Unraveling The Genetic Code That Makes Us Human

Unraveling The Genetic Code That Makes Us Human
The Violinist's Thumb
And Other Lost Tales of Love, War, and Genius, As Written by Our Genetic Code
by Sam Kean
July 23, 2012

There's enough DNA in the human body to stretch from the sun to Pluto and back. But don't confuse DNA with your genes, says writer Sam Kean.

"They are sort of conflated in most people's minds today but they really are distinct things," he tells Fresh Air's Terry Gross. "Genes are like the story and DNA is the language that the story is written in."

In The Violinist's Thumb, Kean goes inside our genetic code, looking at the stories written by the fundamental building blocks within us. The book explains things like why some people can't handle drinking coffee and why some human babies are born with tails. It also delves into the history and science of the story of DNA, a nucleic acid which contains the genetic instructions that form the basis for all living organisms.

Among the stories Kean shares is that of Tsutomu Yamaguchi, who survived the bombing of Hiroshima, took a train home that evening to Nagasaki and then survived a second atomic bomb blast.

"He ended up surviving for an amazingly long time, despite being close to both nuclear bombs," says Kean. "He actually lived until 2010. So he must have had inside his cells a very efficient way to repair DNA and to make sure any mutations he might have had got patched up."

All living things accumulate mutations as they age. Segments of DNA can get cut out or swap with one another or never stop forming.

"Cancer is really a DNA disease," he says. " ... We have these certain genes that prevent our cells from growing out of control at the expense of the body. And it's a pretty good, robust system. But if a couple of these genes fail, then that's when cancer starts and cells start growing out of control."

Interview Highlights

Sam Kean is also the author of The Disappearing Spoon, an investigation into the cultural history of the periodic table.

On genetic tests

"Genes work with probabilities; they don't work with certainties. So most things that you're looking at with these genetic tests, it's not like you're condemned to automatically get the disease or the syndrome. There's a lot of factors in play there."

On babies born with tails

"At some point in our past, we did have a tail. It was interesting to me that in some cases, we have the genetic blueprints to make these atavistic traits inside us like tails. Another famous example is human embryos. You can see our gill slits. So it's interesting to me that we have these remnants that never quite got pruned out. We don't use the DNA for much anymore but every once in a while it can pop up and you get things like a little baby with a tail."
More On 'The Violinist's Thumb'

If You Are Hit By Two Atomic Bombs, Should You Have Kids? July 18, 2012
A 'Thumb' On The Pulse Of What Makes Us Human July 17, 2012

On nature and nurture

"The more that I looked at DNA, the more I realized it was nature and nurture. It's how genes and your environment work together to produce the person you are. So I don't feel like I'm really hemmed in because of my DNA. Obviously there's some things that were never going to happen for me — I was never going to play in the NBA — because I'm not tall enough or bulky enough. But even now we're finding a lot of behavioral traits that have some sort of genetic influence or roots in DNA somehow. We're also finding that those things don't rigidly dictate who we are. Genetic determinism is an idea that really scares people and understandably so. But thankfully the more we find out about our DNA, the more we realize we're not determined by our DNA."

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Excerpt: The Violinist's Thumb

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.

Excerpted from The Violinist's Thumb by Sam Kean. Copyright 2012 by Sam Kean. Excerpted by permission of Little, Brown and Company.