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Therapeutic Pneumothorax and the Nobel Prize

2015; Elsevier BV; Volume: 100; Issue: 2 Linguagem: Inglês

10.1016/j.athoracsur.2015.03.100

1552-6259

Nils Hansson, Igor J. Polianski,

Mental Health and Psychiatry

At the turn of the 20th century, the epidemic proportions of tuberculosis puzzled great parts the scientific community. Thus it is not surprising that well-known scholars who worked on particularly promising solutions to fight the disease were nominated for the Nobel Prize for Physiology or Medicine, perhaps the most prestigious benchmark of scientific excellence. The authors have gathered files on the Italian phtisiologist Carlo Forlanini (1847 to 1918) at the Nobel Prize archive for Physiology or Medicine in Solna, Sweden. Drawing on these files and contemporary publications, the authors discuss the origin of artificial pneumothorax for treating pulmonary tuberculosis, show how it became an international gold standard operation, and trace why the Nobel committee finally chose not to award Forlanini. Twenty Nobel Prize nominations for Forlanini were submitted from 1912 to 1919 exclusively by Italian scholars. In 1913 and 1914, Forlanini was on the shortlist of the Nobel Committee and thus one of the prime candidates for the prestigious prize. Important aspects of the rise, fall, and revival of the artificial pneumothorax from 1815 to 2015 are highlighted along with its benefits and risks. At the turn of the 20th century, the epidemic proportions of tuberculosis puzzled great parts the scientific community. Thus it is not surprising that well-known scholars who worked on particularly promising solutions to fight the disease were nominated for the Nobel Prize for Physiology or Medicine, perhaps the most prestigious benchmark of scientific excellence. The authors have gathered files on the Italian phtisiologist Carlo Forlanini (1847 to 1918) at the Nobel Prize archive for Physiology or Medicine in Solna, Sweden. Drawing on these files and contemporary publications, the authors discuss the origin of artificial pneumothorax for treating pulmonary tuberculosis, show how it became an international gold standard operation, and trace why the Nobel committee finally chose not to award Forlanini. Twenty Nobel Prize nominations for Forlanini were submitted from 1912 to 1919 exclusively by Italian scholars. In 1913 and 1914, Forlanini was on the shortlist of the Nobel Committee and thus one of the prime candidates for the prestigious prize. Important aspects of the rise, fall, and revival of the artificial pneumothorax from 1815 to 2015 are highlighted along with its benefits and risks. At the turn of the 20th century, the artificial pneumothorax (abbreviated PNX) became the treatment of choice in most severe cases of pulmonary tuberculosis. Also known as lung collapse therapy and therapeutic pneumothorax, PNX was unable to cure the disease completely, but it intervened in the disease process, slowing down its progression. However, from its inception collapse therapy was highly controversial due to the frequent complications associated with its use. On the one hand this “great benefit to mankind” (Nobel Archive [NA], nomination for Carlo Forlanini by Camillo Golgi in 1914) was put forward on multiple occasions for the Nobel Prize for Physiology or Medicine. On the other hand the pneumothorax needle was called “the most dangerous weapon ever placed in the hands of a physician” [1Birath G. The place of pneumothorax in the present-day management of pulmonary tuberculosis.Diseases of the Chest. 1959; 35: 1-5Crossref PubMed Scopus (1) Google Scholar]. In the pre-antibiotic era there was no satisfactory alternative. In addition to the infamous spittoon, called “Blue Heinrich,” the pneumothorax device became a distinctive signature of medical culture and everyday life of the early 20th century. In Thomas Mann's novel “Magic Mountain,” for example, a group of patients at a sanatorium in Davos, Switzerland, referred to themselves ironically as “fraction of half lungs” because they were being treated with PNX and whistling from their pneumothorax hole [2Mann T. The Magic Mountain. Secker and Warburg, London1927Google Scholar]. However, after the discovery of specific chemotherapy artificial pneumothorax fell into disuse, and by the beginning of the 1960s the method was seen as obsolete [3Barry V.C. Chemotherapy of tuberculosis. Butterworths, London1964: 270Google Scholar]. But there is life in the old dog yet. Although statistics show that tuberculosis (TB) prevalence and mortality rates are slowly declining each year, it remains one of the world’s deadliest communicable diseases. According to WHO [the World Health Organization] one third of the world’s population is infected with Mycobacterium tuberculosis and about 1.5 million people died from TB in 2013 worldwide. For developed countries the anti-tuberculosis drug resistance might become a major public health problem in the near future. The WHO estimates that there were 480,000 new multidrug-resistant tuberculosis cases in the world in 2013 [4World Health Organization, Global tuberculosis report 2014. Available at http://www.who.int/tb/publications/global_report. Accessed March 20, 2015.Google Scholar]. A recent case report suggests that the therapeutic pneumothorax provides promising results in cases of multiple-drug-resistant TB at least as an adjuvant to antimycobacterials [5Hayes Jr., D. Meyer K.C. Ballard H.O. Revisiting an old therapy for tuberculosis.Resp Care. 2009; 54: 542-543PubMed Google Scholar]. In addition, there are some further lung surgery procedures where application of the lung collapse might be useful; however, not related to TB treatment [6Zhang R. Liu S. Sun H. et al.The application of single-lumen endotracheal tube anaesthesia with artificial pneumothorax in thoracolaparoscopic oesophagectomy.Interact Cardiovasc Thorac Surg. 2014; 19: 308-310Crossref PubMed Scopus (25) Google Scholar, 7Saikawa D. Okushiba S. Kawata M. et al.Efficacy and safety of artificial pneumothorax under two-lung ventilation in thoracoscopic esophagectomy for esophageal cancer in the prone position.Gen Thorac Cardiovasc Surg. 2014; 62: 163-170Crossref PubMed Scopus (35) Google Scholar]. The irony of the story: It was not the first time when PNX first fell into disgrace and was rehabilitated later. In this historical vignette, we will take a closer look at the rise of the PNX with particular focus on the Nobel Prize candidacy of the Italian dermatologist and phthisiologist Carlo Forlanini (1847 to 1918). Although more than 130 years have passed since Forlanini's original paper on PNX was published, it is still cited on a regular basis [8Forlanini C. A contribuzione della terapia chirurgica della tisi polmonare. Ablazione del polmone? Pneumotorace artificiale?.Gazz Osp. 1882; ([Article in Italian]): 68-89Google Scholar]. Drawing on contemporary publications and archive files at the Nobel Archive in Sweden, we will discuss the origin of PNX, how it became an international gold standard, and trace why the Nobel committee finally chose not to award Forlanini. Tuberculosis was still a common cause of death among adults during the early 20th century. On the eve of World War I, the proportion of tuberculosis in the overall mortality rate reached, for example, for the City of Vienna, 20% to 25% [9Junker E. Wallner G. Die Tuberkulosebekämpfung im Wandel der Zeiten [Article in German].Imago Hominis. 2004; 11: 193-206Google Scholar]. In 1914, the pulmonary tuberculosis mortality rate was approximately 10 per 10,000 in Great Britain [10Wilson L.G. The historical decline of tuberculosis in Europe and America: Ist causes and significance.J Hist Med Allied Sci. 1990; 45: 366-396Crossref PubMed Scopus (75) Google Scholar]. The corresponding numbers were 16 in Germany and 23 in France [11Brügmann E. Die Bewegung der Tuberkulosesterblichkeit im I. und II. Weltkrieg und ihre Ursachen.Beitr. z. Klin. der Tuberk. 1947; 101 ([Article in German]): 94-104Crossref Scopus (3) Google Scholar]. After the outbreak of World War I it increased even more dramatically [12Naef A.P. The 1900 tuberculosis epidemic—starting point of modern thoracic surgery.Ann Thorac Surg. 1993; 55: 1375-1378Abstract Full Text PDF PubMed Scopus (13) Google Scholar]. Thus it is not surprising that well-known scholars who worked on particularly promising solutions were nominated for the Nobel Prize for Physiology or Medicine, perhaps the most prestigious benchmark of scientific excellence. For example, Robert Koch (1843 to 1910) had been a nominee more than 50 times before he was awarded the Nobel Prize in 1905 for his investigations and discoveries in relation to tuberculosis. As hinted above, Forlanini was another strong candidate for the Nobel Prize due to his work on artificial pneumothorax. To conduct PNX, Forlanini pumped filtered compressed air into the pleural space. The procedure reminds of thoracentesis, with the difference that no fluid is removed. This mechanical approach allowed further progression of tuberculosis lesions to be prevented in certain circumstances. Various hypotheses have been offered as to the causes of this favorable effect. Some believed that the temporary immobilization of the lung and mechanical pressure permitted the draining and closure of tuberculosis cavities. Other proposed mechanisms included the reduced absorption of toxic metabolites of the pathogen and an increase in the body’s defenses through the stimulation of lymphocytosis [13Riviere C. The pneumothorax treatment of pulmonary tuberculosis. Oxford University Press, London1917: 6-12Google Scholar]. To penetrate and introduce air into the pleural space a “pneumo device” was used, which consisted of a hollow needle, hydraulic pump, and pressure gauge. Forlanini first tested the method in a clinical experiment in 1888 [14Sakula A. Carlo Forlanini, inventor of artificial pneumothorax for treatment of pulmonary tuberculosis.Thorax. 1938; 38: 326-332Crossref Scopus (34) Google Scholar]. The reports of the first successful treatments followed in 1894 and on a more representative and international scale in 1906 [15Forlanini C. Zur Behandlung der Lungenschwindsucht durch künstlich erzeugten pneumothorax.Dt Med Wochenschrift. 1906; 32 ([Article in German]): 1401-1405Crossref Scopus (9) Google Scholar]. General disappointment about the failure of tuberculin as a cure for tuberculosis provided a boost to the development of Forlanini’s method at the beginning of the 20th century. Forlanini achieved a breakthrough in 1912, when his report at the Seventh International Congress in Rome was followed by frenetic applause [14Sakula A. Carlo Forlanini, inventor of artificial pneumothorax for treatment of pulmonary tuberculosis.Thorax. 1938; 38: 326-332Crossref Scopus (34) Google Scholar]. The very same year he attained his first nomination for the Nobel Prize for Physiology or Medicine. From 1912 to 1919, Forlanini was nominated at least 20 times for the Nobel Prize. The historian Elisabeth Crawford has called candidates who attract many votes from one specific country “favourite sons” [16Crawford E. Internationalism in science as a casualty of the First World War: relations between German and Allied scientists as reflected in nominations for the Nobel prizes in physics and chemistry.Social Science Information. 1988; 27 (177ff): 163-201Crossref Scopus (22) Google Scholar]. That label can be attached to Forlanini, as all of his nominators were Italian professors of medicine. They put forward several arguments to try to convince the prize jury why Forlanini should be seen as “the person who shall have made the most important discovery within the domain of physiology or medicine” (Will of Alfred Nobel, 1895) [17Full Text of Alfred Nobel's Will. Available at http://www.nobelprize.org/alfred_nobel/will/testamente.html. Accessed February 13, 2015.Google Scholar]. Three of the nominations for Forlanini were submitted by his close friend Camillo Golgi (1843 to 1926) from Pavia, who, as a former Nobel Laureate (1906) had the right to propose a candidate each year (NA, yearbooks of 1912, 1917, 1919). In his nominations, Golgi argued that Forlanini's PNX method had been of “great benefit to mankind,” another phrase that Alfred Nobel had used in his will. A. de Giovanni from Padua stressed in his nomination letter of 1913 that Forlanini had opened up a new scientific avenue (NA, Giovanni 1913). Because at least some members of the Nobel committee saw great potential in PNX, Forlanini was viewed as one of the prime Nobel Prize candidates during 1913 and 1914. Why did he not receive the Prize? In 1913, Johan Gustaf Edgren (1849 to 1929), professor of internal medicine at the Karolinska Institute Sweden was chosen as Nobel committee evaluator of Forlanini, probably because pulmonary tuberculosis was one of his main scientific interests. Edgren's key arguments for Forlanini were that the method had significant theoretical weight, probably based on earlier observations that spontaneous pneumothorax could promote healing, and sound practical evidence. “Thanks to Forlanini's treatment, a substantial number of hopeless patients have regained their health and their working ability. With more experience and an improved technique, even better results are to expect” (NA, Evaluation of Forlanini by Edgren in 1913). Edgren concluded that Forlanini was prize-worthy, but the other members of the prize jury voted in favor of other candidates. Significant for the non-awarding apparently was a reference to the current debate and confusion about the risks of therapy in the report. Edgren was not as overwhelmed as Forlanini's nominators or other commentators, who proposed that PNX should be considered even for healthy patients to prevent tuberculosis [18Rosenblatt M.B. Pulmonary tuberculosis: evolution of modern therapy.Bull NY Acad of Med. 1973; 49: 163-196PubMed Google Scholar]. He pointed out that the method was tricky, and that it even might be harmful in some cases. Although PNX was associated with a high percentage of favorable outcomes (eg, substantial improvement of symptoms could often be observed within a few days of treatment), frequent complications frustrated its general acceptance. The German phthisiologist Karl Mosheim stated in 1905 that “disparate views” circulate in this question and the “positions are in a state of fermentation” [19Mosheim K. Die Heilungsaussichten der Lungentuberkulose bei spontanem und künstlichem Pneumothorax [Article in German].Beiträge zur Klinik der Tuberkulose. 1905; 3 (p. 334): 331-396Crossref Scopus (1) Google Scholar]. Finally, the pneumothorax itself was regarded as a severe complication of tuberculosis. Thus it was no wonder that most doctors hesitated. During the 1910s in Germany and the United Kingdom, many experts only recommended the so-called gas chest treatment “as a last resort in apparently hopeless cases” after all alternatives had been exhausted [20Morgan P. Artificial pneumothorax in the treatment of pulmonary tuberculosis.QJM. 1917; : 1-17Crossref Scopus (2) Google Scholar, 21Gutstein M. Der künstliche Pneumothorax: Uebersichtsreferat [Article in German].Berl Klin Wochenschrift. 1918; 48: 1152-1155Google Scholar, 22Winkler A. Über plastische Pleuritis bei künstlichem Pneumothorax [Article in German].Beiträge zur Klinik der Tuberkulose und spezifischen Tuberkulose-Forschung. 1923; 54: 335-343Crossref Scopus (2) Google Scholar]. When performed on elderly patients or those with large chest cavities, artificial pneumothorax was associated with a worsening of symptoms. If the lung did not release from the pleura, pleural ruptures and dangerous infections would occur [23Heaton T.G. Complications of artificial pneumothorax. A review.Can Med Assoc J. 1936; 35: 399-405PubMed Google Scholar]. Pneumopleuritis was most feared, which, if it became septic, claimed patients’ lives. Initially, there was no clear understanding of the frequency of pleuritis (10% to 70%, according to different observers), its cause, or its prognosis. Most pulmonologists attributed pneumopleuritis to endogenous factors that could not be influenced by the clinician (eg, the tuberculosis pathogen itself). Some even reported the beneficial side effects of pleural effusions. However, other skeptics cited mechanical irritation, decreasing tissue resistance, and secondary infection as complications of the therapy, stoking fears of its consequences [24von Muralt L. Der künstliche pneumothorax. Springer, Berlin1922Google Scholar]. As a result, use of artificial pneumothorax was widely disputed for some time, a fact that may have influenced the negative decision of the Nobel Committee in 1913. In 1914, the gynecologist and Nobel Committee member Frans Westermark (1853 to 1941) evaluated Forlanini (NA, Westermark 1914). Westermark meant that the value of the operation decreased significantly because of its risks, ranging from pleural effusion, emphysema, pleura-eclampsia and empyema, to cerebral embolism. The intensification of the criticism had to do with a typical paradox of the medical practice. Giovanni emphasized in his nomination letter from 1913: “Promising studies on PNX have now been conducted in Italy, Germany, Austria, Hungary, Russia, France, Switzerland, Denmark, Sweden, Norway, Spain, the USA and South America” (NA, Giovanni 1913). In fact, the treatment enjoyed increasing popularity, acceptance, and distribution. In Russia, for example, the method was applied for the first time as early as 1910 by Arkadij N. Rubel (1867 to 1937) [25Rubel A.N. Bol’šaja sovetskaja ėnciklopedija, tom 37. Sovetskaja ėnciklopedija, Moskva1955: 277Google Scholar]. In 1912 he wrote the very first monograph on this issue and contributed significantly to its popularization in the Russian Empire [26Rubel A.N. Iskusstvennyj pnevmotoraks pri lečenii tuberkuleza legkich. Technika operacii. Praktičeskaja medicina, St. Peterburg1912Google Scholar]. However, the more the method spread, the less strict criteria were applied to the indication of PNX. In case of poor patients it was even considered to apply the PNX in the early stages of TB because it was cheaper than a sanatorium stay [27Blümel Zeitschrift für Tuberkulose [Article in German]. 1915; : 5-23Google Scholar]. Thus the less experienced physicians dared to apply the method. Under these circumstances, the absolute number of reports about complications and deaths grew like a snowball rolling downhill, even though the method itself had been continuously improved [28Sachs T.B. Artificial pneumothorax in the treatment of pulmonary tuberculosis: results obtained by twenty-four American observers.JAMA. 1915; 65: 1861-1866Crossref Scopus (5) Google Scholar]. However, Westermark did not only strengthen the criticism of the method and its side risks. He also pointed out that the PNX method had been investigated twice from different angles by Forlanini's assistants; S. Riva Rocci had worked on pathological, anatomical, and physiological questions, whereas G. Cavallero and Riva Rocci had investigated the respiratory function. Westermark also highlighted other potential scientific priority disputes as other scholars, such as Murphy and his assistant Lemke (USA), Toussaint and Dumarest (France), Brauer, Spengler, v. Muralt (Germany), and Saugmann (Norway), had worked on similar methods. In fact, the US-American surgeon John B. Murphy (1857 to 1916) presumably, though uninformed of preliminary work of Forlanini, suggested the treatment of unilateral disease of the lungs by PNX in 1898. He developed his own version of lung collapse using the open incision of skin and muscle instead of a puncture technique by a needle [29Murphy J.B. Surgery of the lungs.JAMA. 1898; 31 (151.65;208-16;281-97;341–356)Google Scholar]. Although the method did not generate interest in his homeland, it achieved much praise in Germany [14Sakula A. Carlo Forlanini, inventor of artificial pneumothorax for treatment of pulmonary tuberculosis.Thorax. 1938; 38: 326-332Crossref Scopus (34) Google Scholar]. This raised the question of priority and prompted Forlanini in 1906 to publish the results with more international resonance in a German journal [15Forlanini C. Zur Behandlung der Lungenschwindsucht durch künstlich erzeugten pneumothorax.Dt Med Wochenschrift. 1906; 32 ([Article in German]): 1401-1405Crossref Scopus (9) Google Scholar]. However, that could not prevent that the term “Forlanini-Murphy method” infiltrated the professional discourse [30Bände. La Revue Internationale de la Tuberculose. [Article in French] 1913;23-4;137;144.Google Scholar, 31Martin F.H. Surgery, gynecology & obstetrics. Franklin H.30. Martin Memorial Foundation, 1920: 161Google Scholar, 32Fishberg M. Pulmonary tuberculosis. Lea & Febiger, Philadelphia1922: 797Google Scholar]. Certainly the Nobel Prize Committee was aware of it as Murphy was nominated for the Nobel Prize in 1912 by W. A. Evans from Chicago (NA, Nobel Prize nomination for Murphy by Evans in 1912). In conclusion, Westermark found Forlanini's method neither original nor brilliant enough to warrant a Nobel Prize, even if he also gave some optimistic comments. In accordance with the nomination by Giovanni, Westermark acknowledged that Forlanini had directed the interest of numerous scholars to study the pathophysiology of the lung, and that being a fine achievement in itself. He also remarked that Forlanini started his trials on “hopeless cases.” It was only in 1906, when being convinced that the procedure was “pretty safe,” that he made the indication list much broader. But all that was obviously not sufficient. Safety, priority, originality, these criteria were not considered fulfilled. What about Forlanini's predecessors? The Nobel committee member Westermark demonstrated a deeper knowledge of history and mentioned the Scottish physician James Carson (1772 to 1843). If we really could ascribe the priority of the invention to this scholar, then we should celebrate the bicentenary of the method in 2015. In March 1815, originally inspired by his more established colleague John Hunter (1728 to 1793), Carson launched a series of animal experiments on the contractile power of the diaphragm and collapsing of the lungs, which were the starting points for far-reaching and fruitful speculations and considerations about the therapeutic use of pneumothorax [33Carson J. An inquiry into the causes of respiration; of the motion of the blood; animal heat; absorption; and muscular motion; with practical inferences. London: Longman, Rees, Orme, et al. 1815;105-16;231.Google Scholar]. However, it took another 6 years before, in November 1821, he ventured to present his ideas to the Literary and Philosophical Society of Liverpool [34Keers R.Y. Two forgotten pioneers. James Carson and George Bodington.Thorax. 1980; 35: 483-489Crossref PubMed Scopus (8) Google Scholar], where it produced, in his own words, “a considerable sensation” [33Carson J. An inquiry into the causes of respiration; of the motion of the blood; animal heat; absorption; and muscular motion; with practical inferences. London: Longman, Rees, Orme, et al. 1815;105-16;231.Google Scholar]. The idea was, for its time, highly innovative:“It appeared to be practicable to remove those two causes of the impediment to the cure of wounds, by reducing the diseased lung to a state of collapse. This would evidently be done by admitting the air into the cavity of the chest, by an opening through the side, and preserving the passage to it free for a sufficient time. The lung would, by those means, be reduced to a state of quiet collapse, and the wound would be brought together […] The disease, if in one lung only, as frequently happens, would be cured by this process alone.” Almost a year later, the opportunity for a human experiment arose. Carson selected the “hopeless” case of James Sloane, a merchant of Liverpool who returned after an unsuccessful cure travel to West-India in the terminal stage of consumption to Scotland and was willing to undergo the procedure. Unfortunately this trial failed completely because the lung did not collapse due to extensive adhesions in all areas between the lung and pleura [33Carson J. An inquiry into the causes of respiration; of the motion of the blood; animal heat; absorption; and muscular motion; with practical inferences. London: Longman, Rees, Orme, et al. 1815;105-16;231.Google Scholar]. The implementation of the lung collapse and the prevention of gas embolism were only possible when the surgery took place outside of the adhesions zones [35Grenier E. Artificial pneumothorax in the treatment of pulmonary tuberculosis.Can Med Assoc J. 1919; 9: 141-143PubMed Google Scholar]. This became an obstacle for the further fate of the idea. After another operation with disappointing outcome, Carson finished his attempts at collapse therapy completely and turned to alternative methods of treatment [34Keers R.Y. Two forgotten pioneers. James Carson and George Bodington.Thorax. 1980; 35: 483-489Crossref PubMed Scopus (8) Google Scholar]. Besides, if we remember that in the time of Carson antisepsis or asepsis did not yet exist, the long-term opening in the chest wall would have had little chance of success. It was hard to localize adhesions exactly solely by percussion until Murphy introduced X-rays controlled pneumothorax in 1898 [29Murphy J.B. Surgery of the lungs.JAMA. 1898; 31 (151.65;208-16;281-97;341–356)Google Scholar]. The next milestone in the diagnosis and treatment of adhesions followed in 1911, after the Swedish physician Hans Christian Jacobaeus (1879 to 1937) introduced his technique of laparoscopic adhesiolysis [36Jacobaeus H.C. Kurze Übersicht über meine Erfahrungen der Laparo-Thorakoskopie.Münch Med Woch. 1911; 58 ([Article in German]): 1612Google Scholar]. Consequently, the evaluations of the successor generation of physicians were generally pessimistic until the 1860s, even if occasional speculations that spontaneous pneumothorax may be beneficial to the progression of tuberculosis were published [37Toussaint E. Sur la marche de la tuberculisation pulmonaire. Influence du pneumothorax.Méd Paris. 1880; ([Article in French]) (thesis 296)Google Scholar]. Such observations inspired Carlo Forlanini. Fortunately, his younger brother Enrico Forlanini (1848 to 1930), a well-known engineer and inventor, assisted him by developing customized equipment for this purpose [14Sakula A. Carlo Forlanini, inventor of artificial pneumothorax for treatment of pulmonary tuberculosis.Thorax. 1938; 38: 326-332Crossref Scopus (34) Google Scholar]. Thus, the treatment method known as “artificial pneumothorax” was born again. However, the question regarding the priority arose in face of this historical background and simultaneous activities in the USA quite rightly. This was, at the time, all the more the case because in 1909 the preliminary work of Carson was rediscovered by Friedrich Siegfried Daus (1876-?), head of a lung sanatorium in Gütergotz near Berlin. He made plain that all issues of priority were won by Carson [38Daus F.S. Historisches und Kritisches über künstlichen Pneumothorax bei Lungenschwindsucht [Article in German].Die Therapie der Gegenwart. 1909; 1: 221-227Google Scholar]. Due to the First World War, no Nobel prizes were awarded from 1915 to 1918. Because Forlanini died in 1918, he was not personally considered in the post-war deliberations of the committee. However, his work was mentioned in comparison with other achievements later on. In a report about Ferdinand Sauerbruch written by the Nobel committee member Hans Christian Jacobaeus in 1931, Forlanini's work was highlighted once more. Jacobaeus stated in a Nobel prize evaluation of Ferdinand Sauerbruch and Ludolph Brauer, that they could not excel Forlanini in terms of innovative thorax operations [39Hansson N. Schagen U. In Stockholm they apparently had some kind of countermovement” - Ferdinand Sauerbruch (1875-1951) and the Nobel prize.NTM. 2014; 22 ([Article in German]): 133-161Crossref PubMed Scopus (17) Google Scholar]. What does a researcher have to achieve to obtain the Nobel Prize for Physiology or Medicine? The sociologist Robert K Merton has called qualified candidates who finally were not selected into a prestigeful group “occupants of the 41st chair,” based on the rule that a maximum of 40 scholars can be part of the French academy [40Merton R.K. The Matthew effect in science.Science. 1968; 159: 56-63Crossref Scopus (4092) Google Scholar]. Translated into a Nobel Prize context, this means that there are more scholars who would be eligible Nobel Prize laureates than medals to hand out. Forlanini was a strong Nobel Prize candidate in 1913 and 1914, even though the question of priority, negative factors, and side effects of the PNX were stressed by both Nobel committee evaluators. Excellence in medicine was in Forlanini's case not so much a matter of being a first-class physician or researcher, but rather measured by timing and the potential impact of the innovation at hand. The operation got more popular over time; the number of patients treated with PNX grew steadily from 1915 to the 1940s, before the discovery of streptomycin in 1944. However, the 200 year-old operation still is relevant and might have a future [41Balboni G.M. The development in the treatment of pulmonary tuberculosis from 1696 to the present time.N Engl J Med. 1935; 212: 1020-1027Crossref Google Scholar, 42Polianski I. Bolshevik disease and Stalinist terror: on the historical casuistry of artificial pneumothorax.Med Hist. 2015; 59: 32-43Crossref PubMed Scopus (3) Google Scholar]. Files on Carlo Forlanini and John B. Murphy in the Nobel Archive were kindly provided by the Nobel Committee for Physiology or Medicine, Medicinska Nobelinstitutet, Solna, Stockholm, Sweden. We thank Theo Jäger, Cologne, for proofreading the manuscript, and the reviewers' for valuable comments. The authors have not used any grants or financial support for this study.