Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era

John Dalton’s atomic theory and drugs in psychiatry in the 19th century

 (Educational Series 2. Bulletin 4. Chapter 1)



The story that led to the birth of neuropsychopharmacology in the mid-20th- century begins in 1808 with John Dalton’s (1766–1844) postulation that the elementary units of all matter in the universe are indivisible and indestructible atoms (Dalton 1808; Encyclopedia Britannica 1969). Dalton’s “atomic theory” was published in Part 1 of his treatise entitled “New System of Chemical Philosophy” and its impact profoundly affected scientific development in general (Smith 1856). Within the context of our story, it opened the path for synthesizing drugs with different effects, including substances with an effect on behavior and/or mental activity

Instrumental to further development was the research of an 18-year-old English chemist named William Henry Perkins (1838-1907). He was trying to synthesize quinine and ended up with a bluish substance that he extracted from a “black mess” in his test tube, with excellent dying properties. Perkins’ discovery of the first artificial dye in history, variably referred to as aniline purple, tyrian blue or mauve, triggered a chain of events (Golin 1955). Modifications of his process led to the development of many dyes and the emergence of the dye industry in the middle of the 19th century, e.g., Bayer and Ciba in 1859 and Geigy and Sandoz in 1862 (Menzie 1983). 

Recognition that a more complete exploitation of Perkins’ findings would require a new breed of organic chemists gave a strong impetus for the development of organic chemistry (Russell 1871). This, in turn, lead to the synthesis of a rapidly growing number of organic compounds and during the second half of the 19th century many of the dye companies, e.g., Ciba in 1890, Bayer in 1896, extended their activities to the development of drugs. With this development, a new industry, the pharmaceutical industry, was born (Healy 1997).

The rapidly growing pharmaceutical industry during the second half of the 19th century was instrumental to the introduction of several centrally acting drugs. By the end of the 1890s subcutaneously administered morphine (Wood 1855), along with apomorphine and hyoscine (scopolamine) were extensively used in the control of excitement, agitation and aggression; potassium bromide (Lockock 1857), for relieving restlessness, anxiety and tension; and chloral hydrate (Liebreich 1869) and paraldehyde (Cervello 1882) served for calming and inducing sleep.   The judicious use of this first set of drugs in psychiatry provided day- and night-time sedation and allowed the replacement of physical restraint by pharmacological means (Ban 2001; Lehmann and Ban 1970). It was during this period -- between 1850 and 1900 -- that academic psychiatry was born with more than 20 academic departments established in German-speaking universities alone (Shorter 1997).

It was also during this period that lithium was introduced into psychiatry (Ban 2006).

During the second part of the 19th century many physicians believed in a uric acid “diathesis,” a predisposition for the accumulation of urea in the body (Garrod 1859; Johnson 1984) that could cause a variety of disorders from gout and rheumatism to cardiac disease and mental illness (Healy 2002). Since acute symptoms of gout develop suddenly and persist untreated for days or weeks before they remit, William Hammond, at the Bellevue Hospital in New York (USA), had assumed that episodic mood disorders might be a form of cerebral gout and employed lithium successfully in their treatment (Hammond 1871; Yeragani and Gershon 1986). On the basis of the same assumption Carl Lange, a Danish neurologist, treated hundreds of patients with lithium and, in 1886, reported on its prophylactic effect in periodic mood disorders (Lange 1886).  Yet, without the availability of the necessary technology for monitoring blood levels, lithium was too toxic a substance to be clinically employed (Ban 2006).




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Encyclopedia Britannica Volume 5. Chemistry. Chicago/ London/ Toronto/ Geneva/ Sydney/Tokyo/Manila: William Benton Publisher; 1969.


Garrod AB. Gout and Rheumatic Gout. London: Walton and Maberly; 1859.


Golin M. Serendipity – big word in medical progress. Does “pure lack” deserve all the credit? JAMA. 1957; 165: 2084-7.


Hammond WA. A Treatise on Diseases of the Nervous System. New York: Appleton; 1871.


Healy D. The Antidepressant Era. Cambridge; Oxford University Press:  1997.


Healy D. The Creation of Psychopharmacology. Cambridge: Harvard University Press; 2002.


Johnson FN. The History of Lithium. Basingstoke: MacMillan Press; 1984.


Lange C. Om periodiske Depressionstilstande og deres Patagonese. Copenhagen; Jacob Lunds Forlag; 1886.


Lehmann HE, Ban TA. Pharmacotherapy of Tension and Anxiety. Springfield; Charles C. Thomas Publisher; 1970.


Liebreich MEP. Das Chloral hydrate, ein neues Hypnoticum und Anaestheticum, und dessen Anwendung in die Medizin. Eine Arzneimeittel –Untersuchung. Berlin: Müller; 1869.


Lockock, C. Comment in discussion of Edward H. Sieveking. Analysis of fifty-two cases          of epilepsy. Lancet 1857; 2, 136-8.


Menzie E. Geschichte der Chemische Industrie in Basel. Zeitschrift für die Chemische Industrie 1983; 5: 15-30.


Russell CA. The History of Valency. Oxford: University Press: 1871.


Shorter E. A History of Psychiatry. New York: John Wiley & Sons, Inc.; 1997.


Smith RA. Memoir of John Dalton and the history of atomic theory. London: Bailliere; 1856.

Wood A. A new method of treating neuralgia by the direct application of opiates to the painful points, Edinb Med and Surg J 1855; 82: 265 - 81.


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February 8, 2018