JLW Thudichum: neglected “Father of neurochemistry”

JMS Pearce
Hull, England, United Kingdom

 

Johann Ludwig Wilhelm Thudichum photo
Fig 1. Johann Ludwig Wilhelm Thudichum. Photo. National Library of Medicine. Public domain.

Knowledge of diseases of the nervous system reflects an understanding of the basic sciences of neural mechanisms and organization. In the last decade of the nineteenth century, the Nobel prizewinners Camillo Golgi and Santiago Ramón y Cajal founded the neuron doctrine, and Charles Scott Sherrington explained the propagation of the nerve impulse through synapses. Lord Adrian later recorded the electrical discharges in neurons and in single nerve fibers, and he founded the basis for neural transmission elaborated by the 1963 Nobel laureates Sir Andrew Huxley, Sir Alan Hodgkin, and Sir John Eccles.

In two historical papers of notable scholarship, Spillane highlighted in the decade 1874-84 the discoveries of three British physicians of fundamental importance in the history of neurology.1 These pioneers were David Ferrier, Richard Caton, and J.L.W. Thudichum. The fame of the latter two was posthumous. Of equal importance to these outstanding anatomical and physiological investigations was the novel idea of chemical transmission of the nervous impulse. It was here that the controversial investigations of Thudichum played such an important and original role. But when Thudichum died, the British Medical Journal commented, “If his life-long labours in physiological chemistry do not appear to have borne adequate fruit, the subject when he took it up was almost untouched…”

Over twenty years, aside from his clinical practice, Thudichum investigated the chemistry of human and animal brains and amassed a fund of new discoveries.3,7 They extended conventional organic chemistry into a new discipline of physiological chemistry. Thudichum has been described as the “Father of neurochemistry”. In addition, he made pioneering contributions to chemical pathology, surgery, war medicine, and public health.

 

Ludwig Thudichum MD., FRCP.

Johann Ludwig Wilhelm Thudichum (1809-1901) (Fig 1) was born in the German town of Budingen, the eldest son of Georg Thudichum, a Minister of the Reformed Church. He graduated MD at the nearby University of Giessen in 1851.2 He was trained and much influenced by the chemist von Liebig, who from the 1830s was a pioneer in teaching laboratory investigations, and attracted workers from all over Europe.3,4 In 1853 Thudichum failed to obtain the post in pathology at Giessen and came to London (bringing with him a combustion furnace, a present from von Liebig). He married distant cousin Charlotte Dupré in London and became a naturalized British citizen in 1859. He obtained the English diploma MRCS in 1854, MRCP in 1860 and was elected FRCP in 1878. He was appointed professor of chemistry at St. Georges’ hospital in Grosvenor Place in 1855.

He had an extraordinarily original, fertile mind and wrote several books, among which were treatises on the urine,5 on gallstones,6 on diseases of the nose, and public health.7 In his few hours of leisure he published books on The Spirit of Cookery (1895) and with August Dupré A treatise on the origin, nature and varieties of wine (1872). He engaged in clinical practice and from 1865 to 1871 and was lecturer and director of pathological and physiological chemistry in the new laboratories of St. Thomas’s Hospital Medical School. He isolated urochrome pigment in the urine, which in 1864 won him the Hastings Gold Medal of the British Medical Association. Five years later he wrote a classic paper on luteines— pigments now known as carotenoids— obtained from the corpora lutea, which he subsequently isolated from many animals and plants.

His studies of physiological chemistry attracted the attention of Sir John Simon, principal medical officer to the Privy Council, who in 1864 engaged him to undertake researches into parasites of meat sold in the markets. He went on to laboriously characterize and purify 140 distinct chemicals from bovine and human brains.8 Thudichum’s two volumes of Annals of Chemical Medicine, including the application of chemistry to physiology, pathology, therapeutics, pharmacy, toxicology and hygiene (1879, 1881) were annotated summaries of the topics including his own researches. His classic work9 A Treatise on the Chemical Constitution of the Brain (1884) described how he discovered and named phospholipids, cephalin, and sphingomyelin. This led to the identity of several sphingolipidoses, such as Tay-Sachs disease.

When Thudichum started his researches, Liebreich, a German pharmacologist, thought that the brain consisted of one single chemical substance, protagon. During years of meticulous spectroscopic analyses Thudichum showed protagon was a mixture of lipids in the brain: sphingomyelin, sulphatides, galactocerebrosides, ethanolamine, lecithins, and cephalins. He correctly classified the cephalins as phosphatides.

He was criticized for working in relative isolation, training no successors, and for involvement in academic polemics.3 The large number of novel chemicals that he identified provoked much splenetic criticism. A notorious review by Professor Gamgee in 1877 stated that “Dr. Thudichum’s paper bristles with new names for old facts, and with the names of numberless new substances which the author discovered at each step of every investigation . . . every analysis furnishes the material for a new formula, and every formula the excuse for a new name,” and that science had gained little or nothing from these researches.

Perhaps disheartened, he then concentrated on otorhinolaryngology; he invented a nasal speculum still referred to as Thudichum’s speculum. During the Franco-Prussian War, with Simon he raised money to establish a military hospital in 1870 at Bingen, Germany, which treated injured soldiers of both sides.

His discoveries and classification of these new brain chemicals were acknowledged belatedly as major achievements.3,7 He noted how they were distributed in the grey and white matter but made no systematic attempt to relate his findings to disease processes. Nevertheless, he did say “I believe that the great diseases of the brain and spine, such as general paralysis, acute and chronic mania, melancholy and others, will be shown to be connected with specific chemical changes in neuroplasm…in short it is probable that by the aid of chemistry many derangements of the brain and mind which are at present obscure, will become accurately definable.”

Otto Rosenheim, a chemical physiologist at King’s College, while investigating the history of protagon in 1907, was impressed by Thudichum’s work and posthumously bolstered his recognition. In 1931, mainly through Rosenheim’s efforts, a Civil List pension was procured for Thudichum’s daughters. The University of Giessen ceremonially renewed his diploma fifty years after his graduation. A fortnight later, he died of a cerebral hemorrhage. His ashes were buried at Highgate Cemetery and at his request his papers were burnt.

The Thudichum Lectures and Medal began in 1974 under the patronage of the Biochemical Society. The eminent lecturers have included Professors Blashko, Henry McIlwain, Dr. Marthe Vogt, Sir Hans Kosterlitz, Dr. Victor P. Whittaker, Professor R. Levi-Montalcini and Dr. Julius Axelrod.

 

References

  1. Spillane JD. A Memorable Decade in the History of Neurology 1874-84-I. British Medical Journal 1974;4:701-706.
  2. Kosterlitz H. J. L. W. Thudichum. Nature 1959;183:568.
  3. Mcilwain H. Thudichum and the Medical Chemistry of the 1860s to 1880s. Proc Royal Society of Medicine 1957;51:127-132.
  4. Sourkes T L. The life and work of J.L.W. Thudichum, 1829-1901: “… a most celebrated exponent of the art of medicine and chemistry.” Montreal : Osler Library, McGill University, 2003.
  5. Thudichum, JLW. A treatise on the pathology of the urine: including a complete guide to its analysis. London: John Churchill, 1858.
  6. Thudichum, JLW. A treatise on gallstones: their chemistry, pathology, and treatment. John Churchill and Sons, 1863.
  7. Drabkin DL. Thudichum: Chemist of the Brain. Philadelphia: University of Pennsylvania Press, 1958.
  8. Thudichum JLW. A manual of chemical physiology: including its points of contact with pathology. London: Longman, Green, Reader & Dyer, 1872.
  9. Thudichum JLW. A treatise on the chemical constitution of the brain: based throughout upon original researches. London: Baillière, Tindall and Cox, 1884.

 


 

JMS PEARCE is a retired neurologist and author with a particular interest in the history of science and medicine.

 

Winter 2022 | Sections | Neurology