The ideas and concepts of the ancients, through to the anatomists and physiologists of the 17th. and 18th. centuries which provided the foundations for man's motives in understanding the metabolism of nervous systems, and the more biochemical approaches in the 19th. century, have been detailed in the Donald Tower's most enjoyable and scholarly historical articles (Tower, 1958, 1981). Indeed for anyone interested in the development of the subject, these are highly recommended.

The 1981 article appeared originally as the Introductory Chapter to the 3rd edition of a textbook (Basic Neurochemistry), sponsored by the American Society for Neurochemistry (A.S.N.), but unfortunately space forbade its inclusion in subsequent editions. As Tower points out, the first chemical analysis of the brain can probably be attributed to J.T. Hensing, who isolated phosphorus. His book on "The Chemical Analysis of the Brain" published in Giessen in 1719 was translated into English by Tower in 1983 . Although Thudichum is often regarded as the "father of Neurochemistry", the term "Nervenchemie" had been coined by Schlossenberger in the 1850s, well before Thudichum's treatise appeared in 1884 . Neurochemistry, such as it was then in the latter half of the 19th. century, tended to be dominated by organic chemists - analytical chemists like Thudichum seemed antagonistic to the contributions of physiological chemists such as Schlossenberger . The dominance then of organic chemistry over physiological chemistry (which quickly became synonymous with biochemistry) meant that the biological orientation which could have stimulated neurochemistry was essentially ignored. In some countries the rapid development of biochemistry in the first decades of this century led to an integration of neurochemistry with biochemistry. In others it remained constrained by organic chemists (see McIlwain, 1990, 1991).

J. Folch-Pi
J. Folch-Pi

H. McIlwain

H. McIlwain

Around the turn of the century, Garrod had suggested that certain diseases could be caused by inherited disorders of specific metabolic processes, and in the 1930s Folling demonstrated that phenylketonuria, a disease with severe effects on the newborn brain, was an example of Garrod's principle. In the 1920s and 1930s people were bravely pioneering the investigation of the biochemistry of the nervous system : Gerard, Himwich, Page and Sperry in the U.S.A., Dale, Peters, Quastel and Thompson in the U.K., Klenk and Winterstein in Germany and Palladin in the then U.S.S.R. Indeed neurochemical research was often at the forefront of the biochemistry of the 1920s to 1950s, especially with increasing insight into metabolism and metabolic regulation, and was stimulated by the writings of pioneers such as Winterstein (1929), Page (1937), Richter (1944), Himwich (1951) and Peters (1952).

McIlwain regarded 1955 as the coming of age of neurochemistry - that year saw publication of the book which resulted from the first International Neurochemical Symposium (Table 1), the publication of a collation of 32 neurochemical contributions (Elliott et al., 1955), the publication of the first specifically neurochemical textbook (McIlwain, 1955) and the gathering of the manuscripts for the ensuing first issue of the Journal of Neurochemistry.

In the years immediately after the second world war, almost 50% of hospital beds in developed countries were occupied by mental patients, and were seen to be increasing. This was clearly due to improvements in treatment of physical ailments (antibiotics, immunisation and surgery) rather than treatment of psychiatric disorders which remained intractable. Much of the impetus for the growing interest in neurochemistry stemmed from the realization that many neurological and especially psychiatric disorders may be largely "organic" in origin, and therefore likely to have a biochemical basis. Neurochemistry was relatively unfashionable in those days, mainly because the prevailing opinion was that the brain was far too complex for its chemistry to be studied effectively. However some of the early symposia of Table 1 focussed on deranged metabolism and were sponsored or generated by bodies such as the Mental Health Research Fund (M.H.R.F.) of the U.K. Concern over the high incidence of recognised mental diseases had resulted in the foundation of the M.H.R.F. in London as early as 1949; its Honorary Secretary was a neurochemist, Derek Richter. Some of the key early investigations of human brain metabolism were initiated by psychiatrists in the U.S.A., epitomised by the pioneering studies of Kety and his colleagues in the late 1940s. The key seminal and specifically neurochemical conference held in 1965 in Oxford (Table 1) was held under the auspices of the Commission of Neurochemistry of the World Federation of Neurology (W.F.N.).

First International Neurochemistry Meeting - Oxford
First International Neurochemistry Meeting - Oxford

The second World War had stimulated a massive acceleration of scientific research and many historians have argued that the outcome of that war was directly correlated with the quality of the scientific and technological developments. Accordingly there was a rapid expansion of all of the sciences in the post-war era, which included a major impetus to the development of neurochemical research. (It is a sad reflection on human affairs that it takes the bestiality of war to provide the impetus and resources for basic scientific research!). Neurochemistry benefitted, as did biochemistry in general, from the availability of new techniques and instruments. Indeed, Tower (1981) is of the opinion that it was essentially the availability of the new techniques which enabled neurochemistry to emerge as a distinct discipline. Many of our younger colleagues may not realise that chemicals such as ATP and NAD+, and all enzymes, had to be isolated and purified manually in the laboratory (none were commercially available then) and that acetyl CoA had not yet been characterised, being then identified as "active C-2 unit" or "active acetate". Techniques such as electrophoresis, ultracentrifugation, chromatography and radiochemistry were under development ; radioimmune assays and "molecular biological" techniques had not even been envisaged.

 D. Tower

D. Tower