The discovery of vitamin B12 is a compelling story of persistent research, clinical observation, and scientific collaboration spanning decades. It was not a single event but a journey that unfolded in stages, ultimately transforming the fate of patients with a previously incurable condition known as pernicious anemia. This progressive blood disorder, which prevents the body from producing enough healthy red blood cells due to a deficiency in vitamin B12, was once a death sentence. The path to finding its cure, and in doing so isolating the vital cobalamin molecule, is a testament to early 20th-century medicine and chemistry.
The Early Pursuit: Treating Pernicious Anemia
In the early 1920s, Dr. George Hoyt Whipple conducted experiments on dogs rendered anemic. He found that feeding them a liver-rich diet was effective in regenerating red blood cells, providing a critical foundation for human medicine. This led Boston physicians George Richards Minot and William Parry Murphy to apply liver therapy to human patients with pernicious anemia in 1925. Their studies showed that regular doses of liver could control the disease, preventing its fatal outcome. For their work, Whipple, Minot, and Murphy received the Nobel Prize in 1934.
Refining the Treatment and Finding the Missing Link
Liver therapy was effective but demanding for patients. Researchers sought to isolate the active ingredient. In 1928, Edwin Cohn developed a more concentrated liver extract. Around the same time, William Castle proposed that pernicious anemia was caused by a missing substance in the stomach, which he called the "intrinsic factor," necessary for absorbing a dietary component he termed the "extrinsic factor". This advanced the understanding of B12 absorption.
The Breakthrough: Isolation in 1948
The isolation of the extrinsic factor was achieved in 1948 by two groups. A team at Merck, led by Karl Folkers and including Mary Shaw Shorb, used a microbiological assay and isolated red crystals of the active substance. Simultaneously, British researchers at Glaxo Laboratories, led by Baron Alexander Todd and Lester Smith, independently isolated the same compound. This substance was identified as cyanocobalamin and named vitamin B12.
The Elucidation of the Chemical Structure
The exact chemical structure of vitamin B12 was determined in 1956 by British biochemist Dorothy Crowfoot Hodgkin using X-ray crystallography. This complex work earned her the Nobel Prize in Chemistry in 1964 and was vital for the vitamin's mass production.
Discovery Milestones and Contributions
The discovery and characterization of vitamin B12 involved several key milestones and figures:
| Year | Contributor(s) | Discovery/Contribution |
|---|---|---|
| 1920 | George Hoyt Whipple | Demonstrated liver therapy effectiveness in anemic dogs. |
| 1926 | George Minot, William Murphy | Confirmed liver therapy's success in human pernicious anemia patients. |
| 1928 | Edwin Cohn | Prepared a more potent liver extract. |
| 1928 | William Castle | Identified the "intrinsic factor" needed for B12 absorption. |
| 1948 | Karl Folkers (Merck), Mary Shorb, et al. | First isolated and crystallized vitamin B12. |
| 1948 | British researchers (Glaxo) | Independently isolated vitamin B12. |
| 1956 | Dorothy Crowfoot Hodgkin | Determined the complete molecular structure of vitamin B12 using X-ray crystallography. |
Conclusion
In conclusion, when vitamin B12 was first discovered is not a single date but a historical process. Its isolation in 1948 was the result of decades of research driven by the need to treat pernicious anemia. Key contributions included the foundational work on liver therapy, the identification of intrinsic factor, and the chemical elucidation of the molecule. This journey moved medicine from a dietary treatment to understanding the molecular structure, enabling the production of a life-saving therapy.
