The first clinical pharmacology unit in the world was probably founded in Vienna in 1911

Introduction

The history of clinical pharmacology as a standalone medical field is a topic that comes up rather often at various clinical pharmacology symposia, perhaps because the recent discussion about its future [1,2] needs to be rooted in the past. While clinical pharmacology as a concept, in the guise of material medica, is centuries old [3], the term clinical pharmacology itself is rather young coming with the advent of synthetic and purified drugs at the beginning of the 20^th century. Early partial progress in understanding the mechanisms of action allowed experimental pharmacology to translate its findings into clinical practice. The next leap in the development of clinical pharmacology came with the arrival of new drug groups (e.g. antibiotics, antihypertensives, cytostatics, psychoactive drugs) and the ability to measure drugs concentrations thanks to progress in analytical methods after World War II [4].

In one his papers on this topic, Aronson [3] places the origins of the term clinical pharmacology to 1914 in the English translation of the German textbook by Meyer & Gottlieb [5].

While the boom in clinical pharmacology with many standalone departments came after World War II, the first pioneering clinical pharmacology department applying knowledge gained by experimental pharmacology in clinical practice already existed before World War I. In contrast to departments founded in the second half of the 20^th century which took on the multiple roles of clinical pharmacology as we know it today (pharmacokinetics, clinical trials and drug development, pharmacoepidemiology and drug safety, economics, etc.), the original departments were motivated by the sole goal of applying the recent findings of experimental pharmacology in clinical practice, and thus replacing the former purely empiric approach with a more scientific one.

Until recently, we were convinced that the first physician to practice clinical pharmacology by applying knowledge acquired by experimental pharmacology in clinical practice was Professor Dr Emil Starkenstein (1884–1942) [6,7]. As a young associate professor (docent) of pharmacology at the German medical faculty of the German part of Charles University in Prague, at the time of World War I (1914–1918), Starkenstein served as a commander of the Army infectious disease hospital in Radom in Poland (Kommandant des k.u.k. Epidemiespitals in Radom), where he applied his knowledge of anti-inflammatory effects of Atophan (cinchophen) gained from his experimental work [8,9] to treat successfully epidemic typhus, reducing mortality to 2.5% from 16% [10,11]. In a similar fashion, he applied theoretical knowledge of the adsorption effects of carbo animalis in the treatment of dysentery and cholera [9]. On March 16 1918, Starkenstein presented a lecture titled Klinische Pharmakologie – Theorie und Praxis am Krankenbette (Clinical Pharmacology – Theory and practice at the patient's bedside) at a meeting of Austrian army physicians (‘Feldärtzliche Abend’) in Lublin (Poland). In the same year, the full text of the lecture was published in the journal Therapie der Gegenwart [12].

Recently we came across publications by Dr Hans Januschke [13,14] that place the origins of both the term clinical pharmacology and the first pharmacology unit even earlier to 1911.

Methods

We performed a literature search both online (PubMed, Scopus, Springer, Google) and in our archive (including Professor Jezdinský's personal archive and Professor Starkenstein's estate at Charles University in Prague) to identify any publication that would provide information on the early clinical pharmacology unit in Vienna. The search terms used were ‘clinical pharmacology’, ‘klinische pharmakologie’, ‘Meyer’, ‘Pirquet’ and ‘Januschke’.

Results

Publications by Hans Januschke show that after an agreement between the head of the University Department of Pharmacology Professor Hans H. Meyer and the head of the University Paediatrics Clinic Professor Dr C. Frh. v. Pirquet, a standalone Unit of Clinical Pharmacology was founded at this clinic in 1911. Hans Januschke was appointed as its head and in his publication from 1916 [14] he writes (originally in German, translation by authors):

In October 1911, Professor C. Frh. v. Pirquet founded a Clinical Pharmacology Unit at the new Viennese Paediatric Clinic which comprises of a patient ward and a laboratory for experimental pharmacology. The purpose of this unit was to use the knowledge of diseases found in animal experiments in diagnostics and management of human diseases and to base this treatment not only on traditional impressions from practical experience but select and dose therapy under guidance and criticism of physiologic knowledge. So far published research from our Clinical Pharmacology Unit focuses mainly on 1) functional neurological diseases (epilepsy, neurasthenia, hysteria etc.), 2) management of circulatory disorders, 3) suppression of inflammation (common cold and eczema treatment using calcium and analgesics) and 4) bronchial asthma.

The author goes on to state that his knowledge of pharmacology is based mainly on the aforementioned textbook Die experimentelle Pharmakologie als Grundlage der Arzneibehandlung by H. H. Meyer & R. Gottlieb (3^rd edition) from 1914 [15].

Januschke's publication also describes in detail five cases of children and juveniles (10–22 years of age) hospitalized and treated at the Clinical Pharmacology Unit in 1914 and 1915 using the above described application of experimental pharmacology knowledge [14]. This paper also cites a further 17 publications from this unit published between 1912 and 1915. From the publication titled ‘Über Entzündungshemmung’ (On suppression of inflammation) [13] it is clear that Januschke continued his experimental work at the Wiener Kinderklinik in the experimental pharmacology laboratory, which was part of the new Clinical Pharmacology Unit. The literature suggests that Januschke's main interests included treatment of neurologic diseases and bronchial asthma [16]. It is of interest that Professor Starkenstein himself was aware of Januschke's work and cited him in his publication ‘Symptomatische Therapie auf experimentell-therapeutische Grundlage’ (Symptomatic therapy based on experimental foundations) in 1917 [10]. It is our opinion that Starkenstein only became aware of the existence of the Clinical Pharmacology Unit headed by Januschke after forming his own independent concept of Clinical Pharmacology which included approaches studying treatments on large groups including comparison with controls rather than single reports of successful cases.

Discussion

Hans Januschke. Image reproduced from the Picture Archives and Graphics Department of the Austrian National Library, Vienna: 408.740-B with permission

According to Tragl [17], Hans Januschke was born in Troppau (now Opava in the Czech Republic) in 1883 and earned his medical diploma at the Medical Faculty of the University of Vienna where he graduated in 1907. Until 1911, he worked as an assistant professor at the Department of Pharmacology of the University of Vienna and then as a physician at the University Paediatric Clinic in Vienna under the direction of Professor Pirquet. In 1919 he habilitated as an associate professor (Privatdozent) of paediatrics. From his publications from 1926 it is apparent that he held a position at the Pharmacognostic Institute of the Vienna University. From 1938 he took a position as the director of the paediatric hospital Karolinen-Kinderspital in Vienna. The last publication of Januschke from the Clinical Pharmacology unit at the Pirquet's clinic known to us is from the year 1924 [18].

Clemens von Pirquet. Image reproduced from the Picture Archives and Graphics Department of the Austrian National Library, Vienna: 222.062-C with permission

Clemens Peter Freiherr von Pirquet (1874–1929) studied theology in Innsbruck and philosophy in Löwen. After that he studied medicine in Vienna, Königsbeg and in Graz, where he graduated as a medical doctor in 1900. He started working as an assistant physician at the children's hospital St Anna Kinderspital in Vienna. Following his habilitation (Privatdozent) in 1908, he spent a year at the Johns-Hopkins University in Baltimore, USA, where he became a professor of paediatrics. After returning to Europe he worked as a professor of paediatrics at a clinic in Breslau (now Wrocław in Poland). In 1911 he succeeded Professor Theodor Escherich as the head of the Paediatric Clinic of the Vienna University which he led until 1929 when he and his wife Maria Christine committed suicide by potassium cyanide, possibly because of her incurable disease [19]. He is renowned for his work in the field of immunology. Along with Bela Schick he coined the words allergy, allergen and anergy. His idea that tuberculin could cause skin reactions was developed by Mantoux [20].

Hans Horst Meyer. Image reproduced from the Picture Archives and Graphics Department of the Austrian National Library, Vienna: Pf 4747:E(1) with permission

The German pharmacologist Hans Horst Meyer (1853–1939) studied medicine in Königsberg, Leipzig and Berlin, graduating in Königsberg in 1877 [21]. He started working in Strasbourg with Oswald Schmiedeberg, where he habilitated in 1881 after which he moved to Dorpat (now Tartu, Estonia). In 1884 he moved to Marburg where he spent 20 years, twice becoming the dean of the faculty and even the rector of the university. In 1904, he came to Vienna to become the chair of pharmacology, a position which he held until 1924. Meyer was one of the pioneers of modern pharmacology who elucidated the mode of action of tetanus toxin, contributed to understanding the mechanism of action of general anaesthetics and discovered the importance of glucuronic acid for drug metabolism. A number of his collaborators and students went on to become important figures in pharmacology, some even winning a Nobel Prize (Whipple, Heymans, Cori). Together with Rudolf Gottlieb he was the author of a seminal pharmacology textbook ‘Die experimentelle Pharmakologie als Grundlage der Arzneibehandlung’. It seems safe to assume that he was not just the primary author behind the idea of a clinical pharmacology unit but also author of the term ‘clinical pharmacology’ itself. Interestingly, just like Starkenstein, Meyer later also had the experience of applying his knowledge of physiology and pharmacology to the care of the sick and wounded during the First World War [21].

From available sources, we were unable to ascertain the fate of the unit after 1924. Januschke's only two available later publications are from 1926 with his affiliation listed as ‘biologischen Abteilung des pharmakognostischen Institutes der Universität Wien’ (biologic unit of the Pharmacognostic institute of the Vienna University) [22,23]. It is therefore likely that the Clinical Pharmacology Unit ceased to exist with Professor Meyer's resignation as the chair of Pharmacology in 1924 [21]. To our knowledge, none of the departments of clinical pharmacology in Vienna claims continuity with Januschke's Clinical Pharmacology unit at Pirquet's paediatric clinic. It is possible that its existence was forgotten.

While it is true that others had applied experimental knowledge in clinical medicine, for example Sir Robert Christison of the University in Edinburgh [24] half a century earlier, to our knowledge no standalone unit bearing the name of Clinical Pharmacology was founded before 1911.

Conclusion

The aim of this paper is to remember this clinical pharmacology unit, which was possibly the first ever standalone clinical pharmacology unit in the world. Because of the limited knowledge and limited armamentarium with only a few effective drugs available to pharmacology then, it is possible that the concept of the unit was ahead of its time and failed to offer a similar improvement to patient care that modern clinical pharmacology can undoubtedly provide today.

Competing Interests

Both authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years and no other relationships or activities that could appear to have influenced the submitted work.

The authors wish to thank Dr Carole Gedenberg and Professor Simon Maxwell for their valuable input in preparing the manuscript.

Supported by grant CZ.1.07/2.3.00/20.0040