Anthony Cerami Award in Translational Medicine A Journey in Science: Medical Scientist in Translation Göran K Hansson Karolinska Institute, Department of Medicine Solna and Center for Molecular Medicine at Karolinska University Hospital, Stockholm, Sweden Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Mo- lecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these his- tories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed and treated. In this volume, the Cerami Award Monograph is by Göran K Hansson, MD, PhD, Karolinska Institute. A visionary in the field of cardiovascular re- search, this is the story of Dr. Hansson’s scientific journey. Online address: http://www.molmed.org doi: 10.2119/molmed.2014.00092 INTRODUCTION I grew up in a small town in the prov- world politics and student protests. The My decision to go to medical school ince of Bohuslän on the Swedish North 1960s were an exciting time. was based in equal parts on a desire to Sea coast. My dad ran the local newspa- help people, a wish to have a meaning- per of the town, and my mum was a MEDICAL SCHOOL AND HOW TO ful job and the challenge to get into a nurse at its small hospital. The town of SURVIVE IT program that was, at the time, the most Lysekil was dominated by the sea sur- The curriculum in medical school coveted one in the Swedish university rounding it. Commercial fishing, her- started with anatomy. It was a night- system. I had dreams of becoming a ring canneries, and a factory producing mare. We were expected to memorize thoughtful psychiatrist, a decisive cardi- boat engines were its main activities. In Latin names for hundreds of structures ologist or perhaps a doctor for the poor summer, the coast was invaded by on bones—fossae, sulci, capita and so on. somewhere in a developing country. tourists from the big cities—Stockholm, We were incessantly told that knowledge I made it to and through medical school, Göteborg and Oslo. When the sea of all these anatomical details was ab- but I fulfilled none of these dreams. warmed up, we went swimming, canoe- solutely necessary for any clinical doctor. After a short time in internal medicine, ing and sailing. Life was magical for a When I started working as a clinician the research bug had bitten me and I be- teenager—sailing in the day and party- myself, I found this kind of descriptive came a physician-scientist, with the em- ing at night. Winds from the big world anatomy completely useless. In real life, phasis gradually moving toward the lat- brought new influences and new bones have tendons and muscles at- ter part of the term. sounds, such as the Beatles, Bob Dylan, tached; they are not bare except in the cemetery. One day, I saw a poster in the corridor outside the anatomy department. The Address correspondence to Göran K Hansson, Karolinska University Hospital, Center for neighboring department of histology in- Molecular Medicine L8:03, SE-17176 Stockholm, Sweden. E-mail: [email protected]; vited students to an evening with infor- Phone: +46-8-5177-6222. mation about medical research. We talked Submitted May 1, 2014; Accepted for publication May 1, 2014; Epub (www.molmed.org) about it over a beer in the park when we September 5, 2014. were skipping another boring hour of anatomy, and decided to attend. That evening, we met other kinds of teachers. They were scientists and told us about MOL MED 20:381-389, 2014 | HANSSON | 381 A MEDICAL SCIENTIST IN TRANSLATION who had just finished his PhD in Sören’s come and learn. The head of the depart- lab. Göran taught me how to dissect ar- ment was the famous immunologist, teries, analyze cholesterol in tissues and Örjan Ouchterlony, who had invented the label dividing cells with radioactive iso- immunodiffusion method for analyzing topes. I was learning the craft of science antigens. Much of the work in the depart- (Figure 1). ment still dealt with the “Ouchterlony Life was intense. There were lectures technique,” but they were also doing im- and classes in physiology, pharmacology munofluorescence microscopy. I stained and pathology in the mornings and after- normal rabbit arteries for immunoglobu- noons, work to do in the research lab in lins and complement factors and found the evenings, and books to read at night. nothing. But when I applied the same And there were a thousand things to staining protocol to atherosclerotic arter- protest against in endless demonstra- ies of fat-fed rabbits, there were tons of tions, ranging from the war in Vietnam IgG and C3 in the lesions! Something was to the new curricula in universities. My going on. There was an immune activity girlfriend (and future wife), Margareta, of some kind in the atherosclerotic lesion. who was studying psychology, and I For the first time, I had made a discovery. were busy all the time. And things were to get even busier. POSTDOCTORAL STUDY IN A MECCA Margareta was pregnant, and we hadn’t OF VASCULAR BIOLOGY even finished our educations. Our son, I finished my PhD thesis, applied for a Figure 1. Göran Hansson smashes some Emil, was born the day I had my major postdoctoral fellowship and contacted glassware while trying to isolate organelles. exam in internal medicine. Axel followed scientists at the University of Washington Caricature by student colleague Tom Björnheden, 1980; reproduced with permis- 3 years later. Margareta switched from in Seattle, which was a Mecca for vascu- sion from him. psychology to physiotherapy when it be- lar biology and atherosclerosis research. I came obvious that job opportunities was overwhelmed with joy when I was were dwindling in psychology. I contin- awarded a Fogarty International Postdoc- medical problems that needed to be ued in medical school and could even toral Fellowship from the U.S. National solved, pointing out methods for solving continue with part-time research, thanks Institutes of Health and could move to them. And they wanted us to join them in to an understanding wife and a modest Seattle with my little family. that endeavor. We immediately signed up. need for sleep. Seattle was a fun city and the Univer- Our first experiment was not a success. sity of Washington was everything a re- My classmate, Per Elias, and I joined a IMMUNITY IN BLOOD VESSELS? search university should be. I worked neurobiology project to analyze biochem- Immunology immediately captivated with Steve Schwartz, an eccentric, excit- ical changes in the cerebellum after alco- me in medical school. I took immunol- ing and intellectually brilliant scientist in hol exposure. Our main finding was that ogy courses as part of my PhD program the pathology department. Steve’s pas- the cerebellum is completely devoid of and learned about antibodies, vaccina- sion was cell kinetics, and he could argue protein. Neurobiology was not ready for tion and memory. I was fascinated by the for hours about cell cycles and popula- such a paradigm shift, and we decided to fact that this powerful defense system tion dynamics in the endothelium. Next move to other fields. was patrolling our bodies, next to the door was Earl Benditt, the former chair- In the laboratory of Sören Björkerud, I blood vessels where atherosclerosis de- man of the department, who had pro- heard about cardiovascular disease, the veloped. “How would the immune sys- posed that atherosclerosis was a mono- major cause of death in our society. Sören tem react to a pathology that builds up clonal population of smooth muscle cells. was an enthusiastic teacher. It was fasci- in its immediate vicinity?” I asked my- The new chairman, Russell Ross, had an- nating to hear him explain how the cells self. “Someone must know,” I reasoned, other theory—that atherosclerosis was of the blood vessels form a barrier to pre- and I went to the library and read all the caused by the platelet-derived growth vent cholesterol from accumulating and textbooks and review papers I could find factor, which was released when platelets how that barrier could be damaged by about cardiovascular pathology. Not a aggregated at sites of arterial damage. the forces of blood pressure, leading to word was said about the immune sys- Earl and Russell would never reach a atherosclerosis and ultimately to myocar- tem. I asked Göran Bondjers. His answer consensus, but some kind of working re- dial infarction. was “Go and find out.” lationship developed, with Earl being the I was assigned to work with Göran I knocked on the door of the microbiol- king of vascular biology in Seattle and Bondjers, a young physician-scientist ogy department, and they allowed me to Russell in the rest of the world. 382 | HANSSON | MOL MED 20:381-389, 2014 ANTHONY CERAMI AWARD IN TRANSLATIONAL MEDICINE The young generation of cardiovascu- tibodies recognized to characterize the lar scientists was a great crowd. Ron features of the cells forming the lesion. Heimark, a skillful biochemist, patiently I thought I had a better idea and started taught me how to run SDS (sodium do- testing it as soon as I came back to decyl sulfate) gels. Alec Clowes was a Göteborg. promising young vascular surgeon who My idea was to use well-characterized did beautiful work on arterial restenosis, antibodies to known cell types, apply together with his wife Monica, and Alan them to human atherosclerotic lesions Chait, a brilliant endocrinologist study- and find out if they stained any of the ing lipoprotein metabolism.