The entry leaves the catheter in the literature in 1931, with a photograph attached to it and no use. This piece follows the two men who gave it one: what they had been trying to measure for ten years before they picked it up, what they found when they did, and what the Karolinska Institute thought it was rewarding in 1956. Nearly all of it comes from the two Nobel lectures that Dickinson Richards and André Cournand gave in Stockholm on 11 December 1956, the day after the ceremony, and from Göran Liljestrand’s speech presenting the prize.

Two men of sixty-one

Dickinson Woodruff Richards was born in Orange, New Jersey, on 30 October 1895, and went to Yale and then to Columbia. André Frédéric Cournand was born in Paris on 24 September 1895, the son of a dentist, took his first degree at the Sorbonne in 1913 and began medicine in 1914. The war interrupted it: from 1915 to 1918 he was a private in an infantry regiment, then a corpsman, then a battalion surgeon, and came out with the Croix de Guerre and three bronze stars. He became an interne of the Paris hospitals in 1925, worked under de Massary, Achard, Rist, Debré and Guillain, wrote a thesis on acute disseminated sclerosis, and took his doctorate in May 1930. Wanting to work in the United States, he found a residency in the tuberculosis service of the Columbia University division at Bellevue Hospital in New York, directed by James Alexander Miller and J. Burns Amberson, became its chief resident, and was offered the chance to do research on the physiology of breathing under Richards. He stayed, and was naturalised in 1941. The whole of his investigative life was spent in the chest service of Bellevue; when the United Press announced the prize in October 1956 it gave the two men’s ages as sixty-one and sixty-one.

Richards traced what they did to one teacher. The foundation of their work, he said in Stockholm, was that of Lawrence J. Henderson of Harvard, “biochemist, physiologist, natural philosopher, student of Arrhenius, ardent disciple of Claude Bernard,” whose “great single contribution” was the integration of the respiratory function of the blood, and whose horizon was wider than that. “It was from Henderson that we derived the simple but essential concept that lungs, heart, and circulation should be thought of as one single apparatus for the transfer of respiratory gases between outside atmosphere and working tissues.” That was not new, Richards said; it was in the tradition of Krogh, Lindhard and Liljestrand himself, who sat in the audience and had worked out in man, with the methods then available, how the normal apparatus performed at rest and in exercise.

The number they could not get

“During all this time, however, and indeed for a total period of nearly forty years, there was in the study of the heart and circulation in man, one measurement or set of measurements which were conspicuously in default, viz. the state of the blood as it enters the right heart, its respiratory gas contents, its pressure relations, and its rate of flow.”

The reason it mattered was Adolf Fick’s principle of 1870. The oxygen taken up by the lungs in a minute, divided by the difference in oxygen between a unit of blood leaving the lungs and a unit entering them, gives the volume of blood that passed through the lungs in that minute, which is the output of the heart. The oxygen uptake could be measured at the mouth. The arterial blood could be drawn from an artery in the arm. The blood entering the lungs, the mixed venous blood of the right heart, could not be drawn at all. “Only those who have worked through all or a part of those times,” Richards said, “can appreciate how ardently this information was sought after, and by how many devious approaches.” Most of them used the lungs as a tonometer, having the subject rebreathe a gas until the gas in the lungs came into equilibrium with the blood arriving in the pulmonary artery, and reading the blood from the gas: Loewy and von Schrötter, Plesch, Christiansen, Douglas and Haldane, Yandell Henderson. These were the indirect methods, and Liljestrand reminded the audience that they had “yielded valuable results, although they have somewhat undeservedly, as is often the case, been overshadowed by the subsequent conquests,” and that one of their limits was that they needed the active cooperation of the subject, “and this was at times associated with difficulties or was altogether unfeasible.” As late as 1928, he said, a textbook could say with good reason that in man one was “naturally” confined to the indirect methods.

That is what Richards and Cournand set out to do in 1931, on Miller’s service at Bellevue, in patients with chronic lung disease. “There was nothing original in our approach. We simply tried, as others had done before, to establish gaseous equilibrium between lungs and inflowing blood by rebreathing procedures.” Diseased lungs would not mix the gas evenly, “and after three years it became apparent that we had failed completely in these attempts.”

The failure was productive, as Richards was careful to say. Robert Darling, working with them, turned the uneven mixing itself into a measurement, washing the nitrogen out of the lungs with pure oxygen breath by breath; from that came an open-circuit way of measuring the residual volume of the lungs and an index of how well they mixed. With Eleanor Baldwin they built the other practical tests of lung function, helped by parallel work in Knipping and Anthony’s clinic in Hamburg. By the late 1930s they could describe the ventilation of the lungs and, with arterial blood, something of their mixing and diffusion. “But we still could not measure blood flow through the lungs, and could not therefore move into those broader concepts of cardiopulmonary function which now began to be our goal.”

Late in 1940

“We were aware of the earlier experiment of Forssmann and had followed closely its isolated uses in Germany, Portugal, South America, and France.” Richards did not elaborate; Forssmann had just given the audience the history himself. “It suffices for me to say that late in 1940, Cournand and Ranges took up the catheterization technique, showing in their initial studies that consistent values for blood gases could be obtained from the right atrium, that with this, cardiac output could be reliably and fairly accurately determined by the Fick principle, and furthermore that the catheter could be left in place for considerable periods without harm.” Their report, with Hilmert Ranges, was published in 1941. Not long after, through the interest of Homer Smith and with the help of Bradley, pressures recorded through a Hamilton manometer were added, and Gregersen’s method of measuring the blood volume. “By this time, therefore, after ten years of work, we had assembled a fairly comprehensive group of methods for the analysis of cardiopulmonary function, methods which could be applied not only to normal man but to patients even in the most severe and acute stages of decompensation.”

Liljestrand’s account of the same year is the committee’s. “It is, however, characteristic that it was not until after several year’s preparations and much hesitation that the New York school was able, in 1941, to publish a report of cardiac catheterization in man. A few minor improvements were introduced, but the main point was that a well-known research group at a distinguished clinic had set their seal of approval on the method, which then made its triumphant entry into the world of clinical medicine.” Forssmann, in his own lecture, called 1941 “a turning-point in the history of cardiology,” and added that for Cournand and for John McMichael in London “the beginning was not easy. They, too, had strong resistance to overcome,” from people who “did not hesitate to obstruct practical research work with threadbare ethical and moral objections.”

Cournand opened his lecture with the sentence that gives this piece its name. “For us in 1943, the cardiac catheter was only the key in the lock, although this is in no way to minimize Dr. Forssmann’s brilliant and courageous experiment. To guide our hand in turning this key, we had all the knowledge accumulated through the years by physiologists in their studies of animals.” He owed a personal debt to William F. Hamilton for advice and criticism. “Basically our difficulties were then, as they are still, of measuring flow and pressure and volume,” and he spent the first part of his hour on the limits of the methods, because “the reliability of experimental data is no better than the reliability of the measuring techniques employed.” Fick’s principle, he pointed out, assumes a stream of constant velocity entering a chamber of constant volume small enough that an indicator added to it mixes at once; the body supplies none of these, since pulmonary blood flow is pulsatile, the oxygen enters the capillaries in time with breathing and can only be measured at the mouth, and the blood samples are collected over a period rather than from instant to instant. Extensive work in animals and in man had shown that these departures did not introduce a large error, but the point of saying so was that a catheter in the heart is not an answer. It is a way of collecting samples, and everything depends on what is done with them.

What the key opened

The war set the first task. “The United States was by this time at war, and further information on the hemodynamics of shock, quantitative measurements of this, and of the effects of treatment, were urgently needed.” The studies went quickly. With a deficit of forty to fifty per cent in blood volume, the output of the heart and the return of blood to the right heart fell critically, and went on falling as the shock continued; the resistance of the peripheral vessels was maintained in haemorrhage and in injury to the limbs and greatly increased in severe burns, which meant that the flow of blood to the periphery, and particularly to the kidneys, was reduced; and whole blood did more good as sustaining treatment than plasma. Other treatments were measured against these numbers. “In certain cases of severe burn, the catheter was left in place for more than 24 hours, to provide a means of intravenous treatment, with no harm resulting, a further indication of the safety of the procedure.” Vasomotor factors and the problem of what was called irreversible shock “were approached but not solved.”

Even in the war years the method grew. Cournand took the tip of the catheter on from the right atrium into the right ventricle and then into the pulmonary artery, which opened new measurements, “some of them as important physiologically as the original right atrial.” Cases of heart failure with a high cardiac output were separated from the “low output” failures, as McMichael and Sharpey-Schafer in London found independently; Janet Baldwin studied a patient with a hole in the wall between the ventricles. “With the cessation of hostilities in 1945, we were free to look more broadly at problems of disease. By this time others were at work with the same procedures, in various parts of the world.”

The obvious use was in the hearts of children born with the wrong plumbing. Cournand, Baldwin and Himmelstein began it; Bing, Dexter and others extended it. Richards was precise about the order of events: the surgery of congenital heart disease, under Gross, Blalock, Crafoord and Brock, “was under way before cardiac catheterization, and has moved fundamentally on its own. The cardiac catheter has been, however, a primary aid.” By taking blood from each chamber and each great vessel and measuring the pressure at each site, the catheter could say not only where the abnormal connection was but how much blood went through it, usually from the left side of the heart to the right, “thus defining for the surgeon both the nature and extent of the disorder,” and by catheterising the patient again afterwards, how nearly a normal circulation had been restored. The Evening Star’s science writer, summarising what “Nobel experts” had told the United Press on the day of the announcement, put the uses in four lines: as “a doctor’s fingertip” to find abnormal communications between the sides of the heart or between the pulmonary artery and the aorta; to measure pressure in the parts of the heart and vessels; to find out how much blood an ailing heart can handle in a minute; and to inject contrast into the heart to show the defect on an X-ray screen.

Then heart failure in general, which could now be measured during decompensation and again after recovery: pressures and flow in the pulmonary circulation gave an index of the left ventricle, the same measurements in the right heart and great veins an index of the right. Many forms and degrees of failure were defined and their responses to treatment measured. Ferrer and Harvey in the Bellevue laboratory, and McMichael and Sharpey-Schafer in London, worked out how digitalis acts: favourably only on ventricles that are overdilated, with excessive filling pressures and inadequate emptying, and there rapidly, increasing the energy of contraction and the stroke volume, in regular as well as irregular rhythms. The whole body of new numbers put Starling’s principle, that the energy of contraction is proportional to the length of the muscle fibre, back under review, and “contrary to the usual sequence, it was the clinical physiologists who stimulated the general physiologists to further research.” In the last six years before the lecture the method had been turned on mitral stenosis, where the surgeons had learned to relieve the narrowed valve, so that the circulation could be measured before the operation and after it. And beyond all this, Richards said, he and Cournand “have from the beginning thought of ourselves as primarily pulmonary rather than cardiac physiologists,” and the second half of his lecture was about the lungs: the raised pressure in the pulmonary artery that chronic lung disease produces, the strain it puts on the right ventricle, and the reasons for it, which they had taken apart one by one.

Forssmann, in Stockholm, gave the spread of the thing in a paragraph. “The work of Cournand and Richards and their pupils had fanned a small flame into a blazing fire which began to rage all over the world. The Cournand-Richards school achieved particularly fruitful results in the United States and Scandinavia. In England, McMichael is the most important advocate of this method of investigation.” There was now, he said, “an army of diligent men and women at work, an army so big that it is impossible in this context to mention any beyond those named.”

The method as a patient met it in 1956

Walter Theimer, writing for the German-language Washington Journal three weeks after the announcement, described a catheterisation as it was then done, for readers who had never heard of one. A small opening is cut in the main vein of the left arm and a fine plastic tube introduced, a metre long and about as thick as a knitting needle, with a bore the thickness of a stout sewing needle. Blood enters the tube, which carries the pressure at its forward end back to an apparatus at the other; the electrocardiogram is recorded throughout; the patient lies still and feels nothing, and follows the pressure curve and the electrocardiogram on a screen with the doctor beside him explaining them. The tube is visible on the X-ray screen and is pushed on carefully, past the armpit into the chest, until it reaches the heart. “Now the electrocardiogram comes alive”: the heart answers the intruder with extra beats, and the patient may feel a little palpitation. The pressure curve, which until then showed only the small regular waves of the veins, swings up; its large waves announce that the forward end of the tube has reached the chamber. Where the pressure is wrong, the doctor now knows which valve or chamber is at fault, and the surgeon, who has learned in the last decade to open the beating heart, knows where to cut.

That was twenty-seven years after Eberswalde, and in every particular it was what Forssmann had not been able to do: the manometer, the electrocardiograph, the plastic tube, the patient with something wrong.

The men

Richards died in 1973, at seventy-seven. Cournand lived to ninety-two and died in 1988. He wrote the preface to the English edition of Forssmann’s memoir in 1974, and described its author, in a sentence that Morton Meyers quotes, as “not lacking in pride of self, a man at once disputatious, full of resources and will power, and endowed with physical courage, if not with great political perspicacity.” Forssmann’s daughter wrote that her father, who hardly spoke of the prize afterwards, “struck up a friendship with Cournand” in Stockholm.

Sources

• Dickinson W. Richards, “The Contributions of Right Heart Catheterization to Physiology and Medicine, with Some Observations on the Physiopathology of Pulmonary Heart Disease,” Nobel Lecture, 11 December 1956. Henderson and the single apparatus, the forty years in default, Fick, the indirect methods, 1931 and the three years of failure, Darling and Baldwin, Forssmann’s isolated uses, Cournand and Ranges, shock, the congenital lesions, heart failure, digitalis, Starling and mitral stenosis. Nobel Prize
• André F. Cournand, “Control of the Pulmonary Circulation in Man with Some Remarks on Methodology,” Nobel Lecture, 11 December 1956: “the key in the lock,” Hamilton, and the limits of the Fick principle in a pulsatile system. Nobel Prize
• Göran Liljestrand, presentation speech, 10 December 1956: the two factors, the indirect methods and their cooperation, the textbook of 1928, Forssmann’s “intrepidity of youth,” the hesitation of the New York school and its seal of approval. Nobel Prize
• Werner Forssmann, Nobel Lecture, 11 December 1956: 1941 as a turning-point, the resistance met by Cournand and McMichael, the small flame and the army. Nobel Prize
• “André F. Cournand, Biographical,” from Nobel Lectures, Physiology or Medicine 1942-1962: the birth, the war service, the Paris years, Bellevue, Richards and the naturalisation of 1941. Nobel Prize
• “Two Americans and German Share $38,633 Nobel Prize in Medicine,” Evening Star, Washington, 18 October 1956, pages A-1 and A-6: the ages, Richards’s birthplace and career, the Bellevue work on wounded soldiers, and the four uses. Library of Congress
• Walter Theimer, “Ein Schlauch ins Herz,” Washington Journal, 9 November 1956, page 5: the procedure as described for lay readers in 1956. Translated here by the author of this piece. Library of Congress
• Morton A. Meyers, “The Key in the Lock: Cardiac catheterization,” The Pharos, Summer 2016: Cournand’s preface to Experiments on Myself. Alpha Omega Alpha
• Renate Forssmann-Falck, “Werner Forssmann: A Pioneer of Cardiology,” American Journal of Cardiology, 1997: the friendship with Cournand. Elsevier
• Historisches Archiv der Deutschen Gesellschaft für Kardiologie, “Werner Theodor Otto Forßmann”: the deaths of Richards in 1973 and Cournand in 1988. DGK