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HISTORICAL NOTE ON THE WARBURG CONSTANT-VOLUME RESPIROMETER THEODORE I. SOURKES Merck Institute for Therapeutic Research, Rahway, New Jersey
each appointment individually did not yield a living wage." In 1908 he became professor of physiology a t the University of Toronto, but continued his contact with England by returning each summer with his family, for vacation, recreation, and research. While in England in 1916, as a captain in the Canadian Medical Services, he suffered a heart attack and passed away on August 20 a t his Hampstead residence. In addition to his work in renal physiology Brodie was also interested in respiratory changes in disease and injury (in the tradition of J. S. Haldane) and in rehabilitation of disabled men. In a paper (see ref. 2) published in 1910 from his London laboratories (although he was by then in Toronto) Brodie described his "several modifications in the Barcroft-Haldane apparatus to simplify its use and to increase the rapidity of analysis." Some of these modifications were indeed signal improvements and were subsequently incorporated into new models of constant volumevariable pressure instruments used in metabolic research. Brodie introduced an all-glass manometer, avoiding rubber connections between it and the flask so that a constant volume for the apparatus was assured even during shaking. Instead of the old U-ahaped manometer, with a screw device across the bottom to raise or lower fluid, Brodie suggested fusing a short stem at the bottom to which a rubber reservoir (finger cot) could be attached. To make additions to the main compartment of his flask after the flasks were sealed, he fused a small bent glass tube into one side of the hollow stopper of the flask, so that its contents could be emptied in only one position of the stopper, i. e., a t a point where the neck of t&k&tle Sad a small recess moulded into it. The manometer was fixed vertically on a bent metal support which could be suspended from the side of the bath. Accordine to Barcroft? H. E. 'Bmdie described his manometer fluid as f o l l a w n : ~ 5per ~ ~ was ~ partly ~respollsible ~ for l thisl supporting cent bile salt solution "in which a llttle toluol is dissolved; device. The bath waslollgenough to take 20 manomesodium chloride is then added until the specific gravity of the ters, including one for use as a thermoharometer and a solution 1.034." ~h~ low surface tension and high mobility f, the solution was adventsneoua in mskine weurate readines. blank on the rea~ents. Brodie em~hasizedthat with The solution was stable. i n addition, its specific gravity is such the new apparatus two workers couid analyze 16 blood that a column almost exactly 10,000 mm. tall exerts 1 atm. pres- samples in five hours, including time consumed in sure; this is a convenience in manometric calculations. cleaning the glassware. The simple manometer de4 BR,,DIE, T.G., "some new forms of apparatus for the of the gases of the blwd by the chemical method," J . Phu8,sio/., scribed by Warburg in his monograph on themetabolism 39,391-6 (1910). of tumors7 is rather similar to the one 'developed by
T o MANY who have used manometry in the study of tissue metabolism, the name Brodie is merely an adjective to describe the manometer fluid. The formulation of a composition which would facilitate manometric practice1 was a distinct, if not unique, contribution to biochemical technique. This is attested to by the fact that Brodie's solution was adopted for their work by the leading early exponents of manometric methods in biochemistry and physiology, namely Watburg3 and D i ~ o nand , ~ is, or course, widely used today. Perhaps more significant than this innovation but even less well known was Brodie's construction of a respirometer flask, manometer, and incubation bath essentially similar in design to the present equipment known as the Warburg constant volume respirometer or HaldaneBarcroft-Warburg *spirometer. Yet the fact is that during his professional career it was his researches in physiology, especially of the kidney, that brought Brodie most recognition, including fellomhip in the Royal Society. Thomas Gregor Brodie was boru at Xorthampton, England, in 1866, the son of a clergyman. His education a t Cambridge was followed by study for the medical degree at King's College London, n here he was considered an exceptionally brilliant student. Having chosen to make his career in physiology he found teaching positions in London, finally becoming director of the Research Laboratories of the Royal Colleges of Physicians and Surgeons. When the Colleges closed their laboratories for reasons of economy, Brodie was out of work for a short while, but soon found himself with three positions simultaneously: at the Royal Veterinary College, the London School of Medicine for Women, and the Brown Institution of the University of London. A biographer says,="This pluralism was necessary, for
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Wmnmro. 0.. 2. Pkvsiol. Chern... 76.. 331 (1912): . . . Biochem.
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DIXON, M., "Mmometric Methods," Cambridge University
"RARCR~FT, J., Evjeb. Pkysiol., 7 , 699 (1908). ' W A R B ~ R GO., , Wber den Stoff~echsel der Tumoren," Springer-Verlrtg, Berlin, 1926.
z., loo, 230 ( i s i ~ ) .
Press, 1934. B d . Med. J.,1916,11, 342.
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384
The contribution of T. G. Brodie to instrumentation stands midway between that of Barcroft and Haldane, on the one hand, and Otto Warburg, on the other.8 The two eminent British physiologists devised a technique for estimating- gases in small quantities in blood Sir Joseph Barcroft recognized the scientific debt we owe ~ ~ d H~ i called ~ . hirn "the n,mt man in this field" (private cornrnunieation to W.W. L-mhreit, 1947).
JOURNAL OF CHEMICAL EDUCATION
and made manometry a routine practice in the clinical laboratory. The substantial improvements in construction and efficiency of their instrument made by Brodie undoubtedly facilitated the transition from its use in blood-gas analysis to its use, penerallv, in the study of exchange in the tissues, a fidd where Otto Warburg has demonstrated the rare versatility of the mnnometric technique.
