The arrival of maize in Europe after Columbus’s return in 1493 looked, on the initial evidence, like one of the more straightforward pieces of good news in the entire Columbian exchange. The plant grew faster than wheat. It produced more calories per acre than almost any European staple. It thrived on marginal land where oats and barley struggled. And within a few generations of its introduction, corn had become the backbone of the peasant diet across large stretches of northern Italy, Spain, southern France, the Balkans, and eventually the American South. For families whose survival depended on the calorie yield of a small patch of ground, it was, on any straightforward reading of agricultural economics, exactly what they’d been waiting for.
Then something started going wrong.
People whose diets had shifted to depend on corn began developing a disease that nobody in Europe had ever seen before. Their skin turned rough and cracked. Sunlight caused it to blister and peel away, particularly in a distinctive band around the neck and on the backs of the hands. Their digestion collapsed. Their mental state deteriorated. Some became depressed and withdrawn. Others became manic or violently psychotic. Left untreated, they died. And the disease seemed to concentrate in exactly the populations most dependent on the new miracle crop.
This video dives into what exactly was causing the fatal symptoms:
What the disease actually did
According to a 2008 review by Dr Alfredo Morabia, published in the Journal of the Royal Society of Medicine under the title “Joseph Goldberger’s Research on the Prevention of Pellagra,” and hosted in full text on the National Institutes of Health’s PubMed Central repository, the disease acquired a name in 1771 when the Italian physician Francesco Frapolli called it pellagra, from the Lombard dialect words meaning rough or sour skin. It had been described in medical detail thirty-six years earlier by the Spanish physician Don Gaspar Casal, working in the province of Asturias, who called it mal de la rosa and mistook it, initially, for a form of leprosy. Casal’s own detailed clinical description was published posthumously in 1762.
What Casal was describing came to be known in the twentieth century as the four Ds. Dermatitis. Diarrhoea. Dementia. Death. The dermatitis was distinctive. It appeared on sun-exposed areas of the body and produced a specific hyperpigmented band around the neck, which is still called Casal’s collar in modern medical practice. The skin cracked, blistered, and peeled in ways that looked like severe sunburn on people who hadn’t been in the sun any longer than their neighbours. The digestive symptoms followed. Then the neurological ones. Depression. Anxiety. Confusion. Progressing, in advanced cases, to full psychiatric collapse. Then death.
The scale was enormous. By 1784, Italy had built a hospital called Legnago specifically for pellagra patients, because ordinary hospitals couldn’t handle the case load. Reports of the disease then followed the spread of corn cultivation. France in 1829. Romania in 1858. Egypt in 1874. In the twentieth century, the disease reached the United States and settled into the poorer counties of the South, where between 1907 and 1940 approximately three million Americans contracted pellagra and roughly one hundred thousand of them died. The state of South Carolina alone reported 30,000 cases by 1912, with a mortality rate of forty per cent.
Globally, over the roughly two centuries between Casal’s first description and the resolution of the underlying question, the total death toll from pellagra ran into the hundreds of thousands.
Why nobody could work out what was causing it
The problem, from the point of view of the physicians investigating the disease, was that pellagra behaved in ways that didn’t match any of the diagnostic frameworks the medical community had available. It clustered geographically, in ways that suggested some sort of environmental cause. It affected some households and left neighbouring ones alone. It struck poor peasants and rarely the wealthy. It followed corn cultivation with a precision that could hardly be missed, but the exact nature of the connection wasn’t obvious. Corn had been eaten in Mesoamerica for thousands of years without causing anything remotely resembling pellagra, so blaming the plant itself seemed unwarranted.
The prevailing theory through most of the nineteenth century was that pellagra was caused by some sort of toxin in spoiled corn, or by an infectious agent transmitted between people. Both were wrong. The disease was ferociously non-infectious, and the corn itself, on any chemical analysis, was fine.
The breakthrough came from an American public health investigator named Joseph Goldberger. Assigned in 1914 by the US Surgeon General to investigate the American pellagra epidemic, Goldberger noticed something the earlier theories had missed. In the institutional settings where pellagra was rampant, meaning orphanages, prisons, mental hospitals, and mill villages, the inmates and workers ate corn-based diets while the staff and administrators ate more varied food. And the staff didn’t get pellagra. If it were infectious, they should have.
Goldberger ran the crucial experiments. In an orphanage, he cured pellagra in children by improving their diet. On a prison farm, he induced pellagra in eleven healthy volunteer prisoners by restricting them to a corn-based diet, in exchange for early release. And to prove the disease wasn’t contagious, he injected himself, his wife, and several of his colleagues with blood, mucus, and other bodily fluids from pellagra patients. None of them got sick. By 1926, on the primary source record, Goldberger had established that pellagra was a dietary deficiency and that a balanced diet, or even a small amount of baker’s yeast, would prevent it. He didn’t know what the missing nutrient was, but he could show it existed. He called it the P-P factor, for pellagra-preventative.
The identification of the actual missing nutrient came eleven years later. In 1937, an agricultural biochemist named Conrad Elvehjem at the University of Wisconsin cured a condition called black tongue in dogs, which is the canine equivalent of pellagra, by supplementing their diet with nicotinic acid. The compound was renamed niacin. It was vitamin B3. Grain products across the United States began being fortified with it within a few years of the discovery, and pellagra effectively disappeared from the American diet within a generation.
The knowledge Mesoamerica had all along
The stranger part of the whole story, on the historical record, is that the people who had domesticated corn in the first place had known how to prevent pellagra for at least three thousand years. According to the Cleveland Clinic’s own reference material on pellagra, the traditional Mesoamerican preparation of corn for tortillas involved soaking the kernels overnight in an alkaline solution, usually water mixed with wood ash or slaked lime. The process was called nixtamalization, from a Nahuatl word combining nixtli, meaning ash, and tamalli, meaning dough.
What the alkaline soak did, on the modern chemical understanding, was break the outer shell of the corn kernel and release the niacin from a bound form called niacytin, which the human digestive system can’t extract. The nixtamalised corn also, as a side effect, released some of the amino acid tryptophan, which the body can convert into niacin on its own. And the calcium from the lime became a bioavailable source of the mineral in the final tortilla. The whole traditional preparation, worked out over centuries by the original cultivators, produced a food that supplied both niacin and the raw materials for the body to make more of it.
When corn travelled to Europe, this preparation did not travel with it. European peasants adopted the crop enthusiastically, ground it into flour, boiled it into polenta or baked it into bread, and never soaked it in lime because nobody had told them they were supposed to. The result was a population living on a staple grain whose most important nutrient was chemically locked away in a form their digestive systems could not reach. The people whose ancestors had figured out how to unlock it were not consulted. And for the next four centuries, a disease that had been solved on the American continent long before Europeans arrived went on killing hundreds of thousands of people across Europe, Africa, and eventually the American South, while the physicians investigating it worked their way slowly toward a solution the answer to which had been sitting in Mexican kitchens the entire time.
