People say a vegetarian diet has no B12—so how was that experiment done?
In the 1920s, American biologist George Whipple found that feeding dogs large amounts of liver could cure anemia caused by blood loss, and he guessed that humans eating liver might treat pernicious anemia. Experiments proved them right. In 1934, Whipple, along with two collaborators, William Murphy and George Minot, won the Nobel Prize for discovering a treatment for pernicious anemia. But it wasn't clear what the substance in liver actually was. Later, Edwin Cohn prepared a liver extract that was 50 to 100 times more potent than natural liver products for treating pernicious anemia.
Even without knowing what the therapeutic substance was, that didn't stop people from using liver as medicine, and there was huge market demand for liver. This led pharmaceutical companies to try to isolate the bioactive component in liver that treated pernicious anemia. In 1944, Mary Shorb joined the Dairy Industry Bureau of the US Department of Agriculture and studied Lactobacillus lactis Dorner (LLD). This strain is used to make yogurt and dairy products. Culturing it required adding tomato juice and liver extract to the medium, and Mary figured she could use the strain to assay the active substance in liver (the motivation was that her father had pernicious anemia). In 1947, Mary left the Department of Agriculture for the University of Maryland and worked with Merck to develop the LLD assay to detect the active substance in liver, and in 1948 they isolated and purified the substance, naming it vitamin B12. In 1955, biochemist Alexander R. Todd worked out the chemical structure of vitamin B12. He won the Nobel Prize in Chemistry in 1957 for his research on nucleotides and nucleotide coenzymes.
In 1954, Gregory at the British National Institute for Research in Dairying used microorganisms to measure the vitamin B12 content of milk, because vitamin B12 is essential for the growth of certain bacteria. The strain currently used for microbiological assays is Lactobacillus delbrueckii subsp. lactis ATCC7830. (This was the first detection method.)
After the structure of vitamin B12 was discovered, how to synthesize the substance became the next research direction.
In 1972, Woodward completed the total chemical synthesis of vitamin B12, but the yield was below 0.01%, so chemical synthesis wasn't practical.
Later, scientists found that vitamin B12 can only be synthesized by certain bacteria—after all, its discovery came about because of bacteria. Natural sources of vitamin B12 are bacteria and some archaea from the natural world, including: Propionibacterium shermanii, Pseudomonas denitrificans, Streptomyces griseus, Acetobacter, Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Bacillus, Clostridium, Corynebacterium, Flavobacterium, Lactobacillus, Micromonospora, Mycobacterium, Nocardia, Proteus, Rhizobium, Salmonella, Serratia, Streptococcus, and Xanthomonas.
Current industrial production of vitamin B12 uses bacterial fermentation.
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