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Feature Christmas 2018: Look Before You Leap

Adventures in self experimentation

BMJ 2018; 363 doi: (Published 11 December 2018) Cite this as: BMJ 2018;363:k5006

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Self-experimentation and serendipity: How cardiac catheterization led the way to coronary balloon angioplasty

The paper by Parry and Buenz [1] is an enjoyable read on self-experimentation in medicine. The authors report results of their own self-experimentation studies and review some of history of self-experimentation in medicine. With regard to "famous instances of self-experimentation that have led to notable medical advances" the authors mention discoveries by William Stark, Stubbins Firth (at the time a medical student), Jesse Lazear and his colleague James Carrol, Barry Marshall, and August Bier and his Assistant August Hildebrandt.[1] The authors mention Nurse Gerda Ditzen who helped Forssmann with his experiments but do not list his discovery among these self-experiments that have led to notable medical advances.[1]

In 1929 – just out of medical school and in his first year of internship – 25-year old Werner Forssmann in Eberswalde near Berlin - after successfully performing numerous cardiac catheterizations in postmortem studies - catheterized his own right heart and with the catheter in place walked downstairs to the radiology department and obtained chest X-ray showing the catheter located in the right atrium [2]. Shortly thereafter, Forssmann successfully performed cardiac catheterization in a patient who shortly thereafter had died from sepsis that she had developed from puerperal fever, a frequent cause of death at the time; at autopsy Forssmann located the catheter's tip in the patient's right atrium [3]. About at the same time,Otto Klein in Prague, also performed cardiac catheterization in patients and calculated cardiac output in several of the patients [4], and similar studies quickly followed in other European countries and in South America, and later also in North America.

Cardiac catheterization was the first step to allow contrast imaging using X-rays and led to the accidental discovery of selective coronary angiography by Mason Sones at the Cleveland Clinic in 1958 [5]. In fact, to prove that his new method carries little risk Sones asked a colleague to perform coronary angiography on him. Only shortly thereafter, Charles Dotter in Portland accidentally reopened an occluded iliac artery during a routine aortography procedure which laid the basis for deliberate therapeutic interventions using catheters, referred to as co-axial catheter angioplasty [6,7]. Andreas Grüntzig in Zürich developed the Dotter method further. Together with his assistant Maria Schlumpf and their spouses [8] he constructed a coronary catheter with a balloon at its tip allowing him to dilate narrowed coronary arteries and saving patients from coronary artery bypass surgery [9]. Grüntzig always referred to the previous work of Forssmann and Sones and that he was 'standing on the shoulders of giants'.

Parry and Buenz argue that "self experimentation was an important part of the scientific process, allowing medical advances that would have been hard to achieve otherwise because no sane human would agree to be a research participant and no ethical review board in its right mind would approve the experiment." [1]. This is certainly true for many cases, but there have been exceptions, and the individuals involved were likely rather sane: Almost 20 years before Forssmann, Fritz Bleichröder in Berlin performed catheterization studies on his colleague Ernst Unger and also on one of his laboratory technicians [10]. What was perhaps more important is that into the 1960s discovery was often prevented by leading clinicians who preferred dogma to knowledge. As an example, in the early 1960s the Chair of Internal Medicine at the University of Zürich warned students about Swedish surgeon Åke Senning who had just been recruited as the Chair of Surgery. With his index finger raised he warned the medical students about «this dangerous young man from Sweden, who cuts into the heart without any of the respect for this organ that we have acquired in our youth» [11]. Ironically, Senning, a pioneer in his own right who invented a surgical procedure for congenital transposition of the great arteries and placed the first implantable pacemaker in a patient in 1958 [11-13] later became the only supporter of Grüntzig in Zürich and provided Grüntzig with the essential and strong backing for the first coronary balloon angioplasty in 1977 [9,14] against superiors and colleagues did not like to see Grüntzig succeed [8]. Grüntzig's discovery certainly has led to "notable medical advances": With approximately 2 million interventions annually – with about 1 million in the United States alone – coronary balloon angioplasty has now become the most frequently performed medical procedure in the world [15, 16]. Thanks to ballon angioplasty mortality of acute myocardial infarction has been reduced from around 30 percent in the 1960s to around 2-3 percent today.

1. Parry GJ, Buenz EJ. Adventures in self experimentation BMJ 2018; 363 BMJ 2018;363:k5006 doi:
2. Forssmann W. Die Sondierung des rechten Herzens. Klin Wochenschr 1929;8:2085–2087
3. Mueller RL, Sanborn TA. The history of interventional cardiology: cardiac catheterization, angioplasty and related interventions. Am Heart J 1995;129:146–172.
4. Stern S. A note on the history of cardiology: Dr. Otto Klein, 1881 to 1968. J Am Coll Cardiol. 2005;45:446-7.
5. Sones FM, Shirey EK, Proudfit WL, Westcott RN. Cine-coronary arteriography. Circulation (1959) 20:773–4.
6. Dotter CT. Cardiac catheterization and angiographic techniques of the future. background and current status of clinical catheter angiography. Cesk Radiol 1965;19:217–36.
7. Dotter CT. Transluminal angioplasty: a long view. Radiology 1980;135:561–564. doi:10.1148/radiology.135.3.7384436
8. Schlumpf M. 30 Jahre Ballonkatheter: Andreas Grüntzig ein Pioneer in Zürich. Schweiz Ärztezeit 2004; 85:346–351.
9. Grüntzig A. Transluminal dilatation of coronary-artery stenosis. Lancet. 1978;1(8058):263
10. Bleichröder F. Intra-arterielle Therapie. Berl Klin Wochenschr 1912; 49:1503
11. Säuberli HA. Åke Senning - Pionier der Schweizer Herzchirurgie in Zürich. Cardiovasc Med 2011;14:109–110
12. Cooley DA. In memoriam. Tribute to Ake Senning, pioneering cardiovascular surgeon. Tex Heart Inst J 2000;27:234–235
13. Alvarez Diaz F, Cabo Salvador J, Rivas J, Alvarado F, Cordovilla Zurdo G. Technical advances in the Senning operation. Thorac Cardiovasc Surg 1983;31:105–109.
14. Grüntzig AR, Senning Å, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med 1979; 301:61–68.
15. Barton M, Grüntzig J, Husmann M, Rösch J. Balloon angioplasty - the legacy of Andreas Grüntzig, M.D. (1939-1985). Front Cardiovasc Med 2014;1:15.

Competing interests: No competing interests

25 December 2018
Matthias Barton
Professor of Cardiology
University of Zurich
Zurich, Switzerland