The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code

by Sam Kean

  Paul Kammerer had an alchemist’s ambitions to remake nature, coupled with a teenage boy’s talent for harassing small animals. Kammerer claimed he could change the colors of salamanders—or give them polka dots or pinstripes—simply by foisting them into landscapes of unusual hues. He forced sun-loving praying mantises to dine in the dark, and amputated the proboscises of sea squirts just to see the effect on their future children. He even claimed he could grow certain amphibians with or without eyes, depending on how much sunlight they got as youngsters.

  Kammerer’s triumph, and his undoing, were a series of experiments on the midwife toad, a most peculiar species. Most toads mate in water, then let their fertilized eggs float away freely. Midwife toads make love on land, but because tadpole eggs are more vulnerable on land, the male midwife toad ties the bundle of eggs to his back legs like a bunch of grapes and hops along with them until they hatch. Unmoved by this charming habit, Kammerer decided in 1903 to start forcing midwife toads to breed in water, by cranking the heat way, way up in their aquariums. The tactic worked—the toads would have shriveled like dried apricots if they hadn’t spent all their time submerged—and those that survived became more waterlike each generation. They had longer gills, produced a slippery jelly coating to waterproof their eggs, and (remember this) developed “nuptial pads”—black, calluslike growths on their forelimbs, to help male toads grip their slippery mates during aqueous coitus. Most intriguing, when Kammerer returned these abused toads to cooler and moister tanks and let them reproduce, the toads’ descendants (who never experienced the desert conditions) supposedly inherited the water-breeding preferences and passed them along to still more descendants.

  Kammerer announced these results around 1910. Over the next decade, he used this and other experiments (and no experiment of his ever failed, it seemed) to argue that animals could be molded to do or be almost anything, given the proper environment. Saying such things at the time had deep Marxist implications, since Marxism held that the only thing keeping the wretched masses down was their terrible environment. But as a committed socialist, Kammerer readily extended his arguments to human society: to his thinking, nurture was nature, a unified concept.

  Indeed, while biology itself was in serious confusion at the time—Darwinism remained controversial, Lamarckism was all but dead, Mendel’s laws hadn’t yet triumphed—Kammerer promised he could unite Darwin, Lamarck, and Mendel. For instance, Kammerer preached that the proper environment could actually cause advantageous genes to spring into existence. And far from scoffing, people lapped his theories up; his books became bestsellers, and he lectured to SRO audiences worldwide. (In these “big-show talks” Kammerer also suggested “curing” homosexuals with testicle transplants and enacting American-style Prohibition worldwide, since Prohibition would undoubtedly produce a generation of American Übermenschen, a race “born without any desire for liquor.”)

  Paul Kammerer, a tormented Austrian biologist who perpetrated one of the great frauds in science history, may have been an unwitting pioneer in epigenetics. (Courtesy of the Library of Congress)

  Unfortunately, the more prominent Kammerer became—he soon anointed himself a “second Darwin”—the shakier his science looked. Most disturbing, Kammerer had withheld crucial details about his amphibian experiments in his scientific reports. Given his ideological posturing, many biologists thought he was blowing smoke, especially William Bateson, Mendel’s bulldog in Europe.

  A ruthless man, Bateson never shied away from attacking other scientists. During the eclipse of Darwinism around 1900, he got into an especially nasty row with his former mentor, a Darwin defender named Walter Weldon. Bateson quickly went Oedipal on Weldon by landing himself on the board of a scientific society that allocated biology funding, then cutting Weldon off. Things got so bad later that when Weldon died in 1906, his widow blamed Bateson’s rancor for the death, even though Weldon died from a heart attack while cycling. Meanwhile a Weldon ally, Karl Pearson, blocked Bateson’s papers from appearing in journals, and also attacked Bateson in his (Pearson’s) house organ, a journal called Biometrika. When Pearson refused Bateson the courtesy of responding in print, Bateson printed up fake copies of Biometrika complete with facsimile covers, inserted his response inside, and distributed them to libraries and universities without any indication they were fraudulent. A limerick at the time summed things up thus: “Karl Pearson is a biometrician / and this, I think, is his position. / Bateson and co. / [I] hope they may go / to monosyllabic perdition.”

  Now Bateson demanded a chance to examine Kammerer’s toads. Kammerer defied him by refusing to supply specimens, and critics continued to roast Kammerer, unimpressed with his excuses. The chaos of World War I temporarily halted the debate, as it left Kammerer’s lab in shambles and his animals dead. But as one writer put it, “If World War I did not completely ruin Austria and Kammerer with it, Bateson moved in after the war to finish the job.” Under relentless pressure, Kammerer finally, in 1926, let an American ally of Bateson’s examine the only midwife toad he’d preserved. This biologist, reptile expert Gladwyn Kingsley Noble, reported in Nature that the toad looked entirely normal, except for one thing. The nuptial pads weren’t present. However, someone had injected black ink under the toad’s skin with a syringe, to make it appear they were. Noble didn’t use the word fraud, but he didn’t have to.

  Biology erupted. Kammerer denied any wrongdoing, alluding to sabotage by unnamed political enemies. But the howling of other scientists increased, and Kammerer despaired. Just before the damning Nature paper, Kammerer had accepted a post in the Soviet Union, a state favorable to his neo-Lamarckian theories. Six weeks later, Kammerer wrote to Moscow that he couldn’t in good conscience accept the job anymore. All the negative attention on him would reflect badly on the great Soviet state.

  Then the resignation letter took a dark turn. “I hope I shall gather together enough courage and strength,” Kammerer wrote, “to put an end [to] my wrecked life tomorrow.” He did, shooting himself in the head on September 23, 1926, on a rocky rural trail outside Vienna. It seemed a sure admission of guilt.

  Still, Kammerer always had his defenders, and a few historians have built a not unreasonable case for his innocence. Some experts believe that nuptial pads actually appeared, and that Kammerer (or an overzealous assistant) injected ink merely to “touch up” the evidence. Others believe that political opponents did frame Kammerer. The local national socialist party (precursor of the Nazi party) supposedly wanted to tarnish Kammerer, who was part Jewish, because his theories cast doubt on the inborn genetic superiority of Aryans. What’s more, the suicide can’t necessarily be pinned on Noble’s exposé. Kammerer had chronic money problems and had already become mentally unhinged over one Alma Mahler Gropius Werfel. Werfel worked as Kammerer’s unpaid lab assistant for a spell, but she’s best known as the tempestuous ex-wife of (among others) composer Gustav Mahler.* She had a fling with the geeky Kammerer, and while it was just another lay to her, Kammerer grew obsessed. He once threatened to blow his brains out all over Mahler’s tombstone if she didn’t marry him. She laughed.

  On the other hand, a prosecutor in any Kammerer case could point out some uncomfortable facts. First, even the unscientific Werfel, a socialite and dilettante composer of light ditties, recognized that Kammerer was sloppy in the lab, keeping terrible records and constantly (albeit unconsciously, she felt) ignoring results that contradicted his pet theories. Even more damning, scientific journals had caught Kammerer fudging data before. One scientist called him “the father of photographic image manipulation.”

  Regardless of Kammerer’s motive, his suicide ended up smearing Lamarckism by association, since nasty political types in the Soviet Union took up Kammerer’s cause. Officials first decided to shoot an agitprop film to defend his honor. Salamandra tells the story of a Kammerer-like hero (Professor Zange) undone by the machinations of a reactionary priest (a stand-in for Mendel?). The priest and an accomplice sneak into Zange’s lab and i
nject ink into a salamander one night; the next day, Zange is humiliated when someone dunks the specimen into a bath in front of other scientists and the ink leaks out, clouding the water. After losing his job, Zange ends up begging for food in the streets (accompanied, oddly, by a monkey rescued from an evil lab). But just as he decides to off himself, a woman rescues him and drags him away to the Soviet paradise. As laughable as this sounds, the soon-to-be agricultural czar of the Soviet Union, Trofim Lysenko, basically believed the myth: he considered Kammerer a martyr to socialist biology and began championing Kammerer’s theories.

  Or at least parts of them. With Kammerer conveniently dead, Lysenko could emphasize only his neo-Lamarckian ideas, which suited Soviet ideology better. And burning with Lamarckian zeal, Lysenko rose to power in the 1930s and began liquidating scores of non-Lamarckian geneticists (including a protégé of Bateson), either having them killed outright or starving them in the Gulag. Unfortunately, the more people he disappeared, the more Soviet biologists had to pay fealty to Lysenko’s twisted ideas. A British scientist at the time reported that talking to Lysenko about genetics “was like trying to explain the differential calculus to a man who did not know his twelve times table. He was… a biological circle-squarer.” Not surprisingly, Lysenkoism destroyed Soviet agriculture—millions died in famines—but officials refused to abandon what they saw as the spirit of Kammerer.

  However unfair, the association with the Kremlin doomed both Kammerer’s reputation and Lamarckism in the following decades, though Kammerer’s defenders continued to plead his case. Most notably (and ironically, given his denunciation of communism elsewhere) in 1971 novelist Arthur Koestler wrote a nonfiction book, The Case of the Midwife Toad, to exonerate Kammerer. Among other things, Koestler dug up a 1924 paper about the discovery of a wild midwife toad with nuptial pads. This doesn’t necessarily clear Kammerer but does hint that midwife toads have latent genes for nuptial pads. Perhaps a mutation during Kammerer’s experiments had brought them out.

  Or perhaps epigenetics had. Some scientists have noted recently that, among other effects, Kammerer’s experiments changed the thickness of the gelatinous coat that surrounds midwife toad eggs. Because this jelly is rich in methyls, changing the thickness might switch genes on or off, including atavistic genes for nuptial pads or other traits. Equally intriguing, whenever Kammerer mated toads, he insisted that the father’s land/water breeding preference “undisputedly” dominated over the female’s preference in the next generations. If Dad liked dry sex, ditto his children and grandchildren, and the same proved true if Dad preferred water sex. Such parent-of-origin effects play an important role in soft inheritance, and these toad trends echo those from Överkalix.

  To be sure, even if Kammerer did stumble onto epigenetic effects, he didn’t understand them—and he probably still (unless you buy the proto-Nazi conspiracy) committed fraud by injecting ink. But in some ways, that makes Kammerer all the more fascinating. His record of bluster, propaganda, and scandal helps explain why many scientists, even during the chaotic eclipse of Darwinism, refused to consider epigenetic-like theories of soft inheritance. Yet Kammerer might have been both a scoundrel and an unwitting pioneer: someone willing to lie for a greater ideological truth—but someone who may not have been lying after all. Regardless, he grappled with the same issues geneticists still grapple with today—how the environment and genes interact, and which one, if either, dominates in the end. Indeed, it’s poignant to wonder how Kammerer might have reacted if only he’d known about, say, Överkalix. He was living and working in Europe just when some of the transgenerational effects were emerging in the Swedish village. Fraud or no fraud, had he seen even traces of his beloved Lamarckism, he might not have felt desperate enough to take his own life.

  Epigenetics has expanded so rapidly in the past decade that trying to catalog every advance can get pretty overwhelming. Epigenetic mechanisms do things as frivolous as give mice polka-dot tails—or as serious as push people toward suicide (perhaps a final irony in the Kammerer case). Drugs like cocaine and heroin seem to spool and unspool the DNA that regulates neurotransmitters and neurostimulants (which explains why drugs feel good), but if you keep on chasing the dragon, that DNA can become permanently misspooled, leading to addiction. Restoring acetyl groups in brain cells has actually resurrected forgotten memories in mice, and more work emerges every day showing that tumor cells can manipulate methyl groups to shut off the genetic governors that would normally arrest their growth. Some scientists think they can even tease out information about Neanderthal epigenetics someday.

  All that said, if you want to make a biologist cranky, start expounding about how epigenetics will rewrite evolution or help us escape our genes, as if they were fetters. Epigenetics does alter how genes function, but doesn’t vitiate them. And while epigenetic effects certainly exist in humans, many biologists suspect they’re easy come, easy go: methyls and acetyls and other mechanisms might well evaporate within a few generations as environmental triggers change. We simply don’t know yet whether epigenetics can permanently alter our species. Perhaps the underlying A-C-G-T sequence always reasserts itself, a granite wall that emerges as the methyl-acetyl graffiti wears away.

  But really, such pessimism misses the point, and promise, of epigenetics. The low genetic diversity and low gene count of human beings seem unable to explain our complexity and variety. The millions upon millions of different combinations of epigenes just might. And even if soft inheritance evaporates after, say, a half-dozen generations, each one of us lives for two or three generations only—and on those timescales, epigenetics makes a huge difference. It’s much easier to rewrite epigenetic software than to rewire genes themselves, and if soft inheritance doesn’t lead to true genetic evolution, it does allow us to adapt to a rapidly shifting world. As a matter of fact, thanks to the new knowledge that epigenetics lends us—about cancer, about cloning, about genetic engineering—our world will likely shift even more rapidly in the future.

  16

  Life as We Do (and Don’t) Know It

  What the Heck Will Happen Now?

  Around the end of the 1950s, a DNA biochemist (and RNA Tie Club member) named Paul Doty was strolling through New York, minding his own, when a street vendor’s wares caught his eye, and he halted, bewildered. The vendor sold lapel buttons, and among the usual crude assortment, Doty noticed one that read “DNA.” Few people worldwide knew more about DNA than Doty, but he assumed the public knew little about his work and cared less. Convinced the initialism stood for something else, Doty asked the vendor what D-N-A might be. The vendor looked the great scientist up and down. “Get with it, bud,” he barked in New Yawk brogue. “Dat’s da gene!”

  Jump forward four decades to the summer of 1999. Knowledge of DNA had mushroomed, and Pennsylvania legislators, stewing over the impending DNA revolution, asked a bioethics expert (and Celera board member) named Arthur Caplan to advise them on how lawmakers might regulate genetics. Caplan obliged, but things got off to a rocky start. To gauge his audience, Caplan opened with a question: “Where are your genes?” Where are they located in the body? Pennsylvania’s best and brightest didn’t know. With no shame or irony, one quarter equated their genes with their gonads. Another overconfident quarter decided their genes resided in their brains. Others had seen pictures of helixes or something but weren’t sure what that meant. By the late 1950s, the term DNA was enough a part of the zeitgeist to grace a street vendor’s button. Dat’s da gene. Since then public understanding had plateaued. Caplan later decided, given their ignorance, “Asking politicians to make regulations and rules about genetics is dangerous.” Of course, befuddlement or bewilderment about gene and DNA technology doesn’t prevent anyone from having strong opinions.

  That shouldn’t surprise us. Genetics has fascinated people practically since Mendel tilled his first pea plant. But a parasite of revulsion and confusion feeds on that fascination, and the future of genetics will turn on whether we can resolve that push-
pull, gotta-have-it-won’t-stand-for-it ambivalence. We seem especially mesmerized/horrified by genetic engineering (including cloning) and by attempts to explain rich, complicated human behavior in terms of “mere” genes—two often misunderstood ideas.

  Although humans have been genetically engineering animals and plants since the advent of agriculture ten thousand years ago, the first explicit genetic engineering began in the 1960s. Scientists basically started dunking fruit fly eggs in DNA goo, hoping that the porous eggs would absorb something. Amazingly these crude experiments worked; the flies’ wings and eyes changed shape and color, and the changes proved heritable. A decade later, by 1974, a molecular biologist had developed tools to splice DNA from different species together, to form hybrids. Although this Pandora restricted himself to microbes, some biologists saw these chimeras and shivered—who knew what was next? They decided that scientists had gotten ahead of themselves, and called for a moratorium on this recombinant DNA research. Remarkably, the biology community (including the Pandora) agreed, and voluntarily stopped experimenting to debate safety and rules of conduct, almost a unique event in science history. By 1975 biologists decided they did understand enough to proceed after all, but their prudence reassured the public.

  That glow didn’t last. Also in 1975, a slightly dyslexic myrmecologist born in evangelical Alabama and working at Harvard published a six-pound, 697-page book called Sociobiology. Edward O. Wilson had labored for decades in the dirt over his beloved ants, figuring out how to reduce the byzantine social interactions of serfs, soldiers, and queens into simple behavioral laws, even precise equations. In Sociobiology the ambitious Wilson extended his theories to other classes, families, and phyla, ascending the evolutionary ladder rung by rung to fish, birds, small mammals, mammalian carnivores, and primates. Wilson then plowed straight through chimps and gorillas to his notorious twenty-seventh chapter, “Man.” In it, he suggested that scientists could ground most if not all human behavior—art, ethics, religion, our ugliest aggressions—in DNA. This implied that human beings were not infinitely malleable but had a fixed nature. Wilson’s work also implied that some temperamental and social differences (between, say, men and women) might have genetic roots.