Experiments with the heart

Werner Theodor Otto Forssmann's story

Friday, Oct 12^th 1956

That was the fateful day when the motely group comprising members of the Vereinte Aquarienfreunde (united friends of the aquarium) met as usual at the local pub in the spa town of Bad Kreuznach, a locale once famous for radon balneology. That by the way, is where one immerses oneself in waters which had traces of radium, supposedly soothing for rheumatic joints. The people of Kreuznach later built a radon inhalatorium, also popular for a period, into which was piped air from an old mining gallery. Later, during WWI, Kaiser Wilhelm II lived in the spa house and then the town became the seat of the German Army High Command during WWII, only to get bombed with marked regularity by the Allies. Kreuznach was later occupied by US troops in March 1945. But more mundane activities occupied the minds of the group, the plan was to discuss nothing in specific, perhaps they talked about fishes and it is a fact that many years ago, one of the gentlemen among them, a Prussian, used to study protozoa collected from his aquarium, with a Leitz microscope which he had been gifted.

The German urologist had been a prisoner of war between 1937 and 1945, after capture by the allies for having served the Nazi cause and had thence moved to Krueznach. The German urologist had been a member of the NSDAP party between 1937 and 1945, became a prisoner of war after capture by the allies for having served the Nazi cause and had thence moved to Kreuznach. His story is a fairy tale one, and as you will soon observe, many of you continue to live because of him and his firm convictions.

I would guess that the stout Prussian, an urologist in real life, swigging his mug of beer, looked and acted as though he was quite annoyed with life. He did have reasons for that and all his medical life he had been ignored or scoffed at, and his attempts at heading a research team was reaching nowhere. When the barman bawled out at him to attend to a phone call from his agitated wife Elsbet, he suspected nothing. When she told him that some woman with a foreign accent had called to say she wanted to discuss regarding the Nobel Prize, he scoffed at her and continued with his drink. Anyway he dutifully trotted home to attend to the matter. The woman with the foreign accent, Frau Johansson a reporter at Svenska Dagblad called again late at night when he reached home, and asked for an interview.

The lady told him that he had a 25% chance of winning a Nobel Prize. The physician with the gruff voice did not curse Johansson nor did he slam the phone (not that anything would have happened to the phone, for in those days those black phones were made of Bakelite). The next day a letter arrived from the Carolinska institute asking for his photograph. The man who handled the nether regions of the body in hospitals with great dexterity, was quite surprised when a photographer later arrived to take his family photographs. Soon the petite Swede, Frau Johansson, presented herself at his home to state that there was a better chance of his getting a joint Nobel. The press started to hound his house and children, even at school. On Oct 18th, after he had completed surgeries on three kidney patients, the medical director Dr Alfred Behrens came by to formally congratulate him for the Nobel Prize he had won jointly with a French American and an American, and then, finally, realization sank in. That evening his trembling white faced wife collected the formal telegram from Stockholm, one that heralded a new lease of life to the hitherto unknown urologist. As the press entourage arrived to make life complicated for the flabbergasted urologist, he must have wondered, ‘for what’?

Why would somebody who had been told that he had been bestowed a Nobel Prize (nobody gets a Nobel accidentally) ask such a mundane question? As you can imagine there is an interesting story behind it all, and an even more interesting person. This is the story of a German surgeon and Nobel laureate, Werner Theodor Otto Forssmann.

First a bit of perspective - In 1895, Roentgen discovered the existence of x-rays and took the very first X-ray of his wife’s hand, after which he won the first ever Nobel awarded, in 1901. He died in 1923 due to carcinoma of his intestines, contracted perhaps from X ray exposure but then again, X ray therapy was not known to be of any use in treating carcinomas at that time, whereas radiation therapy is extensively used for the same today. Marie Curie who had won twin Nobel prizes since then for her work on radio activity, succumbed to aplastic anemia contracted from long term exposure. Barry Marshall on the other hand, kept saying that H Pylori was the main cause for peptic ulcer while the learned medical fraternity and as it appears, the antacid lobby went against him and prevented his rise to fame for a full two decades, before everybody finally accepted his views and became a Nobel laureate himself. At one point of time, Marshall had to swallow the bacterial concoction himself to prove the point.

The world as you can see, recognizes greatness only after sustained reluctance especially when it relates to these kind of path breaking discoveries. It was the same in the matter concerning Werner Forssmann, a person recently described by a thoughtful blogger as ‘the most badass scientist’.

Many years back, I stood beside an equally brilliant cardiac surgeon, Dr Cherian and watched a complex cardiac bypass surgery which took many hours. I saw and recorded in my mind every step, but I had missed seeing the diagnostic step that preceded it, a procedure called the angiography. In order to map the blockages in the arteries leading to the heart, a dye is injected, then a catheter is threaded through the femoral vein or artery in your groin, all the way to the heart while the path is filmed using X-rays. The doctor thus sees blockages and plans a surgery to bypass them with coronary grafts from the patient’s leg. That in essence is a bypass surgery, the basics of which many people know about today. It is matter of fact, something that has been done very often since R Goetz first performed it in 1960. The procedure is not without complications and rare as they are, sternal infections can lead to death, like it happened in the case of my dear friend Mohan, recently. Cardiac afflictions are still the leading cause of death around the world and as you can imagine, the angiogram or cardiac catheterization is the main tool used by surgeons and cardiac consultants.

Cardiac catheterization was first performed and so named by Claude Bernard in 1844 on a horse, and using a glass thermometer he reached the animals heart, in order to check temperatures. Though it looked challenging, nobody even dreamt of carrying out such a procedure on humans, fearing instant death.

Werner Forssmann had by now become a doctor after fatefully deciding not to become a tradesman, graduating from the Friedrich-Wilhelm-University in Berlin. After many unsuccessful attempts to obtain a residency in internal medicine, he was finally admitted at the Auguste-Victoria-Heim in Eberswalde, a small Red Cross hospital supervised by Dr Richard Schneider..

But as you know youthfulness is often associated (if it fails, such events are classified as ‘stupidity of youth’) with fearlessness. The 25 year old surgical resident Werner Forssmann was one of them but he was sure that his procedure was not reckless. He was particularly interested in analyzing lung damage due to heart valve failures and wondered if one could find a safe path into the heart without anesthesia and without triggering the body’s reflexes. It was his intent to find a path to the heart while at the same time avoiding dangerous surgery. He had seen the work of Claude on a horse, but instead of entering the heart through the jugular, he wanted to get in through the cubital vein with an elevated arm. The median cubital vein is typically used for taking blood samples, for intravenous injections, for blood transfusions, and as Forssmann was about to consider, for the introduction of catheters. People who have seen the TV series ‘Lost’ will remember how Jack the doctor threads a sea urchin needle into his cubital vein for a live ‘person to person’ transfusion.

With a bit of local anesthesia near the venal incision, Forssmann concluded that it was indeed possible to pass a urinary catheter through the vein and all the way to the heart. But to check its efficacy on a live patient, he had to obtain permission from Dr Richard Schneider. Schneider, whose sister was his mother’s friend, refused to give him permission but then, Forssmann persisted stating that he was even willing to experiment on himself. When Schneider refused again, the young Werner was devastated. In those days it was a medical taboo to work directly on the heart for it was a surefire way to invite death. Even if one could access it through the ribs, without piercing the lung, potential hemorrhaging was impossible to stop, if something untoward happened. Also, if the endocardium was irritated, fatal arrhythmia could develop and kill the patient. But it had been done, for in 1903, the famous Dr Sauerbrunch did operate on a woman with an aneurysm of the heart.

You will not believe it, but it was perhaps a risqué joke narrated by his college professor Frederich Kopsch (according to Forssmann’s memoirs) which inspired him. The joke went thus- ‘the only way to a woman’s heart is through her v$%$^na. You go from the uterus and the fallopian tubes to the abdominal cavity, then via the lymphatic space into the lymphatic vessels and veins and thus to the goal’!!!! That ignited the idea of finding an un-traumatic way to the heart.

Most thrillers show the hero in association with a sidekick. Such a sidekick lends both physical and moral support to the protagonist. Werner needed one, not only to witness his next steps, but also to help him get the deed done in the hospital and to obtain the required supplies, which he as in intern, could not. And that is how he selected Nurse Gerda Ditzen, in order to get hold of the hollow needle, scalpels, sutures, urinary catheters, and Novocain for local anesthesia. Gerda was very interested in medicine and so Forssmann plied her with books and explained to her the procedure, step by step. As he narrated later, he went after her ‘like a sweet toothed cat around a cream jug’. After lunches together and further talks, Werner told her that he had been forbidden from doing the procedure. As planned, the nurse suggested that she would be glad to have the experiment done on her. That was just what Werner wanted to hear and quickly he chose an afternoon to do the deed, a time when the hospital staff took their routine siesta.

Gerda Ditzen the surgical nurse, sterilized the equipment and had them all ready for the venesection, including the 30 inch long catheter. Werner asked Gerda to lie down on the surgical table, put her legs through the straps and he then tied her down, explaining to her that it was so that she would not fall over from the effects of the anesthetic.

Behind her head, Forssmann went on to do the unexpected, he dabbed iodine on his left elbow crease and injected the Novocain. As he waited for the anesthesia to take effect, he moved over to Ditzen and dabbed her venal area with iodine, laid gauze over it and talked reassuringly to the heady patient on the gurney, as his own anesthetic took effect. As soon as he felt the deadening on the elbow, he took the scalpel and cut through his skin. The nurse seeing this, watched wide eyed, struggling under the belt but then, he had intentionally tied her down tight and made sure she had no chance to get to the buckles.

The Deschamps aneurism needle was next pushed into his cubital vein and Werner eased it up a foot.You must now understand that this is possible in a vein with little resistance because it moves with the flow of blood towards the heart and in the direction of venal valves. Werner then put gauze over the wound and tied a sterile split over it. After all this was done, he loosened the straps on Ditzen and released her hands. Werner himself felt no pain, just a little feeling of warmth. Gerda was furious at being duped and aghast of course, seeing the doctor with the dawdling catheter, and wondering if and when he was going to die in front of her.

But Forssmann had other ideas. He had to inch up the catheter all the way to the heart and record the event by taking x-rays of the procedure. The problem was that the X-ray room was in the basement, two floors below. As they rushed down the stairs, the word went around the hospital of the bizarre event taking place. The duo reached the x-ray room and a stunned nurse named Eva took orders to ready the equipment for the x-rays. Peter Romeis, a surgery friend and drinking partner of Forssmann burst in screaming and tried to pull the catheter out. Werner was heard to shout back ‘nein nein’ and kicked Romeis in his ankles to get him to stop. It was all melodramatic and in the middle of it all, the Prussian doctor kept barking commands to Eva, for he wanted a mirror to view the fluoroscope display as he threaded the catheter past the collar bone, while Romeis continued his dire threats, and got it past the two foot mark. Soon the tube was inside the heart, its tip near the right ventricle, just as Werner had planned.

Eva was asked to click an x-ray picture which she did and that image burnt the event forever into posterity. Werner pulled out the catheter slowly, sutured and dressed the wound on his elbow and everybody went home, while Werner was summoned by Schneider for a stern lecture. But the senior doctor Schneider saw the value of the experiment and the importance of the x-ray picture. He asked Werner to prepare a paper, gave him advice on how to go about it, by laying some precedence and toning down on the revolutionary aspects, so that it got accepted and then took the young lad for dinner at Kretchmer’s where they consumed several bottles of good wine. The paper was published in Klinische Wochenschrift, in Nov 1929.

As expected, it created a furor and the story became a sensation. Dr Ernst Unger another doctor who had done experiments on volunteers protested, stating that he had already done it in 1912. But they had never recorded the results or taken x-rays, so their claim reached nowhere (In reality there was one attempt carried out during the 1830’s by the founder of modern plastic surgery, Johan Dieffenbach who used a catheter to drain ‘bad’ blood from the heart of a man afflicted with cholera, a fact that Forssmann himself heard about, only in 1971).

Schneider seeing the boys genius, recommended him to a position under Sauerbrunch at Charit’e, the mecca of surgery. The collaboration was not to last long and he was fired for his new ideas while other doctors felt that he was a danger to their patients. The great Sauerbrunch then stated publically that Werner belonged in a circus, not a hospital. The hurt young man slunk back to his old position under Dr Schneider and continued self-experimentation to herald contrast radiography, this time injecting dyes into his circulation system and taking x-rays, just as they do in today’s angio-cardiography. It was as you can imagine, events benefiting the future of medicine. He published yet another paper and was invited back to Sauerbrunch’s hospital only to leave the hospital again in a huff. At this juncture, Germany was in the grip of nationalism and Nazism and like most young men, Werner was drawn into it in 1932 and to the Nazi party by a friend in Sauerbrunch’s hospital.

It was in 1932 that he met the Dr Elsbet Engel at Mainz and by 1933 they were married. His next experiment was aortography, but the painful procedures on himself were finally stopped at the insistence of his wife. He continued to experiment with catheterization in dogs and it is also rumored good naturedly that he stopped self-experimentation only when he had used all of his veins with 17 cut downs.

He never did any more experiments on himself and moved away from cardiology to work as an urologist and practice general surgery. Karl Heusch, who had been trained by Sauerbruch, opened the Virchow Krankenhaus urology department at a city hospital in Berlin, and when Heusch offered Forssmann a position as senior physician, he accepted it after some hesitation. He excelled in the position, publishing many papers on kidney, bladder, and prostate surgery. By 1936 he had moved to work with Professor Fromme in Dresden, and in 1938 he moved to the Third Surgical University Clinic in Berlin. In 1939 he was called up for military reservist training, with World War II beginning shortly afterward. Until the end of the war, Forssmann served as a frontline medical officer in Poland, Russia, and Norway.

Until 1945, he could be seen tending to the sick and injured at the war front. Towards the end, faced with the Red army on one side, Werner fled toward the Americans swimming across the Elbe, while getting strafed by the SS, and was caught and imprisoned as a POW. All he had on him were his family photos and a copy of Gothe’s Faust.

Werner Forssmann and family
(Pic Credit Werner Forssmamn: A pioneer of cardiology Forssmann-Falck, R)

When he came out of prison in 1946, life was changed. He was forbidden from practicing medicine for having collaborated with the Nazi’s. It was only in the 1950’s after the ban was rescinded that he could work again. The doctor had initially settled with his wife Elsbet in the small town of Wambach in the Black Forest and eventually, in 1950 took a position as the director of the Department of Urology in Bad Kreuznach.

The world had moved on by then, the medical field had developed further and many new techniques including Werner’s own methods were being practiced. There was a new catheterization lab in Basel and in 1951 he met Cournand. In 1954 he was awarded the highly esteemed Leibniz Medaille by the German Academy of Science in Berlin, but his attempts at becoming a professor was not to become successful because they said he had not obtained a PhD. The world passed Forssmann by, and the man who once had glory in cardiology in his sights was now tending to kidneys and bladders. As he said later after the Nobel ceremony, it was painful so see others gathered at the harvest in his own apple orchard, laughing at him.

Now we go across the pond to America to meet the other two doctors who won the prize with him, namely Andre Cournand and Dickenson Richards, who worked at the Bellevue hospital in New York. By 1930, Cournand was qualified to enter private practice and trained in pulmonary medicine at the renowned Columbia Chest Service at the Bellevue Hospital. During this residency, Cournand participated in studies of pulmonary physiology with Dr. Richards after bidding goodbye to Paris.

(Pic Credit Werner Forssmamn: A pioneer of cardiology Forssmann-Falck, R)

As Enson and Chamberlain explains, Cournand and Richards were aware of Werner Forssmann’s report of catheterizing his own heart in 1929 and of subsequent pioneering work by European radiologists who injected contrast material into the right atrium for diagnostic purposes. Despite the opposition of many renowned cardiologists of the time, over the next four years Cournand worked to demonstrate the feasibility and safety of catheterizing the right heart, first in dogs, then in a chimpanzee, and, finally, in humans. In all the early procedures, the catheter tip was positioned in the right atrium. It was feared that attempts to catheterize the pulmonary artery might be excessively dangerous. The catheters were permitted to remain in that position for prolonged periods without side effects or complications. As a consequence catheterization of this vessel became a routine feature of hemodynamic evaluations.

All this while Forssmann lived in relative obscurity, until the phone call came on Oct 12^th, 1956. As Renate Flack (his daughter) writes - The Nobel ceremony was moving and overwhelming. My father while giving his Nobel address struggled with emotions and was close to tears when he received the award by the Swedish King. Forssmann later said, “No one in West Germany has paid any attention to me,” he told reporters. “The Americans were the ones who recognized my work.” He added that in 1929, when he performed the first of nine dangerous catheterization experiments on himself, “the time was not yet ripe for this discovery.” Still, it was “a very satisfying feeling to know that my research was right.”

Upon his return from the ceremonies in Stockholm, he tried again to obtain a better position but did not succeed. In 1958, Forssmann was appointed as the Chair of Surgery at the Evangelische Krankenhaus, a large hospital in Dusseldorf, where after initial problems, he worked on as a general and trauma surgeon until his retirement in 1969.

Werner Forssmann died on June 1, 1979, following two myocardial infarctions (heart attack due to blockages in the vessels to the heart). Ironically, it was his own heart and vascular system that did him in….

He and his wife, who died in 1993, are buried in the country cemetery of Wies. His wife Elsbet was among the first women physicians in urology when she received her board certification in 1954.  All of his 6 children excelled in their careers, and among them his son, Wolf Georg, became an internationally renowned peptide researcher, and his son Bernd developed the HM1 lithotripter.

The operating room, where Werner opened his vein and inserted the catheter, and the x-ray room, where the x-rays were taken, are still in use today. I do not know if the Vereinte Aquarienfreunde meet for drinks on weekends, but I won’t be surprised if they still do though it is unlikely they have heard of the great Werner Forssmann who once drank there. I am also not aware of what happened subsequently to nurse Ditzen, technician Eva and Dr Romeis.

My son does his medical studies at the New York University and is often with patients at the Bellevue hospital, the very hospital where Cournand and Richard furthered the path breaking research of Werner Forssmann.

References

Experiments on myself – Werner Forssmann

Who Goes First? The Story of Self-experimentation in Medicine - Lawrence K. Altman

Werner Forssmann: A German Problem with the Nobel Prize H.W. HEISS, M.D.

Journey into the Heart - David Monagan

Werner Forssmann: surgeon, urologist, and Nobel Prize winner - Michael C. Truss á Christian G. Stief á Udo Jonas

Werner Forssmann: A Pioneer of Cardiology Renate Forssmann- R Falck, MD

Cournand, Richards and the Bellevue Hospital Cardiopulmonary Laboratory by Yale Enson and Mary Dickinson Chamberlin

Tailnote

Approximately 4 million cardiac catheterizations are being performed annually in the US alone. They are also performed daily in untold numbers around the world. However, in recent years, with the push to make medical care as noninvasive as possible and with the development of possible alternatives, less invasive means of monitoring are being developed, and you will see methods using nanotechnology, embedded nanobots and so on in the fore….