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

by Sam Kean

  This incest likely compromised Tut’s immune system and did the dynasty in. Akhenaten had, one historian noted, “a pathological lack of interest” in anything beyond Egypt, and Egypt’s foreign enemies gleefully raided the kingdom’s outer edges, imperiling state security. The problem lingered after Akhenaten died, and a few years after the nine-year-old Tut assumed the throne, the boy renounced his father’s heresies and restored the ancient gods, hoping for better fortune. It didn’t come. While working on Tut’s mummy, scientists found scads of malarial DNA deep inside his bones. Malaria wasn’t uncommon then; similar tests reveal that both of Tut’s grandparents had it, at least twice, and they both lived until their fifties. However, Tut’s malarial infection, the scientists argued, “added one strain too many to a body that”—because of incestuous genes—“could no longer carry the load.” He succumbed at age nineteen. Indeed, some strange brown splotches on the walls inside Tut’s tomb provide clues about just how sudden his decline was. DNA and chemical analysis has revealed these splotches as biological in origin: Tut’s death came so quickly that the decorative paint on the tomb’s inner walls hadn’t dried, and it attracted mold after his retinue sealed him up. Worst of all, Tut compounded his genetic defects for the next generation by taking a half sister as his own wife. Their only known children died at five months and seven months and ended up as sorry swaddled mummies in Tut’s tomb, macabre additions to his gold mask and walking sticks.

  Powerful forces in Egypt never forgot the family’s sins, and when Tut died heirless, an army general seized the throne. He in turn died childless, but another commander, Ramses, took over. Ramses and his successors expunged most traces of Akhenaten, Tut, and Nefertiti in the annals of the pharaohs, erasing them with the same determination Akhenaten had shown in erasing other gods. As a final insult, Ramses and his heirs erected buildings over Tut’s tomb to conceal it. In fact, they concealed it so well that even looters struggled to find it. As a result, Tut’s treasures survived mostly intact over the centuries—treasures that, in time, would grant him and his heretical, incestuous family something like immortality again.

  To be sure, for every well-reasoned retrodiagnosis—Tut, Toulouse-Lautrec, Paganini, Goliath (gigantism, definitely)—there are some doozies. Probably the most egregious retrodiagnosis began in 1962, when a doctor published a paper on porphyria, a group of red-blood-cell disorders.

  Porphyria leads to a buildup of toxic by-products that can (depending on the type) disfigure the skin, sprout unwanted body hair, or short-circuit the nerves and induce psychosis. The doctor thought this sounded a lot like werewolves, and he floated the idea that widespread fables about wolf-people might have a medical basis. In 1982 a Canadian biochemist went one better. He noted other symptoms of porphyria—blistering in sunlight, protruding teeth, bloody red urine—and started giving talks suggesting that the disease seemed more likely to inspire tales about vampires. When pressed to explain, he declined to write up a scientific paper, and followed up instead (not a good sign) by appearing on a national U.S. talk show. On Halloween. Viewers heard him explain that “vampire” porphyrics had roamed about at night because of the blistering, and had probably found relief from their symptoms by drinking blood, to replace missing blood components. And what of the famously infectious vampire bite? Porphyric genes run in families, he argued, but it often takes stress or shock to trigger an outbreak. A brother or sister nipping at you and sucking your blood surely qualifies as stressful.

  The show drew lots of attention and soon had worried-sick porphyrics asking their physicians if they would mutate into blood-lusting vampires. (A few years later, a deranged Virginia man even stabbed and dismembered his porphyric buddy to protect himself.) These incidents were all the more unfortunate because the theory is hogwash. If nothing else, the traits we consider classically vampiric, like a nocturnal nature, weren’t common in folklore vampires. (Most of what we know today are late-nineteenth-century tropes that Bram Stoker invented.) Nor do the supposed scientific facts tally. Drinking blood would bring no relief, since the blood components that cure porphyria don’t survive digestion. And genetically, while many porphyrics do suffer from sunburns, the really horrific, blistering burns that might evoke thoughts of supernatural evil are limited to one rare type of porphyria mutation. Just a few hundred cases of it have been documented, ever, far too few to explain the widespread vampire hysteria of centuries past. (Some villages in eastern Europe were tilling their graveyards once per week to search for vampires.) Overall, then, the porphyria fiasco explains more about modern credulity—how willingly people believe things with a scientific veneer—than the origins of folklore monsters.

  A more plausible (but still hotly disputed) case of history pivoting around porphyria took place during the reign of Great Britain’s King George III. George didn’t burn in sunlight but did urinate what looked like rosé wine, among other signs of porphyria, such as constipation and yellowed eyes. He also had rambling fits of insanity. He once solemnly shook hands with an oak branch, convinced he’d finally had the pleasure with the King of Prussia; and in an admittedly vampiric twist, he complained he couldn’t see himself in mirrors. At his shrieking worst, ministers confined George to a straitjacket. True, George’s symptoms didn’t fit porphyria perfectly, and his mental fits were unusually intense for porphyrics. But his genes might have carried complicating factors: hereditary madness was endemic among European royalty between about 1500 and 1900, and most were George’s relatives. Regardless of the cause, George suffered his first fit in early 1765, which frightened Parliament enough to pass an act clarifying who should assume power if the king went stark mad. The king, offended, sacked the prime minister. But amid the chaos that spring, the Stamp Act had passed, which began to poison the American colonies’ relationship with George. And after a new prime minister took over, the scorned former prime minister decided to focus his remaining power on punishing the colonies, a favorite hobby. Another influential statesman, William Pitt, who wanted to keep America in the empire, might conceivably have blunted that vengeance. But Pitt suffered from another highly heritable disease, gout (possibly triggered by a rich diet or by drinking cheap, lead-tainted Portuguese wines). Laid up, Pitt missed some crucial policy debates in 1765 and afterward, and mad King George’s government eventually pushed the American colonists too far.

  The new United States rid itself of dynastic lines and bypassed the hereditary insanity that demented European rulers. Of course, U.S. presidents have had their own share of ailments. John F. Kennedy was congenitally sickly—he missed two-thirds of kindergarten owing to illness—and was (incorrectly) diagnosed with hepatitis and leukemia in prep school. When he reached adulthood, doctors sliced open his thigh every two months to insert hormonal pellets, and the family reportedly kept emergency medicine in safety-deposit boxes around the country. Good thing. Kennedy collapsed regularly and received last rites multiple times before becoming president. Historians now know Kennedy had Addison’s disease, which ruins the adrenal glands and depletes the body of cortisol. One common side effect of Addison’s, bronze skin, might well have supplied Kennedy with his vivacious and telegenic tan.

  But it was a serious disease overall, and although his rivals for the presidency in 1960—first Lyndon Johnson, then Richard Nixon—didn’t know exactly what ailed JFK, they didn’t shy away from spreading rumors that he would (cringe) die during his first term. In response, Kennedy’s handlers misled the public through cleverly worded statements. Doctors discovered Addison’s in the 1800s as a side effect of tuberculosis; this became known as “classic” Addison’s. So Kennedy’s people could say with a straight face that he “does not now nor has he ever had an ailment classically described as Addison’s disease, which is a tuberculose destruction of the adrenal gland.” In truth most cases of Addison’s are innate; they’re autoimmune attacks coordinated by MHC genes. Moreover, Kennedy probably had at least a genetic susceptibility to Addison’s, since his sister Eunice also suffered from i
t. But short of disinterring Kennedy, the exact genetic contribution (if any) will remain obscure.

  With Abraham Lincoln’s genetics, doctors have an even trickier case, since they don’t know for certain if he suffered from a disease. The first hint that he might have came in 1959 when a physician diagnosed a seven-year-old with Marfan syndrome. After tracking the disease through the boy’s family tree, the doctor discovered, eight generations back, one Mordecai Lincoln Jr., the great-great-grandfather of Abe. Although this was suggestive—Lincoln’s gaunt physique and spidery limbs look classically Marfan, and it’s a dominant genetic mutation, so it runs in families—the discovery proved nothing, since the boy might have inherited the Marfan mutation from any of his ancestors.

  The mutated Marfan gene creates a defective version of fibrillin, a protein that provides structural support for soft tissues. Fibrillin helps form the eyes, for instance, so Marfan victims often have poor eyesight. (This explains why some modern doctors diagnosed Akhenaten as Marfanoid; he might naturally have preferred his kingdom’s sun god to Egypt’s squinting nocturnal deities.) More important, fibrillin girds blood vessels: Marfan victims often die young after their aortas wear out and rupture. In fact, examining blood vessels and other soft tissue was the only sure way to diagnose Marfan for a century. So without Lincoln’s soft tissues, doctors in 1959 and after could only pore over photos and medical records and argue about ambiguous secondary symptoms.

  The idea of testing Lincoln’s DNA emerged around 1990. Lincoln’s violent death had produced plenty of skull bits and bloody pillowcases and shirt cuffs to extract DNA from. Even the pistol ball recovered from Lincoln’s skull might have traces of DNA. So in 1991 nine experts convened to debate the feasibility, and ethics, of running such tests. Right away a congressman from Illinois (natch) jumped into the fray and demanded that the experts determine, among other things, whether Lincoln would have endorsed the project. This proved difficult. Not only did Lincoln die before Friedrich Miescher even discovered DNA, but Lincoln left no statement (why would he?) of his views on privacy in posthumous medical research. What’s more, genetic testing requires pulping small bits of priceless artifacts—and scientists still might not get a solid answer. As a matter of fact, the Lincoln committee realized disturbingly late in the process how complicated getting a diagnosis would be. Emerging work showed that Marfan syndrome could arise from many different fibrillin mutations, so geneticists would have to search through long swaths of DNA to diagnose it—a much harder prospect than searching for a single-point mutation. And if they found nothing, Lincoln still might have Marfan’s, through an unknown mutation. Plus, other diseases can mimic Marfan’s by garbling other genes, adding to the complications. A serious scientific venture suddenly looked shaky, and it didn’t bolster anyone’s confidence when garish rumors emerged that a Nobel laureate wanted to clone and hawk “authentic Lincoln DNA” embedded in amber jewelry. The committee eventually scrapped the whole idea, and it remains on hold today.

  Though ultimately futile, the attempt to study Lincoln’s DNA did provide some guidelines for judging the worth of other retrogenetics projects. The most important scientific consideration is the quality of current technology and whether (despite the frustration of waiting) scientists should hold off and let future generations do the work. Moreover, while it seems obvious that scientists need to prove they can reliably diagnose a genetic disease in living people first, in Lincoln’s case they started rushing forward without this assurance. Nor could the technology in 1991 have skirted the inevitable DNA contamination of well-handled artifacts like bloody cuffs and pillowcases. (For this reason, one expert suggested practicing first on the anonymous bones of Civil War amputees piled up in national museums.)

  As far as ethical concerns, some scientists argued that historians already invade people’s diaries and medical records, and retrogenetics simply extends this license. But the analogy doesn’t quite hold, because genetics can reveal flaws even the person in question didn’t know about. That’s not so terrible if they’re safely dead, but any living descendants might not appreciate being outed. And if invading someone’s privacy is unavoidable, the work should at least attempt to answer weighty or otherwise unanswerable questions. Geneticists could easily run tests to determine if Lincoln had wet or dry earwax, but that doesn’t exactly illuminate Lincoln the man. A diagnosis of Marfan syndrome arguably would. Most Marfan victims die young from a ruptured aorta; so perhaps Lincoln, fifty-six when assassinated,* was doomed to never finish his second term anyway. Or if tests ruled out Marfan, they might point toward something else. Lincoln deteriorated visibly during his last months in office; the Chicago Tribune ran an editorial in March 1865 urging him, war or no war, to take time off and rest before stress and overwork killed him. But perhaps it wasn’t stress. He might have been afflicted with another Marfan-like disease. And because some of these diseases cause significant pain and even cancer, Lincoln might conceivably have known he’d die in office (as FDR later did). This would put Lincoln’s change of vice presidents in 1864 and his plans for postwar leniency toward the Confederacy in new light. Genetic tests could also reveal whether the brooding Lincoln had a genetic predilection for depression, a popular but largely circumstantial theory nowadays.

  Similar questions apply to other presidents. Given Kennedy’s Addison’s, perhaps Camelot would have expired prematurely no matter what. (Conversely, Kennedy might not have pushed himself and risen so quickly in politics if he hadn’t sensed the Reaper.) And the genetics of Thomas Jefferson’s family brings up fascinating contradictions about his views on slavery.

  In 1802 several scurrilous newspapers began suggesting that Jefferson had fathered children with a slave “concubine.” Sally Hemings had caught Jefferson’s eye in Paris when she served him during his stint as American minister there. (She was probably his late wife’s half sister; Jefferson’s father-in-law had a slave mistress.) Sometime after returning home to Monticello, Jefferson allegedly took Sally as his lover. Jefferson’s newspaper enemies jeered her as the “African Venus,” and the Massachusetts legislature publicly debated Jefferson’s morals, including the Hemings affair, in 1805. But even friendly eyewitnesses recall that Sally’s sons in particular were cocoa-colored doppelgängers of Jefferson. A guest once caught one Hemings boy in tableau behind Jefferson’s shoulder during a dinner party, and the resemblance flabbergasted him. Through diaries and other documents, historians later determined that Jefferson was in residence at Monticello nine months before the birth of each of Sally’s children. And Jefferson emancipated each of those children at age twenty-one, a privilege he did not extend to other slaves. After moving away from Virginia, one of those freed slaves, Madison, bragged to newspapers that he knew Jefferson was his father, and another, Eston, changed his surname to Jefferson partly because of his resemblance to statues of TJ in Washington, D.C.

  Jefferson always denied fathering any slave children, however, and many contemporaries didn’t believe the charges either; some blamed nearby cousins instead, or other Jefferson relatives. So in the late 1990s scientists effectively hooked Jefferson up to a genetic polygraph. Because the Y chromosome cannot cross over and recombine with other chromosomes, males pass down the full, unchanged Y to each son. Jefferson had no recognized sons, but other male relatives with the same Jefferson Y, like his uncle, Field Jefferson, did have sons. Field Jefferson’s sons had their own sons in turn, and they their own sons, and the Jefferson Y eventually got passed down to a few males living today. Luckily, Eston Hemings’s line had also produced males every generation, and geneticists tracked members of both families down in 1999. Their Ys were perfect matches. Of course, the test proved only that a Jefferson had fathered Sally Hemings’s children, not which specific Jefferson. But given the additional historical evidence, a case against Jefferson for child support looks strong.

  Again, it’s undeniably titillating to speculate about Jefferson’s private life—love blossoming in Paris, his pining for Sally while
stuck in sultry D.C.—but l’affaire also illuminates Jefferson’s character. He would have fathered Eston Hemings in 1808, six years after the first allegations appeared—which reveals either enormous hubris or sincere devotion to Sally. And yet like many of the English monarchs he despised, Jefferson disavowed his bastard children, to salvage his reputation. Even more uncomfortably, Jefferson publicly opposed, and authored legislation to make illegal, marriages between blacks and whites, pandering to fears of miscegenation and racial impurity. It seems a damning account of hypocrisy in perhaps our most philosophical president.

  Since the Jefferson revelations, Y-chromosome testing has become an increasingly crucial tool in historical genetics. This does have one downside, in that the patrilineal Y defines someone rather narrowly: you can learn about only one of his many, many ancestors in any generation. (Similar limitations arise with matrilineal mtDNA.) Despite this caveat Y can reveal a surprising amount. For example, Y testing reveals that the biggest biological stud in history probably wasn’t Casanova or King Solomon but Genghis Khan, the ancestor of sixteen million men today: one in two hundred males on earth carries his testes-determining chromosome. When the Mongols conquered a territory, they fathered as many children as possible with local women, to tie them to their new overlords. (“It’s pretty clear what they were doing when they weren’t fighting,” one historian commented.) Genghis apparently took on much of this burden himself, and central Asia is littered with his litters today.

  Archaeologists have studied the Y and other chromosomes to untangle Jewish history as well. The Old Testament chronicles how Jews once divided themselves into the kingdoms of Judea and Israel, independent states that probably developed distinct genetic markers, since people tended to marry within their extended family. After many millennia of Jewish exiles and diasporas, many historians had given up hope of tracing exactly where the remnants of each kingdom had ended up. But the prevalence of unique genetic signatures (including diseases) among modern Ashkenazi Jews, and other unique genetic signatures among Sephardic and Oriental Jews, has allowed geneticists to trace ancient lineages, and determine that the original biblical divisions have largely persisted through time. Scholars have also traced the genetic origins of Jewish priestly castes. In Judaism, the Cohanim, who all supposedly descended from Aaron, brother of Moses, have special ceremonial roles in temple rites. This honor passes from Cohanim father to Cohanim son, exactly like the Y. And it turns out that Cohanim across the world do indeed have very similar Ys, indicating a single patriarchal line. Further study shows that this “Y-chromosomal Aaron” lived, roughly, in Moses’s time, confirming the truth of Jewish tradition. (At least in this case. Levites, a related but distinct Jewish group, also pass down religious privileges in a patrilineal way. But Levites around the world rarely share the same Y, so either Jewish tradition bungled this story,* or Levite wives slept around behind their husbands’ backs.)