Within a month of the paper’s appearance a Berlin professor had written to say that it had all been done before, and in one sense he was right. This piece sets out what had been done before, in 1831, in 1912 and in the months around Forssmann’s own experiment, and what each of the earlier attempts lacked, because the lack is the point of the entry.

A sheep, a horse and a cholera patient

Forssmann gave the ancestry himself in Stockholm. “As far as I know, the credit for carrying out the first catheterization of the heart of a living animal for a definite experimental purpose is due to an English parson, the Reverend Stephen Hales,” who in 1710 bled a sheep to death, led a gun barrel from the neck vessels into the still-beating heart, filled the chambers with molten wax and measured the cast. Chauveau and Marey in 1861 “were the first to achieve measurement of blood pressure inside the heart and the recording of pressure curves from the interior of the heart of a living animal,” with manometers led from the neck vessels of a horse into both chambers of the right heart and into the left ventricle. That was the picture in the physiology textbook.

What Forssmann did not know, and could not have, is that a catheter had been in a living human being’s heart, or near it, in Berlin almost a century before him. Johann Friedrich Dieffenbach, the surgeon who later held the chair at the Charité, published in 1834 his observations on the cholera patients of the Berlin epidemic of 1831. The French translation of 1835 gives the passage. The useless attempts to take blood from cholera patients who were “cold, blue, without pulse,” in order to relieve “the heart filled with a thickened blood,” gave him the idea of “extraordinary means to reach this end; for a disease against which man can do so little allows unaccustomed attempts.” In a patient “almost dying, and who suffered greatly from anxiety and want of air,” he opened, in agreement with Dr Casper, the brachial artery in its upper third; not a drop of blood came. “I introduced, as I had resolved in advance, an elastic probe through the vessel as far as the heart, as I think; however not a drop of blood came out through the probe either. During these manoeuvres the beats of the heart became more distinct and more frequent, and I withdrew the probe; it was completely empty.” He regretted that “this operation, so interesting for the whole of physiology,” had been made on a man so near his end, who died soon afterwards in cramps; but the patient had felt nothing, “and earlier experiments on animals had taught me that the introduction of foreign bodies into the heart, by the great vessels, was often borne in an astonishing manner.” It was known, he added, that the heart was to a certain point insensible to mechanical irritation of its outer surface; it had not been established, to his knowledge, “that it was nearly the same for the walls of its cavities.”

So the thing had been done, up an artery, against the flow of blood, in a dying man, with no way of knowing where the probe had stopped, and recorded in a passage of a book on cholera. The German cardiologists’ archive notes that this came to light shortly before Forssmann’s death, and that he could not have known it when he wrote.

Bleichröder, Unger and Loeb, 1912

The claim that reached Forssmann in December 1929 concerned a paper in the Berliner klinische Wochenschrift of 1912, and the paper can be read. It is in three parts, under the heading “Intra-arterial therapy,” and the first is the lecture that Fritz Bleichröder gave to the Hufeland Society in Berlin on 9 May 1912.

He began with an apology of his own. “I shall report on experiments that I made years ago; they had scarcely any practical significance, but may perhaps acquire value in consequence of the rise of chemotherapy.” They had begun as a way of taking blood, for metabolic experiments, from the inferior vena cava of a dog at the point where the hepatic vein joins it. Laparotomy was clumsy, so he had freed the femoral vein and passed “a ureteral catheter, smoothed outside and inside with liquid paraffin, through a slit in the vessel up to the desired height within the vessel.” This catheterism of the venous system, “which has also been used before for many physiological experiments,” he had done on dogs “well over a hundred times,” had left the catheter in for hours, and had never seen the slightest disturbance, so that the moistening with leech extract he had considered against clotting was not needed. It was then natural, he said, to try the same on arteries: a drug could be added to the blood flowing to one organ and reach the diseased tissue in far higher concentration than by the usual injection under the skin or into a vein, where it was diluted through the whole arterial system; and with concentration, as Professor Loeb would explain, the speed of a chemical reaction rises.

“Before I applied the method in man, I convinced myself of its harmlessness by two experiments on myself, for particular reasons on the vein: Colleague Unger pushed a catheter through a slit in a vein of the forearm up inside the arm as far as the armpit. Later the attempt was repeated at the thigh and a catheter pushed up in the vena cava. As in my case, the experiment went off entirely without reaction in Colleague Nathanblut” (so the scan gives the name) “, a laboratory servant and another gentleman who had offered themselves.” Then the patients. “I have now tried four times to influence severe puerperal sepsis, in which complications could not be clinically established, by intra-arterial injection of collargol”: the femoral artery exposed under local anaesthesia, two threads passed under it to empty it, a small cut the diameter of the ureteral catheter, the catheter filled with the drug pushed up past the bifurcation of the aorta, both femoral arteries compressed, and the fluid injected so that part of it flooded the uterus. The result, he said, “was not encouraging, but not discouraging either”: these were the gravest cases, in which the sepsis had already seeded the lungs, and three of the four women died, three, four and twenty-one days after the injection; in the fourth, injected on the twenty-fourth day of her illness, the temperature fell almost critically, which “perhaps” was the injection. He thought of tetanus, of inoperable cancer of the womb, and of a surgeon operating on a bloodless limb after a balloon on the catheter had been blown up in the artery, which Unger had tried in a dog.

Unger’s remarks follow. Catheters passed into the bloodstream must carry nothing that could cause clotting; they had sterilised theirs only in steam under tension. In the experiments “on the colleagues, of whom Herr Bleichröder spoke,” he had been able to introduce the tube into the vein under local anaesthesia without technical difficulty, on the back of the hand or at the elbow. In two cases of embolism of the iliac artery he had opened the femoral artery, passed the catheter up through the clot and established how far it reached, and in one of them extracted it with a narrow forceps, after which the artery blocked again. He suggested the catheter for experiments in which a dye is carried by the blood to one organ in a living animal, which he demonstrated with a dog’s kidney stained with Indian ink.

That is the whole of it. Four human beings had had a catheter in a vein of the arm or in the vena cava; no one had taken an X-ray; no one had intended the heart; the paper does not contain the word. The provincial German papers that reported the dispute on 10 December 1929 had the measure of it. The professors Unger, Bleichröder and Loeb, they said, had come forward to show that they had made “the same experiment” seventeen years before: “they too pushed the probe deep into the blood vessels, once from the arm vein into the armpit, another time from the thigh into the vena cava. In this last experiment the probe did enter the heart, which however the researchers did not mention in their publication.” And: “Priority, in any case, does not count for much in medical experiments of this kind. The main thing remains that here is, so to speak, an anticipated confirmation of Forssmann’s experiments by other researchers.”

Forssmann’s daughter adds the mechanics. The editor of the Klinische Wochenschrift had searched the literature before printing the paper, knew of Unger’s work, and assured Forssmann that his claim to be first was sound; Forssmann nonetheless printed an addendum on page 2287 of the same volume acknowledging the earlier work. By the memoir’s account, as the German encyclopaedia summarises it, Unger’s letter had also gone to Sauerbruch, and had reached him before the paper did. In Stockholm Forssmann gave the 1912 work its due and its limit in four sentences: Unger, Bleichröder and Loeb “were at that time aiming at a special chemotherapy for puerperal sepsis,” wanted to bring a drug “in the greatest possible concentration to the place where it was needed,” carried out “vein probings on four people as a preliminary trial,” which “caused no ill effects. No X-ray checks were used, nor were the cardiological aspects taken into consideration.”

Montanari, Klein and the sceptics, 1928 to 1932

Two more names stand close to 1929. “In 1928, the Italian Montanari carried out probing of the right heart on animals and on the human cadaver,” Forssmann said in his lecture; Arrigo Montanari also put a note “On the probing of the vascular system” into the Klinische Wochenschrift in 1930, after Forssmann’s paper, which the German encyclopaedia lists among the priority claims.

The other is Otto Klein, and his is the case that the German cardiologists’ archive says was simply overlooked. Klein was born in Pilsen in 1891, qualified at Prague in 1915, served as an army doctor on the eastern and Italian fronts, and from 1919 worked at the German medical clinic of the university in Prague, where he became a professor in 1933. Forssmann’s paper appeared on 5 November 1929. By the end of that month Klein was lecturing in Prague on what he had done with it. He had passed ureteral catheters by Forssmann’s route in eighteen patients and reached the heart in eleven; in the other seven the catheter had gone into the jugular vein or stopped in the vena cava. From the eleven he drew the mixed venous blood that physiologists had wanted for forty years, measured its oxygen against the arterial blood and the oxygen taken up by the lungs, and calculated by Fick’s principle the first cardiac outputs ever measured directly in living people: in three patients with sound hearts, between 4.5 and 6.7 litres a minute. He presented the results to the congress of internal medicine at Wiesbaden in April 1930 and published them on 1 August 1930 in the Münchener medizinische Wochenschrift, in two pages that cite Forssmann correctly and praise him as the pioneer; the cardiologists’ archive observes that his account of the vein, the preparation of the catheter, the X-ray control, the sampling and the oxygen measurement “could not have been done better ninety years later.” Then his chief, Wilhelm Nonnenbruch, who saw no interest in the work and did not grasp what the output of the heart would mean to medicine, forbade him to continue.

Klein did not. In 1939, visiting Boston, he tried to persuade the physicians there of the method and found no hearing; the archive notes that medicine then waited twelve more years for Cournand and Richards. In January 1939 he gave up his post, and in March, a Jew with the Wehrmacht at the border, left by way of Britain for Argentina, where he ran the department of pathological physiology at the Durand hospital in Buenos Aires and did no more catheterisations. He came back to Prague once, at seventy-three, for a European congress of cardiology, and was pleased to find that a younger man there knew what he had done. He died in Buenos Aires on 19 April 1968. Forssmann, in his lecture, gave him a sentence: “in 1930, about six months after my first publication, O. Klein reported from Nonnenbruch’s Prague clinic on a series of patients whose heart minute-volumes he had ascertained according to Fick’s principle, by means of the heart catheter. This procedure has its place even today in the standard practice of heart and lung clinics.” In 2000 the Czech cardiologists held a symposium in his name, and in 2005 another, on “the world first diagnostic cardiac catheterization in humans 1930.”

Others followed in the three years after the paper, as Forssmann’s daughter lists them: a physiologist at Leipzig who used the catheter to study the glucose metabolism of animals; investigators in Spain, in Cuba, in Argentina. In Germany, Hans Baumann measured the output of the human heart in 1930 by puncturing it through the chest, apparently unaware of the alternative. And the authority on the subject in English, Arthur Grollman, whose acetylene rebreathing method was the standard indirect measurement, disposed of the catheter in his book of 1932 on the cardiac output of man in a paragraph that Forssmann’s daughter quotes. The method was “not only dangerous to the subject but useless so far as cardiac output determinations are concerned. The formation of thrombi which is very likely with the introduction of a foreign body into the blood stream renders the method too hazardous for its possible future use. The nature of the operation also precludes its use as a means of determining cardiac output for the unavoidable psychic effect accompanying the procedure will elevate the cardiac output considerable and thus vitiate any results obtained. This method must thus be considered merely as a clinical curiosity.” Cournand later referred to that book as one of the things that had discredited the method. It took ten more years to show that both predictions were wrong.

After the prize

The question of who was first came up once more, after it could matter least. Ernst Derra, the chair of surgery at Düsseldorf, challenged Forssmann’s priority shortly after the prize of 1956, his daughter wrote, “unsuccessfully though.” The nominations in the Nobel archive show how the prize had come about: in 1952 Nicolai Guleke, emeritus professor of surgery at Jena, nominated “Dr Werner Forssmann, urology, Bad Kreuznach,” alone; in 1953 William P. Murphy of Boston, laureate of 1934, nominated Forssmann and Cournand together, and Ludwig Heilmeyer of Freiburg nominated Forssmann again. The citation of 1956 was for “their discoveries concerning heart catheterization and pathological changes in the circulatory system.” The German cardiologists’ archive, which gives Klein a page of his own under the heading “the overlooked pioneer,” concludes that he should have been among the laureates, and offers as the only explanation that “he was overlooked.”

What the claims have in common

Dieffenbach’s probe went up an artery into a dying man and was never seen. Bleichröder’s catheter went up a healthy man’s vena cava and was never looked for. Montanari’s went into animals and corpses. Each of these men did a part of what Forssmann did, and none of them did the part that counts, which is to put the tip where it could be photographed and then to photograph it. The 1912 paper shows how little the difference is in the hands and how much it is in the head: the same ureteral catheter, the same slit in a vein at the elbow, the same oil, the same absence of any reaction, and a title about the arteries and the womb. What Forssmann added was not courage, which Bleichröder and his colleagues had, but a purpose that required a picture, and the walk downstairs to get it. What Klein added, in the same month, was the purpose that required a measurement, and he was stopped before he could take a second one. The entry’s lesson stands on both: a result nobody recorded is a story, and a method nobody is allowed to use is a photograph.

Sources

• Werner Forssmann, Nobel Lecture, 11 December 1956: Hales, Chauveau and Marey, Unger, Bleichröder and Loeb, Montanari and Klein. Nobel Prize
• J. F. Dieffenbach, Observations physiologiques et chirurgicales faites sur les cholériques, the French translation (1835) of the Physiologisch-chirurgische Beobachtungen bei Cholerakranken of 1834, pages 12 to 14: the brachial artery, the elastic probe “jusque dans le coeur, à ce que je pense,” the empty probe, and the animals. Translated here by the author of this piece. archive.org
• F. Bleichröder, “Intraarterielle Therapie,” E. Unger, “Bemerkungen zur intraarteriellen Therapie,” and W. Loeb, Berliner klinische Wochenschrift, volume 49, 1912, pages 1503 to 1505. The lecture of 9 May 1912, the dogs, the self-experiments, the four cases of puerperal sepsis, and Unger’s remarks on sterilisation, embolectomy and vital staining. Translated here by the author of this piece. archive.org
• Wiedenbrücker Zeitung, 10 December 1929, page 9: the professors’ claim and the newspaper’s verdict on priority. Translated here by the author of this piece. Deutsches Zeitungsportal
• Renate Forssmann-Falck, “Werner Forssmann: A Pioneer of Cardiology,” American Journal of Cardiology, 1997: the editor’s search of the literature, the addendum, Derra, Baumann, Thomas, the Spanish, Cuban and Argentine workers, Grollman’s paragraph and Cournand’s reference to it. Elsevier
• Historisches Archiv der Deutschen Gesellschaft für Kardiologie, “Prof. Dr. med. Otto Klein: Der übersehene Pionier”: Klein’s life, the eighteen attempts and eleven catheterisations, the outputs, the lectures of November 1929, Wiesbaden, the paper of 1 August 1930, Nonnenbruch, Boston, the emigration and death, and the symposia of 2000 and 2005; and the archive’s page on Forßmann, for Dieffenbach’s coming to light. Klein, Forßmann
• Nobel Prize nomination archive, Werner Forssmann: the nominations of 1952 and 1953. Nobel Prize
• German Wikipedia, “Werner Forßmann,” for Montanari’s note of 1930 (Klinische Wochenschrift, volume 9, page 501), Unger’s letter to Sauerbruch and the addendum. Wikipedia