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

by Sam Kean

  As detailed in A Guinea Pig’s History of Biology, Galton had gathered some of his evidence for bell curves in his typically eccentric way, at the International Health Exhibition in London in 1884. The expo was as much a social affair as a scientific endeavor: as patrons wandered through exhibits about sanitation and sewers, they gulped mint juleps and spiked arrack punch and kumiss (fermented mare’s milk produced by horses on-site) and generally had a gay old time. Galton set up a booth at the expo as well and doggedly measured the stature, eyesight, and hearing of nine thousand occasionally intoxicated Englishmen. He also tested their strength with fairground games that involved punching and squeezing various contraptions, a task that proved more difficult than Galton had anticipated: oafs who didn’t understand the equipment constantly broke it, and others wanted to show off their strength and impress girls. It was a true fairground atmosphere, but Galton had little fun: he later described “the stupidity and wrong-headedness” of his fellow fairgoers as “so great as to be scarcely credible.” But as expected, Galton gathered enough data to confirm that human traits also formed bell curves. The finding further bolstered his confidence that he, not Cousin Charles, understood how evolution proceeded, and that small variations and small changes played no important role.

  This wasn’t the first time Galton had thwarted Darwin, either. From the day he published On the Origin of Species, Darwin was aware that his theory lacked something, badly. Evolution by natural selection requires creatures to inherit favorable traits, but no one (save an obscure monk) had any idea how that worked. So Darwin spent his last years devising a theory, pangenesis, to explain that process.

  Pangenesis held that each organ and limb pumped out microscopic spores called gemmules. These circulated inside a creature, carrying information about both its inborn traits (its nature) and also any traits it acquired during its lifetime (its environment, or nurture). These gemmules got filtered out by the body’s erogenous zones, and copulation allowed male and female gemmules to mix like two drops of water when males deposited their semen.

  Although ultimately mistaken, pangenesis was an elegant theory. So when Galton designed an equally elegant experiment to hunt for gemmules in rabbits, Darwin heartily encouraged the emprise. His hopes were soon dashed. Galton reasoned that if gemmules circulated, they must do so in the blood. So he began transfusing blood among black, white, and silver hares, hoping to produce a few mottled mongrels when they had children. But after years of breeding, the results were pretty black-and-white: not a single multishaded rabbit appeared. Galton published a quickie scientific paper suggesting that gemmules didn’t exist, at which point the normally avuncular Darwin went apoplectic. The two men had been warmly exchanging letters for years on scientific and personal topics, often flattering each other’s ideas. This time Darwin lit into Galton, fuming that he’d never once mentioned gemmules circulating in blood, so transfusing blood among rabbits didn’t prove a damn thing.

  On top of being disingenuous—Darwin hadn’t said boo about blood not being a good vehicle for gemmules when Galton was doing all the work—Darwin was deceiving himself here. Galton had indeed destroyed pangenesis and gemmules in one blow.

  together on one chromosome: Sex-linked recessive traits like these show up more often in males than in females for a simple reason. An XX female with a rare white-eye gene on one X would almost certainly have the red-eye gene on the other X. Since red dominates white, she wouldn’t have white eyes. But an XY male has no backup if he gets the white-eye gene on his X; he will be white-eyed by default. Geneticists call females with one recessive version “carriers,” and they pass the gene to half their male children. In humans hemophilia is one example of a sex-linked trait, Sturtevant’s red-green color blindness another.

  produce millions of descendants: Many different books talk a bit about the fly room, but for the full history, check out A Guinea Pig’s History of Biology, by Jim Endersby, one of my favorite books ever. Endersby also touches on Darwin’s adventures with gemmules, Barbara McClintock (from chapter 5), and other fascinating tales.

  his reputation would never lapse again: A historian once wisely noted that “in reading Darwin, as in reading Shakespeare or the Bible, it is possible to support almost any viewpoint desirable by focusing on certain isolated passages.” So you have to be careful when drawing broad conclusions from Darwin quotes. That said, Darwin’s antipathy for math seemed genuine, and some have suggested that even elementary equations frustrated him. In one of history’s ironies, Darwin ran his own experiments on plants in the primrose genus, just like de Vries, and came up with clear 3:1 ratios among offspring traits. He obviously wouldn’t have linked this to Mendel, but he seems not to have grasped that ratios might be important at all.

  inside fruit fly spit glands: Drosophila go through a pupa stage where they encase themselves in gluey saliva. To get as many saliva-producing genes going as possible, salivary-gland cells repeatedly double their chromosomes, which creates gigantic “puff chromosomes,” chromosomes of truly Brobdingnagian stature.

  Chapter 3: Them’s the DNA Breaks

  the “Central Dogma” of molecular biology: Despite its regal name, the Central Dogma has a mixed legacy. At first, Crick intended the dogma to mean something general like DNA makes RNA, RNA makes proteins. Later he reformulated it more precisely, talking about how “information” flowed from DNA to RNA to protein. But not every scientist absorbed the second iteration, and just like old-time religious dogmas, this one ended up shutting down rational thought among some adherents. “Dogma” implies unquestionable truth, and Crick later admitted, roaring with laughter, that he hadn’t even known the definition of dogma when he defined his—it just sounded learned. Other scientists paid attention in church, however, and as word of this supposedly inviolable dogma spread, it transmogrified in many people’s minds into something less precise, something more like DNA exists just to make RNA, RNA just to make proteins. Textbooks sometimes refer to this as the Central Dogma even today. Unfortunately this bastardized dogma seriously skews the truth. It hindered for decades (and still occasionally hinders) the recognition that DNA and especially RNA do much, much more than make proteins.

  Indeed, while basic protein production requires messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), dozens of other kinds of regulatory RNA exist. Learning about all the different functions of RNA is like doing a crossword puzzle when you know the last letters of an answer but not the opening, and you run through the alphabet under your breath. I’ve seen references to aRNA, bRNA, cRNA, dRNA, eRNA, fRNA, and so on, even the scrabbulous qRNA and zRNA. There’s also rasiRNA and tasiRNA, piRNA, snoRNA, the Steve Jobs–ish RNAi, and others. Thankfully, mRNA, rRNA, and tRNA cover all the genetics we’ll need in this book.

  can represent the same amino acid: To clarify, each triplet represents only one amino acid. But the inverse is not true, because some amino acids are represented by more than one triplet. As an example, GGG can only be glycine. But GGU, GGC, and GGA also code for glycine, and that’s where the redundancy comes in, because we really don’t need all four.

  onto the succeeding generation: A few other events in history have exposed masses of people to radioactivity, most notoriously at the Chernobyl nuclear power plant in modern Ukraine. The 1986 Chernobyl meltdown exposed people to different types of radioactivity than the Hiroshima and Nagasaki bombs—fewer gamma rays and more radioactive versions of elements like cesium, strontium, and iodine, which can invade the body and unload on DNA at short range. Soviet officials compounded the problem by allowing crops to be harvested downwind of the accident and allowing cows to graze on exposed grass, then letting people eat and drink the contaminated milk and produce. The Chernobyl region has already reported some seven thousand cases of thyroid cancer, and medical officials expect sixteen thousand extra cancer deaths over the next few decades, an increase of 0.1 percent over background cancer levels.

  And in contrast to Hiroshima and Nagasaki, the DNA o
f children of Chernobyl victims, especially children of men near Chernobyl, does show signs of increased mutations. These results remain disputed, but given the different exposure patterns and dosage levels—Chernobyl released hundreds of times more radioactivity than either atomic bomb—they could be real. Whether those mutations actually translate to long-term health problems among Chernobyl babies remains to be seen. (As an imperfect comparison, some plants and birds born after Chernobyl showed high mutation rates, but most seemed to suffer little for that.)

  Sadly, Japan will now have to monitor its citizens once again for the long-term effects of fallout because of the breech of the Fukushima Daiichi nuclear power plant in spring 2011. Early government reports (some of which have been challenged) indicate that the damage was contained to an area one-tenth the size of Chernobyl’s exposure footprint, mostly because radioactive elements at Chernobyl escaped into the air, while in Japan the ground and water absorbed them. Japan also intercepted most contaminated food and drink near Fukushima within six days. As a result, medical experts suspect the total number of cancer deaths in Japan will be correspondingly small—around one thousand extra deaths over the next few decades, compared to the twenty thousand who died in the earthquake and tsunami.

  just beginning to explore: For a full account of Yamaguchi’s story—and for eight other equally riveting tales—see Nine Who Survived Hiroshima and Nagasaki, by Robert Trumbull. I can’t recommend it highly enough.

  For more detail on Muller and many other players in early genetics (including Thomas Hunt Morgan), check out the wonderfully comprehensive Mendel’s Legacy, by Elof Axel Carlson, a former student of Muller’s.

  For a detailed but readable account of the physics, chemistry, and biology of how radioactive particles batter DNA, see Radiobiology for the Radiologist, by Eric J. Hall and Amato J. Giaccia. They also discuss the Hiroshima and Nagasaki bombs specifically.

  Finally, for an entertaining rundown of early attempts to decipher the genetic code, I recommend Brian Hayes’s “The Invention of the Genetic Code” in the January–February 1998 issue of American Scientist.

  Chapter 4: The Musical Score of DNA

  even meant, if anything: Zipf himself believed that his law revealed something universal about the human mind: laziness. When speaking, we want to expend as little energy as possible getting our points across, he argued, so we use common words like bad because they’re short and pop easily to mind. What prevents us from describing every last coward, rogue, scuzzbag, bastard, malcontent, coxcomb, shit-for-brains, and misanthrope as “bad” is other people’s laziness, since they don’t want to mentally parse every possible meaning of the word. They want precision, pronto. This tug-of-war of slothfulness results in languages where common words do the bulk of the work, but rarer and more descriptive words must appear now and then to appease the damn readers.

  That’s clever as far as it goes, but many researchers argue that any “deep” explanation of Zipf’s law is, to use another common word, crap. They point out that something like a Zipfian distribution can arise in almost any chaotic situation. Even computer programs that spit out random letters and spaces—digital orangutans banging typewriters—can show Zipfian distributions in the resulting “words.”

  evolution creeps forward: The analogy between genetic language and human language seems fuzzy to some, almost too cute to be true. Analogies can always be taken too far, but I think that some of this dismissal stems from our sort-of-selfish tendency to think that language can only be sounds that humans make. Language is wider than just us: it’s the rules that govern any communication. And cells as surely as people can take feedback from their environment and adjust what they “say” in response. That they do so with molecules instead of air-pressure waves (i.e., sound) shouldn’t prejudice us. Recognizing this, a few recent cellular biology textbooks have included chapters on Chomsky’s theories about the underlying structure of languages.

  sator… rotas: The palindrome means something like “The farmer Arepo works with his plow,” with rotas, literally “wheels,” referring to the back-and-forth motion that plows make as they till. This “magic square” has delighted enigmatologists for centuries, but scholars have suggested it might have served another purpose during imperial Roman reigns of terror. An anagram of these twenty-five letters spells out paternoster, “Our Father,” twice, in an interlocking cross. The four letters left over from the anagram, two a’s and two o’s, could then refer to the alpha and omega (famous later from the Book of Revelation). The theory is that, by sketching this innocuous palindrome on their doors, Christians could signal each other without arousing Roman suspicion. The magic square also reportedly kept away the devil, who traditionally (so said the church) got confused when he read palindromes.

  his boss’s lunatic projects: Friedman’s boss, “Colonel” George Fabyan, had quite a life. Fabyan’s father started a cotton company called Bliss Fabyan and groomed Fabyan to take over. But succumbing to wanderlust, the boy ran away to work as a Minnesota lumberjack instead, and his outraged and betrayed father disinherited him. After two years, Fabyan tired of playing Paul Bunyan and decided to get back into the family business—by applying, under an assumed name, to a Bliss Fabyan office in St. Louis. He quickly set all sort of sales records, and his father at corporate HQ in Boston soon summoned this young go-getter to his office to talk about a promotion. In walked his son.

  After this Shakespearean reunion, Fabyan thrived in the cotton business and used his wealth to open the think tank. He funded all sorts of research over the years but fixated on Shakespeare codes. He tried to publish a book after he supposedly broke the code, but a filmmaker working on some adaptations of Shakespeare sued to stop publication, arguing that its contents would “shatter” Shakespeare’s reputation. For whatever reason, the local judge took the case—centuries of literary criticism apparently fell under his jurisdiction—and, incredibly, sided with Fabyan. His decision concluded, “Francis Bacon is the author of the works so erroneously attributed to William Shakespeare,” and he ordered the film producer to pay Fabyan $5,000 in damages.

  Most scholars look on arguments against Shakespeare’s authorship about as kindly as biologists do on theories of maternal impressions. But several U.S. Supreme Court justices, most recently in 2009, have also voiced opinions that Shakespeare could not have written his plays. The real lesson here is that lawyers apparently have different standards of truth and evidence than scientists and historians.

  to rip off casinos at roulette: The casino gambit never paid off. The idea started with the engineer Edward Thorp, who in 1960 recruited Shannon to help him. At the roulette table, the two men worked as a team, though they pretended not to know each other. One watched the roulette ball as it spun around the wheel and noted the exact moment it passed certain points. He then used a toe-operated switch in his shoe to send signals to the small computer in his pocket, which in turn transmitted radio signals. The other man, wearing an earpiece, heard these signals as musical notes, and based on the tune, he would know where to toss his money. They painted any extruding wires (like the earpiece’s) the color of flesh and pasted the wires to their skin with spirit gum.

  Thorp and Shannon calculated an expected yield of 44 percent from their scheme, but Shannon turned chicken on their first test run in a casino and would only place dime bets. They won more often than not, but, perhaps after eyeing some of the heavies manning the casino door, Shannon lost his appetite for the enterprise. (Considering that the two men had ordered a $1,500 roulette wheel from Reno to practice, they probably lost money on the venture.) Abandoned by his partner, Thorp published his work, but it apparently took a number of years before casinos banned portable electronics outright.

  Chapter 5: DNA Vindication

  an inside-out (and triple-stranded): For an account of the embarrassment and scorn Watson and Crick endured for this odd DNA model, please see my previous book, The Disappearing Spoon.

  complex and beautiful life: For
a more detailed account of Miriam’s life, I highly recommend The Soul of DNA, by Jun Tsuji.

  the oldest matrilineal ancestor: Using this logic, scientists also know that Mitochondrial Eve had a partner. All males inherit Y chromosomes from their fathers alone, since females lack the Y. So all men can trace strictly paternal lines back to find this Y-chromosomal Adam. The kicker is that, while simple laws of mathematics prove that this Adam and Eve must have existed, the same laws reveal that Eve lived tens of thousands of years earlier than Adam. So the Edenic couple could never have met, even if you take into account the extraordinary life expectancies in the Bible.

  By the by, if we relax the strictly patrilineal or strictly matrilineal bit and look for the last ancestor who—through men or women—passed at least some DNA to every person alive today, that person lived only about five thousand years ago, long after humans had spread over the entire earth. Humans are strongly tribal, but genes always find a way to spread.

  got downgraded: Some historians argue that McClintock struggled to communicate her ideas partly because she couldn’t draw, or at least didn’t. By the 1950s molecular biologists and geneticists had developed highly stylized cartoon flowcharts to describe genetic processes. McClintock, from an older generation, never learned their drawing conventions, a deficit that—combined with the complexity of maize in the first place—might have made her ideas seem too convoluted. Indeed, some students of McClintock recall that they never remember her drawing any diagrams, ever, to explain anything. She was simply a verbal person, rutted in logos.