Discover how a common child bone deformity led scientists to uncover a hormonal powerhouse that continues to surprise researchers today.
Imagine a world where a mysterious disease causes bone deformities in children, leaving them with bowed legs and painful movements. For centuries, rickets plagued industrial cities during the 19th century, earning the nickname "the English disease" for its prevalence in darkened urban centers. This childhood affliction would eventually lead scientists on a journey to discover what we now call vitamin D—a substance that technically isn't a vitamin at all, but a powerful steroid hormone essential to human health.
Vitamin D is technically not a vitamin but a hormone, as it can be synthesized by the body when skin is exposed to sunlight.
The history of vitamin D begins with the detailed documentation of rickets. In 1645, Daniel Whistler provided one of the first clear descriptions of rickets in the Netherlands, followed closely by Francis Glisson's comprehensive 1650 treatise "De Rachitide" featuring lithographs of children with classic skeletal deformities 2 .
The Industrial Revolution dramatically increased rickets cases as people moved into smoke-filled cities where sunlight rarely reached the ground.
The Dickensian character Tiny Tim likely represented a child with rickets, a common sight in 19th century cities 2 .
For nearly 300 years, the cause remained mysterious. The scientific community divided into two camps—one believing rickets was nutritional, the other convinced it was environmental. The environmental theory gained support from observations like those of Sniadecki in Poland, who noted differential incidence between city-dwellers and rural-dwellers, suggesting sunlight exposure played a role 2 .
The early 20th century witnessed a dramatic resolution to the rickets mystery through two parallel discoveries:
Sir Edward Mellanby in Great Britain deliberately fed dogs a diet similar to that consumed by Scottish people (primarily oatmeal) while keeping them indoors. The dogs developed rickets, which Mellanby could cure with cod liver oil 8 .
The critical clarification came from Elmer McCollum at Johns Hopkins University, who bubbled oxygen through cod liver oil to destroy vitamin A. This modified preparation still cured rickets, proving that a separate substance—which he called "vitamin D"—was responsible 8 . This discovery in 1922 ushered in the era of vitamin D, the fourth vitamin to be identified 4 .
Meanwhile, physicians across Europe made a separate crucial discovery. Huldshinsky in Vienna and Chick in England found that children with rickets could be cured by exposing them to sunlight or artificially produced UV light 2 8 .
This seemingly magical cure demonstrated that something in sunlight could prevent and reverse the disease.
How could both cod liver oil and sunlight cure the same disease?
The connection between these two pathways was established through the brilliant work of Professor Harry Steenbock at the University of Wisconsin. Having noticed that goats kept outdoors in summer showed positive calcium balance while indoor winter-housed goats did not, Steenbock made a mental connection between sunlight and calcium retention 8 .
Steenbock discovered that irradiation of both animals and their food could prevent or cure rickets. He correctly concluded that an inactive lipid present in both skin and food could be converted by UV light into an active anti-rachitic substance 8 . This explained the mysterious connection between sunlight and diet—both could generate the same biological activity through UV exposure.
| Scientist | Year | Contribution |
|---|---|---|
| Daniel Whistler | 1645 | Early description of rickets |
| Francis Glisson | 1650 | Comprehensive treatise on rickets |
| Theobald Palm | 1890 | Documented geographical patterns of rickets |
| Edward Mellanby | 1919-1922 | Produced rickets in dogs, cured with cod liver oil |
| Huldshinsky & Chick | 1919 | Cured rickets with UV light |
| Elmer McCollum | 1922 | Identified vitamin D as distinct from vitamin A |
| Harry Steenbock | 1924 | Demonstrated UV irradiation creates vitamin D |
Following these physiological discoveries, the race was on to identify the chemical structure of vitamin D. In 1932, Askew and colleagues successfully isolated vitamin D2 (ergocalciferol) from irradiated ergosterol 8 . Windaus and Bock identified vitamin D3 (cholecalciferol) in 1937 as the natural form produced in skin 8 .
The chemical pathway was finally illuminated: 7-dehydrocholesterol present in skin converts to pre-vitamin D3 when exposed to UVB light, which then isomerizes to vitamin D3 8 .
This process was conclusively proven in 1978 when Esvelt and colleagues isolated and identified vitamin D3 from human skin using mass spectrometry 8 .
| Form of Vitamin D | Chemical Name | Origin |
|---|---|---|
| Vitamin D1 | Molecular compound of ergocalciferol with lumisterol | Historical artifact |
| Vitamin D2 | Ergocalciferol | Plants/irradiated fungi |
| Vitamin D3 | Cholecalciferol | Animal sources/skin synthesis |
| Vitamin D4 | 22-dihydroergocalciferol | Synthetic analog |
| Vitamin D5 | Sitocalciferol | Synthetic analog |
What makes vitamin D unusual among vitamins is that it's not technically a vitamin—a term defined as a trace dietary constituent required for normal physiological function that must be supplied regularly in the diet 1 . Vitamin D becomes a true vitamin only when sunlight exposure is insufficient 1 .
Vitamin D is technically a hormone, not a vitamin, as it can be synthesized by the body and functions as a steroid hormone.
In reality, vitamin D functions as a steroid hormone. The discovery of its metabolic activation pathway in the late 1960s revealed that vitamin D itself is biologically inert 1 . It requires conversion to an active hormone:
Vitamin D3 converts to 25-hydroxyvitamin D3 [25(OH)D3] in the liver
25(OH)D3 converts to 1α,25-dihydroxy-vitamin D3 [1α,25(OH)2D3] in the kidneys 1
This active metabolite, calcitriol, functions as a steroid hormone by binding to vitamin D receptors (VDR) located in the nuclei of target cells throughout the body, regulating gene expression in everything from bone cells to immune cells 5 .
| Compound | Formation Site | Biological Activity | Half-Life |
|---|---|---|---|
| Vitamin D3 (Cholecalciferol) | Skin from 7-dehydrocholesterol via UVB | Biologically inert | ~1 day |
| 25(OH)D3 (Calcidiol) | Liver | Partial activity | 10-20 days |
| 1,25(OH)2D3 (Calcitriol) | Kidneys, various tissues | Fully active steroid hormone | 4-6 hours |
Our understanding of vitamin D has depended on several crucial research tools:
Mercury arc lamps and other UV sources enabled early researchers to demonstrate the photochemical production of vitamin D 2
Essential for separating and identifying the various forms of vitamin D, leading to the structural elucidation of vitamins D2 and D3 8
Critical for conclusively proving the synthesis of vitamin D3 in human skin by identifying the molecular structure 8
The initial focus on vitamin D as a bone-building nutrient has expanded dramatically. We now recognize that vitamin D receptors exist in nearly every tissue in the body, suggesting roles far beyond skeletal health 4 . The active hormone influences immune function, cell growth, neuromuscular activity, and inflammation 5 .
The active vitamin D hormone is now known to influence:
What began as a quest to understand a childhood bone disease has revealed a complex hormonal system that continues to surprise and challenge researchers.
The story of vitamin D exemplifies how scientific understanding evolves—from initial observations of disease patterns to molecular understanding of hormonal action, with each discovery raising new questions about this "sunshine hormone" that continues to fascinate scientists nearly a century after its discovery.
The history of vitamin D reminds us that sometimes what we call something—in this case, a "vitamin"—may reflect historical accident rather than biological reality, and that scientific progress often depends on connecting seemingly unrelated observations into a coherent picture of how our bodies interact with our environment.