Lessons from History | 3. Pellagra & Misinformation
Despite ample evidence gathered over centuries in Europe & US in favor of a dietary cause, Pellagra was believed by many to be an infectious disease until the mid 1900s.
What is Pellagra?
Pellagra is a disease caused by deficiency in niacin (vitamin B3) - a precursor of NAD+ (Nicotinamide adenine dinucleotide), which is central to metabolism.
Pellagra has probably been the most devastating vitamin deficiency epidemic of all. Between 1906 and 1940, more than 3 million Americans suffered, with over 100K deaths.
Symptoms of pellagra include inflamed skin, diarrhea, sores, and dementia.
Much like the story of Scurvy & Vitamin C - Niacin was not isolated until the mid 1930s, providing cover for the microbe-hunters to pursue their infectious ideas with little friction.
Corn was introduced to Europe from the New World in the 15th century, and soon became the staple of poor Europeans.
However, Native Americans who first domesticated corn prepared it by a process called nixtamalization - in which the grain is treated with alkali fluid, such as lime. This renders the niacin bioavailable and prevents pellagra.
Don Gasper Casal, a Spanish Court physician, first described this syndrome in 1735. Casal noted a malady among poor peasants of Asturias, and called it mal de la rosa - reflecting reddish and glossy rash on the back of hands and feet.
Casal observed that the afflicted were poor, subsisted mostly on corn, and rarely ate fresh meat.
Francesco Frapoli, Italian physician, used the term pellagra in 1771 (pell = skin + agra = sour).
An Epidemic of the Poor
Pellagra grew into an epidemic in Italy, and spread throughout the Mediterranean in the 19th century. Various populations turned to corn as a substitute for other vegetables. Pellagra appeared wherever corn became a dietary mainstay. Because of the way corn was processed (without nixtamalization), niacin was not bioavailable and led to ‘outbreaks.’
European doctors considered the early sentimen that pellagra was not contagious - as evidenced by the lack of spread outside of the corn-eating subpopulations. Furthermore, in the 1790s it was observed that pellagrinis (those suffering from pellagra) would be cured with a balanced diet.
However, doctors unfamiliar with pellagra proposed it was contagious. In the 1700s, several doctors blamed the disease on miasms (bad air). German doctor Titius, foreign to epidemic regions, simply called it infectious in 1791.
In the early 1800s, multiple doctors formulated several related hypotheses speculating that corn itself or a fungus on moldy corn caused pellagra. In his doctoral thesis, Jean-Marie Hameau thought the disease was transmitted by sheep. The typical approach to treating pellagra was as an infection - either with blood-letting, quinine, or arsenic.
The Great Microbe Hunt
The success of Louis Pasteur and Robert Koch was widely popular, and researchers flocked to bacteriology. The microbe-hunting sight was now set on pellagra.
In 1881, Majocchi was the first to isolate a bacterium from spoiled corn and the blood of pellagrinis. Several discovered that this microbe was the same previously identified bacterium found in potatoes. However, they could not find it in the blood of pellagrinis. Instead, it was found in the intestines of all humans, including those without disease.
At the turn of the 20th century, an Italian researcher Ceni generated a large number of publications claiming that corn fungus excreted by chickens caused pellagra in humans. Ceni then expanded his list to two, then four separate fungi that he thought would all cause it. Despite the fact that these fungi did not flourish in the body, Ceni insisted they could release poisons.
The volume of Ceni's research forced scientists to spend a great deal of effort refuting his claims. In 1906, Tizzoni began reporting experiments on two strains of bacteria - blaming pellagra on both of them. Having discovered the bacteria in pellagrinis, they caused sickness in monkeys and guinea pigs. Tizzoni declared, “It would seem to be settled that pellagra is a bacterial disease.”
Famous last words.
Because, several scientists could not isolate these bacteria from people with pellagra.
Pellagra Invades the USA
Support for microbe-hunters multiplied dramatically once pellagra appeared in the United States.
The first case appeared in Georgia, a single farmer in 1902. This did not garner much attention. But then, pellagra appeared in an Alabama hospital for the ‘Insane.’ Eighty-eight people became ill, and most of them died.
Dozens of cases appeared throughout southern states. Facing an epidemic, the head of a hospital for the insane in South Carolina (James Woods Babcock MD) visited Italy in 1908, and decisively concluded that the American epidemic was indeed pellagra.
The Public Health Service (PHS - which houses the NIH, CDC & FDA) established a small laboratory for pellagra research in South Carolina. Claude Lavinder was the boss, and conducted three lines of research: experiment, treatment, and public relations.
They searched for a microbial cause by injecting animals with bodily fluids from pellagrinis. This proved unsuccessful. Treatments also failed, as the mainstay was arsenic and mercury.
But, the media was effectively mobilized to convince Americans they were facing a deadly epidemic that could easily affect any person, rich or poor, young or old.
The first National Conference on Pellagra in South Carolina was held in 1909. The evidence of pellagra's association with corn-based diets was clearly recognized at the meeting.
But, the age of microbe hunting was still in full swing. Although many scientists investigated corn, the conference also set in motion a revived hunt for a pellagra microbe!
Louis Sambon, in 1905, announced after a brief visit to Italy that he believed pellagra to be an infectious disease. Building on his work on malaria, Sambon stated in 1910 that the disease was transmitted by either flies or buffalo gnats. Though he failed to notice that pellagra, unlike malaria, did not spread out of its endemic populations.
Microbe-hunters get Creative
The PHS lab discovered an amoebal microbe in the intestines of pellagrinis and declared it the cause in 1910. Lavinder also caught onto Sambon’s work. Convinced of the insect hypothesis, he published evidence in 1912 that airborne insects crowded nearby water during seasons that pellagra was worst.
One research team created a complex hypothesis of insect transmission in Kentucky, reasoning that insects caught it from horses, then transferred it to blackbirds that carried the germ to unsuspecting humans. It’s all fascinatingly circuitous. Then, Department of Agriculture sent a select team of entomologists to study insects in South Carolina in 1912.
Newspaper articles served to fan public fears as the epidemic grew, not unlike our COVID-19 response:
Segregation? Censorship? Oh, dear.
Remind you of anything?
A second National Conference on Pellagra was held in 1912. The Federal government initiated the Thompson-McFadden Commission, which demonstrated a bias for an infectious cause. Casually dismissing dietary connections, the commission turned its attention to studies of sewage, insect, and microbes. Some even suggested that Italian immigrants had brought the disease with them.
Ultimately, the stable fly (stomoxys calcitrans) was officially blamed by the Commission for spreading the contagion responsible for pellagra.
The prestige spurred the PHS to renew its efforts at finding the pellagra microbe in 1913. Fueled, no less, by the promise of further funding to do so.
The Pellagra Hospital in Spartanburg, South Carolina, was the nation's first dedicated to discovering the cause of pellagra. Established in 1914 with a special Congressional appropriation to the PHS, and primarily for research.
A Light in the Darkness
The epidemic tallied 200,000 victims in 1914, and the Thompson-McFadden Commission continued to issue its reports. But, PHS replaced Lavinder with a Hungarian named Joseph Goldberger, to run the team.
Goldberger saw something the entire medical establishment and its experts had failed to notice in their zeal to identify a causative microbe. He was astonished to find that even where pellagrinis were concentrated, their doctors and nurses did not catch it. He also observed that the doctors primarily consumed meat and vegetables, while the farmers consumed their corn-based diets.
With this new information at hand, he cured pellagra by changing diets in orphanages, hospitals, and prisons.
Goldberger drew the inescapable conclusion of a dietary deficiency. After publicly stating his hypothesis in 1914, he was attacked by doctors who insisted the disease was contagious.
At a medical conference, where the leaders of the Thompson-McFadden Commission presented further findings on infection, Goldberger stirred up intense anger and controversy by critiquing the commission's latest study.
When he presented his results, two leading advocates of the contagion view backed down - one a leader of the Thompson-McFadden Commission, the other withdrawing his paper for publication.
When the media gave Goldberger's results favorable publicity, pellagra microbe hunters reacted with alarm and anger.
Doctors joined in a growing chorus against the supposedly dangerous deficiency hypothesis, arguing that the public was now being misled.
The Thompson-McFadden Commission struck back especially hard in 1916. They reiterated their conclusions, and emphasized the dangers of insects.
Opponents continued to attack or ignore Goldberger for several more years, while their ranks gradually reduced over time. Goldberger continued studying the disease until his death in 1929.
Niacin was extracted by Conrad Elvehjem in 1937. He identified the active ingredient, and referred to it as pellagra-preventing factor or Vitamin PP.
Back to Basics
Once you dig into the historical record, it is marvelous to behold the simplicity that lies behind a veil of lingo, ‘expertise,’ and obfuscation.
Scurvy → Vitamin C → Ascorbic Acid → A-Scorbutic
The more I think about this, the more I realize that there isn’t really a discrete category of “vitamins.” There was this chemical structure (above) found in people who did not have scruvy, and not found in people who did have scurvy. Hence, the a-scorbutic acid.
We observe an analogous history with Vitamin B3.
Pellagra → Niacin → Vitamin PP → Pellagra-Preventing
If we define a drug as a substance with a physiologic impact on humans.
Then vitamins, and broadly nutrients, are merely drugs which lack intellectual property ownership and marketing campaigns.
The arrogance of man knows no bounds. The potential damage is likewise unlimited.
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