Wilhelm Bernhard

1920-1978

Wilhelm Bernhard was born November 8, 1920, in the village of Worb, Switzerland. As a youth he pursued his earliest scientific interest, astronomy, grinding his own telescope mirror to scan the sky. After completing his studies at Berne and Geneva for the M.D. degree in 1946, he served briefly in the Swiss Army as physician for ski-borne troops, scaling the heights with his patrol. In 1947 he went to Paris, France, for training in pathology where he met Professor Charles Oberling, early propounder of the viral theory of cancer. They discovered in each other a mutual boundless curiosity, zest for life, and love of history and the arts. Professor Oberling invited Dr. Bernhard to head the new laboratory of electron microscopy in Villejuif, one of the first established in France

Some of the earliest descriptions of the ultrastructure of cell organelles (nucleolus, endoplasmic reticulum, Golgi apparatus, lysosomes, centrioles, microtubules) emanated from this laboratory, where students and guests from many countries gathered to learn and to collaborate. But during the early years, Dr. Bernhard’s primary interest was to study the neoplastic cell and the viruses known to induce certain animal tumors, with the ultimate goal of determining whether viruses could be causally linked to human cancer. Thus, between 1953 and 1966 he and his colleagues demonstrated the structure and intracellular development, first of the Rous sarcoma virus and then, successively, the viruses associated with the Shope fibroma, mouse mammary tumor, Murray-Beg avian endothelioma, avian erythroblastosis and myeloblastosis, murine leukemia, the polyoma, and SV40 viruses and adenoviruses. It was he who proposed the now established classification of types A, B, and C murine oncogenic viruses. It was he who wrote, after years of comparative studies, especially of human leukemias, that there is no specific ultrastructural change in neoplastic cells.

Dr. Bernhard’s first task at Villejuif in 1947 had been to develop procedures for obtaining sections of cells thin enough for high resolution electron microscopy. With the first premethacrylate waxes that he tested after shivering through long hours of sectioning in a cold room, he was not only able to obtain ultrathin sections but also to stain adjacent sections and demonstrate that the newly discovered granular endoplasmic reticulum was indeed the basophilic ergastoblasm of Garnier and Bouin. From that time , he eagerly sought new cytochemical techniques that would extend even further the information that could be gained from the electron microscope. With his colleagues, he pioneered in the development and utilization of electron microscope autoradiography, water-miscible embedding resins, enzymic digestion of specific components of cells, cryoultramicrotomy, immunocytochemistry with peroxidase as marker, concanavalin A labeling of cell membranes, a specific stain for DNA, and a selective stain for ribonucleoprotein.

At a time when most electron microscopists focused primarily on the myriads of structures in the cytoplasm, Dr. Bernhard attempted to decipher the ultrastructure of the nucleus. The perichromatin fibrils and their role in RNA synthesis, the phenomenon of nucleolar segregation, the existence of different types of perichromatin granules, and the formation of abnormal nuclear bodies were all described in his laboratory, using cultured cells treated with various drugs and hormones and processed by cytochemical procedures. At the time of his death, he and his colleagues were pursuing nonnucleolar transcription units and the organization of DNA in interphase nuclei.

Dr. Bernhard’s influence was felt well beyond his laboratory. He was a charter member of the Société Française de Microscopie Èlectronique and the European Cell Biology Organization. He founded and ran the highly successful European Nucleolar Workshop (now Wilhelm Bernhard Workshop on the Cell Nucleus). He was the driving force behind the annual Franco-Russian cell biology conferences, and represented the Ministère des Affaires Etrangères in scientific missions in South America, India, Japan, and South Korea. A strong advocate of the thesis that science should have no national boundaries, he visited and invited to his laboratory scientists from all parts of the world.

His influence was not limited to the world of biology. Among his friends were sculptors, poets, philosophers, and painters. He was an illuminating guide to concerts, exhibitions, and architectural gems of Paris, the antique shops of the flea market, and the churches and chateaux of the Loire region. He transformed a large quarry behind the laboratory into an extraordinary rose garden. He liked Mozart, Proust, and…. American Westerns. All who knew him were touched by his charm and elegance , and his taste for beauty and adventure.

Dr. Bernhard rose through the ranks of the Centre Nationale de Recherches Scientifique from Attaché (1948 to 1953), Chargé de Recherches (1953 to 1956), Maître de Recherches (1956 to 1961), to Directeur de Recherches (1961). Throughout this period he was Chef du Laboratoire de Microscopie Électronique at the Institut de Recherches Scientifiques sur le Cancer at Villejuif. He was named Chevalier de l’Ordre Nationale du Mérite (1973), held honorary membership in the Royal Microscopical Society, the Spanish Society of Pathology , and the Académie Leopoldina, Halle (Germany), and was awarded the title Doctor Honoris Causa by the Université de Bruxelles (1969) and by the Université de Bale (1969). He was awarded the Prix Louise Darracq (Lauréat de l’Académie des Sciences, 1957); Prix du Lauréat du Concours de la Ligue Nationale Suisse Contre le Cancer, 1960; Grand Prix Scientifique de la Ville de Paris, 1964; Prix Paul Ehrlich (with R. Dulbecco), Frankfurt, 1967; Hartmann Muller Memorial Lecturer, Zurich, 1968; Ricketts Award, University of Chicago, 1972; Schleiden Medal, Académie Leopoldina, Halle, 1976. On December 4, 1978, he received posthumously the Prix Lacassagne of the Ligue Nationale Française Contre le Cancer.

 In a philosophical essay entitled “Spiritualité et Neant dans la Science”, completed a month before his death, Dr. Bernhard began with two quotations that expressed his themes:

 “Science sans conscience n’est que ruine de l’ame” (F. Rabelais, 1532)

 “The only wisdom we can hope to acquire is the wisdom of humility. Humility is endless” (T.S. Eliot, “Four Quartets”).

 On October 9, 1978, Dr. Wilhelm Bernhard died suddenly in Buenos Aires, on his way to a scientific meeting in Mendosa. Thus ended the career of an adventurous pioneer in electron microscopy applied to cancer research.

 Elizabeth H. Leduc and Etienne de Harven, Cancer Research 39:2811 (1979)

In memoriam: Wilhelm Bernhard

A few days after Wilhelm Bernhard’s sudden death on Buenos Aires airport on September 24, 1978, a plane took off from Orly, chartered by Roger Monier, Directeur de l’Institut Gustave Roussy in Villejuif, to bring a group of his French friends and colleagues to Switzerland and the little village of Worb, where he was born in 1920. Standing there around his tomb, embedded in the green countryside of Bern and looking up to the surrounding mountains, it was like a family mourning its father. Indeed, beyond the admired master of science, all of us had strong human ties to him – nobody could be indifferent to his charm and genuine personal interest and affection. Wilhelm Bernard was not only an enthusiastic researcher but also a humanist, a sage embedded in arts, music, literature, philosophy, and he cared to transmit his knowledge and spiritual experience. Admirer of French poets and writers and in particular Proust – his home on Boulevard Haussmann transpired real Proustian atmosphere – he also knew most of Swiss and German literature and much appreciated the prince of the latter: Goethe.

It was typical for him that he recovered in Jena’s botanic garden a seedling of the “Goethepflanze” (Kalanchoe pinnata) to create in his lab offspring, from which visitors he cared for received a plant along with a poly-copied print telling its significance and history. Goethe personally had brought the specimen from Palermo to Jena, where it was cultivated during a century. When Jena stood in ruins after the 2^nd world war, it was saved by a caretaker in his home. The plant produces on the edge of the leaves miniature copies of itself that easily fall down and grow up as new plants; a perfect illustration of Faust’s “homunculus“, the miniature human supposed to reside in the sperm.

It was wonderful to stroll with Wilhelm though the Parisian flea markets where he spotted the really beautiful and outstanding items and commented about them. Once, he encouraged me to buy an Ashanti doll and some other pieces of African art. He was a collector of rare books and art, in particular of East Asian sculptures that he brought home from his trips throughout the world. Along another line, visiting him after a tour in Mexico, he solemnly opened a tin can and made us eat the content: ants conserved in oil! His office was a harbour of peace and intellectual exchange; we spent many hours of discussion switching from French to our native Swiss when personal and political matters came up.

His interest in people from all over the world was genuine, and thus he tried to implement international collaboration, particularly important in those Cold War years, convinced he was that science had the possibility – and thus the duty – to overcome political borders.

I first met Wilhelm Bernhard in America, in the lab of Elizabeth Leduc at Brown University in Providence, Rhode Island. I drove down to see him from Cambridge, Massachusetts, towards the end of my post-doc at MIT. In Jim Darnell’s lab we just had discovered “giant” RNA and RNA processing. Thus he kindly offered me a position with the aim to introduce a branch of Molecular Biology into his team. But, having just become a molecular biologist, I did not dare to pretend playing such a role before having acquired more experience. Thus I then went to the lab of Francois Gros, first at the Pasteur Institute and later at the Institut de Biologie Physico-Chimique, but stayed in contact and collaborated with Wilhelm Bernhard’s team and, in particular, with Nicole Granboulan, a most outstanding scientist and person. In Bernhard’s laboratory we developed for the first time a method to spread RNA for EM; thus far only the double-stranded DNA had been spread routinely. She was also the one who discovered by EM the prosome particles in preparations of ribonucleoproteins, which later turned out to also form the core of the 26S proteasomes.

Nicole was for Wilhelm Bernhard the daughter he did not have and it was marvel ous to observe this human relation in which he cared for her family, being for her children sort of an adopted grandfather. Terrible was our pain when she died in a car accident on the highway from Geneva to Lausanne where she was spending a sabbatical year in our lab. Wilhelm was devastated by this tragedy that hit her family in the first place, but also her colleagues and collaborators.

Getting cellular and molecular biologists together was one of the reasons Wilhelm founded the Nucleolar Workshop, as it was called at the beginning given his focus on the nucleolus. At that time, the field of cell biology was very structural and static – the “Parthenon-view” of the cell – whereas Wilhelm realized that a more dynamic view had to be added, to be introduced possibly by the upcoming molecular biology. This prescient outlook was typical of his open-minded and non-dogmatic view. He encouraged me and others to propose molecular biologists to be invited to the Workshops, starting with the program of the inaugural, 1967 meeting in Liblice, Czechoslovakia. The connected themes of molecular and cell biology have remained the defining principle of the Wilhelm Bernhard Workshops ever since.

Wilhelm Bernhard’s desire to bring together, beyond the strictly scientific agenda, scientists from all countries, overcoming the political borders of the Cold War, was from the onset decisive in the organisation of the Workshops. The basic rule was to have, on a biennial schedule, meetings alternatively in East and West, moving from one country to another. At that time, many Eastern European colleagues were not allowed to travel, not even within the Soviet bloc, and in particular not to the West. Furthermore, with more and more colleagues from the USA participating, the Wilhelm Bernhard Workshop became a rare spot where Russian and American scientists could meet.

In those days it was hard to do advanced research in the Soviet world, due to lack of equipment and, in particular, information. The Wilhelm Bernhard Workshops were like windows to the Western world allowing flow of information from West to East. But it was not unidirectional. Lack of equipment led to imaginative inventions. A classical example was electrophoreses of RNA in gels, introduced in 1965 by Roumen Tsanev from Sofia because he had no access to ultracentrifugation.

Another important point was Wilhelm Bernhard’s intense commitment to give young scientists the opportunity to present their data to a circle of established investigators and to meet experienced colleagues in their field of research. In all this, Wilhelm Bernhard gave the general lines but let the local organizers in each country design each conference according to their interests and at their pace. But he insisted very much that some cultural events be put on the program and we experienced some unforgettable concertos thanks to his love of music.

In a nutshell: mix colleagues from advanced and developing countries, from East and West, young and old, elder statesmen of science and students, these were the principles governing Wilhelm’s workshops. These rules were carried over to the – still running – Arolla Workshops devoted to molecular biology and genetics. It was Wilhelm Bernhard who had suggested Arolla as an ideal place, way up in the Swiss Alps, to have a regular scientific meeting.

It is not the place here to review the scientific achievements of Wilhelm Bernhard; the article on his work by Elizabeth Leduc and Etienne de Harven (Cancer Research 39:2811, 1979) that also is on the WBW website gives an excellent review. Let us just recall that, with his teacher Charles Oberling, Wilhelm was at the origin of the demonstration that cancer may be induced by some types of viruses; he defined and named the intracellular viral particles of A, B, and C type. His EM techniques to differentially stain DNA and RNA in thin sections, inventing all kinds of fixation and embedding materials, became world famous. He used these methods to study DNA and RNA dynamics in the nucleolar and nuclear space, being particularly interested in transcription.

Being honoured by many scientific prizes and election to academic societies, Wilhelm Bernhard remained an outstanding example of humility. Science was for him not only a pleasure and an enthusiastic endeavour but also a moral duty. He believed in the Faustian promise : “Wer immer strebend sich bemüht, den werd’ ich in die Klarheit fähren” (Who ever strives with all his might will soon lead him into clarity). Wilhelm Bernhard was a genuine Faustian spirit.

Klaus Scherrer
June 27, 2013