Here are various discursions and distractions that didn’t find their way into The Violinist’s Thumb—not because they’re un-fun or un-illuminating, but because paper is more expensive than electrons, and I had to cut something.

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Chapter One:

The Elephant Man and Maternal Impressions

The idea of maternal impressions, while scientifically laughable by the later 1800s, persisted in the popular imagination for much longer. Joseph Merrick, the “elephant man,” believed that his condition resulted from an incident in which an elephant scared his pregnant mother.

Mendel’s funny side

Though widely regarded (at least until his final years) as a warm man, Mendel took science all too seriously. As the official chief experimenter at his abbey, Mendel sometimes had to teach students how to design experiments using plants, and he used to flare up at the inevitable tittering that arose when a celibate monk began explaining plant sex in graphic detail. “Do not be stupid!” he once barked. “These are natural things.”

Mendel’s tornado

After a tornado tore the roof off his monastery in 1870, Mendel (then the abbot) compensated somewhat for his lack of time in the garden by redecorating the ceiling with four trompe-l’oeil portraits, one in each corner. One panel depicted two bulls dragging a plow through a field, as well as St. Isadore, patron saint of agriculture. The second depicted two men grafting branches of apple trees in an orchard. The third showed a straw beehive. The fourth showed a mess of scientific instruments, including a globe, telescope, sundial, thermometer, and compass.

By the by, Mendel couldn’t help himself when the tornado ripped through the monastery—he peeked out from his hiding spot to observe it, and later gave an account of its behavior to a scientific society, a talk much more well-received than his pea work.

Mendel’s successor

Anslem Rambousek, Mendel’s successor at St. Thomas and the man ultimately responsible for burning his papers, proved himself a better politician than Mendel. Rambousek not only got government officials off the monastery’s back regarding taxes, but succeeded in wringing a check out of the national treasury for almost twenty-thousand gulden, for lost income.

Mendel on Darwin?

We know Mendel read Darwin (viz., the second German edition of On the Origin of Species) and underlined many passages, but his exact attitude remain a subject of debate. Some historians claim that the jolly friar agreed with Darwin, others that he loathed evolution. The truth is probably somewhere in the middle.

And there’s long been a reciprocal rumor that Darwin received a copy of Mendel’s pea paper in the 1860s but neglected to read it. How this anecdote began to circulate remains mysterious—there’s no evidence for it, not a scrap—but it might conflate two real but less dramatic events. First, Mendel did try to circulate his paper to Europe’s top biologists, and although there’s no record of this, he might well have tried to send one to Darwin, the topmost biologist at the time. (Regardless of whether he sent one, Darwin’s executors found no evidence Darwin ever received one.) Second, Darwin did have a copy of one of the few publications that referenced Mendel’s work before 1900, a book. But it only referenced the paper—it didn’t summarize it—and we know Darwin never read it anyway. Books at the time were often printed on oversized sheets that were folded over and sewn together. Readers literally had to cut pages open to get at the print, and Darwin never cut the pages that mentioned Mendel’s paper.

Chapter Two:

Morgan’s absent-mindedness

Like Friedrich Miescher, Morgan sometimes got a little wrapped up in his science. He missed the birth of his third child, Lillian, while at work but rushed to the hospital and arrived at his wife’s bedside minutes later. She was exhausted from labor, but politely asked, “Well, how is the fly?” This happened in 1910, just after Morgan had discovered his first real mutants, and he immediately started babbling about all the recent discoveries he’d made and all the work he hoped to do and what it all meant—and plum forgot to ask after his new daughter.

Morgan’s generosity

As another example of his generosity, when Morgan realized that Sturtevant was struggling to pay for school at Columbia, he went to some administrators and pulled some strings to secure a scholarship for his young protégée. (On the other hand, there’s no evidence he did the same for Bridges, an orphan, or Mueller, who had to care for his mother…)

The etymology of gene

Johannsen admitted he’d coined the knock-off word “gene” in part because, as a short word, scientists could conjoin it with and affix other words to it easily. He invested serious time into thinking about this, because he knew, like it or not, a catchy name can help determine whether a scientific idea spreads and gets a fair hearing.

As Johannsen did, Scientists still use “gene” to refer to an abstract unit of inheritance. But today it can also mean a physical stretch of DNA that creates a protein, or, more generally, a set of instructions that causes (in various ways) a trait to appear. So if the word began as a linguistic fiction, it remains somewhat ambiguous a century later—a “deceptive little word,” as one scientist put it.

Clarification

To explain a point that I glided over in the book. The cells of many organisms go through two types of division when making more cells. Most human cells, for example, start with forty-six chromosomes—twenty-three pairs of near-identical twins—and end with the same number. (If you’re channeling high-school bio, this is mitosis.) When making sperms and eggs however (meiosis), cells drop from forty-six to twenty-three. This halving is necessary because if both parents contributed all forty-six chromosomes, the child would have 46 x 2 = 92. Its children would have 92 x 2 = 184, its children 184 x 2 = 368, etc., until chromosomes were piling up like the proverbial rice on the chessboard.

Chromosome doublings

The doubling and redoubling of chromosomes in fruit fly spit glands may impress you, but it’s nothing compared to the multiplications that plants can pull off. Through various processes, one plant species, the so-called adder’s-tongue, a short green shoot, can crowd up to 1,260 chromosomes into one cell.

Chapter Three:

Er, about that “universal” code…

Though the DNA/RNA/protein code is as good as universal, two teeny-weeny exceptions exist. In the presence of both the element selenium and another special enzyme, cells can run through the UGA stop sign and add the amino acid selenocysteine instead. Some species of bacteria can also run the UAG stop sign and add the amino acid pyrrolysine. Other than these special cases, all (known) life uses the same code for the same canonical twenty amino acids.

RNA Tie Club tie pin snafu

In addition to $4.00 ties, each of the twenty RNA Tie Club members got a $6.00 tie pin with “his” amino acid on it. Only instead of the molecular structure of his amino acid (pretty hard to see on a tie pin), each member had the three-letter abbreviation for it inscribed on the pin instead, like a monogram.

This sartorial flair apparently got Tie Club founder George Gamow into some trouble once while visiting Las Vegas. Though not a gambler, he managed to run clean out of cash, and given all the lowlifes and grifters around Sin City, he had a hell of time getting anyone to cash a check. He finally approached a teller at a bank, but she didn’t believe him either. (It’s not clear if Gamow didn’t have ID along, or she didn’t trust what he had…) Regardless, Gamow was reduced to tramping to a nearby bookstore, writing a check for a copy of a book he’d recently written, and returning to show the teller his picture on the dust jacket. You can just about imagine her crossing her arms and making a face, but she finally relented. That is, until she noticed his tie pin—ALA, for alanine. Why would a supposed “George Gamow” have the initials ALA?, she demanded, and turned Gamow away without a cent.

Higher than what?

In referring to “higher” animals like reptiles, birds, mammals, and especially humans, I’m probably incurring the wrath of Darwin, not to mention some of his strident descendents. Darwin once wrote, “It is absurd to talk of one animal being higher than another,” and then added, “Never say higher or lower!”, exclamation point sic. Richard Dawkins later added, “I recommend that evolutionary writers should no longer, under any circumstances, use the adjective ‘higher’ and ‘lower.’” Well, I do. It’s not that Darwin and Dawkins have erred—“higher” does have connotations of “closer to perfection” and from a biological point of view, humans are no better suited to their environments (and in some cases less suited) than most creatures. At the same time, humans do differ from other creatures—silly to deny it. We’re smarter, and we can’t help but make value judgments based on that. However imperfectly, “higher” does get at that sense without introducing a bunch of mealy-mouthed apologies. No doubt elephants would do the same, but because this book builds toward human evolution, I’ll continue to use that adjective. Just understand the implicit scare quotes around it every time.

Crazy gene names

For a list of wacky and irreverent gene names, in fruit flies and other organisms, visit this site here.

Chapter Four:

Kelvin on knots

More specifically, Kelvin believed that all atoms were knots of “aether,” the mythico-scientific substance that supposedly permeated all space and provided a medium of propagation for light. Most scientists considered aether quite labile and supple, and Tait inspired Kelvin’s conjecture vis-à-vis knots with a series of experiments on how smoke rings twirl and twist and intersect. By the by, Tait, a proper Scotsman, also penned a celebrated treatise on the aerodynamics of golf balls.

Stray notes on DNA & music

(1) One scientist rather cleverly composed DNA music by converting amino acid triplets on one helix strand into notes and putting those on the treble clef. He then converted the opposite, complementary strand into notes in the same way, and plucked those onto the bass clef.

(2) Other scientists have translated the amino acid sequence from Beethoven DNA into music, although they cheated by using DNA from his descendents only. They had tried to get a lock of hair from Ludwig van, but whoever owns such things turned the scientists down.

(3) Some non-musician, non-scientists types—lawyers—have also examined DNA-inspired music, albeit with a predatory interest. The attorneys had wanted intellectual property protection on some DNA, and thought if they converted it into a musical score—which would be protected by copyright—they could strengthen their case.

Hapax and dis

As a corollary of the main law, Zipf’s also predicts that rare words are paradoxically common within a language. Specifically, if you list all the different words in a text and count how many appear just once, they account for half the total vocabulary.

Words that appear just once in a text, or in an author’s collected works, or even in the full written record of a language, have a special name—hapax legomenon (idiomatically, “one-offs”). Again, roughly half the vocabulary words in any work are hapax (around fifteen percent are dis legomenon, two-offs), although the exact percentage varies from author to author. Because of that variability some philologists have suggested that counting the frequency of hapax words could expose frauds or settle disputes over who wrote what ancient texts. But the hapax rate varies too much even within a single author to be much use. Shakespeare’s Hamlet and Troilus and Cressida contain over ten hapax per page, while Julius Caesar and Two Gentleman of Verona contains fewer than four. Nowadays, any forger worth his salt could do a statistical analysis of his work anyway.

Y chromosome death

In one rodent species, Ellobius lutescens, a.k.a. the transcaucasian prairie vole, the Y chromosome did accumulate too many mutations and lacked the requisite number of palindromes to save it. Luckily for all the lady voles, males themselves didn’t vanish. They developed another way to produce testes and now lack a second X chromosome altogether. (They’re considered X0.)

Even this sex-determining system hardly counts as bizarre among animals. Slipper limpets stack themselves into “mating chains” on the sea floor, towering Dagwood sandwiches of organisms. The bottom of the stack is always female, and when she dies, the male above her quite obligingly becomes a female himself. There’s also the system used by an ocean worm, Bonellia viridis. Females of this worm swallow sexless juvenile members and expose them to chemicals that turn them male. The males then become helpless prisoners inside her genital sac, totally reliant on the misses for room, board, and mere life.

Overwriting genes clarification

With regard to “overwriting” genes on the Y chromosome: To be sure, the overwriting process happens on all chromosomes, and can lead to mistakes on non–sex chromosomes as well. That is, a good gene can be overwritten with a bad one at other spots in the genome besides the Y. However, regular chromosomes overwrite genes only at certain times during the cell reproductive cycle. The Y can overwrite genes at almost any time. Plus, the Y has so many repeats and palindromes where similar segments can line up and overwrite each other that it falls into this trap far more often. Finally, deleting a functioning Y gene is rarely fatal, while destroying other genes can easily lead to a non-viable fetus, so non-Y mistakes often don’t last.

Chapter Five:

DNA phone home

During one chaotic scene in ET, someone examining the little alien announces “He’s got DNA!” This opens up the possibility that ET’s kind had seeded our planet long ago and simply returned to see how things had turned out. (Not well.) That scenario’s obviously doubtful in real life, but some scientists have suggested that microbes at least might have rocketed to Earth from another planet on a meteor. Meteors from Mars land on Earth regularly, and one could certainly crash-land here from farther afield. Of course this doesn’t explain where that life came from, but it could hold a clue.

DNA in space

Astronomers have recently discovered, near the center of our galaxy, two long thin clouds of space dust (nebulae) wrapped around each other—a gigantic interstellar double helix! They speculated that the helix formed from the complicated interaction of spewing gas jets, strong magnetic fields, and a black hole.

Butterfly DNA

True to her reputation, Margulis allegedly ramrodded a paper into print in a prestigious academic journal in 2009—subverting peer review and pissing off loads of colleagues—simply because the paper promoted genome mergers in butterflies. Butterflies of course metamorphose from sluggish caterpillars into delicate winged creatures, and the paper (by retired scientist Donald Williamson) argued that butterflies first appeared when sperm from a strictly caterpillar-like ancestor accidentally inseminated eggs from a strictly butterfly-like ancestor (or vice-versa) long ago. If true, this would boost the genome-merger theory immensely—merging microbes is one thing, merging multicellular creatures far more impressive. And if butterflies flourished after a merger, why couldn’t tadpoles and frogs have, too? Or duck-billed platypuses? Or all multicellular creatures?

It’s a bracing idea, one you just wish could be true. Alas, entomologists have mapped the genes of butterflies and found that—instead of one set of genes controlling early development, another set controlling later development, as you might expect from a genome merger—the butterfly uses the same genes to control many body parts in both larval and adult stages. These genes may be unusually flexible, but the same ancestral genes do all the work.

Like Williamson, novelist Vladimir Nabokov—a dedicated amateur lepidopterist—had his own idiosyncratic theory about butterfly evolution. Nabokov believed that his pet taxon of butterflies, the Polyommatus blues, had migrated (somewhat like early American humans) across the Bering land bridge linking Asia to Alaska a few million years ago and had colonized North and South America. Though a far less ambitious theory than Williamson’s, professional lepidopterists dismissed it as about on the same level. Genetic analysis, however, has vindicated Nabokov. The Polyommatus blues were Asian immigrants indeed.

Chapter Six:

More on Hox

While the Hox genes in vertebrates and invertebrates look largely the same and function largely the same way, they do display one major difference: the genes that build invertebrate bellies build the backs of vertebrates, and vice-versa. Somewhere along the line, amid hundreds of millions of years of evolution, something got cross-wired.

He couldn’t have known the genetic details of course, but the early-nineteenth-century French biologist Étienne Geoffroy Saint-Hilaire somehow intuited this reversal by examining the larvae of invertebrates and the embryos of vertebrates, and figuring out which parts were homologous. Saint-Hilaire promoted this idea widely, but unfortunately ran into the formidable Baron Cuvier, who hated the notion and tried to squash it. The two men engaged in eight fraught public debates on biology between February and April of 1830, and though most observers thought Saint-Hilaire held his own, his ideas fell into disrepute among most thinkers.

P.S. If you want to know more about the seemingly arcane differences between homeobox, homeotic, homeodomain, etc., check out this link.

Spemann’s daughter’s hair

In his lab files Hans Spemann actually preserved the lock of blonde hair from his daughter that he used in his experiments on salamander embryos. Parents often save locks of their children’s hair for sentimental reasons, but little Margrette Spemann’s forelock deserved it! You can see a picture on this site if you scroll down.

The once and future polar bear

Like most species (humans included), polar bears can’t brag about any sort of pure and pristine genetic history. The mtDNA of polar bears suggests that, beyond their roots in Alaskan and Siberian bears, they received a significant genetic contribution from Irish brown bears, a now-extinct species that mated with polar bears less than 50,000 years ago (when polar ice sheets extended to Ireland). In fact, one Irish brown bear was the “mitochondrial Eve” of the polar bears, the last common female ancestor. Incidentally, as Arctic ice caps shrink and polar bears travel farther afield for food, they have started encountering and interbreeding with brown bears (including grizzlies) all over again, producing a new generation of “pizzlies.” So the hanky-panky of thousands of years ago could be a preview of things to come.

The Mawson saga

(N.B.: This is a mini-essay about explorer Douglas Mawson, whose adventures with vitamin A poisoning rival that of Barentsz’s men. In fact, Mawson’s tale is one of the most ghastly in polar history, which is saying something…)

That January was the most wretched month of Douglas Mawson’s life. He’d lost nineteen beloved huskies, as well as two close friends, men he’d been to the ends of the world with—one careening down an open pit, the other succumbing to delirium and dying in a coma. Mawson himself had half starved on the trek across Antarctica, and by this point—it was a sunny, unrelenting summer in the southern hemisphere—his sun-burnt, wind-burnt eyes could barely see, and he took to medicating them with cocaine. Once he slipped down a crevasse and found himself dangling upside down by fourteen feet of thin rope. After four hours of inching his dead weight up to the lip, he managed to slip back in, and he debated with himself over cutting the rope—an honorable suicide—or climbing back out and facing god knows what else.

But of all the things Douglas Mawson confronted that January of 1913, the most horrific was his feet.

Numb tip to toe on the homeward journey, Mawson had barely registered at first that his feet felt “lumpy and sore” and that they squished each step like rain-sodden boots. When the pain grew acute one morning, he sat down on the rough ice, peeled his socks off—and watched as the soles of his feet peeled off with them. The thick skin had simply come apart at the seams, leaving the soles dangling like something you’d fry up in a pan. The skin on his ears was also flaking off in casts, like the molted skins of snakes, and his testicles and penis had rubbed down to the raw, red epidermis. Mawson didn’t know it—he was an explorer and a geologist, not a biologist—but the reason for his peeling feet and ears and balls could be traced to a revolt in his genes, a revolt enflamed by vitamin A.

Not that that knowledge would have done him a fat lot of good in Antarctica. So, with miles to go that morning, Mawson pulled a tin of lanolin from his dwindling supply kit and buttered up his feet. He tied his dead soles back on with cloth bandages, gi-i-i-ingerly pulled on six pairs of socks, and laced his boots, to keep marching.

Some days, like the ides of January, he made only one mile. The slow progress that day must have struck him as especially cruel because it was also the day that his ride home, the boat Aurora, back at the expedition base camp, would leave for Australia with or without him. He was still eighty of the longest miles you could find anywhere on earth away.

Mawson’s crew had set out in November 1912 to explore the coast of Antarctica, and promptly barreled into the single windiest corridor on earth, with gusts topping 200 mph. To make headway when walking, his men sometimes had to lean at 45° angles. Mawson’s was one of four scientific teams, mostly Australians, exploring Antarctica that season, making maps and turning up whatever they could find—one party discovered the first Antarctic meteorite. Mawson, 30, commanded three sledges, nineteen huskies, and two men—British army lieutenant Belgrave Ninnis, 24, and Swiss ski champion Xavier Mertz, 29. Beyond the wind, they encountered endless ridges of ice, which hobbled any hopes of smooth sledding, and occasionally they heard echoes or avalanches beneath the weak ice at their feet as they mushed along. Ninnis even slipped into one crevasse before climbing back out. Still, the team cruised through 315 miles in thirty days, with Ninnis and Mertz tending to the huskies and Mawson making meteorological observations and other notes.

On December 14, Mawson took a longitude and latitude reading from the sun at noon, and skied ahead to catch Mertz. Ninnis followed a ways behind. Mawson had one sledge and six inferior dogs with him, and he went before Ninnis so that if the ground opened up, the least valuable supplies would go down. But Ninnis—and some historians blame Mawson, team leader, for this lack of discipline—was trudging alongside his sledge in boots instead of skiing. So while Ninnis’s sleds slipped right over a hidden chasm, the concentrated weight of Ninnis’s footfall punctured the ice roof and brought the whole shebang—dogs, supplies, Ninnis himself—down.

With a hat on, and with the surround-sound wind muffling most noises, Mawson heard nothing and kept skiing. But after a spell, the constant nothing he heard behind him became reason to worry. After a quarter mile, he and Mertz doubled back to find an open pit eleven feet wide, a pit effectively bottomless, with sheer ice walls. Food lay on a ledge 150 feet down, as did a single dog, who shortly ceased his whimpering. No supplies, no fuel, no Ninnis in sight. Mertz and Mawson called and called, and held out until 9 p.m. before reading the requisite burial service.

At this point, Mawson made his second mistake. Instead of crossing to the Antarctic coast—a arduous route back, but stocked with fish and penguins—he chose to cut straight back to camp via an inland route. For food, Mawson had other ideas. The first night they dashed back to a sled they’d discarded days earlier, and fashioned a tent from it. For dinner, the men fed their dogs extra boots and clothes. They repeated that meal each night thereafter until one dog, George, died. Per Mawson’s plan, George was skinned and fed to the other dogs, who happily chowed down. (Huskies on that trip had already, as dogs do in lean times, eaten litters of their pups, so they weren’t exactly sentimental.) But Mawson and Mertz reserved for themselves the softer viscera of George.

As the journey continued, the huskies would pull the sledge day after day for miles without slowing or slackening or even wavering—pulling with full enthusiastic vigor right until they collapsed into a coma. When this happened a bullet, and dinner, followed. The dog Johnson was dispatched this way next, then Mary. Mawson and Mertz found the flesh tough and stringy, but swallowed every scrap, even boiling the paws into a jelly. Pavlova and Ginger soon succumbed, and then Haldane, all dead before the new year. Both men suffered stomach cramps on the diet, but dog meat proved especially hard on Mertz, a near vegetarian and the dogs’ caretaker. For this reason, some historians speculate that Mawson took the tougher (and recognizable-as-dog) muscle for himself and gave Mertz more digestible pieces like the liver. As Mawson himself later said, “It was a happy relief when the liver appeared; even if little else could be said for its flavor, it was easily chewed and demolished.”

Regardless, Mertz began ingesting large quantities of vitamin A from the husky liver (which, as chapter six of The Violinist’s Thumb explains, can be fatal even at low doses.) Two weeks into this diet, right around New Year’s Day, Mawson noticed Mertz looking “off-colour.” Mertz soon insisted on spending whole days resting in his sleeping bag, flaring into a rage whenever Mawson suggested they make at least a little progress that day.

With every bite of liver, the level of retinol, a nasty metabolite of vitamin A, in Mawson’s blood would inched higher. With every increase in retinol, the symptoms of vitamin A poisoning—headaches, psychosis, and the loss of whole sheets of skin—would have ratcheted up in step. And within a short time, with his skin tearing off his body and with the wind and the ice and the blank whiteness haunting him on all sides, Mertz began to lose contact with this world altogether. Mawson recounts having to hold Mertz down at one point, lest he rise up and, in his raving and flailing, destroy their tent. That wasn’t the worst of it. Once, apparently thinking that Mawson was lying to him about his frostbitten fingers, Mertz put the pinky of his left hand into his mouth, and bit. He didn’t register the pain until he coughed up the severed tip. Not long after, Mertz fouled his bed one morning. Mawson cleaned him up and tucked him back in, but he died that night, January 8th, at 2 a.m. Mawson buried him in the sleeping bag he’d so often refused to leave.

Alone now, Mawson soldiered on. He sawed the last sledge (which he was dragging himself) in half with a penknife, and threw away every extra ounce on him, even the blank pages in his diary. Some historians have questioned whether Mawson ate Mertz. Those who knew Mawson swear it’s inconceivable. But to be frank, Mawson might have been better off if he had. Instead, he continued to eat stores of dog meat, oblivious that it was probably weakening him even beyond the inhuman cold. Mawson too had lost skin all over his body, but being generally unwilling to remove his boots, he did not notice that the soles of his feet had detached until January 11th. On January 17th, he fell into the crevasse, climbed back up, and slipped back in before deciding he’d try to continue his life after all. He celebrated making it out alive with what he declared an “orgy” of dog meat.

Two more aching weeks passed. The end came in early February. Like a mirage, Mawson spotted something black on the ice ahead of him, an anomaly on that landscape. He trudged over to discover a black blanket covering a cairn of food—laid just hours before by a rescue party searching for Mertz, Ninnis, and him. Mawson took the food and recuperated for a few days at a nearby cave. On February 8th, Mawson at last crept down into the windy valley of the base camp—just in time to see the Aurora, the rescue ship, sail off.

But a few men had remained at camp for the winter, just in case. He was saved.

In later years, Mawson was knighted and even returned to Antarctica to claim more land for the British Crown. But he looked like anything but a knight when he darkened the door of the base camp on February 8th, 1913. Most of the men who watched the emaciated figure stagger in could find nothing to say. Only one spoke. “My god,” he whispered. “Which one are you?”

Chapter Seven:

More thieving

In case you’re not worried and/or grossed out enough already about Toxo, other microbes, including gonorrhea bacteria, have also swiped human DNA.

Feminist bugs

A biologist once quipped, perhaps in poor taste, that male-murdering Wolbachia bacteria were the “ultimate feminist weapon.” But for the males that manage to survive Wolbachia, life becomes a sexual Valhalla. In one population of infected butterflies, nineteen of every twenty living members was female—which left the males in high. During one mating season, in fact, the women reportedly exhausted every vestige of interest the male folk had in sex, perhaps a first in the animal kingdom.

Toxo and free will

One Stanford neuroscientist who studies Toxo, Robert Sapolsky, announced in an interview: “This is a protozoan parasite that knows more about the neurobiology of anxiety and fear than 25,000 neuroscientists standing on each other’s shoulders.” Sapolsky went so far as to say that Toxo upsets some of our fond hopes that humans have free will. “God knows what other unseen realms of biology make our behavior far less autonomous than lots of folks would like to think.”

Chapter Eight:

Hox and MHC similarity

Although we humans can tolerate far more introns in general, two classes of our genes tend to lack introns, Hox genes and MHC genes. Presumably, Hox lack them because we inherited these genes from simple, squishable, ancient animals that never had them in the first place. And we haven’t added introns to them in the millions of years of meantime because, again, animals tend to leave well enough alone when it comes to crucial, powerful, and widely influential genes like Hox. As for MHCs, scientists don’t know why they lack many introns, but some have suggested that the MHC evolved from retroviruses and their scanty genomes, which would again explain the austerity.

Eating DNA

You might be wondering why, if our bodies freak out at the mere thought of a cell with an MHC “beard” invading our bloodstreams or tissues, we can nonetheless eat these cells without any ill effects. Basically, it’s because the stomach lacks immune cells, and because digesting food down to its constituent organic rubble will destroy any complex features like the MHC beard. This fact renders ridiculous the idea that eating genetically modified food (GM food, a.k.a., “Frankenfood) might cause our bodies irreparable harm. There are reasons to be cautious with GM foods, but that ain’t one of them.

Mother-fetus-cancer rates

Of the few dozen known cases of simultaneous mother-fetus cancer since the 1860s, nearly a quarter occurred in the past fifteen years, probably because doctors have become more aware of the possibility, and because doctors in even rural and impoverished places can now report such occurrences. As a sub-note, 75 percent of the cancer-stricken fetuses are male. No one knows why.

Sibling influence

Again, mothers and fetuses do swap a few cells during a pregnancy, cells that each one of them then carries the rest of his/her life. Something similar can happen if the mother has another child. If one of those roaming cells from child number one happens to slip past the placenta again (in the reverse direction this time), it can enter child number two and lodge in him. As an oldest child, I find this empowering.

Chapter Nine:

DNA and vision

If living in trees and scampering about at night sounds dangerous, you’re right, and these early primates might have developed specialized night vision to lessen the hazards of their lifestyles. In fact some recent fossil work suggests that demands for better vision (a sense that diverts loads and loads of the brain’s resources) may have given primates their first big brain boost. (A rival theory, however, suggests that we relied more on smell to navigate, and that the early mammalian brain ballooned because of our increased olfactory powers and prowess.)

Night vision might also have changed the very structure of some of our DNA. In the rod cells of our eyes, the densest clumps of DNA form in the center of the nucleus, with looser coils on the margins, a pattern that scatters light as it passes through and helps cut down on the sun’s glare. But the rod cells of some nocturnal animals such as mice invert the pattern—the centers are less dense than the margins. As a result, these nuclei act as lenses: they focus light and coax it deeper into the eye, allowing the animal to see more stuff with less input. So it’s possible that, as our branch of primates drifted away from being nocturnal, our optical DNA had to turn itself inside out.

Chromosomes count

One key scientist who helped ferret out the true chromosome number in humans—a native of Java named Joe Hin Tijo—was captured by the Japanese military in 1942 and spent WWII being tortured for military information. Afterward, he moved to Holland and resumed his scientific career, much of which he spent studying the Philadelphia swap. One geneticist has suggested that if Tijo and a colleague, Albert Levan, hadn’t re-investigated the evidence for the human chromosome count in 1955, geneticists might not have learned the true number until the Human Genome Project got underway.

Stalin rumors

Again, the claims that Stalin himself took a personal interest in Ivanov’s work because he wanted an ape-man army seem to have arisen from a chain of newspaper stories, and one observer noted that everything started with an op-ed in The New York Times in 2005, which mentioned Ivanov’s experiments. A few Russian newspapers piggybacked on this “news” but scrambled some of the details during translation. Ten days later some British newspapers not exactly known for their scrupulous fact-checking standards got hold of the Russian version and retranslated it, and that’s when things got out of hand on the Internet. It was basically a cross-continental game of pseudo-scientific “telephone.”

Chapter Ten:

For all the linguistic masochists…

As if they didn’t have enough to spar over, a few archaeologists began pushing a few years ago to change the official umbrella term for ancient humans and their extinct relatives from hominid to hominin. (Under this scheme hominid now includes not only bipedal primates but chimps, gorillas, and orangutans.) Frankly, the change from –d to –n introduced loads of unnecessary confusion since older papers used the words in different ways, and the meanings might not ever stabilize over time now. As one scientist put it, “when scientists use the word hominin today, they mean pretty much the same thing as when they used the word hominid twenty years ago. When these scientists use the word hominid, they mean pretty much the same thing as when they used the [broader] word hominoid twenty years ago. Of course, there are still plenty of scientists around today that use the words exactly the way they used them twenty years ago.” You can read the whole tortured discussion right here.

Oh, and just to lessen the confusion I also stick with the more traditional Neanderthal instead of the new, trendy, Teutonicky, aitch-less Neandertal.

Only 80 million years off

As an example of the sort of embarrassing retractions that paleogeneticists have had to make, scientists in Utah in 1994 announced the discovery of 80-million-year-old dinosaur DNA. They had to recant just a few years later, when other scientists proved that the DNA in question was, ahem, human.

Hardcore DNA sampling

If the pressure of handling priceless and easily contaminated samples of material starts to rattle scientists (and you can see how it might), they might call in an Ocean’s Eleven–esque paleoDNA specialist and turn the job over. The best known agent for this purpose spent his Buckland-like boyhood hiking across Siberia hunting moose, and he has earned a reputation both for going to ridiculous lengths to get pristine DNA samples. People compliment his work in terms just as appropriate for bounty hunters or wiseguys: “You provide him with samples, you get results.”

The really oldest DNA

The 100,000-year degradation limit is only rough. There are reports of bacterial DNA surviving for hundreds of thousands of years in permafrosted Siberian soil. However, it’s not clear if this bacteria was alive in some sort of special suspended deep-hibernation, in which case the microbes might have been very slow repairing any degradation. Regardless, these are maximally optimal DNA-preservation circumstances, and no DNA has ever survived beyond 1.5 million years even then.

From C to T

Incidentally, the addition of methyl groups to C is what causes, over time, the degradation of C into T. That extra methyl group makes C look somewhat like T structurally, and if the chemical conditions favor it, the full transformation will take place naturally.

Skin grafts

Although humans went through a pretty stringent bottleneck, it’s wasn’t as constricting as the one some wild animals endured. With cheetahs, you can actually graft skin from one cat directly onto another and it will “take” without any medication or precaution. Cheetahs are that closely related. Still, humans are fairly unusual, and we can graft certain skin cells between non-relatives without much trouble. A scientist demonstrated this fact in 1999 by transplanting hair follicles from his scalp to a patch of skin beneath his wife’s arm. They sprouted right up.

Twice lice

Regarding the difference between body lice and head lice: The impetus and inspiration for this discovery came when a scientist’s son was sent home from school one day after contracting head lice. This happened to get the scientist interested in the biology of lice, which got him thinking about their evolution. The god of science works in mysterious ways.

Chapter Eleven:

More brain measures

Studies like Cuvier’s to measure brain size are often big, fat invitations to do really bad science, since we already “know” the answer—that humans must emerge on top in any measure of how wickedly smart various animals are—and there’s an irresistible temptation to tweak or twist results to get that answer. Nevertheless, some modern scientists have devised a more sophisticated measure of brain-to-body hypertrophy called the encephalization quotient. The idea here is that what really matters isn’t brain size or brain/body ratio but how much bigger your genes can build a brain compared to most creatures your size. More precisely, encephalization takes the general form E = CSx, where x varies species by species and is the crucial number. Most animals hover around one. For the average monkey, the quotient is around two, giving the Einsteinian result that E = CS2. For humans, we once again get the answer we want—that Homo sapiens have the most sapiens—but with less of a cushion than some people like. According to this measure, humans have a brain about seven times larger than expected, but some studies have put dolphins right up there at six.

Blister on the brain

Doctors also found a baseball-sized “blister” on Kim Peek’s skull when he was born. When the growth retracted at age three, it damaged part of his cerebellum, which helps control motor coordination, leaving Peek clumsy. Many of Peek’s obits claimed this blister appeared on the left side of his head, which would help explain (above and beyond FG syndrome) the damage in his left hemisphere. But this could be an error: Peek’s father remembers the blister on the right, and whenever the doctors who worked closely with Peek for decades mentioned the blister, they merely said it appeared toward the back of his skull, and never mentioned left or right.

Chapter Twelve:

Matisse the chemist

Matisse knew he owed a lot to the scientific endeavors that gave him his beautiful pigments. He even boasted once about being “a good half a scientist” himself.

DNA art details

The full quote from Genesis is: “Let man have dominion over the fish of the sea, and over the fowl of the air, and over every living thing that moves upon the earth.” The artist—Eduardo Kac, who also made the freaky glowing bunny—also engineered the bacteria that harbored this DNA quote to glow a cyan color. Similarly, at least one writer has encoded his own poems in bacterial A’s, C’, G’s, and T’s, again with an eye toward making his verse eternal.

Cloning has also become a means to create art. One project cloned sheets of human skin cells, exposed them to the incendiary weapons of modern warfare, then magnified them so viewers could see the effects. Another artist cloned bovine skin cells and grew a seamless and “victimless” miniature “leather jacket” in a sealed flask, the biotech (and haute couture) version of those little hobby sloops in glass bottles.

DNA and books

Art historians, and specifically book historians, have found clever ways to utilize DNA as well—not the DNA of authors, but of the goats, sheep, and other animals whose skins were stretched to make parchment for Bibles and other illustrated books. Most importantly scholars have used DNA to trace the provenance of manuscripts, many of whose origins they could only guess at before, based on dialect and handwriting styles. Along these lines, scientists have proposed using DNA analysis to piece together the almost innumerable one- and two-letter scraps of the Dead Sea Scrolls, since the fragments with identical DNA probably all came from the same sheet.

Darwin in song

On the topic of music and biology, I’d be remiss not to point out the surprisingly widespread and persistent tradition of writing musicals about Darwin and his theories. For details see “Singing his praises: Darwin and his theory in song and musical production,” by V.B. Smocovitis, in the September 2009 issue of Isis.

Cave art DNA

Ancient equine bones and teeth have revealed that the Paleolithic artists who decorated the caves of Europe many generations ago were not taking artistic or spiritual liberties when they portrayed the horses of the era as spotted. Archaeologists had long puzzled over the spotted horses, since none exist today, but genetic testing of the bones has revealed extinct “leopard” patterning DNA in the horses’ ancestral stock. This fact helps disprove the theory that people had imbued the horse pictures with a deeper symbolic meanings. Instead they seemed to have focused on capturing their natural environment.

At least in some ways. Reminiscent of the murals from the Pharaoh Akhenaten’s reign (see next chapter), these anonymous Picassos may have depicted certain animals in stunningly realistic ways, but they often neglected the human form, either leaving the humans looking alien or rendering them as mere stick-figures.

The Gopniks

For you New Yorker fetishists, the linguist that first tested the KE family for linguistic deficits was Myrna Gopnik, mother of writer Adam Gopnik, as well as art critic Blake Gopnik and noted infant psychologist and author Alison Gopnik.

Paganini’s overzealous friend

Though Paganini had a good sense of humor about the stories of necromancy that swirled about him, some of his followers did not. After Paganini held one of his trademark concerts in a cemetery on an island off Venice, a friend hopped on a gondola back to the city, along with a Dominican monk. The monk began badmouthing the violinist, saying that he’d “profaned a holy place” (the cemetery) with his performance. At which point the friend tossed the monk into the drink, and the boat abandoned him.

Neanderthal beauty

Anthropologists long thought that Neanderthal noses and mouth had changed shape and evolved to help them breathe in cold European weather, while our gracile faces and relatively retracted lower jaws helped us speak more fluidly. In addition, those changes presumably underline why we humans find human faces more attractive than ape-like faces—we’re unconsciously selecting for jaws that speak well. But the presence of foxp2 in Neanderthals throws a spanner into things, since their big jaw might have been just as nimble as ours. And nowadays, some scientists argue that purely random mutations might be more responsible for our distinct faces than natural selection was anyway. In other words, if you rewound the tape of human evolution and played it again, we might look like Neanderthals, and vice-versa. There but by the grace of Darwin goes us.

Questioning Toulouse-Lautrec’s diagnosis

Because scientists don’t know what genetic disorder Henri Toulouse-Lautrec had, there’s been a great deal of debate about possible symptoms and whether they’re germane to making a diagnosis or false leads. For instance some scientists and historians disagree about whether Henri Toulouse-Lautrec had stunted and stubby fingers or had normal or even long fingers. Some primary diaries and letters seem to support stubbiness, as do some pictures. But in other pictures his fingers do indeed appear rather long.

Scholars have also debated the length of Toulouse-Lautrec’s penis. You might think that rumor and hearsay (or at best, diary entries) would be all the evidence we have, but nope: there are at least a few pictures of the painter naked—one of him being throw off a boat naked, another of him defecating on a public beach, and so on. (He ran with a rowdy crowd.) But again, it’s not clear due to the angles and poor lighting how well-hung he was.

(And just because you want to know, no, scientists have not yet sorted out the complicated genetics of penis size, though they have identified genetic disorders that can cause birth defects down there. One of the most common in this class, hand-foot-genital syndrome, also messes with the development of the limbs. One of the Hox genes appears responsible for HFG syndrome.)

Chapter Thirteen:

Non-vampires

The scientist who first made the porphyria-vampire connection even argued, based on absolutely no evidence, that garlic probably contained chemicals that made porphyria worse—hence the vampiric dread of the bulb.

Along these lines, some creative historians have tried to link Vlad Tepes of the House of Dracul—the supposed real-life inspiration for Dracula—with porphyria, but the “evidence” here is about as tenuous as you can imagine.

Royal blood

Speaking of hemophilia, it afflicted various royal families in Europe, including Queen Victoria’s. Scholars had always suspected it appeared among Russian royalty as well, but only in 2009 did they confirm this by extracting DNA from Romanov bones. This bolstered the suspicion of some historians that hemophilia helped toppled the Romanovs. Queen Alexandra retained the notorious monk Rasputin as a royal aid partly because he calmed the hemophiliac Prince Alexei, and helped him manage the disease. This talent in turn gave Rasputin a license to misbehave, and he took full advantage, drinking heavily, blaspheming anything he could, even raping a nun at one point. Rasputin eventually became a symbol to revolutionaries of hateful Romanov decadence.

Another Y chromosome test

Legends had always circulated after the French Revolution that, when its leaders executed Louis XVI in 1793, peasants had rushed the guillotine platform and dabbed their handkerchiefs in the king’s blood. In 2009, one such handkerchief turned up (it had been stored in a family heirloom—ironically, a carved gourd decorated with the faces of the Revolution’s heroes), and when scientists analyzed the blood, it seemed a perfect match to the blue-eyed king’s male descendents, confirming the legend.

Chapter Fourteen:

Gritty details of Sanger sequencing

Again, as a first step Sanger heated up the DNA in question until it unwound, then started to built the complement with special, radioactive bases. However, the bases were actually special in two ways. Beyond being radioactive, they were also “terminator” bases. Inside the test-tube (or beaker, or whatever he used), a terminator base would get added to the complement just like normal bases. Except that, when added, terminators physically block the complement from growing any longer—they truncate it. I’ll call the terminators A*, C*, G*, and T*.

Into his first test tube of DNA to sequence, Sanger poured in lots of regular A, C, G, and T, as well as a few A*. Overall, then, each time an enzyme added adenine to the complement, it had a choice. If it randomly picked A, construction continued. If it randomly picked A* (the terminator), construction ceased. As a result, Singer ended up with fragments of different lengths in this test tube, each terminating at an adenine: he might have CTTTA*, CTTTAGCA*, CTTTAGCAGA*, and so on. In fact, Sanger ended up with every possible fragment that ended in adenine. Sanger then sorted these fragments by length, by running them through a column of viscous gel. Small fragments sped through the gel, large fragments got gummed up and lagged behind. As a result the smallest pieces ended up at one end of the column, the largest pieces at the other, and the medium pieces in between.

Next, Sanger repeated this process three times, in three more test tubes. But the second time (in addition to lots of regular A, C, G, and T), Sanger sprinkled in C* as well. This gave him every possible fragment that ended in cytosine. In steps three and four, he sprinkled in G* and T*, which of course gave him every fragment that ended in guanine and thymine. Overall, then—here’s the key—between all four test tubes Sanger had fragments of every possible length.

Sanger sorted the C*, G*, and T* fragments by length in columns of gel, like before. He then lined the four gel columns up next to each other, in parallel, like lanes in a swimming pool. At this point, the radioactivity came into play. Sanger would go to the top of the columns, where the short fragments resided, and use a radioactivity detector to determine which of the four lanes the radioactivity was coming from. If it came from the A* column, he knew that an adenine was first in the sequence. He would shift down, to fragments heavier by one base, and repeat the process—maybe the radioactivity came from the G* column this time. So the sequence was A-G. He’d then shift down again—maybe it’s thymine, A-G-T—and again and again, until he had the entire sequence. Excruciating, but ingenious.

Sanger’s other first

In addition to sequencing the first full genome of a virus, Sanger sequenced the full DNA sequence of human mitochondria, a major achievement.

Why DoE?

Another reason the Department of Energy kick-started the first genome sequencing effort was that it had experience running massive scientific projects—experience the National Institutes of Health lacked.

Why patents?

The NIH filed patent claims in the first place, its lawyers argued, as a defensive maneuver—to gain control before someone else with mercenary motives could do the same. It promised it would never squeeze scientists for cash, but its protestations and half-promises didn’t appease many.

Collins’s other inspiration

In addition to the encouragement of God, Collins joined the government’s human genome project for the (massively ironic, it turned out) reason that he thought the project would be unique in history. In his words, “there is only one human genome project.”

“DNA Alley”

Despite (or perhaps because) of all the scientific cat-fighting, the public followed the Human Genome Project more closely than probably any scientific endeavor since the moon landing. The British Royal Mint struck later coins to honor the Sanger Institute’s sequencing, and one stretch of suburban Maryland near Washington, D.C.—where both Venter and the N.I.H. ran their sequencing headquarters—became popularly known as “DNA Alley.” Maryland and other states even began offering license plates with wispy double helixes on them—a sort of DNA vanity plate.

Caveat and context

Regarding the consortium’s failure to finish more than four percent of the sequence after eight of its planned fifteen years: To be fair, the consortium had never planned to be halfway through sequencing at the halfway point (partly because they’d planned to spend years mapping chromosomes first). However, even with this caveat, it seemed doubtful to many observers that they would finish on time in any case.

Chapter Fifteen:

Lamarck and Love

Two other Lamarck facts. He had at least six children from at least three wives, the first of which he married only on her deathbed after living in sin with her for fifteen years. And though Lamarck’s ideas later fell into disfavor among scientists, artists adored them as a gentler alternative to cutthroat Charles D. Walt Whitman and George Bernard Shaw in particular were devoted Lamarckians.

Lamarck abused?

To be fair, some historians argue that Lamarck got a bum deal when other scientists accused the animals in his theories of “desiring” to perfect themselves. These historians argue that Lamarck’s word for “want,” the French besoin, could also be interpreted as “need.” So in this view, creatures get stronger or faster over their lifetimes less because they want to than they must, or they die out—a less mockable idea, almost Darwinian.

This mis-translation would have primarily colored the views of foreign scientists, of course. But because the most important thinkers on evolution, the Charleses Darwin and Lyell, both wrote and spoke exclusively in English, it might have been damning. It’s a rather scary notion overall—that someone not paying attention in French lecture one afternoon may have destroyed Lamarck’s reputation for centuries!

More on toad sex

Just f.y.i., I called toad sex “aqueous coitus,” but to a toadologist, their act of sweet, sweet lovemaking is a form of pseudo-coitus, called amplexus.

Tom Lehrer lyrics

As promised, you can find the full lyrics to Tom Lehrer’s “Alma” song right here.

Kammerer suicide note

In its November 19, 1926, issue, Science magazine reprinted part of a translation of Kammerer’s suicide note. It read:

IVF epigenetics

Scientists have discovered recently that babies born through in vitro fertilization (IVF)—while almost entirely normal in every other way—tend to have lower birth weights than naturally begotten children, a trait associated with obesity, high blood pressure, and diabetes. Some scientists believe epigenetic mechanisms must cause the low birth weight, but it’s not clear if the IVF process itself fouls up the epigenetics, or if the incorrect epigenetics simply accompanies the other, deeper infertility problems that pushed the parents to seek IVF in the first place.

Paramutations

Another cool epigenetic effect is paramutation, which involves passing to your children not DNA but RNA. Eggs and sperm both need RNA to function, especially large complex eggs. And this RNA of course arises, originally, from DNA in the cells of mom. But consider this scenario. Say that one of mom’s genes has two different versions, and each produces different RNA. Neither is harmful, just different. All her body cells—including the precursor cells that will form eggs when the time comes—have full sets of this DNA, including both versions of the gene. As a result, they’ll have both types of RNA floating around in the cytoplasm.

Now, when the division to form the egg does take place, each egg can contain only one version of the gene, because half the chromosomes got pulled one way during meiosis, half the other way. But if there was enough RNA from the absent gene floating around in the cytoplasm before, that RNA will remain in the egg even though the gene that produced it is no longer there. Baby will inherit this RNA, which can (because RNA is such a flexible, self-sufficient molecule) go about its work with the DNA. In other words, the trait this RNA produces got inherited, without changing the genetic sequence, a prime example of epigenetics. Paramutations might be responsible for the polka-dotted mouse tails I mentioned at chapter’s end.

On the epigenetics “revolution”

You can certainly see why scientists get annoyed by all the attention epigenetics gets. Calling epigenetics “revolutionary” implies that stubborn old biologists once believed that genes determined everything, and epigenetics finally disabused them. But the vast majority of biologists were never genetic determinists, and they already knew that environment was critical. There’s also a popular tendency to conflate something “anti-Mendelian,” like epigenetics, with “anti-evolution,” which epigenetics isn’t. Evolution could embrace both Mendel and Lamarck.

Chapter Sixteen:

Other bad memories…

This chapter’s summary of lowlights in twentieth-century genetic engineering and cloning has necessarily skimmed past some other incidents that helped pummel public opinion and instill fear in people.

Some incidents were ridiculous—like an announcement by the Raelians, a cult that believes human beings are clones and were planted here 25,000 years ago by green, four-foot aliens. In 2003 the Raelian claimed that they had somehow cloned a human baby in turn. More than a little suspiciously, they refused to let anyone see it, much less test it.

Some incidents were sad—like the death of eighteen-year-old Jesse Gelsinger after a failed attempt at gene therapy, which uses retroviruses to insert missing DNA into the cells of people (like Geslinger) with acute genetic diseases.

Some were disgraceful—like the forgeries of South Korean scientist Hwang Woo-suk, who falsely claimed to have cloned human embryos.

Some were plain wrong—like the “ear mouse,” a supposedly genetically engineered rodent with a human ear growing out of its back, a picture of which appeared, with an erroneous caption, in an advertisement in major newspapers. The ear was actually cow cartilage and plastic, and the mouse had never been genetically manipulated. But what are facts in the face of public outrage?

Till Doomsday

About the Aborigines breeding till Doomsday in Ireland: To be clear, I mean that the man and wife themselves, if they should somehow become immortal, would never produce the pasty Seamus. If their children kept breeding and their children kept breeding and no one moved out of Ireland, then of course at some point lighter skin might well show up in their descendents.

PS If you read The Violinist’s Thumb in its entirety; and you polished off all of its notes; AND you devoured these web notes as well—then wow, congratulations! Drop me a line to say hello…