department of pharmacology, university college london department of pharmacology, university college london the department of pharmacology at the university college london, the first of its kind in england, was founded in 1905 and remained in existence until 2007. early history ucl pharmacology department door, 22 oct 2002 university college london (ucl) was founded in 1826. it was born in the ferment of radical london in the 1820s and 1830s and was heavily influenced by the scottish and french enlightenments. ucl was part of the radical opposition to the hegemony of oxford and cambridge. in medicine, ucl was a force in combatting the conservative and religious monopoly of the royal colleges of physicians and surgeons although edinburgh university was well ahead at the time, ucl had a professor of materia medica and pharmacy, a.t.thomson, from the start. later this was renamed as the chair of materia medica and therapeutics. its best known holder was sydney ringer (1878–87), who worked on the isolated beating heart and is renowned for his eponymous salt solution which he designed to maximise the viability of isolated hearts. his textbook ‘handbook of therapeutics’ ran for 13 editions between 1869 and 1897. in 1905. pharmacology was established as a distinct discipline within basic medical sciences at ucl. it was the first department of pharmacology in england. most of the people involved in the development of quantitative analysis of drug-receptor interactions worked at some time in ucl's departments of pharmacology, or of physiology or of biophysics. the department of pharmacology arthur robertson cushny frs a.r. cushny arthur cushny (1866–1926) was the first holder of the newly instituted chair of pharmacology, from 1905 until 1918. after graduating in medicine from aberdeen, cushny had studied in berne, würzburg, and strasbourg, where he became assistant to the famed oswald schmiedeberg. in 1893, at the age of 27, he was appointed professor of pharmacology at the university of michigan, ann arbor. eight years later cushny came to the chair at ucl where he soon expanded the department from the single room he had been given. he raised the funds for the building which the remnants of the department still occupies. his main interests were in the heart and kidney. his work on the involvement of calcium in the action of digitalis was prescient. he was interested in optical isomers. data from an early clinical trial using hyoscine isomers was used by william sealy gossett who, under the pseudonym "student" published in 1908 the first small-sample test of significance, student's t test. his use of these data has given rise to much discussion. later reanalysis of the same data by a randomisation tests gave a similar result. cushny published a textbook textbook of pharmacology and therapeutics (eighth edition 1924). he introduced the cushny myograph, an ingenious arrangement of counterbalanced levers that allowed the faithful recording of the rate and force of contraction of the rapidly beating animal heart. it was still in use in practical classes at ucl, and elsewhere, in the 1960s. cushny left ucl in 1918, to become professor of materia medica and pharmacology at edinburgh. he was succeeded by a.j. clark/ alfred joseph clark frs a.j. clark a.j. clark, frs (1885–1941) held the established chair of pharmacology from 1918 to 1926. after qualifying in medicine, and serving as a field medical officer throughout the first world war, clark had been appointed professor of pharmacology at the university of cape town where he remained until accepting the chair of pharmacology at ucl in 1920. his influence on the subject was profound. the distinguished physiologist and nobel laureate a.v. hill (archibald hill) had begun the quantitative study of the action of agonists on an isolated tissue (frog skeletal muscle) some years earlier. clark took this much further and extended it to examine the actions of antagonists. the data he gathered on the exact relationship between agonist concentration and response, and on how this changed in the presence of a competitive antagonist, were published in two classic papers in the journal of physiology in 1926,. but he failed to work out a method for analysing properly the results of experiments with antagonists: that had to wait for his successor, heinz schild. nevertheless, clark was largely responsible for the transition of pharmacology from a descriptive subject to the quantitative science that it is today - this emphasis on quantitative approaches has remained strong throughout the subsequent history of the department. clark's book the mode of action of drugs on cells (williams & wilkins, 1933) is a classic and the following quotation from it set the tone for the department for many years. "in the first place, there is no advantage in fitting curves by a formula unless this expresses some possible physico-chemical process, and it is undesirable to employ formulae that imply impossibilities. it is a question of finding a few systems so simple that it is possible to establish with reasonable probability the relation between the quantity of drug and the action produced." while at ucl clark wrote the first edition of his textbook applied pharmacology in 1923, a book that was to be updated by two of his successors as head of department, first by h.o. schild and later by h.p. rang, and is still extant in the form of the widely used textbook rang & dale's pharmacology. in 1926 clark followed his predecessor in moving to the university of edinburgh. e.b.verney frs ernest basil verney (1894–1967) succeeded clark. he held the chair of pharmacology from 1926 to 1934. while at ucl verney discovered the antidiuretic hormone and also the mechanism by which structures in the brain sense minute changes in blood osmotic pressure. both findings were of profound importance for the understanding of water and electrolyte balance. verney was also instrumental in arranging for otto krayer to come to the department, albeit for only a short period, following krayer's exclusion from all academic positions in german universities because of his objection to the expulsion of jewish scientists from their posts. krayer was later to head the department of pharmacology at harvard with the greatest distinction. in 1934 verney moved to an academic post at the university of cambridge where he later became the first sheild professor of pharmacology j.h. gaddum frs john henry gaddum john gaddum (1900–1965) held the chair of pharmacology from 1935 to 1938. like a.j. clark, he had a profound interest in quantitative methods. he extended a.j. clark's work on competitive antagonism, and applied the law of mass action to describe the relationship (the gaddum equation) between receptor occupancy and the concentrations of an agonist and a competitive antagonist at equilibrium with the receptors in a tissue. the theory for two or more competing ligands had been known since michaelis & menten (1914), but gaddum was the first to apply it in a pharmacological context). like clark before him, gaddum failed to spot how to use the theory to estimate equilibrium constants. gaddum was also a master of bioassay which was then the preferred, and usually the only, way to determine the concentrations of biologically active molecules such as labile neurotransmitters and the neuropeptides. f.r. winton frank r. winton frank winton (1894–1985) held the chair of pharmacology from 1938 to 1961. his main scientific interest was in the control of blood flow to the kidney. winton ran the department through the difficult war years when the medical school was evacuated to leatherhead, surrey. he appointed the first two female academics in the department. mary lockett (1911–1982) was a lecturer in the department from 1945 - 1950. hannah steinberg arrived in the uk from vienna on a kindertransport train while still a schoolgirl, and she eventually became professor of psychopharmacology. winton also worked hard and successfully to ensure that pharmacology had an appropriate place in the preclinical curriculum. he oversaw the extension of the department, including the pharmacology lecture theatre (now the schild theatre). he was the author, with leonard bayliss, of a widely used textbook human physiology, first published in 1932. the 6th edition, 1968 was written by olof j.c. lippold and f.r winton h.o. schild frs heinz otto schild (1908-1984) heinz otto schild (1906–1984) held the chair of pharmacology from 1961 to 1973. he was born in fiume (now rijeka, croatia), in 1908, when it was part of the austro-hungarian empire. he qualified in medicine in munich and then worked with straub, the leading german pharmacologist of the time. by good fortune, schild had been accepted as a visiting worker by sir henry dale and was in england when the national socialists came to power in germany. he decided to stay in britain and became an assistant in the department of pharmacology in edinburgh, then headed by a.j. clark. when j. h. gaddum was appointed to the chair at ucl, he invited schild to join him as a demonstrator. so began his long association with ucl, interrupted only by his bizarre internment on the isle of man as an ‘enemy alien’ at the outbreak of the second world war. following his release (greatly aided by f.r winton's and sir henry dale's appeals to the home office) he returned to his work in the department, then based in leatherhead, and in 1961 became winton's successor as head of department and professor of pharmacology. schild made major contributions to receptor pharmacology, to the understanding of the mechanism of histamine release and to bioassay. like gaddum and clark, he used quantitative approaches whenever possible. his name is immortalised by the schild equation. he built on the work of clark and gaddum on competitive antagonism, by realising that the null method was key to extraction of physical equilibrium constants from simple functional experiments. rather than looking at the depression by antagonist of the response to a fixed agonist concentration, he measured the dose-ratio, the factor by which the agonist concentration had to be increased in order to restore a given response in the presence of the antagonist. by measuring the dose-ratio as a function of antagonist, it was possible to estimate the dissociation equilibrium constant for the combination of the antagonist with its receptor. crucially the estimate is not dependent on the nature of the agonist. although schild's derivation used the simplest possible model, it was subsequently shown that his equation is valid under much more general conditions. a.j. clark's textbook was continued by schild as clark's applied pharmacology by wilson & schild. heinz schild was a generous and kindly head of department. he appointed the third female member of academic staff, dr m. maureen dale, a co-author of rang & dales pharmacology. he oversaw the planning and introduction of a three-year b.sc. course in pharmacology which began in 1967 and continues to this day. medical students were able to enter its final year and schild, who never lost sight of the roots of the subject in medicine, was delighted that many took this opportunity. j.w.black frs sir james w. black (1924-2010) sir james whyte black om frs frse frcp (1924–2010) held the chair of pharmacology from 1973 to 1978. jim black and heinz schild knew each other well because schild had acted as a consultant to the then smith, kline & french company during the time when black was leading the team that developed the histamine receptor antagonists, h2 antagonists, which reduce secretion of gastric acid and which, at the time, transformed the treatment of gastric ulcers. schild's methods for quantitative methods for analysis of drug antagonists were crucial for this work. black introduced many changes to teaching in the department. one of the most important was the introduction of a bsc course in medicinal chemistry. his long experience in the pharmaceutical industry had convinced him that organic and physical chemists working on drug development with pharmacologists and biochemists would benefit greatly from a substantial knowledge of biology, certainly enough to allow them to understand and assess the kinds of measurements that their biological colleagues undertook. though the students were based in the department of chemistry, they took also courses in physiology and pharmacology, particularly its molecular aspects. this bsc course, like that in pharmacology, also flourished and continues today. another important change was a sharp reduction in the number of experiments with animal tissues undertaken by medical students during their course in pharmacology. at the same time, the