Thread by @fioraesoterica

You probably know of a few vitamins. But maybe not this massive boy: Vitamin B12. It's the coolest vitamin, and has a fascinating history.

B12 is an absolutely bizarre vitamin. Yes, that's a COBALT atom in the center there. WTF? It's by far the most complex vitamin by structure.

The human body only needs about 2 micrograms per day. Yes, micrograms.

What does it do? It takes part as a coenzyme in some obscure reactions.

But if you don't have it, your entire nervous system starts to break down.

Don't get scared though; you probably get enough.

Your body can store a rather large amount of it -- 3 to 5 milligrams (or a couple years worth!), so running out is fairly difficult under normal circumstances. Very few diets lack B12 to that degree.

Where can you get it? Mostly animal products (lack of B12 is a potential concern for strict vegan diets).

What actually makes it? Bacteria and archaea; no eukaryote can produce it! Fun fact: some gut bacteria can make it, but they're in the colon, so it all gets wasted :(

So beyond being this weird chemical structure with a freaking cobalt and only made by bacteria, why is it cool?

Vitamin B12 is directly or indirectly responsible for six different nobel prizes. SIX!!!!! and the stories behind this are fantastic.

let's start from the beginning.

you may wonder how such a vitamin was even discovered if you only need 2 micrograms per day.

it all starts in 1849, when Thomas Addison did the first write-up on an illness that would later be named "pernicious anemia", a strange disease for which no cause was known.

for the next few decades, much study was made into the features of the disease, noting very particular effects on blood cells, bone, etc.

but no treatment was found, nor was there even a clue as to the cause.

The first break was in 1907. William Bosworth Castle did a wild experiment: he ate raw hamburger meat, regurgitated it after an hour, and fed it to 10 patients. another 10 received normal raw hamburger meat.

the first 10 patients showed symptom improvements. the controls did not

this confirmed his hunch: there was what he called an "intrinsic factor", present in the stomach, that was lacking in people with pernicious anemia.

finally, they had a lead.

in 1920, George Whipple and Frieda Robscheit-Robbins discovered that dogs with anemia improved by ingesting liver. He hypothesized it could help pernicious anemia too.

George Minot and William Murphy verified this theory and set to work on making an extract.

Soon, people with pernicious anemia began drinking liver juice in huge quantities. And it worked. It *DID* treat the disease.

In 1928, Edward Cohn created an extract that removed most irrelevant compounds but kept whatever it was that cured the disease. Finally a practical cure.

By the way, Murphy, Minot, and Whipple shared the Nobel Prize in 1934 for discovering the cure. Robscheit-Robbins of course got Rosalind Franklin'd. Whipple decided to share his third of the prize money with her.

But they still had no idea what the relevant chemical actually was. And nobody knew what "intrinsic factor" was either, or why someone would lack it.

Mary Shaw Shorb received her immunology degree in 1933, with her doctoral dissertation being a new antigen for pneumonia.

Life went downhill from there; with the Depression in full swing, she was a social worker for a few years. World War 2, however, brought new opportunities.

She got a job as a low-level technician for the Department of Agriculture, thanks to the jobs opened up by soldiers leaving for the front lines.

It was mostly grunt work: her job was to culture Lactobacillus lactis Dornier (LLD), used for yogurt.

Everyone there knew that of course you had to add liver extract to make LLD grow. That's just how it worked. But nobody knew why. She tried to look into it, but it was hard as a low-level tech, and she was bumped from the job by returning soldiers in 1946.

She managed to get a small lab at a university, but had no real funding.

In a chance meeting, she met Karl Folkers, a Merck pernicious anemia researcher, and convinced him to fund her wild idea for a bioassay for the substance, whatever it was, that treated pernicious anemia.

It worked.

Within 3 months, the substance now known as vitamin B12 had been isolated and crystallized by Merck's researchers. Merck gave her a pension for life.

A few years later, in 1956, Dorothy Hodgkin managed to derive the molecular structure for this beast of a molecule using x-ray crystallography. Dorothy managed to not get snubbed, and won the 1964 Nobel Prize for this.

In 1972, after a great deal of work by over 100 people in 19 nations, led by Nobel laureates, a total synthesis for Vitamin B12 was developed. It takes 72 steps and has a yield of 0.01%. It is, of course, completely impractical, but was still an enormous achievement.

Remember that many bacteria can make B12 efficiently.

Humans are low-tier wannabes in the chemical synthesis world!

Anyways there's no real point to this thread other than a) vitamin B12 is awesome and b) god damn look at all those cool science women

/fin

oh right, and to finish the hanging loose thread: "intrinsic factor" turned out to be a protein that is responsible for B12 uptake! en.wikipedia.org/wiki/Intrinsic…

and pernicious anemia? an autoimmune response that results in insufficient Intrinsic Factor and thus low B12 uptake.

uh a small note to add to the end: apparently b12 deficiency is more common than i thought, especially if you take antiacids

one more loose thread: why did liver juice treat pernicious anemia if they lacked Intrinsic Factor to absorb the B12? Apparently if you eat enough, it will absorb through other means, but at very poor rates (<1% of normal) so you need >100x the normal dose orally

hence why B12 supplements are often an enormous % of daily value (and because it’s hard to OD; more than a few ug/day is generally just excreted)