text: Island of Autoimmunity
  
  One blustery spring day in Sardinia, I find myself wandering around a crumbling Bronze Age tower made of black volcanic stone. A neurologist named Stefano Sotgiu accompanies me. He expounds on the mysterious structure looming over us. It is called a nuraghe; nur translates roughly to “hollow” or “pile of stones” in the language spoken before the Romans brought Latin to Sardinia. More than seven thousand of the edifices dot the island, and they were already ancient — 1,500 years old — when the Romans arrived more than two millennia ago. They serve as an important cultural reference point: While the rest of Christendom begins its calendar with the birth of Jesus, Sardinians, Sotgiu explains, divide history into pre- and post-nuraghe — a nearly 2,000-year head start.
  
  For Sotgiu and me, the nuraghi furnish a ready-made metaphor for our conversation. Sardinians inexplicably have one of the highest prevalences of autoimmune disease in the world—the reason I’ve come to the island. They’re between two and three times as likely to develop multiple sclerosis compared with mainland Italians, or people from nearby islands, such as Corsica to the north or Sicily to the southeast. And they’re second only to the Finns in their vulnerability to autoimmune (type-1) diabetes.
  
  Why?
  
  The fallback explanation imputes genes, which is probably roughly accurate. But Sotgiu has taken the “bad genes” hypothesis a step further than usual. He’s asked what these “autoimmune” gene variants might be for — what’s their purpose? And why are they so common among Sardinians?
  
  He didn’t have to delve far into the past for an answer. Malaria was endemic on the island until just sixty years ago. His parents, uncles, and aunts all survived it, and their parents and grandparents before them. Until the mid-twentieth century, malarial fevers were a rite of passage on the island, and had been for millennia. Those who were resistant to the parasite survived; those who weren’t died. Gene variants that helped defend against it became enriched among Sardinians. Much like the mysterious nuraghi that characterize the island’s landscape, these protective genes now define the Sardinian genome. These same variants, Sotgiu thinks, also increase the chances of developing autoimmune disease. The price Sardinians pay for excellent antimalarial defense is a tendency to fall ill with multiple sclerosis.
  
  I follow Sotgiu up a winding staircase of rough-hewn stone. We emerge on a dais about sixty feet high with a commanding view. A wind-whipped grassy plain stretches before us, framed by flat hills in the distance. Trenches dug on Benito Mussolini’s orders in the 1930s cut through the meadow below. They were meant to drain the malarial marshes once and for all. Cone-shaped, thatch-roof huts, a design common to old Europe, rise here and there from the tall grass. They’re mostly used to house sheep these days, says Sotgiu. But people lived in them once. Birds hover at our eye level, held aloft by the northwesterly wind, which in Sardinia and greater Italy has its own name — il vento maestrale.
  
  'Sardinians need to engage with their old foe to avoid the demons lurking within.'
  
  Traditionally, outsiders have regarded Sardinia as a backwater, he explains, an island of rough peasants and shepherds who prefer to be left alone. (Later I learn that when the animated American show The Simpsons is dubbed into Italian, groundskeeper Willie, who’s Scottish in the U.S., has a Sardinian accent.) The feeling of distrust is mutual. “We have suspicion with regards to outsiders,” says Sotgiu. For three thousand years, wave upon wave of would-be rulers arrived from the sea. Sardinians responded by retreating to the island’s interior. “That’s probably why we weren’t changed by all the invasions,” says Sotgiu. This insularity, both figurative and literal, partly explains the Sardinian genome’s uniqueness, and its vulnerability to autoimmune disease.
  
  Today, 1 in 430 Sardinians has multiple sclerosis, a degenerative disease of the central nervous system that, as it progresses, steals one’s ability to move limbs, to see, and eventually to breathe. (That’s the official number, but Sotgiu confides that unpublished data put it higher still.) One in every 270 Sardinians has type-1 diabetes, an autoimmune condition in which the immune system attacks the body’s insulin-producing organ, the pancreas.
  
  The stats weren’t always like this here. In Sardinia, there’s a distinct Year Zero for autoimmune disease. Just after the eradication of malaria in the 1950s, immune-mediated diseases began increasing precipitously. Sotgiu thinks the timing isn’t coincidental. Malaria may have selected for ­autoimmunity-prone genes. But infection with the malaria parasite Plasmodium falciparum likely protected against the dark side of the very genes it helped shape. In this aspect, Sotgiu’s hypothesis departs from more run-of-the-mill invocations of genetics. He suspects that the highly specialized Sardinian immune system functions properly only in the context of the invader it evolved to thwart. Sardinians need to engage with their old foe, in essence, to avoid the demons lurking within.