Abstract

Professor emeritus Morten Harboe, the first Norwegian professor of Immunology, died peacefully at St. Hans Haugen omsorgssenter 1 April 2021. Harboe, named Morten after his father, who also was a doctor, was born in Lavik, grew up in Kragerø and moved to Gjøvik with his family, where he made his gymnasium examination. He married Sissel Lippestad in 1959, and together, they had 3 children, Ingrid, Henrik and Morten jr Harboe graduated from the University of Oslo as an MD, and after his internship and military service, he started his scientific career in 1957 at the National Hospital in Oslo (Rikshospitalet). His first papers appeared in 1957 and 1959 and covered topics within medical biochemistry. His first highly cited paper was a methodological paper on the determination of haemoglobin using ultraviolet light.1 However, the topic of his PhD thesis would take a different turn as he diverted his interest to immunoglobulins and thereby established himself as the leading immunologist in Norway. Rune Grubb, at the University of Lund, Sweden, had discovered the first allotype on immunoglobulins, termed Gm(a) in 1956,2 and Harboe made his entrance into the field by subsequently characterizing a serum that agglutinated red cells coated with immunoglobulins that did not match Gm(a).3 He could show that this serum defined a different genetic property of human immunoglobulins than Gm(a). He then went on and discovered other Gm types. This work was to become a very focused and strong PhD thesis in 1961, ‘Studies on the gamma globulin (Gm) serum groups’.4 He was the sole author of all but one of the papers included in the thesis, where his supervisor, professor in forensic medicine, Jon Lundevall, also contributed. At that time, there was considerable interest in discovering allotypic traits in humans, using sera from different sources, and targeting various human components. The purpose was to improve the methods used for crime investigation and determination of paternity. Harboe's PhD was to become an important contribution to this endeavour. The personal copy of his thesis, that Harboe used to keep in his office, was full of handwritten notes in his characteristic handwritten style, all of them made during the dissertation. Apart from demonstrating his dedication, these meticulous notes show that the dissertations at that time went into considerable detail. As it became important to clarify the various findings within the field of Gm types, Harboe later told that when the scientists gathered internationally to do comparative experiments in the laboratory, and to compare their results, he had an advantage over those scientists who had access to technical assistance, because he had done all the laboratory work himself. After his PhD, he went to the Rockefeller Institute in New York to work with Henry Kunkel from 1961 to 62. After his return to Norway in 1962, he worked at the Institute of Experimental Medical Research at Ullevål Hospital in Oslo and continued to pursue research within general immunology. Harboe was awarded Anders Jahre's Prize for Young Medical Investigators in 1968 for his discoveries of the Gm allotypes. In 1972, he was appointed as the first chair professor in Immunology in Norway at the University of Oslo, where he was dean at the faculty of medicine during the period 1978 - 1982. Harboe was opponent at Jacob B. Natvig's doctoral dissertation in Bergen in 1966. As Harboe had done earlier, Natvig went to Kunkel's laboratory after his PhD. Harboe was involved when the Institute of Immunology and Rheumatology, Rikshospitalet, was established in 1967 with Natvig as its first director. In 1972, they founded Scandinavian Journal of Immunology together with Gunnar Bendixen, Olli Mäkelä and Hans Wigzell. Jacob Natvig died just one day after Morten Harboe. In 1969, Harboe went to Ethiopia to stay for one year with his family to build up Armauer Hansen Research Institute in Addis Ababa, which was officially opened in 1970 by the Ethiopian emperor Haile Selassie in the presence of Harboe. AHRI was dedicated to leprosy research and has become Ethiopia's leading biomedical research institute and is an essential scientific institution for mycobacterial research in Africa. The involvement at AHRI also started Harboe's interest and dedication to mycobacterial research. During the 1970ties, he would establish immunoprecipitation techniques together with Otto Closs at the Institute for Experimental Medical Research at Ullevål Hospital. The development was inspired by Nils H. Axelsen who had written a handbook on these techniques and who became a close friend of Harboe. He helped out to establish the new methods that turned out to be instrumental for characterization of mycobacterial antigens.5 In 1983, Harboe became director of the Institute of Immunology and Rheumatology at Rikshospitalet. At the same time, Sadamu Nagai from Osaka visited Harboe's laboratory for a year. Nagai was a quiet and laborious man who was dedicated to the purification of Mycobacterium bovis, BCG and Mycobacterium tuberculosis proteins. This was the start of a very fruitful collaboration, and typically, Harboe spotted the significance of secreted mycobacterial antigens as an explanation for why the BCG vaccine must be viable to be effective. Characterization of the components of the antigen 85 complex as the main secreted antigens of mycobacteria was one of the main achievements.6 Another significant advancement was the collaborative efforts with Peter Lawaetz Andersen in Copenhagen on ESAT-6.7 This field developed into a very competitive area during the 1990ties and led to the development of new vaccine candidates against tuberculosis. Harboe became interested in the complement system quite early in his career and published his first paper on the topic in 1961.8 However, his major interest in complement returned when Tom Eirik Mollnes came to Harboe as a dr med. fellow in 1983. At the Institute of Immunology and Rheumatology, Tor Lea had established methods for the generation of monoclonal antibodies, and together, they developed an approach to select antibody specificities that would react with neoepitopes, that is epitopes that appeared on complement after its activation.9 This line of research led to several excellent PhD theses, and Mollnes who were to follow in Harboe's position developed a very prolific career. After Harboe retired, he contacted Mollnes, leading the complement group and said: ‘to be honest, it is too early for me to start “feeding the pigeons” – may I join your group's projects meetings?’ The answer was certainly yes. He not only attended the Complement Research group, but got a place in the laboratory and a bioengineer as well. He stayed in the group for 15 years and published 12 excellent scientific papers. He documented for the first time the quantitative role of the alternative pathway as an amplification loop for the classical and lectin pathway.10 Furthermore, he documented, in contrast to what was accepted in the literature, that properdin was not a major recognition molecule in the alternative pathway,11 and he wrote an excellent review on the role of the properdin in the complement system.12 As a supervisor, Harboe would sit down with the student and make handwritten notes in a systematic and orderly way, checking that there would be no misunderstanding. His handwriting was very clear and easy to read and always made an impact because it conveyed a message that, what is written here, is important, particularly when added as comments to a manuscript. Harboe was always very focused when discussing a project or write-up of a scientific paper and did not accept distractions. He would then become quiet for a few moments before continuing. As a supervisor, he would supply new information when he recognized that the student was ready for it and could take advantage of it. Among students and colleagues in the laboratory, Harboe always insisted on using his given name. He had an open-door policy and was always readily available for his PhD and post doc students. Harboe was very open-minded and interested in new ideas and approaches, and he had a unique ability to spot essential information that makes a difference. Harboe was a gentleman and widely recognized for fair play and honesty. He was highly respected among colleagues, and he had a unique way of approaching difficult situations. His leadership and ability to solve conflicts were much sought, and consequently, he led several important committees and boards. Many medical doctors in Norway are familiar with his popular textbook of medical immunology, which he wrote together with Natvig, in 1975. The textbook underwent regular revisions up to 1991 and was also issued in German, Japanese and Spanish. Harboe was an excellent teacher and his lectures were popular among medical students in Oslo as he introduced them to immunology. Harboe was elected member of the Norwegian Academy of Science and Letters. He was also very engaged in societal work, and he has been chairman of the Norwegian Save the Children and the Norwegian Cancer Society. In 2000, King Harald awarded him the Order of St. Olaf, Knight 1st Class. Harboe was employed at the Institute for Experimental Medical Research at Ullevål Hospital from 1962 to 1983, and at the Institute of Immunology and Rheumatology, Rikshospitalet, Oslo from 1983 to 1999. The institute was merged with the Institute for Transplantation Immunology to become Institute of Immunology when Rikshospitalet moved to new premises at Gaustad in Oslo, and Harboe stayed with the new institute as professor emeritus and became part of his former PhD student, Tom Eirik Mollnes’ group on complement research. Harboe worked daily with Mollnes until 2017 and finished his scientific career with a groundbreaking paper in PNAS on properdin,11 which solved years of contention in the complement field. He will be remembered equally much in Ethiopia where a lecture hall with 600 people capacity in the new laboratory building will have his name. Harboe was a significant figure in the field of Immunology. He was very dedicated to research and appreciated the challenges in science. He was a dedicated person and followed the scientific development with great admiration as long as his health allowed. Harboe was a person with great integrity. We will remember him as a great scientist, a dear friend, supervisor and collaborator. The data that support the information are available on request from the corresponding author.

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