Earlier, when I was teaching and discussing the cardiovascular system with medical students or nurses, I would at times tell them of Werner Forssmann’s epic experiment of self-characterization, but I knew of no other Forssmann until I learned a Dr. Wolf-Georg Forssmann was one of two German professors who had nominated me for a German Humboldt Prize.

After receiving the award, I traveled to Germany and settled in at the Klinikum Innenstadt of the University of Munich, where I worked during my Humboldt tenure. Not long after my arrival, I traveled to Hannover to meet Professor Wolf Forssmann and present a seminar in his department. He then kindly invited me and several members of his staff to dinner at his home.

During a lull in conversation during that pleasant evening, I asked Professor Forssmann, “Are you by chance related to the Werner Forssmann who catheterized his own heart?”

“I am his son,” he said. He went on to tell a bit about his father, much of which I already knew, for I had read his father’s autobiography and other articles he had published. Wolf Forssmann affirmed that his father had faced rough times after he published the account of catheterizing his own heart. His father had written, I was utterly disappointed and bewildered during this time because I felt completely misunderstood and at times rejected. The onslaught so overwhelmed the elder Forssmann that he changed his focus to urology.

But his singular experiment soon began to influence others. His methods were adopted by investigators in Prague and Lisbon, and more importantly they lit a flame in the laboratory of Drs. Andre Cournand and Dickinson Richards in New York City. Within a decade the two men were employing Forssmann’s methodology in patients, pushing their catheters into pulmonary arteries and using other techniques to accurately measure their patients’ cardiac output (the volume of blood pumped by the heart per minute). Their reports spread among clinical circles, and they credited Werner Forssmann for providing the impetus for their work. The world of cardiology was changing rapidly, a change duly noted in Sweden.

In 1956, the Nobel Prize in Physiology or Medicine was awarded jointly to André Cournand, Werner Forssmann and Dickinson Richards “for their discoveries concerning heart catheterization and pathological changes in the circulatory system.”

It’s generally reported that Forssmann was shocked when he received that special telephone call informing him that he had won the prize. Some accounts claim that he responded by asking, “For what?”

Werner Forssmann’s fame grew quickly as the news spread. He received other honors, and his sudden prestige led to his being named chief of the surgical division of the Evangelical Hospital in Düsseldorf, a far cry, and sudden jump, from his days of private practice. One wonders. Did his honors, and his sudden fame, erase the pain of his earlier treatment? This is what he later wrote:

Even later recognition or fame cannot eliminate the scars which he [the young scientist] acquired during his struggle.  Few have the good fortune after self-denial and personal renunciation, enmities, and humiliations, to achieve recognition and the crown of glory from a grateful younger generation, and even this is no consolation for what the scientist has been through. The young scientist of which he spoke surely was his earlier self.

As he wrote in his autobiography (Experiments on Myself: Memoirs of a Surgeon in Germany [English translation published in 1974] St. Martin’s Press, New York). The Nobel Prize changed our life drastically. Let me say at once this had nothing to do with the money that came with it. In fact the practice Elsbet and I had built up in Bad Kreuznach was so profitable that we had no worries. And one page later, One unpleasant aspect was that we had suddenly become socially desirable.

His autobiography also reveals the thoughts he’d had while listening to the Nobel lectures given by Cournand and Richards. Those lectures revived for me the old doubts of which I’d never been able to dispel. It was true that I had opened the door to modern cardiology. But in the meantime it had outgrown me, and I would never be able to catch up. In my youth I had tried to plant a lovely garden, and now, as an old man I was forced to watch over the hedge while others picked the apples.

I’ll end this story of Werner Forssmann with three sentences that make me smile. They appear near the end of his autobiography.

At the same time I realized I had indeed reached the height of fame. My son, Knut, sent me from Barcelona the wrapper from a new brand of Spanish cigars, on which my picture was printed. You can’t go much further than that.

Some medical discoveries fade as they settle into history. Others glow brightly. Here’s a little quiz for you. The poliomyelitis virus was a nasty crippler and killer that terrorized the world until the mid-1950s. Which of the following won the Nobel Prize for their work on the polio virus?

1. John Enders
2. Jonas Salk
3. Thomas Weller
4. Frederick Robbins

Most of you probably think that’s way too easy. Well, let’s see how you did. If you answered 1, 3, and 4, you’re an undisputed champion. Congratulations! You nailed it! Enders, Weller, and Robbins won the Nobel Prize in Physiology or Medicine in 1954, winning that prestigious award for developing a method to culture the polio virus in human tissues, the vital discovery that enabled production of enough virus to develop a vaccine.

I mention this bit of history not to disparage Salk, who never won a Nobel Prize but later was the first to develop a successful vaccine against polio, and thus became justifiably famous after standing on the shoulders of the above three. Albert Sabin was another vaccine developer. A few years after Salk’s contribution, Sabin came up with an effective oral vaccine.

Now let’s shift our attention to the heart with another quiz, one likely to stump most of you. Which of the following won the Nobel Prize for their work on cardiac catheterization in 1956, the time when such catheterizations were beginning to take off?

1. André. Cournand
2. Samuel Pepys
3. Dickinson Richards
4. Werner Forssmann

Okay, I rigged this one, making the same three choices correct. Yep, 1, 3, and 4 ring the correct bell. Oh, raise your hand if you smiled when you saw Samuel Pepys.

Until the 20th century, the human heart understandably was an organ doctors stayed away from. So when a man’s beating heart finally was invaded by a catheter, an event documented by x-rays, the news flew around the world.

That first catheterization wasn’t performed, as you might expect, in a major academic institution. It was done nearly a century ago in a small hospital some 30 miles from Berlin by an unsupervised 25-year-old German doctor. His name was Werner Forssmann, and the heart he catheterized was his own.

Forssmann was a surgical resident in 1929, when he calmly anesthetized the inner side of his left elbow, sliced through his skin with a scalpel, and inserted a catheter into the arm vein he had exposed. After pushing most of the catheter’s two-foot length into his body, Forssmann walked the long distance from the surgery suite to the x-ray department and even climbed a stairway with blood dripping as the catheter dangled from his arm. At last he stood in front of a fluoroscopy screen and viewed his insides through a mirror held by an obliging nurse. He could see plainly the end of the catheter twitching within his right atrium. He took x-ray films of his chest and arm to document his achievement.

 

Sorry, this a copy of a copy and it doesn’t show up very well. but perhaps you can at least see the dark thin line (the catheter) going up from the arm to the upper part of the chest before it turns down toward the heart.

His intent, the young German doctor wrote later that year, had been to devise a better way to administer drugs directly into the heart during certain emergencies, the prevailing method at the time being to jam a long needle through the patient’s chest wall and blindly inject substances directly into the heart, a method more likely to kill than cure.

“While sliding the catheter in I had a feeling almost of soft warmth on my vein wall,” he wrote, and when the catheter entered his chest, “an especially intense warmth behind the clavicle [collarbone].” He also noted a dry cough, presumably triggered when the catheter’s movement irritated nerves in his chest.

Other than these sensations during the episode, the young doctor reported, “I felt nothing.” Even afterward he felt nothing detrimental, “aside from a slight inflammation at the site of the venesection, which probably resulted from faulty sterilization during my self-operation.” His method, he added with justifiable youthful pride, “opens up countless vistas of new possibilities.”

Surely the young Forssmann never imagined the extraordinary advances that ultimately followed his brave solo venture with a catheter. Nor did he foresee the troubles soon to strike him, the jabs and insults whipped up by his daring experiment, woes that followed him through much of his life.

The story will continue.

This piece is a bit different from others I’ve written here. I wrote this one years ago and published it in the Kansas City Star. I dug out a clipping of it today, retyped it with minimal changes (it originally was written with a typewriter), and here it is, an old story revived. I hope it holds your interest.

Medical researcher takes 2 ½ times the lethal dose of South American arrow poison – and survives. That might have been the gist of a newspaper headline years ago, if the press had been notified of a dramatic medical experiment that received little attention at the time.

Consider this background. A purified preparation of the arrow poison, curare, became available for medical use in the 1940s, and small doses of the purified preparation (d-tubocurarine) proved to be extremely useful during surgical operations, because the drug caused muscular relaxation and eased the work of surgeons.

Claude Bernard, the great 19^th century physiologist, had shown that curare causes paralysis by blocking nerve impulses just as they reach voluntary muscles at a site called the neuromuscular junction. That’s how the poison kills. It paralyzes the muscles of respiration and produces asphyxia. But no one knew whether curare had anesthetic effects on the brain.

Curare almost always was given along with a general anesthetic, but on rare instances it had been used as the sole agent during operations on infants and children. Did they feel pain? Nobody knew. They may have suffered needless pain during their operations.

Some scientific reports indicated that the drug did reduce or even abolish the electrical activity of brain cells in experimental animals, and one investigator believed his results with dogs demonstrated that curare caused complete unconsciousness or amnesia, but his conclusions were widely criticized.

A group of anesthesiologists in Salt Lake City decided to do what was needed, an experiment on a trained medical observer given large doses of curare. One of the group, Dr. Scott M. Smith, 34, volunteered to be the guinea pig.

The experimental plan was simple. When the paralysis from curare became so severe that it prevented Dr. Smith from talking, he would indicate affirmative answers by contracting whatever muscles he could still move. When paralysis was complete, he would make mental notes of his experiences. The team would keep him alive with artificial ventilation.

The experiment was performed one January afternoon at the University of Utah Medical Center in 1946. Electrodes were placed on Dr. Smith’s scalp and arms to record his brain waves and electrocardiogram. His initial blood pressure was 130/70; pulse 92; respiratory rate 16.

A catheter was placed into one of his arm veins, and an infusion of saline began flowing into his blood stream. Curare was injected through the catheter.

Dr. Smith reported feeling “a bit of a glow.” His jaw muscles weakened. He found it “hard to talk.” Swallowing was difficult. Keeping his eyes open was an effort. His legs felt weak.

Seven minutes after he began receiving the drug, he requested oxygen by face mask. “Can hardly bring teeth together,” he said. One hundred units of curare had been given.

Moments later he lost his ability to speak, though he could make sluggish movements of his hands and head. He signaled that he was clear mentally and that he could hear distinctly. Artificial respiration was started when his breathing weakened.

After receiving one hundred and fifty units of curare: blood pressure, 130/70; pulse, 106; respiration now maintained artificially.

Thirteen minutes into the experiment, strain as he might Dr. Smith no longer could move his head or open his eyes. He answered questions by wrinkling his forehead. Yes, he could see clearly when his eyelids were elevated manually by another member of the team.

He could barely move his limbs, yet he indicated he wanted the experiment to continue. Questions restated in the negative or double negative were answered correctly by appropriately wrinkling or not wrinkling his forehead.

A pin was jabbed into his skin. Yes, he felt the pain. Two hundred units of curare had been given.

Nineteen minutes into the experiment: blood pressure, 130/70; pulse, 100. Paralysis of his diaphragm and chest wall made him totally dependent upon artificial respiration. Secretions accumulated in his throat. These were removed with a suction tube. Wrinkling of his forehead grew weaker.

Dr. Smith indicated that he wanted the next 100 unites of curare rapidly, as planned. The drug was given; 300 units had been administered.

Slowly, inexorably, the curare sapped Dr. Smith’s remaining strength. His voluntary movement now consisted of a slight twitch of his left eyebrow. When his eyelids were manually elevated, he would report later, he saw double images. Paralysis of his eye muscles prevented him from aligning his eyes, thus causing the double vision. He perceived objects clearly when they were placed in his line of gaze.

Did he want an additional 100 units of curare? His left eyebrow twitched the answer. Yes.

His communication with the rest of the team was limited to an almost imperceptible movement of the inside portion of his left eyebrow. He indicated that he was perfectly conscious. He wanted an additional 100 units of curare. This final dose was given rapidly.

For the next 11 minutes, Dr Smith was unable to communicate with the rest of the experimental team. He was totally paralyzed, his life completely in the hands of the experienced team surrounding him.

He could not talk. He could not breathe. He could not open his eyes. He could not signal any discomfort or any need. Yet, as he was later to relate he was “clear as a bell” during this entire time. Blood pressure, 130/84; pulse, 120.

A co-worker removed Dr. Smith’s face mask and slipped a breathing tube into his throat, through his voice box and into his windpipe. This was a check of the subject’s perception of internal pain. The procedure caused less pain than anticipated, he later related, probably because of his extreme muscular relaxation. Several breaths of air were forced in and out of his lungs before the tube was withdrawn and artificial respiration was resumed through the face mask.

“I felt that I would give anything to be able to take one deep breath,” he said following the experiment. “The period of a few seconds taken for the tracheal intubation seemed unusually long, and I was awfully glad when artificial respiration was resumed.” Sensations of “shortness of breath” and “choking” troubled him during the period of paralysis even though he received adequate oxygen.

Neostigmine, a drug which counteracts the effects of curare, was injected into Dr. Smith’s blood stream. Blood pressure, 130/100; pulse, 100. He still could not move a single muscle.

More neostigmine was injected. As the antidote began to take effect, the subject was able to move the inside portion of his left eyebrow. The last muscle to become paralyzed was the first to recover.

Communication was now reestablished. Dr. Smith signaled he could hear and see normally. He indicated he wanted more neostigmine. Droplets of moisture formed on his forehead. His eyes watered.

Fifty minutes into the experiment: blood pressure, 140/90; pulse, 80. Weak breathing movements appeared.

Moments later he could open his eyes with difficulty. More neostigmine was administered. His breathing movements became more prominent. Large quantities of secretions collected in his throat. These were aspirated periodically by one of his colleagues.

Dr. Smith’s forehead began wrinkling vigorously. By a long series of questions it was finally discovered that the accumulating secretions were most annoying to him. He desired more frequent aspiration of the secretions.

One hour had elapsed since the first dose of curare had been injected. In spite of the frequent aspirations, he continued to experience a “choking” sensation. Rivulets of sweat ran from his forehead.

Even the briefest moment of discontinuing artificial respiration was most uncomfortable to him. He signaled that it be continued without pause. He regained some voluntary control of his tongue, but he could not yet speak. More neostigmine was injected at his request.

One hour and fifteen minutes into the experiment. With great effort, he was able to say several words, weak and slurred, but understandable.

His speech gradually became clear. “I probably could get by without artificial respiration, but still want it.” He could open his eyes more easily. He preferred to keep them shut.

“Will be glad when I can swallow.” He was able to cough weakly. Blood pressure, 120/70; pulse, 88.

Artificial respiration was stopped one hour and 20 minutes after it had begun. The subject could swallow with difficulty.

His use of voluntary muscles gradually returned. Two hours and 25 minutes after the initial dose of curare, he was talking freely, describing his unusual experience. A short time later he sat on the edge of the bed, with assistance.

He later complained of feeling drowsy (for the first time) and reported feeling “uneasy.” He also was nauseated for a brief time.

He improved progressively over the next several hours, but some muscle weakness persisted throughout the evening.

Dr. Smith’s keen awareness through the entire experiment clearly indicated that curare did not depress the brain. In fact he believed that his hearing may have been more acute under curare. He distinctly heard remarks whispered some 20 feet away.

He and his co-workers published their findings in the journal Anesthesiology, advising that “curare not be used alone in surgical procedures but that it be employed only as an adjuvant with agents capable of relieving pain and obtunding consciousness. This suggestion holds not only for adults but also for children in whom a painful experience, even though not reportable to the physician, may constitute a serious psychic trauma.”

After this report was published, Dr. Smith received many requests for additional information concerning his experience while under influence of curare, among them being psychiatrists who wanted to psychoanalyze him, presumably to determine what sort of person would volunteer for such an experiment, or maybe to learn whether his experience had any residual effect on him. Apparently it did not. Dr. Smith went on to a distinguished career in anesthesiology.