The Initial Breakthroughs and the Nobel Prize
The story of vitamin B12's discovery is inextricably linked to the search for a treatment for pernicious anemia, a deadly blood disorder. While physicians had observed the disease for decades, its underlying cause was a mystery. The first major step forward was taken by Dr. George Whipple in the 1920s, who discovered that a liver-rich diet helped dogs recover from anemia due to blood loss. This observation laid the groundwork for human clinical trials.
The Liver Therapy Revolution
Building on Whipple's work, Dr. George Minot and Dr. William Murphy at Boston's Peter Bent Brigham Hospital began a series of carefully designed clinical studies with human patients in 1926. They instructed patients with pernicious anemia to consume large amounts of raw liver daily. The results were astounding; patients showed rapid symptomatic improvement and a significant increase in their red blood cell count. For their groundbreaking work, Whipple, Minot, and Murphy were jointly awarded the Nobel Prize in Physiology or Medicine in 1934.
The Intrinsic Factor
Despite the success of liver therapy, the exact mechanism and component responsible remained unknown. In 1928, American physician William Castle conducted further research and discovered that a substance produced in the stomach, which he called "intrinsic factor," was necessary for the absorption of the anemia-curing substance, or "extrinsic factor," from the diet. This explained why patients with pernicious anemia, who lacked this intrinsic factor, could not properly absorb the nutrient.
The Isolation of Vitamin B12 in 1948
The search for the precise chemical compound continued for decades. It was a race led by chemists and pharmaceutical companies around the world. The final breakthrough came through a serendipitous collaboration.
- The Microbiological Assay: A key advancement was made by microbiologist Mary Shaw Shorb. She discovered that a specific bacterium, Lactobacillus lactis Dorner, required a certain factor from liver extracts to grow. This provided a crucial biological assay that replaced slow, difficult human trials.
- The Merck Collaboration: Shorb collaborated with Merck & Co. chemist Karl Folkers, using her bacterial assay to track the purification of the active substance from liver extracts. Folkers' team observed that the most potent fractions were a distinctive red color.
- Isolation and Crystallization: In 1948, Folkers and his team successfully isolated tiny, bright red crystals of the active compound and named it vitamin B12 (cobalamin). A year later, it was successfully tested on a patient with pernicious anemia, confirming its therapeutic effect.
The Chemical Structure
The story doesn't end with isolation. Determining the complex chemical structure of vitamin B12 was another scientific feat. This monumental task was accomplished by British biochemist and X-ray crystallographer Dorothy Crowfoot Hodgkin, along with her research team. Using X-ray crystallography, she successfully determined the full structure of the vitamin in the mid-1950s (published in 1955 and 1956) and was later awarded the Nobel Prize in Chemistry in 1964 for her efforts.
Comparison of Early Therapy vs. Modern Treatment
| Feature | Early Liver Therapy (1926-1940s) | Modern Vitamin B12 Treatment (Post-1948) |
|---|---|---|
| Substance Used | Large quantities of raw or concentrated liver extract | Purified cyanocobalamin (Vitamin B12) |
| Administration | Oral consumption (daily dose) or early, crude injections | Oral supplements, injections (IM), nasal gels, sublingual tabs |
| Potency | Variable; dependent on quality of liver extract | Consistent and highly potent |
| Patient Experience | Unpleasant, requiring consumption of half a pound of liver daily | Convenient, well-tolerated, simple dosing |
| Understanding of Cause | Based on observational study (liver factor) | Precise knowledge of the required nutrient (cobalamin) |
| Mechanism | Unknown at first; later linked to intrinsic factor | Absorption dependent on intrinsic factor binding to B12 |
The Lasting Legacy of the Discovery
The discovery of vitamin B12 had a profound impact on medicine and human health. Not only did it turn a previously fatal disease into a manageable condition, but it also spurred new research into the function of vitamins and their role in overall health. Today, synthetic vitamin B12 is produced via bacterial fermentation, providing a reliable and accessible treatment for deficiency and pernicious anemia globally. The story serves as a testament to the cumulative nature of scientific progress, with multiple researchers and discoveries spanning decades contributing to the final outcome.
For more detailed information on the biochemical processes involving vitamin B12, consult resources from the National Institutes of Health.
Conclusion: A Collaborative Quest
The question of when was vitamin B12 discovered does not have a single simple answer. The story is a rich tapestry woven from the threads of multiple scientific breakthroughs. From Whipple, Minot, and Murphy identifying the curative properties of liver, to Castle's discovery of the intrinsic factor, and finally to Shorb and Folkers' successful isolation of the chemical compound in 1948, the journey highlights the collaborative and persistent nature of medical science. The determination of its structure by Dorothy Hodgkin was the crowning achievement, unlocking the final secrets of this vital nutrient.
