The Early Days of Research on Carbonic Anhydrase

My first encounter with the combination of F. J. W. Roughton and carbonic anhydrase occurred on the afternoon of Friday, June 18, 1937, when I sat for the fourth paper in the Final Honour School of Animal Physiology at Oxford University (FIG. 1). Roughton was the External Examiner, and C. W. Carter and E. G. T. Liddell were the Internal Examiners. The paper they set contained twelve questions, and it was headed: “Candidates are asked to attempt NOT LESS THAN THREE and NOT MORE THAN FOUR questions.” The first question was in German and the second in French. The sixth question was: “Explain how carbonic anhydrase came to be discovered and give an account of its properties and functions.” I attempted to answer the German question, not in German I am afraid, and one about the determination of pH in biological materials, but I did not tackle the sixth question. I didn’t know enough to do so. Now, a little over fortysix years later, I shall attempt to say how carbonic anhydrase came to be discovered and leave its properties and functions to others at this conference. The description of blood as a physical chemical system has been a major accomplishment of physiology. Cambridge University was one of the centers of the work, largely because Joseph Barcroft had started his career there attempting to measure oxygen consumption of salivary glands. That led him to measurement of the combination of oxygen with hemoglobin. One brilliant Cambridge physiologist said to me, “You know, Barcroft was a very stupid man. He got all hot and bothered if you suggested he use a logarithm.” The only trouble with that judgment is that, from the day he started until the day he died at the age of 75, Barcroft made profoundly important contributions to physiology.? Francis John Worsley Roughton was a Cambridge undergraduate during the First World War, and he was fortunate in having paroxysmal tachycardia. He didn’t go into the army and be killed as most of his contemporaries were. His case history has been published. “In two attacks of paroxysmal tachycardia in which the pulse was upwards of 200 the minute-volume sank from 5-6.1 litres to 2.8-2.1 litres per minute, or roughly to half to a third of the normal value. . . . The systolic output was 77.5 to 12.9 c . c . ” ~ Roughton was scheduled to give apaper on hemoglobin to one of the innumerable undergraduate clubs that abound in Cambridge and Oxford. When he read Barcroft’s papers, he discovered that Barcroft really didn’t understand the work being done by Bohr and his school in Copenhagen. Characteristically, Roughton went up to Barcroft and said, in effect, “Dr. Barcroft, you don’t know what you are talking about.” Barcroft demonstrated how to be a great man by replying, “Wonderful, come work with me and show me how to do it right.” From then on, Roughton’s devotion to Barcroft was unbounded. The experiments that established the physical chemical nature of blood were all equilibrium studies. One took a sample of blood from Arlie V. Bock or from a