Dr. Daniel Whistler and the first description of a vitamin D-deficiency

The term ‘rickets’ first appeared in 1634 when listed as a cause of death in London’s Annual Bill of Mortality.

The first scientific description of a vitamin D-deficiency, namely rickets, was provided in the 17th century by both Dr. Daniel Whistler and Professor Francis Glisson.

It was that English physician Dr. Daniel Whistler described its symptoms in 1645. The publication by Whisker was a concise monograph of only 14 pages and was written when author was 26 years old. It represented the thesis required for his degree of doctor of medicine. His thesis was ‘De morbo perili Anglorum’ - The Children’s disease of the English.

The Latin thesis was read at Leiden on 18th October 1645. The importance of this thesis lies in the fact that it contained the first complete clinical account of rickets. Whistler's book was published a short time after the reading of his thesis in 1645. It was a small quarto volume of some eighteen pages, though when it was reprinted in 1684, it was in octavo.

In his thesis Dr. Whistler proposed a wide range of suggestions for treatment from crow’s or frog’s livers, application of leeches, purgation, poultices of snails and salt placed on the belly, and grease from mainly pork fat, goosegrease and butter to be smeared on the swollen epiphyses.

Dr. Daniel Whistler and the first description of a vitamin D-deficiency

First scientific description of a vitamin D-deficiency by Francis Glisson (1597–1677)

Rickets, a disease of vitamin D deficiency, al-though rare, is still diagnosed in the United States. The discovery of vitamin D began with the recognition of rickets as childhood bone disease by Francis Glisson in 1650.

Born in 1597, Francis was the second son of William Glisson of Rampisham of Dorset. Admitted to Caius College, Cambridge in1617, he took a degree in Arts in 1620, was incorporated MA at Oxford in 1627, and turning to the study of physics, graduated MD from Cambridge in 1634

In 1650, Glisson published in Latin a treatise on rickets titled “DeRachitide.”7,8Glisson’s work remains a classic among medical texts. Glisson’s sound and elegant observation of rickets is based on clinical and postmortem experience.

Glisson’s treatise addresses the clinical features of rickets in a scientific tone, but lapses into medieval mysticism while discussing the etiology of rickets. Glisson ascribed the etiology of rickets to “cold distemper, that is moist and consisting of penury or paucity of and stupefaction of sprits.”

He was the first to appreciate that infantile scurvy was a separate entity, although it might coexist with rickets, whereas the profession generally considered them to be one disease until Barlow’s paper was published 200 years later. Glisson recognized, too, that rickets were neither congenital nor inherited, were not contagious, nor caused by syphilis.

The association between rickets and a lack of sunlight exposure was reported by Sniadecki in 1822.

First scientific description of a vitamin D-deficiency by Francis Glisson (1597–1677)

Sir Edward Mellanby and study of rickets

Rickets in young children, known for centuries as the English disease, was fully described in 1650 by Francis Glisson, Regius Professor of Physic at Cambridge, and also four years earlier in a thesis presented to the University of Leyden by Daniel Whistler, a medical student from Oxford. Whistler published a monograph titled “Inaugural medical disputation on the disease of English children which is popularly termed the rickets.”

Whistler provided a succinct description of the signs and symptoms of rickets in his thesis and used an alternate term called “Paedosteocaces” to describe the clinical symptoms of rickets.

It was in 1919/20 that Sir Edward Mellanby, an English physician, working with dogs raised exclusively indoors (in the absence of sunlight or ultraviolet light), devised a diet that allowed him to unequivocally establish that the bone disease, rickets was caused by a deficiency of a trace component present in the diet.

Vegetable oils such as olive oil, cotton seed oil and linseed oil permitted development of rickets, where as it could be prevented or cured with cod liver oil or egg yolk. Mellanby concluded that a vitamin substance preventing rickets was present in these fats.

In 1921 he wrote, "The action of fats in rickets is due to a vitamin or accessory food factor which they contain, probably identical with the fat-soluble vitamin." Furthermore, he established that cod liver oil was an excellent antirachitic agent.

Mellanby had presumed that calcium and phosphorus were adequate in all of his rachitic diets but it was soon established that all of his diets were relatively deficient in calcium and lacked favorable calcium phosphorus ratios. Mellanby’s work clearly established the role of diet in the cause of rickets.
Sir Edward Mellanby and study of rickets

History of rickets

There is evidence that rickets occurred in Neanderthal man about 50,000 BC.

The name rickets is from the Old English wrickken, to twist. The more technical medical term, rachitis, which comes from Greek, the spine, was suggested by anatomist Francis Glisson. He described detailed clinical features of rickets in 1651.

Some of the important scientific discoveries leading to the understanding of rickets were dependent on the development of an appreciation of the complexity of bone.

At the turn of the industrial revolution, ‘the English disease’, resulting from vitamin D deficiency, spread among city-dwelling poor children and became endemic in cities.

Rickets was a rare disease until many people began to leave farms and migrate to cities during the industrial revolution. The sun didn’t penetrate the pollution as easily, and people stayed indoors most of the day.

It was not until the works of Julius O. Miller and Thomas Barlow that a clear distinction between rickets and infantile scurvy was made clinically.

In 1885, Gustav Pommer wrote the first pathological description of the rachitic skeleton. In 1919 Huldschinsky demonstrated that ultraviolet rays were effective in healing rickets.
History of rickets

Discovery of vitamin D

Vitamin D was discovered in 1922 as a substance in cod liver that cured sick dogs of a bone disorder called rickets. The earliest publication to acknowledge the medicinal use of cod liver oil for treatment of rickets appeared in the German literature in 1824 and is credited to D. Schutte.

Because the substance was proven to be something different than vitamin A which had also been characterized in cod liver oil, and a vitamin B and C had already been claimed, the new substance was called vitamin D.

From irradiation of mixtures of plant sterols, Adolf Windaus and colleagues isolated a material that was active in healing rickets. The structure of the substance was not determined.

The British group led by Askew was successful in isolating and determining the structure of the first vitamin D, vitamin D2 or ergocalciferol from irradiation of plant sterols.

In 1936, Windaus succeeded in identifying the structure of vitamin D3; vitamin D1 had been isolated earlier by Windaus and his colleagues but was later shown to be combination of vitamin D2 and an irradiation side product, lumisterol.

With the discovery of the oil soluble vitamin D the healing power of the sun known since the days of Hippocrates, known as the father of medicine, who live approximately 2300 years ago was finally understood.

Some doctors started to utilize the sun for the treatment of difficult skin related illnesses, but with the development of a modern pharmaceuticals industry in the 1950s after World War II such treatments were gradually stopped.

The addition of vitamin D to milk in the 1930’s essentially eradicated rickets in Europe and America.

In the 1980s, the effect of active vitamin D on inducing cell differentiation was discovered, suggesting that vitamin D not only modulates minerals homeostatic, but also regulates various cell functions.
Discovery of vitamin D

The Disease of Rickets

The rickets were first know in the West of England, in the counties of Dorset and Somerset.

The rickets appeared first about the year 1620 an afterwards travel into all parts of England. It is an old disease that became epidemic after 1650 when soft coal was introduced as a fuel source.

The origin of the term is uncertain. Suggestion have included English racket – short of breath, and rucken – to rock or reel.

The term ‘rickety’ came to mean ‘shaky or tottering’ because the person so afflicted were impaired in posture and gait.

Rickets might be an Anglicized corruption of the Greek rhachitis, or it might have originated in the Old English ‘wricken’, ‘to twist’.

Whatever origin, the word ‘rickets’; first appears in a Bill of Mortality for 1634 as accounting for fourteen death, the number from that cause increasing year by year until 1659 when surprising figure of 476 out of less than 15,000 burials or 3% of total deaths is recorded.

The first full description of the disease was written in the seventeenth century by the English physician Glisson.

While rickets has a distinguished antiquity, historically, it came to medical attention particularly in the seventeenth and eighteenth centuries in Europe, not appearing in the U.S.A until the latter part of the nineteenth century.

In 1822, a Polish physician observed that children in Warsaw suffered severely from rickets, yet rickets was unheard outside of the city, he concluded that sunbathing was the cure for rickets.

Huldschinsky, in 1919, was the first to prove that exposure of the skin to ultraviolet radiation could cure rickets.

Within two years, Hess and Unger reported that exposure of several rachitic children to sunlight was adequate for curing this bone deforming disease.

Rickets has been recognized in nonhuman primates since ancient times. Rickets have also been found among the skeletons of captive baboon from the dynastic tombs of ancient Egypt.

Perhaps some of the earliest evidence of rickets is to be found in ancient Egyptian wall illustrations, where bow legged individuals are represented.

Some medical authorities have suggested that people described as ‘crook backed’ in the bible had a spinal curvature caused by rickets.

About 130 CE, the noted physician Soranus of Ephesus referred to a disease that caused ‘backbone bending’ and twisted thighs.
The Disease of Rickets