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Obituary – In Memoriam Per Brandtzaeg

2016; Wiley; Volume: 84; Issue: 6 Linguagem: Inglês

10.1111/sji.12505

1365-3083

Frode L. Jahnsen, Finn‐Eirik Johansen, Guttorm Haraldsen,

Immune Response and Inflammation

Professor Per Brandtzaeg, world leader in mucosal immunology for 5 decades and former president of Scandinavian Society for Immunology, passed away on 11 September 2016. Per Brandtzaeg was born in Bergen on the Norwegian west coast on 6 June 1936, but spent his infanthood in Fredrikstad close to the border with Sweden. His father died when Per was only 4 years old, and his mother then moved with three young children to her home region of Ørskog on the west coast near Ålesund. At age 16, Per left home to go to high school in Volda, and after graduation, he moved to the nation's capital to attend dental school at the University of Oslo. After graduating dental school with flying colours, he joined the Norwegian army as a lieutenant for his mandatory national service. It was during his military service, working on gingivitis under the supervision of Professor Jens Waerhaug that Per's passion for research was first lit. With the help of Professor Waerhaug, he later obtained a Fulbright scholarship in 1962 to study medical microbiology, immunology and pathology at University of Alabama in Birmingham, Alabama, USA. For his Master of Science degree in Alabama, he worked with professor Frederick W. Kraus. During his stay, Per became involved in the work on the immunological defence of human mucous membranes, the main interest of his supervisor, Dr. Kraus, who was a pioneer in the field. A major part of Per's work was based on immunofluorescence for the localization of immunoglobulins and other proteins in human tissue sections. Per was fascinated by this powerful technique, and once he returned to Norway in 1964, he was urged by professor of pathology, Olav Torgersen, to establish a laboratory at the National Hospital (Rikshospitalet), which could further develop the technology for the benefit of Norwegian pathology. In 1965, Per founded Laboratory of Immunopathology and Immunohistochemistry (LIIPAT). It was as the founder of LIIPAT and its leader for more than 40 years that Per became internationally recognized and a true leader in the field of immunology. The mucosal immune system was a new area of research. Per used physiochemical and immunochemical methods to study immunoglobulins in external secretions and defended his PhD degree in 1971 entitled ‘Human Secretory Immunoglobulins’. Staining tissue sections with antibodies was a new discipline, and Per developed this method to study immune cells in situ. With novel microscope technology, he was able to perform paired immunofluorescence staining of two antigens in the same tissue section. Through his pioneering work of the secretory IgA system, which included both structural characterization of IgA and studies on the transport mechanism for IgA, Per's scientific breakthrough came in 1974 when he described the model by which secretory antibodies are selectively translocated through the glandular epithelia. This finding stimulated a broad international interest in this field, and over the next few years, the ‘Norwegian’ model was supported by many international laboratories. Indeed, the model now found in most immunology textbooks such as Janeway's Immunobiology describes how transmembrane secretory component (SC, known as poly immunoglobulin receptor, pIgR, today) acts as a receptor/carrier protein for polymeric IgA across epithelia. About the same time, Per also showed that the small polypeptide associated with polymeric IgA and pentameric IgM, joining chain (J chain), was a product of plasma cells synthesized independently of the class of immunoglobulins present in the same cell. Important to Per's model was the fact that only J chain-containing IgA and IgM could bind SC/pIgR. Human pIgR was cloned in Per's laboratory in 1991, and later, Per and his co-workers performed several important studies on the regulation of this sacrificial transport protein. The final proof that the transport model was correct came in 1998 when Per and co-workers demonstrated the absence of epithelial IgA transport in mice deficient for pIgR. LIIPAT expanded rapidly, and over the next 40 years, he supervised more than 40 PhD students and numerous post-docs. The seminal studies on the transport of secretory antibodies were followed by a series of both clinically and basic-oriented work of mucosal immunology. Brandtzaeg and co-workers performed detailed characterization of the phenotype and function of many types of immune cells at mucosal tissues such as B cells, T cells, macrophages, eosinophils and endothelial cells and studied the immunopathology of diseases such as inflammatory bowel disease, coeliac disease, food intolerance, chronic gastritis, bronchitis, rhinitis, tonsillitis, periodontitis and Sjøgren's syndrome of the salivary glands and various immunodeficiencies. Together, Per published more than 600 articles, eight monographs and 132 book chapters. As head of LIIPAT, Per created a strong and dynamic scientific environment. By his enthusiasm for science, his creativity and his stamina, he was a great role model for young students, and as a supervisor, he was very supportive and conscious about giving his students freedom to follow their own ideas. Apart from his scientific involvement, Per will always be remembered for his ability to create a very good social environment, and particularly for the way he cared about the technical staff. When LIIPAT celebrated its 25th anniversary, Per wrote a chapter called ‘A wonderful technical staff’ where he praised the quality and efficiency of their work, their loyalty, their friendliness and ability to create an easy-going atmosphere. And he ended by saying that the successful relationship between researchers and technicians was the main reason for the remarkable scientific productivity of LIIPAT. Per regularly invited the laboratory to his summer house, his wife's farm or to his home. The LIIPAT’ annual Christmas party became a classic where Per brought the famous LIIPAT Christmas cake (made by his wife Tulla) on his bicycle (Per biked all year round). Per had a strong impact on the development of both pathology and immunology in Norway. He was the Chairman of the Organizing Committee that founded the Norwegian Society for Immunology (1981–82) and its president from 1984 to 1986. He became honorary member of both the Norwegian Society of Pathology and the Norwegian Society of Immunology. He was very active in both societies and was an inspiring person for many young doctors and researchers in Norway. Per recognized early the importance of establishing binding collaborations between research groups to move the field of immunology forward, and in 2002, he formed the thematic research group ‘Centre for Vaccinology and Immunotherapy’ consisting of five research groups at the University of Oslo. This thematic research group was the forerunner for the ‘Centre of immune Regulation’, a Centre of Excellence, appointed by the Norwegian Research Council in 2007 and a FOCIS Centre of Excellence since 2010. Per trained a large number of Norwegian scientists and used his international stature to help them build international network and advance their careers. He was strongly connected to his roots, proud of his heritage and contributed in many ways to the advancement of Norwegian and Scandinavian immunology. He authored or co-authored no less than 42 papers in Scandinavian Journal of Immunology and encouraged laboratory members to submit some of their best work to the journal. He served as president of The Scandinavian Society for Immunology from 1990 to 1992 and managing editor of SJI for 5 years from 1994 to 1999. Before, during and after his tenure as managing editor, he reviewed an enormous number of papers for the SJI, always with the same rigour that was Per's trademark. His busy schedule permitting, he would always attend the SSI annual meeting, and even though he was in poor health the last couple of years, he was present and gave a lecture at the most recent SSI meeting in Turku in May of 2016. Per loved to share his knowledge with others, particularly early career scientists and students in the health professions. Internationally, he was an extremely sought-after lecturer and he has taught immunology to students in many parts of the world, but particularly to students in the Scandinavian countries. Per was extremely hard working throughout his career and displayed a remarkable perseverance. He fought for knowledge and scientific values not only in his own work as a scientist, but also for these values to permeate decision-making and policies in society. He wanted decisions to be based on facts and participated eagerly in the national debate on research policies. Curious by nature, he was a firm believer in curiosity-driven basic research. Nevertheless, he was keen to see beneficial applications of his own research results. His career starting out with investigations into the nature of simple component of mucosal immunity, and how these contributed to immune effector mechanisms, developed into a deep interest for vaccinology and how the mucosal immune system could be better exploited to promote human health. In a famous and widely debated murder case in Norway, Per sided with the lawyers for the defendant in their attempt to get the case retried. Per did this not because he had an opinion on whether the convicted person was guilty or not, but because he firmly believed that the physical evidence presented by the prosecution in the original trial and which was accepted by the court as proof of guilt was of poor scientific quality even by the standards of the day of the original trial. Even though the case was not accepted for a retrial, Per's relentless fight to impose stronger scientific standards for evidence in the court of law gained national attention, and in a famous interview, he exclaimed that this case was ‘science against madness’ (vitenskap mot galskap). Per was a highly acclaimed international scientist and was instrumental in turning the research field of mucosal immunology into the prominent discipline that it is today. Per was a councillor of the Society for Mucosal Immunology (SMI) from 1991 to 1993 and became the first non-American president of the SMI from 1994 to 1996. What was less visible was the scholarship and support that he provided to younger colleagues around the world and his anonymous contribution to an enormous number of papers from other researchers. As a sign of his position as a leading international scientist, he received numerous prizes, for example Anders Jahre's Nordic Senior Medical Research Prize, the Norwegian Research Council's Prize for Outstanding Research and in 2014 the Fernström Foundation Nordic Prize. He also received numerous honours for his work including Honorary Professor, Old University of Herborn, Germany; Honorary Doctor, University of Århus, Denmark; Honorary Doctor University of Bergen, Norway; Honorary Doctor of Medicine, Freie Universität Berlin, Germany; Distinguished Scientist Achievement Award, SMI; and in 2006, he became Commander of the Royal Norwegian Order of St. Olav, which was the second time he was granted an audience with the Norwegian king. After his retirement in 2006, Per continued as an active researcher. He was regularly invited to give talks at scientific meeting and participated on many scientific advisory boards and other scientific committees and he continued to write both reviews and original scientific papers. Over the last few years, Per experienced increasing health problems, but it did not stop him from scientific work. Per turned 80 in the beginning of June, and a week later, LIIPAT celebrated its 50 years anniversary where Per gave a speech to thank all past and present members for their efforts through the years. In June this year, Per was invited to participate in the Karolinska Research Lectures at NOBEL FORUM in 2017. Although he was in the hospital when he received the invitation, he accepted the invitation without hesitation. Quintessentially Per: constant optimism and relentless pursuit of new scientific discoveries.