit around and wait for mutations to pop up. They could mass-produce them. The discovery gave Muller the scientific standing he deserved—and knew he deserved.Continues...
Excerpted from The Violinist's Thumb by Sam Kean Copyright © 2012 by Sam Kean. Excerpted by permission.
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Table of Contents
Introduction 3
Part I A, C, G, T, and You: How to Read a Genetic Score
1 Genes, Freaks, DNA: How Do Living Things Pass Down Traits to Their Children? 13
2 The Near Death of Darwin: Why Did Geneticists Try to Kill Natural Selection? 31
3 Them's the DNA Breaks: How Does Nature Read-and Misread-DNA? 54
4 The Musical Score of DNA: What Kinds of Information Does DNA Store? 72
Part II Our Animal Past: Making things that Crawl and Frolic and Kill
5 DNA Vindication: Why Did Life Evolve So Slowly-Then Explode in Complexity? 95
6 The Survivors, the Livers: What's Our Most Ancient and Important DNA? 118
7 The Machiavelli Microbe: How Much Human DNA Is Actually Human? 138
8 Love and Atavisms: What Genes Make Mammals Mammals? 157
9 Humanzees and Other Near Misses: When Did Humans Break Away from Monkeys, and Why? 178
Part III Genes and Geniuses : How Humans Became all too Human
10 Scarlet A's, C's, G's, and T's: Why Did Humans Almost Go Extinct? 203
11 Size Matters: How Did Humans Get Such Grotesquely Large Brains? 226
12 The Art of the Gene: How Deep in Our DNA Is Artistic Genius? 245
Part IV The Oracle of Dna: Genetics in the Past, Present, and Future
13 The Past Is Prologue-Sometimes: What Can (and Can't) Genes Teach Us About Historical Heroes? 271
14 Three Billion Little Pieces: Why Don't Humans Have More Genes Than Other Species? 294
15 Easy Come, Easy Go? How Come Identical Twins Aren't Identical? 314
16 Life as We Do (and Don't) Know It: What the Heck Will Happen Now? 336
Epilogue: Genomics Gets Personal 355
Acknowledgments 361
Notes and Errata 363
Selected Bibliography 385
Index 391
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