Ernst von Leyden (1832-1910): a pioneer in making oncology a respected medical discipline.

PURPOSE: This article presents new research on the role of the renowned German physician Ernst von Leyden (1832-1910) in the emergence of oncology as a scientific discipline. METHODS: The article draws on archival sources from the archive of the German Society of Haematology and primary and secondary literature. RESULTS: Leyden initiated two important events in the early history of oncology: the first international cancer conference, which took place in Heidelberg, Germany, in 1906, and the founding of the first international association for cancer research (forerunner of today's UICC) in Berlin in 1908. Unfortunately, these facts are not mentioned in the most recent accounts. Both had a strong impact on the professionalization of oncology as a discipline in its own right. CONCLUSION: Although not of Jewish origin, von Leyden was considered by the National Socialists to be "Jewish tainted", which had a lasting effect on his perception at home and abroad.

Why so few Nobel Prizes for cancer researchers? An analysis of Nobel Prize nominations for German physicians with a focus on Ernst von Leyden and Karl Heinrich Bauer.

PURPOSE: To date, 11 scientists have received the Nobel Prize for discoveries directly related to cancer research. This article provides an overview of cancer researchers nominated for the Nobel Prize from 1901 to 1960 with a focus on Ernst von Leyden (1832-1910), the founder of this journal, and Karl Heinrich Bauer (1890-1978). METHODS: We collected nominations and evaluations in the archive of the Nobel committee of physiology or medicine in Sweden to identify research trends and to analyse oncology in a Nobel Prize context. RESULTS: We found a total of 54 nominations citing work on cancer as motivation for 11 candidates based in Germany from 1901 to 1953. In the 1930s, the US became the leading nation of cancer research in a Nobel context with nominees like Harvey Cushing (1869-1939) and George N. Papanicolaou (1883-1962). DISCUSSION: The will of Alfred Nobel stipulates that Nobel laureates should have "conferred the greatest benefit to mankind". Why were then so few cancer researchers recognized with the Nobel medal from 1901 to 1960? Our analysis of the Nobel dossiers points at multiple reasons: (1) Many of the proposed cancer researchers were surgeons, and surgery has a weak track record in a Nobel context; (2) several scholars were put forward for clinical work and not for basic research (historically, the Nobel committee has favoured basic researchers); (3) the scientists were usually not nominated for a single discovery, but rather for a wide range of different achievements.

Who is who in cardiovascular research? What a review of Nobel Prize nominations reveals about scientific trends.

BACKGROUND: Since 1901, at least 15 scholars who contributed to cardiovascular research have received a Nobel prize in physiology or medicine. METHODS: Using the Nobel nomination database (nobelprize.org), which contains 5950 nominations in the accessible period from 1901 to 1953 in physiology or medicine, we listed all international nominees who contributed to cardiovascular research. We subsequently collected nomination letters and jury reports of the prime candidates from the archive of the Nobel Committee in Sweden to identify shortlisted candidates. RESULTS: The five most frequently nominated researchers with cardiovascular connections from 1901 to 1953 were, in descending order, the surgeon René Leriche (1879-1955) (FR) with a total of 79 nominations, the physiologist and 1924 Nobel laureate Willem Einthoven (1860-1927) (NL) (31 nominations), the surgeon Alfred Blalock (1899-1964) (US) (29 nominations), the pharmacologist and 1936 Nobel laureate Otto Loewi (1873-1961) (DE, AT, US) (27 nominations) and the paediatric cardiologist Helen Taussig (1898-1986) (US) (24 nominations). The research of these scholars merely hints at the width of topics brought up by nominators ranging from the physiological and pathological basics to the diagnosis and (surgical) interventions of diseases such as heart malformation or hypertension. CONCLUSION: We argue that an analysis of Nobel Prize nominations can reconstruct important scientific trends within cardiovascular research during the first half of the twentieth century.

Otorhinolaryngologists nominated for the Nobel Prize 1901-1940.

PURPOSE: Several scholars with links to ENT have received the Nobel Prize in physiology or medicine. This overview takes into account ENT Nobel nominees, who never received the award. METHODS: Drawing a comparison on the nominations collected in the archive of the Nobel Committee for physiology or medicine in Stockholm, the Nobel archive database and secondary literature; the paper analyzes for the first time the nominations of Hans Schmid (Stettin), Hermann Gutzmann (Berlin), Karl Wittmaack (Hamburg), and Chevalier Jackson (Chicago). We also bring up nomination letters written by prominent German nominators such as Hermann Schwartze (one of the founders of this journal) and August Lucae. RESULTS: Hans Schmid was the first surgeon to be brought up in a Nobel Prize nomination for an ENT procedure (1901), but since he had passed away 5 years earlier he was not evaluated by the Nobel Committee. Hermann Gutzmann was a strong candidate in 1917 and reached the shortlist because of his pioneering work on stutter, but no Nobel Prize in physiology or medicine was awarded that year. In the 1930's, both Karl Wittmaack and Chevalier Jackson were repeatedly nominated for ENT research. CONCLUSION: Nobel Prize nominations are to date underused sources that shed new light on some scholars in ENT history.

Scientific language trends among Swedish urologists and surgeons 1900-1955.

PURPOSE: Before English took the lead as the prime scientific language among northern European urologists and surgeons, German was widely regarded as the "lingua franca". This shift has to date not been systematically reconstructed. This article provides insights into the question how political and social factors influence how physicians communicate with each other, what they read, and how the constellations of international scientific communities in medicine change over time. METHODS: Through a language analysis of more than 2000 articles, including their references, in major Swedish medical journals as well as surgical doctoral dissertations defended at Swedish universities, this paper explores scientific language trends during the first half of the twentieth century among Swedish physicians for the first time on a large scale. RESULTS AND CONCLUSIONS: The study shows that Swedish urologists and surgeons generally did not switch to English during the years immediately after the First World War, as has been documented in other countries. After a decrease during the first 10 years after the First World War, the German language dominated among Swedish urologists and surgeons from the 1930s until the early 1940s, when English first dominated at large. The rapidity of this process shows that almost all surgical researchers had changed from German to English within just a few years.

Myocardial Oxygen Consumption and Efficiency in Patients With Cardiac Amyloidosis.

Background This study evaluated myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) in patients with cardiac amyloidosis (CA). Furthermore, we compared MEE and MVO2 in subjects with light chain amyloidosis versus transthyretin (ATTR) amyloidosis. Methods and Results The study population comprised 40 subjects: 25 patients with confirmed CA and 15 control subjects. All subjects underwent an 11C-acetate positron emission tomography. Furthermore, the CA patients underwent comprehensive echocardiography and right heart catheterization during a symptom-limited, semi-supine exercise test. MEE was calculated from 11C-acetate positron emission tomography as the ratio of left ventricular (LV) stroke work and the energy equivalent of MVO2. Myocardial work efficiency was calculated as echocardiography-derived work pressure product divided by three-dimensional LV mass. CA patients had significantly lower LV-ejection fraction (54±13% versus 63±4%, P<0.05) and LV-global longitudinal strain (LVGLS) (12±4% versus 19±2%, P<0.0001) and a more restrictive filling pattern (E/e'-ratio 18 [12-25] versus 8 [7-9], P<0.0001) than controls. MEE was severely reduced (13±5% versus 22±5%, P<0.0001) whereas total MVO2 was higher (18±6 mL/min versus 13±3 mL/min, P<0.01) in CA patients than controls. MEE decreased with increasing New York Heart Association symptom burden ( P<0.0001). We found a good relationship between MEE and peak exercise systolic performance (LVGLS: R2=0.60, P<0.0001; myocardial work efficiency: R2=0.48, P<0.0001; cardiac index: R2=0.52, P<0.0001) and between MEE and myocardial blood flow ( R2=0.44, P<0.0001). Conclusion Myocardial oxidative metabolism is disturbed in CA patients with increased total MVO2 and reduced MEE. MEE correlated significantly with echocardiographic derived systolic parameters such as myocardial work efficiency and LVGLS that might be used as surrogate MEE markers.

Excellence in orthopaedic surgery: an overview of Nobel Prize nominees 1901-1960 with focus on Friedrich Pauwels and Gerhard Küntscher.

PURPOSE: This paper provides for the first time an overview of orthopaedic surgeons nominated for the Nobel Prize in physiology or medicine during the first six decades of the twentieth century. The study is part of the project "Enacting Excellency: Nobel Prize nominations for surgeons 1901-1960". METHODS: The nomination letters were gathered in the archive of the Nobel Committee at the Karolinska Institute in Solna, Sweden. RESULTS: Among the nominees, we find renowned scholars like Pierre Delbet, Themistocles Gluck, Gerhard Küntscher, Adolf Lorenz, Friedrich Pauwels, Leslie Rush, and Marius Smith-Petersen. The focus of the paper is on nominations for Pauwels (work on biomechanics) and Küntscher (the Küntscher nail). Both were nominated by German surgeons. CONCLUSIONS: Although no orthopaedic surgeon has yet received a Nobel Prize for an orthopaedic achievement, Nobel archive files can help reconstruct important trends in the field during the twentieth century.

["When all of you will be forgotten, the name Israel will still be shining" : James Israel (1848-1926): a career in the German Empire and his nomination for the Nobel Prize]. / "Wenn Sie alle vergessen sein werden, wird der Name Israel noch leuchten" : James Israel (1848­1926): Eine Karriere im Deutschen Kaiserreich und seine Nominierung für den Nobelpreis.

In 1902, the Berlin Jewish urologist James Israel was nominated for the Nobel Prize in physiology or medicine. Taking scholar, social, and political aspects into consideration, this biographical essay traces how James Israel gained a sound scientific reputation especially in kidney surgery within Imperial Germany and its antisemitic attitude and how he promoted urology to become a specialty in its own right.

Myocardial Oxygen Consumption and Efficiency in Aortic Valve Stenosis Patients With and Without Heart Failure.

BACKGROUND: Myocardial oxygen consumption (MVO2) and its coupling to contractile work are fundamentals of cardiac function and may be involved causally in the transition from compensated left ventricular hypertrophy to failure. Nevertheless, these processes have not been studied previously in patients with aortic valve stenosis (AS). METHODS AND RESULTS: Participants underwent 11C-acetate positron emission tomography, cardiovascular magnetic resonance, and echocardiography to measure MVO2 and myocardial external efficiency (MEE) defined as the ratio of left ventricular stroke work and the energy equivalent of MVO2. We studied 10 healthy controls (group A), 37 asymptomatic AS patients with left ventricular ejection fraction ≥50% (group B), 12 symptomatic AS patients with left ventricular ejection fraction ≥50% (group C), and 9 symptomatic AS patients with left ventricular ejection fraction <50% (group D). MVO2 did not differ among groups A, B, C, and D (0.105±0.02, 0.117±0.024, 0.129±0.032, and 0.104±0.026 mL/min per gram, respectively; P=0.07), whereas MEE was reduced in group D (21.0±1.6%, 22.3±3.3%, 22.1±4.2%, and 17.3±4.7%, respectively; P<0.05). Similarly, patients with global longitudinal strain greater than -12% and paradoxical low-flow, low-gradient AS had impaired MEE (P<0.05 versus controls). The ability to discriminate between symptomatic and asymptomatic patients was superior for global longitudinal strain compared with MVO2 and MEE (area under the curve 0.98, 0.48, and 0.61, respectively; P<0.05). CONCLUSIONS: AS patients display a persistent ability to maintain normal MVO2 and MEE (ie, the ability to convert energy into stroke work); however, patients with left ventricular ejection fraction <50%; global longitudinal strain greater than -12%; or paradoxical low-flow, low-gradient AS demonstrate reduced MEE. These findings suggest that mitochondrial uncoupling contributes to the dismal prognosis in patients with reduced contractile function or paradoxical low-flow, low-gradient AS.

Nobel Prize nominees and the rise of urology in Europe around 1900.

PURPOSE: Recent historical research has reconstructed the roads leading to the Nobel Prize for the trained urologists Werner Forssmann (1904-1979) in 1956 and Charles Huggins (1901-1997) in 1966. However, the story of urology and the Nobel Prize does not start and end with the laureates. Taking James Israel (1848-1926), Félix Guyon (1831-1920), and Peter J Freyer (1852-1921) as examples, this paper shows that pioneers in urology were in fact runners-up for the award much earlier. METHODS: The study is based on an analysis of original files in the Nobel Prize archive in Stockholm, scientific publications of the early twentieth century, and secondary literature. RESULT AND CONCLUSION: We argue that Israel's, Guyon's, and Freyer's candidacies reflect not only scientific trends and controversies in urology at the turn of twentieth century, but that the development of the specialty itself was reflected in nominations of physicians working on problems of the genito-urinary system.

Nominee and nominator, but never Nobel Laureate: Vincenz Czerny and the Nobel Prize.

PURPOSE: The Heidelberg surgeon Vincenz Czerny (1842-1916) is remembered as pioneer of innovative operations as well as entrepreneur of interdisciplinary cancer therapy. The purpose of this paper is to describe his role during the early history of the Nobel Prize in physiology or medicine. METHOD: Based on documents from the Nobel Archive, this paper investigates how Czerny contributed, both as nominee and nominator, in shaping the early years of Nobel Prize history. RESULTS: Vincenz Czerny was nominated at least three times for the Nobel Prize, but he was never selected. Czerny's own nomination letters pinpoint important trends in medicine around the turn of the century. At least seven of the candidates he put forward, became Nobel Laureates. CONCLUSION: Czerny-like many other internationally renowned surgeons during the first decades of the twentieth century-missed out on the Nobel Prize, partly because it is not a lifetime award and his work would have to have been more recent. However, with his nominations, Czerny helped to shape the Nobel Prize to become the most important scientific award worldwide.

The Nobel Prize and otolaryngology: 'Papa Gunnar's' promotion of his peers Gustav Killian and Themistocles Gluck.

OBJECTIVES: This study is part of a larger project investigating the enactment of excellence in medicine, with a focus on the Nobel Prize. It takes a closer look at two promising candidates for the Prize in the 1920s and 1930s, Gustav Killian and Themistocles Gluck, and aims at reconstructing their Nobel careers as well as taking Gunnar Holmgren's role as a nominator and evaluator behind the curtains into account. METHOD: Besides the files collected at the Nobel Archive, the paper is based on a review of scientific publications and ergo-biographical sketches. RESULTS: An analysis of Nobel Prize nominations and evaluations offer a unique perspective to study aspects of the history of otolaryngology. CONCLUSION: Using original files in the archive of the Nobel committee for physiology or medicine in Sweden, this historical vignette explores judgments of scientific innovation and performance in the history of otolaryngology during the first half of the 20th century. This study shows that Gunnar Holmgren, the founder of Acta Oto-Laryngologica in 1918, repeatedly put forward scholars within the field as prime contenders for the award.

Remembering Charles B. Huggins' Nobel Prize for Hormonal Treatment of Prostatic Cancer at its 50th Anniversary.

Charles B. Huggins received the Nobel Prize in 1966. Based on archival sources from the Nobel archive we have found that nominators emphasised the practical therapeutic applications of his discoveries that were showing 25 yr after his key publications.

A fatal case of primary cardiac chondrosarcoma presenting with amaurosis fugax.

A 64-year-old previously healthy woman consulted her general practitioner because of recurrent episodes of right-sided monocular transient visual loss (ie, amaurosis fugax). At first, these symptoms were followed over time, but as the attacks worsened, and were accompanied by dizziness and general discomfort, the patient was admitted to the department of neurology for further investigations. CT of the brain was normal; however, during admission, the patient developed rapid atrial fibrillation and was transferred to the department of cardiology. Transthoracic echocardiography revealed a massive tumour on the atrial side of the anterior mitral valve leaflet, partly obstructing the mitral valve inflow. The tumour was excised and a biological prosthetic mitral valve inserted. The tumour was histologically determined to be a highly malignant dedifferentiated chondrosarcoma. After 6 months, the tumour relapsed and expanded aggressively to completely obstruct the mitral valve inflow, ultimately leading to cardiac arrest and death.

Therapeutic Pneumothorax and the Nobel Prize.

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.

["A change in medical thinking?" or "over-eager literary activity?" August Bier, homeopathy and the Nobel Prize 1906-1936]. / Ein "Umschwung des medizinischen Denkens" oder "eine übereifrige literarische Tätigkeit"? August Bier, die Homöopathie und der Nobelpreis 1906-1936.

This essay explains the nomination and evaluation procedure for the Nobel Prize for Physiology or Medicine. Its research is based on original files and on the example of August Karl Gustav Bier (1861-1949). It discusses the minutes of the Nobel Committee for physiology or medicine, which are kept in the Nobel Archives, as well as the unusually high number of nominations of August Bier and the nominations submitted by him; it also describes the reasons why August Bier, in the end, never received the Nobel Prize. The essay focuses mainly on the reception of Bier's homeopathic theses by the Nobel Prize Committee and his nominators.

Why did Alfred Blalock and Helen Taussig not receive the nobel prize?

BACKGROUND: From the 1940s to the 1960s, the number of cardiac surgeons nominated for the Nobel Prize for Physiology or Medicine grew rapidly. These nominations pinpoint major developments ranging from the first closed extracardiac operations to the era of complete intracardiac repair and treatment of congenital heart diseases. The aim of this article is to present the motivations for the numerous Nobel Prize nominations for the cardiac surgeon Alfred Blalock and the pediatric cardiologist Helen B. Taussig, and to show why the Nobel committee finally chose not to award them for the development of the Blalock-Taussig shunt. METHODS: The authors have gathered and analyzed files on Blalock and Taussig from the Nobel Prize archive for Physiology and Medicine in Solna, Sweden. RESULTS AND CONCLUSIONS: More than forty scholars, primarily from the United States and Europe, nominated Blalock and Taussig for the Nobel Prize for Physiology or Medicine. Such a strong transatlantic support is rare for nominated surgeons. The authors discuss why the number of Nobel Prize nominations for cardiac surgeons in general reached a climax around the 1950s and formulate open research questions on why relatively few surgeons have received the prestigious prize for the development of surgical procedures.

"Highly qualified loser"? Harvey Cushing and the Nobel Prize.

Neurosurgery, in particular surgery of the brain, was recognized as one of the most spectacular transgressions of the traditional limits of surgical work. With their audacious, technically demanding, laboratory-based, and highly promising new interventions, prominent neurosurgeons were primary candidates for the Nobel Prize. Accordingly, neurosurgical pioneers such as Victor Horsley and, in particular, Harvey Cushing continued to be nominated for the prize. However, only António Egas Moniz was eventually awarded the prestigious award in 1949 for the introduction of frontal lobotomy, an intervention that would no longer be prize-worthy from today's perspective. Horsley and Cushing, who were arguably the most important proponents of early neurosurgery, remained "highly qualified losers," as such cases have been called. This paper examines the nominations, reviews, and discussions kept in the Nobel Archives to understand the reasons for this remarkable choice. At a more general level, the authors use the example of neurosurgery to explore the mechanisms of scientific recognition and what could be called the enacting of excellence in science and medicine.