“And then I met Ewald Weibel”
2020; American Physical Society; Volume: 319; Issue: 3 Linguagem: Inglês
10.1152/ajplung.00313.2020
ISSN1522-1504
Autores ResumoEditorial“And then I met Ewald Weibel”Matthias OchsMatthias OchsInstitute of Functional Anatomy, Charité–Universitätsmedizin Berlin, Berlin, GermanyGerman Center for Lung Research (DZL), Berlin, GermanyPublished Online:20 Aug 2020https://doi.org/10.1152/ajplung.00313.2020This is the final version - click for previous versionMoreSectionsPDF (297 KB)Download PDFDownload PDFPlus ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmail Ewald Rudolf Weibel, professor emeritus of anatomy and former director of the Institute of Anatomy at the University of Bern, passed away on February 19, 2019, at the age of 89. He was active until his final hospitalization, working on the introduction to a manuscript he considered his “ultimate project.” His scientific career spanned more than six decades and included studies on the architecture and ultrastructure of the lung, electron microscopic cell biology, morphometry based on stereological methods, and comparative physiology of the respiratory system. In all of these fields, he was a giant. Moreover, he was a wonderful and elegant writer, a charismatic teacher and mentor, and an influential leader in science and science administration (Fig. 1).Fig. 1.Ewald R. Weibel (March 5, 1929–February 19, 2019). [Photo courtesy of Ewald Weibel.]Download figureDownload PowerPointEwald Weibel was born on March 5, 1929, in Buchs within the Swiss canton of Aargau. His father was a typewriter mechanic, his mother a seamstress. While attending the cantonal school in Aarau, he became interested in natural sciences due to excellent teaching. Later, he spoke fondly about this school (the “Alte Kanti”), his teachers, and his classmates (which included Werner Arber, who received the Nobel Prize in Physiology or Medicine in 1978). Another pupil of this school, 50 years earlier, was Albert Einstein, who also lauded its liberal and scientific spirit.Ewald Weibel went to medical school at the University of Zurich and graduated in 1955. During his studies, he became interested in the physiology of hearing and approached his professor of physiology, Walter R. Hess (who had received the Nobel Prize in Physiology or Medicine in 1949). But Hess advised him to study the morphology of the inner ear first. This early lesson told him that the road to function leads via structure. So he did his doctoral thesis with the professor of anatomy, Gian Töndury, on the epithelial differentiation in the cochlear duct. Töndury was a great teacher, and he taught Ewald Weibel the science that eventually became his professional home—he made him become an anatomist. It was not easy for his family to make ends meet, so he had to find employment after graduation, but at that time clinical interns were expected to work at no pay for the first two years. He was promised a salary in pathology if he had finished a study on the anastomoses between the bronchial and the pulmonary arteries first. So, for money’s sake, Ewald Weibel went into lung research while earning his living as a teaching assistant in anatomy.After successfully finishing this study, Ewald Weibel decided not to go into pathology but to take the opportunity of a research fellowship awarded to him by the Swiss Academy of Medical Sciences to do a postdoc abroad. His first choice was André F. Cournand at Columbia University in New York. Cournand headed the Cardiopulmonary Laboratory at Bellevue Hospital, part of the First Medical Division directed by Dickinson W. Richards and a scientific mecca at that time (they were awarded the Noble Prize in Physiology or Medicine in 1956). But Ewald Weibel’s first class airmail letter to Cournand went without reply. His second choice, Averill A. Liebow at Yale, accepted him immediately. Together with his wife Verena, he went to Yale in June 1958. After several months, the letter written to Cournand bounced back with the remark “Addressee unknown.” It turned out that the address was incomplete, and Columbia University was not able to find its most recent Nobel laureate. Eventually, Ewald Weibel got in contact with André Cournand, who invited him to give a seminar at Bellevue Hospital. This seminar took place on February 19, 1959, exactly 60 years before the day he passed away. After his presentation, Cournand and Richards told him that they wanted him to come and work with them. When he asked what they expected him to do, their answer was: “Do anything on the structure of the lung that is of interest to physiology.” Ewald Weibel accepted on the spot, went back to Yale, finished his two-year project within one year, and, together with Verena, moved to New York where he started working on September 1, 1959.The answer to the question what to do on the structure of the lung that could be of interest to physiology came by asking the right questions. These questions were asked by Domingo M. Gomez, a Cuban refugee who had just arrived in Cournand’s laboratory. Gomez studied medicine and mathematics in Paris, trained as a cardiologist, and had a strong interest in biophysics. The questions he was asking were about the number of alveoli in the lung, the size of the alveolar surface area, the amount of capillary blood, all questions on quantitative characteristics of structure—and this information is indeed of interest to physiology because it extends qualitative morphologic description to quantitative morphometric measurement. Some methods to obtain such morphometric data based on sampling and measurements of micrographs were already available (mainly in geology and material sciences), while others had to be developed. Together with Gomez, Weibel established these and applied them to a series of five human lungs (20). Thus, at that time they did lung stereology before it was named stereology. The term “stereology” was actually coined at a meeting of a small group of scientists that founded the International Society for Stereology under the leadership of Hans Elias in Feldberg in the Black Forrest in 1961 (see 28). So, stereology evolved as the singular tool to make structure interesting for physiology.Weibel’s early studies were performed using light microscopy, which, however, cannot sufficiently resolve the tissue barrier separating air and blood. Therefore, in 1961, in agreement with Cournand, he went on to the Rockefeller Institute to work with one of the pioneers of biological electron microscopy, George E. Palade (who would later be awarded the Nobel Prize in Physiology or Medicine in 1974). A serendipitous finding happened to Ewald Weibel on Valentine’s day in 1962, his father’s 60th birthday. Sitting at the electron microscope, he discovered previously undescribed rod-like, membrane-bound structures containing tubules in endothelial cells of rat lung arteries. These organelles, later to be found to contain von Willebrand factor, a key component of coagulation, are now known as Weibel-Palade bodies (22).After three and a half years in the United States, Ewald Weibel planned his return to Switzerland. For an assistant professorship at the University of Zurich, he had to fulfill the formal requirements of a habilitation (venia docendi) for anatomy. This included a written habilitation thesis in the form of a monograph. At least, the faculty allowed him a text in English. So he summarized most of his scientific work up to that point in a book entitled “Morphometry of the Human Lung” (21). This monograph marks the beginning of modern quantitative lung morphology: clearly and elegantly written, innovative and ground-breaking, still a major reference.In December 1962, Verena and Ewald Weibel took a ship back to Europe. From 1963 to 1966, Ewald Weibel worked as assistant professor at the Institute of Anatomy in Zurich where he set up the first electron microscopy laboratory. In 1966 he moved on to become professor and chairman of the Institute of Anatomy at the University of Bern, a position he held for 28 years until his retirement. His inauguration lecture was entitled “Order and life.” Weibel made his Institute the place to be for research on lung structure. Over the decades, many coworkers went on to their own independent careers, either inside or outside the Institute. Moreover, scientists from all over the world went on a pilgrimage to the time-honored building at Bühlstrasse 26 to study with the master of quantitative lung morphology.The main focus of Weibel’s work remained structure-function relationships in the respiratory system based on morphometry. Equipped with excellent financial resources, he expanded his team and his research program considerably. The time spent in George Palade’s laboratory heavily infected him with electron microscopy. So he went on with studies on the ultrastructure of surfactant, being the first to describe a particular morphological subtype in the alveolar lumen which he termed “tubular myelin” (23) and, after careful fixation “from behind” (i.e., vascular perfusion), the first to reveal the duplex nature of the alveolar lining layer with a surface film at the air-liquid interface and an aqueous hypophase underneath (9, 24). He then investigated the alveolar epithelium, solving the mystery of “non-nucleated plates,” originally described by Albert Kölliker using light microscopy in 1881. In fact, these seemingly non-nucleated cytoplasmic plates are extensions of type 1 alveolar epithelial cells through the alveolar septal wall onto the opposite side of the septum (26). Studies on the divisibility of alveolar epithelial cells were followed by investigations on ultrastructural alterations in acute respiratory distress syndrome (ARDS) (4, 5, 27). Furthermore, he went to postnatal lung development (6) and extended morphometry of the human lung to the level of electron microscopy (7, 8). His interest in stereology as a scientific discipline culminated in two monographs on the subject that defined the gold standard at the time (28, 29). Further topics included alveolar micromechanics (1–3, 10) and post–pneumonectomy lung growth (11, 12).In line with the concept of making the investigation of lung structure useful for physiology, one particular interest of Ewald Weibel was the morphometric estimation of pulmonary diffusion capacity (25, 33). This resulted in a shift towards comparative physiology where you let nature do the experiments. Consequently, Weibel expanded his focus and looked beyond the lung by combined morphometric and physiological studies across species on the whole respiratory system, from the lungs to muscle mitochondria. He found a congenial partner in Charles Richard Taylor, who directed the Concord Field Station of Harvard University. They met for the first time in 1975 at a lunch at the Harvard Faculty Club. This lunch was the start of a most extraordinary collaboration—and friendship—which lasted until Taylor’s untimely death in 1995 (30, 34).In context with this collaboration, Weibel was invited to give a series of Agassiz Lectures on “Structure and function in the respiratory system” at Harvard University. These were later used as the basis for his monograph “The Pathway for Oxygen,” published in 1984 and considered by many as one of the best and most elegant books ever written on the respiratory system (31). Out of this collaboration also evolved the concept of “symmorphosis” in the respiratory system (32, 35). Across all steps of the respiratory cascade, the structural design should be economic (enough, but not too much structure adapted to the functional needs and balanced to each other). However, there is one notable exception: of all things, the lung. In larger species with larger acini, like humans, there is excess alveolar surface area. This seeming imperfection in the functional design of the lung troubled Weibel and led to what he called his “ultimate project”: searching for a remedy for the failure of symmorphosis at this pivotal point. This project now remains to be finished.In 1994, Ewald Weibel retired, not because he wanted to but because he had to. The mandatory retirement age for university professors in Switzerland was 65, and no exceptions were made. But that of course could not stop his scientific mind, and, exempt from teaching and administrative duties, he continued working as an emeritus, although with somewhat limited resources: a desk in a shared office, a phone line, and an email account. According to his closest collaborator and friend, Hans Hoppeler, Ewald Weibel published 88 papers with a Hirsch index of 33 after his formal retirement. That publication record would have made an impressive second academic career (for examples of his postretirement publications, see e.g., 13–16, 19). Because he always enjoyed the personal interactions and discussions with colleagues, he continued participating and presenting at conferences with his imposing presence. In several of his later publications, he reflected on his early years in science, e.g., at the occasion of 50 years of the discovery of the Weibel-Palade bodies (18) or 50 years of the publication of “Morphometry of the Human Lung” (36). In 2017, he was interviewed by Max Gassmann for the Living History Project of the American Physiological Society (https://www.youtube.com/watch?v=dBsNrUlE4GU). For anyone who wants to remember him or to get to know him, this document is highly recommended.Ewald Weibel received many honors and awards during his long career. Among them were the Marcel Benoist Price of the Swiss Federal Government (often called the “Swiss Nobel Price”) in 1974, Honorary Fellow of the Royal Microscopical Society (1979), Felix Fleischner Medal (1979), Foreign Associate of the U.S. National Academy of Sciences (1981), J. Burns Amberson Lecture of the American Thoracic Society (1983), Fellow of the American Association for the Advancement of Science (1985), and Honorary Foreign Member of the American Academy of Arts and Sciences (2000). He held honorary doctoral degrees of the Universities of Edinburgh (1988) and Geneva (1999). Weibel served on the editorial boards of many journals (e.g., American Review of Respiratory Diseases, American Journal of Physiology, Journal of Microscopy) and in many national and international academic functions. These include President of the International Society for Stereology (1967–1971), Member of the Swiss National Research Council (1969–1980, Vice President and Chairman of the Division of Biology and Medicine 1974–1980), President of the Fleischner Society (1988–1989), President of the Swiss Academy of Medical Sciences (1997–2000), and President of the International Union of Physiological Sciences (1997–2001). When the University of Bern celebrated its 150th birthday in 1984, Ewald Weibel became its Rector. During his office, he organized an appropriate anniversary present. The former guest house of Theodor Kocher (the first surgeon to win the Noble Prize in Physiology or Medicine in 1909), known as the Kocher-Villa, was renovated and turned into the “Haus der Universität” which housed the Faculty Club. Ewald Weibel made frequent use of it when he invited visiting colleagues or guest speakers into the Kocher-Villa. One of the last occasions was the dinner after the symposium held to celebrate the dedication of the beautiful old lecture hall at the Institute of Anatomy as “Auditorium Ewald Weibel” in 2016.I had my first encounter with Ewald Weibel after finishing my preclinical medical studies at the University of Göttingen in 1989. My professor of anatomy, Joachim Richter, gave me a copy of a book with the words “read this, and if you understand and like it, you can do your doctoral thesis with me.” The title of the book was “Morphometry of the Human Lung,” and its author was Ewald Weibel. It became my initiation into science. Later, and after a first personal encounter during a visit at his Institute (which felt for me like an audience with the Pope in the Vatican), Ewald Weibel served as an external reviewer of my doctoral thesis, and also, some years later, as a reviewer for my application to the Alexander von Humboldt Foundation for a scholarship that I used for a one-year stay in the laboratory of Sam Hawgood at the Cardiovascular Research Institute of the University of California San Francisco. At the end of this research stay, an open position at the Institute of Anatomy in Bern was announced. I was offered this position which eventually opened the doors to the holy halls of lung morphology for me. I stayed from early 2005 to late 2009. The greatest excitement, challenge, fun, and pleasure were the close interactions with Ewald. When I started in Bern, he was already retired for over 10 years. Nevertheless, he came to his former Institute almost every day, dropping by my office, chatting and discussing about the lung and beyond. Although I considered myself already as a well-trained and experienced anatomist, electron microscopist, and stereologist, I realized that there was so much more to learn from these conversations. Talking to Ewald was like seeing the lung with new eyes. He enjoyed the scientific exchange with the representative of a new generation, almost 40 years his junior. We collaborated and published several original articles, reviews, and book chapters. Our last paper, which reinvestigated the “non-nucleated plates” and the topological complexity of type 1 alveolar epithelial cells by 3D electron microscopy, was published after his death (17). So, over the course of 30 years, the once role model and mentor became a friend.As a scientist, Ewald Weibel was a perfectionist. Bright and passionate, he could be very demanding—to himself as well as to others, in particular coworkers and close collaborators. He was his (and others) toughest critic, with the highest possible quality standards. He was notorious for the seemingly endless process of selecting electron micrographs for publications. In the pre-digital (and pre-image-manipulation) era, a laboratory technician responsible for artwork and micrographs said about him: “Professor Weibel always uses a big magnifying glass and finds something to complain about.” Being an aesthete and art lover, Ewald knew about the importance of pictures to make the scientific point. Each of his published electron micrographs of the lung is still worth more than a thousand words. Experts can tell the master’s style. These micrographs are so unique that one can easily recognize them as an “original Weibel,” being both scientific documents and masterful pieces of art.As a person, Ewald was charming, warm, humorous, and generous. He was married to Verena since 1956, and they enjoyed life together in their beautiful house in Herrenschwanden overlooking the Swiss Alps. He cultivated his own small vineyard in the garden in which one could also stumble over alba truffle in the ground. He affectionately took care of Verena when her health declined. Although they had no children, they had a large scientific family, with Ewald as father and grandfather. At the occasion of his 80th birthday in 2009, this extended family came together from all over the world for a scientific symposium at his former Institute and a banquet in the impressive grand ballroom of the Bellevue Palace Hotel in Bern. The main speakers at the symposium paid tribute to his landmark contributions in stereology (Terry Mayhew), quantitative assessment of lung structure (James D. Crapo), and comparative physiology (Stan Lindstedt). The last presentation was given by Ewald himself. Reflecting on his then 50 years of science, he ended by showing some of his most famous micrographs accompanied by the words:“I have to confess that I always gained particular pleasure simply at being a morphologist. Sitting at the microscope to search for the best pictures of alveoli or capillaries or of cells, to explore the patterns of airways and blood vessels and how they establish an order that appears essential for the efficient performance of function. All this to discover the beauty hidden in lung structure.”Looking at the life and legacy of Ewald Weibel, one is reminded of a quote attributed to the Swedish author Per Olov Enquist: “One day we shall die. But all the other days we shall be alive.” What Ewald Weibel did on the structure of the lung that is of interest to physiology was unique. Based on the knowledge we owe to him, the history of lung morphology may be divided into two periods: before and after Weibel. It was a privilege to know him and to work with him. His scientific children and grandchildren are deeply grateful for his inspiration, his guidance, his mentorship, and his friendship. And we miss him sorely.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author.AUTHOR CONTRIBUTIONSM.O. drafted manuscript; edited and revised manuscript; and approved final version of manuscript.ACKNOWLEDGMENTSThe title of this editorial is based on a quote by Luis Cruz-Orive, a Spanish stereologist who worked with Ewald Weibel at his Institute in Bern from 1976 to 1993. I heard this sentence for the first time from Luis many years ago, and then from several colleagues when we exchanged our memories of Ewald, and I also used it myself. It reflects the fact that Ewald Weibel had a decisive influence on the scientific directions and careers of a great many people.REFERENCES1. Bachofen H, Gehr P, Weibel ER. Alterations of mechanical properties and morphology in excised rabbit lungs rinsed with a detergent. J Appl Physiol 47: 1002–1010, 1979. doi:10.1152/jappl.1979.47.5.1002. Link | ISI | Google Scholar2. Bachofen H, Wangensteen D, Weibel ER. Surfaces and volumes of alveolar tissue under zone II and zone III conditions. J Appl Physiol 53: 879–885, 1982. doi:10.1152/jappl.1982.53.4.879. Link | ISI | Google Scholar3. Bachofen H, Schürch S, Urbinelli M, Weibel ER. Relations among alveolar surface tension, surface area, volume, and recoil pressure. J Appl Physiol (1985) 62: 1878–1887, 1987. doi:10.1152/jappl.1987.62.5.1878. Link | ISI | Google Scholar4. 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I. Model and method. Respir Physiol 11: 54–75, 1970. doi:10.1016/0034-5687(70)90102-7. Crossref | PubMed | Google Scholar26. Weibel ER. The mystery of “non-nucleated plates” in the alveolar epithelium of the lung explained. Acta Anat (Basel) 78: 425–443, 1971. doi:10.1159/000143605. Crossref | PubMed | Google Scholar27. Weibel ER. A note on differentiation and divisibility of alveolar epithelial cells. Chest 65: 19S–21S, 1974. doi:10.1378/chest.65.4_Supplement.19S. Crossref | PubMed | ISI | Google Scholar28. Weibel ER. Stereological Methods. Vol 1. Practical Methods for Biological Morphometry. London: Academic, 1979.Google Scholar29. Weibel ER. Stereological Methods. Vol 2. Theoretical Foundations. London: Academic, 1980.Google Scholar30. Weibel ER, Taylor CR. Design of the mammalian respiratory system. I-IX. Respir Physiol 44: 1–164, 1981.Crossref | PubMed | Google Scholar31. Weibel ER. The Pathway for Oxygen. Structure and Function in the Mammalian Respiratory System. Cambridge, MA: Harvard Univ. Press, 1984.Google Scholar32. Weibel ER, Taylor CR, Hoppeler H. The concept of symmorphosis: a testable hypothesis of structure-function relationship. Proc Natl Acad Sci USA 88: 10357–10361, 1991. doi:10.1073/pnas.88.22.10357. Crossref | PubMed | ISI | Google Scholar33. Weibel ER, Federspiel WJ, Fryder-Doffey F, Hsia CCW, König M, Stalder-Navarro V, Vock R. Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity. Respir Physiol 93: 125–149, 1993. doi:10.1016/0034-5687(93)90001-Q. Crossref | PubMed | Google Scholar34. Weibel ER, Taylor CR, Weber JM, Vock R, Roberts TJ, Hoppeler H. Design of the oxygen and substrate pathways. I-VII. J Exp Biol 199: 1643–1709, 1996.PubMed | ISI | Google Scholar35. Weibel ER. Symmorphosis. On form and function in shaping life. Cambridge, MA: Harvard Univ. Press, 2000.Google Scholar36. Weibel ER. A retrospective of lung morphometry: from 1963 to present. Am J Physiol Lung Cell Mol Physiol 305: L405–L408, 2013. doi:10.1152/ajplung.00169.2013. Link | ISI | Google ScholarAUTHOR NOTESCorrespondence: M. Ochs (matthias.[email protected]de). Back to Top Next FiguresReferencesRelatedInformationRelated articlesConjunction junction, what’s the function? CCN proteins as targets in fibrosis and cancers 18 May 2020American Journal of Physiology-Cell PhysiologyThe role of the sphingolipid pathway in liver fibrosis: an emerging new potential target for novel therapies 18 May 2020American Journal of Physiology-Cell PhysiologyWound healing and fibrosis: a contrasting role for periostin in skin and the oral mucosa 18 May 2020American Journal of Physiology-Cell PhysiologyCited ByCall for Papers: “Morphology is the link between genetics and function”: a tribute to Ewald R. WeibelChristian Mühlfeld, Connie C. W. Hsia, George D. Leikauf, Sandra Orgeig, Louise V. Wain, and Matthias Ochs18 February 2021 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 320, No. 2Stereology as the 3D tool to quantitate lung architecture13 October 2020 | Histochemistry and Cell Biology, Vol. 155, No. 2World Lung Day 2020 at the Journal of Applied Physiology and the American Journal of Physiology-Lung Cellular and Molecular PhysiologySue C. Bodine and Rory E. Morty4 September 2020 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 319, No. 3 More from this issue > Volume 319Issue 3September 2020Pages L403-L407 Copyright & PermissionsCopyright © 2020 the American Physiological Societyhttps://doi.org/10.1152/ajplung.00313.2020PubMed32640838History Received 2 July 2020 Accepted 2 July 2020 Published online 20 August 2020 Published in print 1 September 2020 Keywordslungmorphologymorphometryphysiologystereology Metrics Downloaded 1,226 times
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