Vitamin A

670,000 children under 5 years old die, and up to 500,000 children go blind every year from vitamin A deficiency.

The results of vitamin A deficiency may have been discovered by accident by an absolute horror of a man, François Magendie, in 1816. While he is revered as a pioneer of experimental physiology, this is a man who nailed a greyhound to the ground by the ears and paws so that he could perform a dissection on the poor dog while it was still alive, in front of an audience. After dissecting half of the face, he left the animal nailed to the stage overnight to continue the next day.

In an experiment (French, English pp. 483-485), he fed a three-year-old dog nothing but sugar and distilled water. It died on the 32nd day after first going blind in the third week (corneal ulcerations appeared). This was repeated with a second dog. This showed that sugar alone is not enough to keep a dog alive. His reasoning for the experiment was that he wanted to know if it was possible to survive on foods that did not include the "azotic aliments" (chemicals containing nitrogen). Vitamin A is not an azotic molecule, so the experiment missed the mark slightly.

In his next experiment, he then fed two healthy dogs high quality olive oil and nothing else. The dogs died on the 36th day, but no corneal ulcerations appeared this time, showing that there was something in the olive oil, that is not in pure sugar, that is needed for clear eyesight.

We know today that olive oil contains vitamin A.

Apart from full-on blindness caused by corneal ulcerations, night blindness is also common. This is a disease (nyctalopia) where the eyes cannot adjust to low-light conditions.

In 30AD, Aulus Cornelius Celsus wrote a book called De Medicina, in which he suggested that sufferers of night blindness should "anoint their eyeballs with the stuff dripping from a liver whilst roasting, preferably of a he-goat, or failing that of a she-goat; and as well they should eat some of the liver itself". The first part is rubbish, but the second part, almost merely an aside, works, because liver contains vitamin A in high concentration.

In 1852, the French physician Pierre Bitot became chief surgeon of Bordeaux orphanages. Over the next ten years, he catalogued 29 cases of night blindness with xerophthalmia (inability to form tears) in a population of 400 children. his observations were similar with those of another orphanage doctor, João Clemente Mendes of Portugal who observed 24 cases in a population of 202 children.

Bitot noted that the night blindness and xerophthalmia resolved itself in children once they had left the orphanage, but it never occured to him to figure out why. We can surmise today that the orphanage's diet was strictly controlled, and probably poor in comparison to any diet the child would encounter once out of the orphanage's care.

France during the early 19th century had a strict nutritional policy for its publically-funded enterprises. but, because of the low understanding of nutrition at the time, this meant that the diet, despite efforts, was inadequate. Orphanages, hospices and hospitals were given foods such as gelatine, which is the boiled remains of animals after the meat has been stripped. It was in order to measure the nutritional value of gelatine that Magendie was originally tasked, but the results (gelatine is inadequate) did not filter into public policy until decades later.

In 1881, a Russian surgeo, Nikolai Lunin, did an experiment where he fed mice on a diet of protein, sugar, fat and salts. None of the mice lived longer than just over a month. However, he found that if he added a tiny bit of milk to the mix, the mice lived for more than twice as long, showing that protein, sugar, fat and salt are not all that you need to survive. Milk has something extra that is needed. He suggested it would be important to see what is it that the milk has that was so important, but he never carried on the research himself to find that out.

Paul Knapp, an ophthalmologist, ran a similar experiment (a purified diet, and the same diet with milk) on rats in 1909 and noted that before the purified diet rats died, they had conjunctivitis and corneal ulcers. He was the first person to clinically record xerophthalmia in an animal, and to finally recognise that the ulcers and the xerophthalmia were caused by a mysterious ingredient in milk that was not in the recognised food groups of the time.

One reason it took so long to figure this out is that germ theory was very popular at the time (since the late 19th century), and it was believed that diseases are caused not by the absence of ingredients, but by the addition of bactieria or other impurities.

The evidence was piling up, though. Cornelius Adrianus Pekelharing repeated Lunin's experiments in 1905 and said there was something in the milk that was necessary, pointing out that it was just the tiniest amount of milk that was needed, but that it was essential. Frederick Hopkins published a year later, stating that there were "unsuspected dietetic factors" necessary for life.

In 1909, a student, Willhelm Strepp, had an original idea. Why not turn it completely around - instead of starting with a minimal diet and add little bits until you find the missing ingredient, why not start with a full diet, and remove bits until you come across a deficiency?

Through experimentation, he found that something in the food that he prepared was heat-sensitive, and if the food was heated to 100°C and kept at that heat for a while before cooling and serving, then that mysterious something was destroyed, and the food became malnutritious.

By 1911, thiamin (vitamin B) had been extracted by another scientist, Casimir Funk. He named it "vitamine", because it was vital to life, and was an amine. Strepp wanted to know if that was the mysterious factor he was looking for, so he tested whether adding thiamin to the malnutritious prepared food would fix it. It didn't, showing that factor he was looking for was not thiamin.

Vitamin A was eventually identified and formulated chemically by Paul Karrer, who won a Nobel prize for his work.