Blogging the Human Genome

Did Lincoln Have Marfan Syndrome? Did Darwin Have Smoldering Hepatitis?
Each one has a story
July 26 2012 6:01 AM

Blogging the Human Genome

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Did Lincoln have Marfan syndrome? Did Darwin have smoldering hepatitis? The strange allure of retro-diagnosis.

Blogging the Human Genome Entry 15

Illustration by Andrew Morgan

All of them are past helping, so it’s not clear why we bother. But whether it’s Frederick Chopin (cystic fibrosis?), Edgar Allan Poe (rabies?), Jane Austen (adult chicken pox?), Vlad the Impaler (porphyria?), or Vincent van Gogh (half the DSM), we’re incorrigible when it comes to diagnosing the famous dead. We persist in guessing despite a rather dubious record, in fact. Even fictional characters sometimes receive unwarranted medical opinions. Doctors have diagnosed Ebenezer Scrooge with OCD, Sherlock Holmes with autism, and Darth Vader with borderline personality disorder.

You might think that modern genetic testing could answer some of these questions decisively. After all, if we can read the DNA of Neanderthals who died 50,000 years ago, what’s so hard about reading the DNA of someone who died 150 years ago? But while our amplified knowledge of genetics—and the increasing precision of the field—does make it tempting to take on celebrity cases, retro-genetics can’t always provide clear answers.

One early attempt to retrodiagnose someone using DNA involved Abraham Lincoln. The story started in 1959: A doctor diagnosed a 7-year-old boy with Marfan syndrome, and then traced the boy’s family line back to 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 mutation so it runs in families—the genealogy proved nothing, since the boy might have inherited the Marfan mutation from any of his ancestors.

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The mutated Marfan gene creates a defective version of fibrillin, a protein that provides structural support for soft tissues like blood vessels. Marfan victims often die young, in fact, after their aortas grow threadbare and rupture. So diagnosing Lincoln with Marfan’s could potentially change our view of history: Perhaps Lincoln, 56 when assassinated, was doomed to never finish his second term anyway.

Given Lincoln’s messy, public death, there’s plenty of Lincoln DNA on bloody shirt cuffs and pillowcases; we even have skull fragments that were never buried. So in 1991 a few scientists met to debate the feasibility, and ethics, of running some DNA tests on these materials. Right away a congressman from Illinois (natch) butted in and demanded that the experts first determine, among other things, whether Lincoln would have endorsed the project. This proved difficult. Not only did Lincoln die before anyone 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. Indeed, the Lincoln committee soon realized how complicated getting a diagnosis would be. Emerging work at the time showed that Marfan syndrome could arise from many different mutations, so geneticists would have to search through long swaths of DNA—a much harder task than searching for a single point mutation. And if they found nothing, Lincoln still might have had Marfan’s, through an unknown mutation. With the venture suddenly looking shaky, the committee scrapped the whole idea, and plans remain on hold today. (A few years later, a Nobel laureate revealed plans to clone and hawk authentic Lincoln DNA embedded in jewelry, which didn’t exactly bolster anyone’s desire to revisit the matter.)

At least with Lincoln, geneticists have an idea of what to look for. Not so with Charles Darwin—he remains a medical enigma. After returning from the Beagle voyage and marrying, Darwin deteriorated into a wheezing wreck. He suffered from boils, fainting fits, heart flutters, numb fingers, insomnia, migraines, dizziness, eczema, and “fiery spokes and dark clouds” before his eyes. The strangest symptom was a ringing in the ears, after which he’d always pass horrendous gas. But above all Darwin barfed. He barfed after breakfast, after lunch, after dinner, brunch, tea, whenever—and kept going until he was dry-heaving. In peak form he vomited 20 times an hour, and once vomited 27 days running. Mental exertion invariably made his stomach worse, and even Darwin, the most intellectually fecund biologist ever, could make no sense of this. “What thought has to do with digesting roast beef,” he once sighed, “I cannot say.”

Some enterprising biologists recently pegged Darwin’s troubles on something called cyclic vomiting syndrome, which is pretty much what it sounds like. Many cases of—apologies to your local drugstore—CVS arise from mutations in the mitochondria, little sparkplugs in your cells that produce energy. Mitochondria have the distinction of being the only structures outside your chromosomes that house DNA. (Chromosomes sit inside the cell nucleus, while mitochondria swim around outside the nucleus.) And unlike other DNA, you inherit all your mitochondria from your mother. This means that mitochondrial diseases like CVS run in maternal lines. Intriguingly, Darwin’s mother’s family was a sickly lot. His mother died young (Charles was just 8) after suffering from undiagnosed gastrointestinal pain.

That said, dozens of other medical sleuths—each one quite confident—have put forward their own Darwin retrodiagnosis: middle ear damage, pigeon allergies, arsenic poisoning, lactose intolerance, Chagas disease, lupus, narcolepsy, agoraphobia, chronic fatigue syndrome, an adrenal-gland tumor, and something called “smoldering hepatitis.” DNA testing could rule out some of these diagnoses, and with CVS at least, because cells have so many copies of mitochondria (sometimes thousands), mitochondrial DNA is the easiest type of DNA to excavate from old bones. But there’s something unseemly about turning Darwin out of his grave to gratify our curiosity, and so far Westminster Abbey has refused all applicants.

I admit I’m a sucker for retrodiagnoses. There’s not an emperor or artist out there I won’t read a medical history of, even if—or especially if—the author uses that medical history to spin out wild counterfactuals about how wars or masterpieces might have turned out differently. They’re like delicious philosophical mints to roll around inside your mouth, just to see how they taste.

In writing The Violinist’s Thumb, however, I saw many retrodiagnoses fall apart. (My favorite swing-and-miss involved blaming porphyria, a red-blood-cell disease, for ancient superstitions about blood-guzzling vampires.) I believe we can diagnose some people from the past. But our stumbling around in people’s genes could well look naïve someday, the way that ancient theories about black bile, phlegm, and other “humours” look quaint to us. As historian Axel Karenberg—author of the paper “Next Emperor, Please! No End to Retrospective Diagnostics”—told me, once doctors discover a new disease or condition, you can be fairly sure that, within about a decade, some historical celebrity will be diagnosed with it. In fact, Karenberg says, the history of retrodiagnoses closely parallels the history of medicine itself. It can thus reveal less about the past than the present.

Sam Kean is the best-selling author of The Disappearing Spoon and The Violinist’s Thumb. His new book, The Tale of the Dueling Neurosurgeons, comes out May 6.

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