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

by Sam Kean

  Scientists realized in 2006 that this difference between sex and nonsex chromosomes might explain a funny characteristic of human DNA. After the initial split between their lines, protochimps and protohumans should have started down different paths and accumulated different mutations on each chromosome. And they did, mostly. But when scientists look at chimps and humans today, their Xs look more uniform than other chromosomes. The DNA clock on X got reset, it seems; it retained its girlish looks.

  We hear the statistic sometimes that we have 99 percent of our DNA coding region in common with chimps, but that’s an average, overall measure. It obscures the fact that human and chimp Xs, a crucial chromosome for Ivanov’s work, look even more identical up and down the line. One parsimonious way to explain this similarity is interbreeding and the war of attrition that would probably have eliminated one type of X. In fact, that’s why scientists developed the theory about protohuman and protochimp mating in the first place. Even they admit it sounds a little batty, but they couldn’t puzzle out another way to explain why human and chimp X chromosomes have less variety than other chromosomes.

  Fittingly, however (given the battle of the sexes), research related to Y chromosomes may contradict the X-rated evidence for human-chimp interbreeding. Again, scientists once believed that Y—which has undergone massive shrinkage over the past 300 million years, down to a chromosomal stub today—would one day disappear as it continued to shed genes. It was considered an evolutionary vestige. But in truth Y has evolved rapidly even in the few million years since humans swore off chimpanzees (or vice versa). Y houses the genes to make sperm, and sperm production is an area of fierce competition in wanton species. Many different protogents would have had sex with each protolady, so one gent’s sperm constantly had to wrestle with another gent’s inside her vagina. (Not appetizing, but true.) One evolutionary strategy to secure an advantage here is to produce loads and loads of sperm each time you ejaculate. Doing so of course requires copying and pasting lots of DNA, because each sperm needs its own genetic payload. And the more copying that takes place, the more mutations that occur. It’s a numbers game.

  However, these inevitable copying mistakes plague the X chromosome less than any other chromosome because of our reproductive biology. Just like making sperm, making an egg requires copying and pasting lots of DNA. A female has equal numbers of every chromosome: two chromosome ones, two chromosome twos, and so on, as well as two Xs. So during the production of eggs, each chromosome, including the Xs, gets copied equally often. Males also have two copies of chromosomes one through twenty-two. But instead of two Xs, they have one X and one Y. During the production of sperm, then, the X gets copied less often compared to other chromosomes. And because it gets copied less often, it picks up fewer mutations. That mutation gap between X and other chromosomes widens even more when—because of Y chromosome–fueled sperm competition—males begin churning out loads of sperm. Therefore, some biologists argue, the seeming lack of mutations on X when comparing chimps and humans might not involve an elaborate and illicit sexual history. It might result from our basic biology, since X should always have fewer mutations.*

  Regardless of who’s right, work along these lines has undermined the old view of the Y as a misfit of the mammal genome; it’s quite sophisticated in its narrow way. But for humans, it’s hard to say if the revisionary history is for the better. The pressure to develop virile sperm is much higher in chimps than humans because male chimps have more sex with different partners. In response, evolution has remade the chimp Y thoroughly top to bottom. So thoroughly, in fact, that—contrary to what most men probably want to believe—chimps have pretty much left us guys in the dust evolutionarily. Chimps simply have tougher, smarter swimmers with a better sense of direction, and the human Y looks obsolete in comparison.

  But that’s DNA for you—humbling. As one Y-chromosome specialist comments, “When we sequenced the chimp genome, people thought we’d understand why we have language and write poetry. But one of the most dramatic differences turns out to be sperm production.”

  Talking about Ivanov’s experiments in terms of DNA is a little anachronistic. But scientists in his day did know that chromosomes shuttled genetic information down through the generations and that chromosomes from mothers and fathers had to be compatible, especially in numbers. And based on the preponderance of evidence, Ivanov decided that chimps and humans had similar enough biologies to push forward.

  After securing funds, Ivanov arranged through a colleague in Paris to work at a primate research station in colonial French Guinea (modern Guinea). The conditions at the station were deplorable: the chimps lived in cages exposed to the weather, and half of the seven hundred chimps that local poachers had netted and dragged back had died of disease or neglect. Nevertheless Ivanov enlisted his son (another triple i: Ilya Ilich Ivanov) and began chugging thousands of nautical miles back and forth between Russia, Africa, and Paris. The Ivanovs eventually arrived in sultry Guinea, ready to begin experiments, in November 1926.

  Because the captives were sexually immature, too young to conceive, Ivanov wasted months furtively checking their pubic fur each day for menstrual blood. Meanwhile fresh inmates kept piling in, right up until Valentine’s Day 1927. Ivanov had to keep his work secret to avoid angry questions from the Guineans, who had strong taboos against humans mating with primates, based on local myths about hybrid monsters. But finally, on February 28, two chimps named Babette and Syvette had their periods. At eight o’clock the next morning, after visiting an anonymous local donor, Ivanov and son approached their cages armed with a syringe of sperm. They were also armed with two Browning pistols: Ivanov Jr. had been bitten and hospitalized a few days before. The Ivanovs didn’t end up needing the Brownings, but only because they more or less raped the chimps, binding Babette and Syvette in nets. The virgin chimps thrashed about anyway, and Ivanov managed to jam the syringe only into their vaginas, not into their uteruses, the preferred spot for deposits. Not surprisingly, this experiment failed, and Babette and Syvette got their periods again weeks later. Many juvenile chimps died of dysentery in the following months, and Ivanov managed to inseminate just one more female that spring (she was drugged). This attempt also failed, meaning Ivanov had no living humanzees to haul back to the Soviet Union to win more funding.

  Perhaps wary that the commissar of enlightenment might not give him a second chance, Ivanov began pursuing new projects and new avenues of research, some in secret. Before leaving for Africa, he’d helped break ground on the first Soviet primate station, in Sukhumi, in modern-day Georgia, one of the few semitropical areas in the Soviet empire, and conveniently located in the homeland of the new Soviet leader, Joseph Stalin. Ivanov also courted a wealthy but flaky Cuban socialite named Rosalià Abreu, who operated a private primate sanctuary on her estate in Havana—partly because she believed that chimpanzees had psychic powers and deserved protection. Abreu initially agreed to house Ivanov’s experiments but withdrew her offer because she feared newspapers would get hold of the story. She was right to worry. The New York Times caught wind of the story anyway after some of Ivanov’s American supporters appealed to the publicity-hungry American Association for the Advancement of Atheism for funding and it began trumpeting the idea. The Times story* prompted the Ku Klux Klan to send out letters warning Ivanov about doing his devil’s work on their side of the Atlantic, as it was “abominable to the Creator.”

  Meanwhile Ivanov was finding it expensive and annoying to keep a large chimp harem healthy and safe, so he devised a plan to turn his experimental protocol inside out. Females in primate societies can have children only so quickly, while one virile male can spread his seed widely at little cost. So instead of keeping multiple female chimps around to impregnate with human sperm, Ivanov decided to secure one male chimp and impregnate human women. Simple as that.

  To this end, Ivanov made secret contact with a colonial doctor in the Congo and asked the doctor to let him inseminate patients. When the docto
r asked why on earth his patients would consent, Ivanov explained that they wouldn’t tell them. This satisfied the doctor, and Ivanov beat cheeks from French Guinea down to the Congo, where everything seemed ready to go. At the last second, however, the local governor intervened and informed Ivanov that he could not perform the experiment in the hospital: he had to do it outdoors. Offended at the interference, Ivanov refused; the unsanitary conditions would compromise his work and the safety of his patients, he said. But the governor held firm. Ivanov called the debacle a “terrible blow” in his diary.

  Until his last day in Africa, Ivanov kept hunting down leads for other women to inseminate, but nothing came of them. So when he finally left French Guinea in July 1927, he decided no more fooling around in far-flung places. He would shift his operations to the newly opened Soviet primate station at Sukhumi. He would also sidestep the hassles of female chimp harems by finding one reliable male stud and coaxing Soviet women to reproduce with him.

  As feared, Ivanov had trouble finding funding for his revised experiments, but the Society of Materialist Biologists took up Ivanov’s work as a proper Bolshevik cause and ponied up. Before he could get started, however, most of the Sukhumi primates fell sick and died that winter. (Though balmy by Soviet standards, Sukhumi was pretty far north for African primates.) Luckily, the one primate to pull through was male—Tarzan, a twenty-six-year-old orangutan. All Ivanov needed now were human recruits. Officials, though, informed Ivanov he could not offer the recruits money for being surrogates. They had to volunteer, out of ideological amour for the Soviet state, a less tangible reward than a bounty. This further delayed things, but nevertheless, by spring 1928, Ivanov had his mark.

  Her name comes down to us only as “G.” Whether she was slender or stout, freckled or fair, a madame or a charwoman, we have no idea. All we have is a heartrending and elliptical letter she wrote to Ivanov: “Dear Professor[:] With my private life in ruins, I don’t see any sense in my further existence…. But when I think that I could do a service for science, I feel enough courage to contact you. I beg you, don’t refuse me.”

  Ivanov assured her he wouldn’t. But as he made arrangements to bring G to Sukhumi and inseminate her, Tarzan died of a brain hemorrhage. No one had had time to milk him for sperm, either. Once again the experiment stalled.

  This time, permanently. Before he could round up another ape, the Soviet secret police arrested Ivanov in 1930 for obscure reasons and exiled him to Kazakhstan. (The official charge was that old standby, “counterrevolutionary activities.”) Already past sixty, Ivanov took to prison about as well as his primates had, and his health grew fragile. He was cleared of the bogus charges in 1932, but the day before he was to leave prison, he, like Tarzan, had a brain hemorrhage. Within a few days, he joined Tarzan in that giant primate research station in the sky.

  Soviet biologist Ilya Ivanovich Ivanov went further than any scientist ever has in trying to breed primates with humans. (Institute of the History of Natural Sciences and Technology, Russian Academy of Sciences)

  After Ivanov died, his scientific agenda disintegrated. Few other scientists had the skill to inseminate primates, and just as important, no scientifically advanced country was as willing as the Soviet Union to trash every ethical guideline out there and fund such work. (Although to be fair, even hardened Politburo officials threw up in their mouths when Ivanov revealed his clandestine attempt to impregnate hospitalized women in the Congo with chimp sperm.) As a result, since the 1920s scientists have done virtually no research on human-primate hybrids. Which means that Ivanov’s most pressing question remains open: could G and a beast like Tarzan have produced a child?

  In one way, maybe. In 1997 a biologist in New York applied for a patent on a process to mix embryonic cells from humans and chimps and gestate them in a surrogate mother. The biologist considered the project technically feasible, even if he himself never intended to make a humanzee chimera; he merely wanted to prevent some nefarious person from obtaining a patent first. (The patent office turned the claim down in 2005 because, among other things, patenting a half human could violate the Thirteenth Amendment’s prohibition against slavery and owning another human.) However, the process would have required no actual hybridization—no actual mixing of the two species’ DNA. That’s because the chimp and human embryonic cells would have come into contact only after fertilization; so each individual cell in the body would retain its wholly chimp or wholly human nature. The creature would have been a mosaic, not a hybrid.

  Nowadays scientists could easily splice bits of human DNA into chimp embryos (or vice versa), but this would be little more than a tweak biologically. True hybridization requires the old-fashioned fifty-fifty mingling of sperm and eggs, and almost all respectable scientists today would lay money on human-chimp fertilization being impossible. For one, the molecules that form a zygote and start it dividing are specific to each species. And even if a viable humanzee zygote did form, humans and chimps regulate DNA very differently. So the job of getting all that DNA to cooperate and turn genes off and on in sync and make proper skin and liver and especially brain cells would be daunting.

  Another reason to doubt that humans and chimps could produce children is the different chromosome count in the two species, a fact that emerged only after Ivanov’s time. Getting an accurate chromosome count was surprisingly tricky for most of the twentieth century. DNA remains quite tangled inside the nucleus except for the few moments right before a cell divides, when compact chromosomes form. Chromosomes also have a bad habit of melting together after cells die, which makes counting harder still. Counting is therefore easiest in recently living samples of cells that divide often—like the sperm-making cells inside male gonads. Finding fresh monkey testes wasn’t too onerous even in the early 1900s (Lord knows they killed enough monkeys then), and biologists determined that close primate relatives like chimps, orangutans, and gorillas all had forty-eight chromosomes. But lingering taboos made obtaining human testes more difficult. People didn’t donate their bodies to science back then, and some desperate biologists—much like those anatomists in the Renaissance who robbed graves—took to lurking near the town gallows to harvest the testicles of condemned criminals. There was simply no other way to get fresh samples.

  Given the difficult circumstances, work on human chromosome number remained sketchy; guesses ranged from sixteen to fifty-some. And despite the constant counts in other species, some European scientists beholden to racial theories proclaimed that Asian, black, and white people clearly had different numbers of chromosomes. (No points for guessing who they thought had most.) A Texas biologist named Theophilus Painter—who later discovered the gigantic salivary chromosomes in fruit flies—finally killed the theory of varying chromosome number with a definitive study in 1923. (Rather than depend on the criminal-justice system for raw material, Painter counted his blessings that a former student worked at a lunatic asylum and had access to freshly castrated inmates.) But even Painter’s best slides showed human cells with either forty-six or forty-eight chromosomes, and after going round and round and counting and recounting them from every which angle, Painter still couldn’t decide. Perhaps worried his paper would be rejected if he didn’t at least pretend to know, Painter acknowledged the confusion, took a breath, and guessed—wrongly. He said that humans have forty-eight, and that became the standard figure.

  After three decades and the invention of far better microscopes (not to mention an easing of restrictions on human tissues), scientists had rectified the boner, and by 1955 they knew that humans had forty-six chromosomes. But as so often happens, deposing one mystery just inaugurated another, because now scientists had to figure out how humans ended up two chromosomes down anyway.

  Surprisingly, they determined that the process started with something like a Philadelphia swap. Around a million years ago, in some fateful man or woman, what were the twelfth and thirteenth human chromosomes (and still are the twelfth and thirteenth chromosomes in many primates) e
ntwined their arms at the very tip, to try and swap material. But instead of separating cleanly, twelve and thirteen got stuck. They fused together at their ends, like one belt buckled onto another. This amalgam eventually became human chromosome number two.

  Fusions like this are actually not uncommon—they occur once every thousand births—and most tip-to-tip fusions go unnoticed because they don’t upset anyone’s health. (The ends of chromosomes often contain no genes, so nothing gets disrupted.) However, notice that a fusion by itself can’t explain the drop from forty-eight to forty-six. A fusion leaves a person with forty-seven chromosomes, not forty-six, and the odds of two identical fusions in the same cell are pretty remote. And even after the drop to forty-seven, the person still has to pass his genes on, a serious barrier.

  Scientists did eventually puzzle out what must have happened. Let’s go back a million years, when most protohumans had forty-eight chromosomes, and follow a hypothetical Guy, who has forty-seven. Again, a chromosome fused at the tips won’t affect Guy’s day-to-day health. But having an odd number of chromosomes will cripple the viability of his sperm, for a simple reason. (If you prefer to think of a female, the same arguments apply to her eggs.) Say the fusion left Guy with one normal chromosome 12, one normal 13, and a 12-13 hybrid. During sperm production, his body has to divide those three chromosomes into two cells at one point, and if you do the math, there are only a few possible ways to divvy them up. There’s {12} and {13, 12-13}, or {13} and {12, 12-13}, or {12, 13} and {12-13}. The first four sperm either are missing a chromosome or have a duplicate, practically a cyanide capsule for an embryo. The last two cases have the proper amount of DNA for a normal child. But only in the sixth case does Guy pass the fusion on. Overall, then, because of the odd number, two-thirds of Guy’s children die in the womb, and just one-sixth inherit the fusion. But any Junior with the fusion would then face the same terrible odds trying to reproduce. Not a good recipe for spreading the fusion—and again, that’s still only forty-seven chromosomes, not forty-six.