Jan Lännergren
Karolinska Institutet, Sweden

https://doi.org/10.36866/pn.97.14

Bernhard Frankenhaeuser was born in 1915 in the small town of Borgå in the south of Finland where his father was an architect. He went to school in Borgå and then started to study medicine in Helsinki in 1934. Late in 1939 the Soviet Union attacked Finland and the so-called Winter War started. Bernhard was called into the Finnish army and served as military doctor both in the Winter War and in the so-called Continuation War (1941-44). Very much later, he told dramatic stories about narrow escapes from the advancing enemy. When the war was over, Bernhard finished his studies and obtained his medical degree in Helsinki in 1946. In that year he also met Marianne von Wright and they married after having known each other for just a few months. Marianne later became a world authority in stress research. They had their only child, a daughter named Carola, in 1949. She is married (Lidén) and is now a Professor of Occupational and Environmental Dermatology at the Karolinska Institutet.

By 1939, Bernhard had already come into contact with Ragnar Granit, then Professor in Physiology at the University of Helsinki. After the war, Granit helped Bernhard to go to Oxford. There he met William Rushton who made a deep impression on him, as did the whole British School of Physiology. In Oxford, Bernhard undertook the experimental work that was the foundation of his doctoral thesis, which he defended in Stockholm in 1949. Bernhard had been in contact with Granit during the years after the war and moved to Stockholm (with Marianne) in 1946. Granit had already moved to Sweden in 1940 and set up a laboratory at the old Karolinska Institutet. In 1946, Granit was offered a chair at the new Karolinska and his own institute, which he accepted. Bernhard joined Granit at the new Nobel Institute for Neurophysiology in 1947.

Between 1950 and 1952, Bernhard worked on accommodation in single nerve fibres of the frog. He was also interested in the mechanism of saltatory conduction in myelinated nerve fibres. In 1952 Bernhard met Alan Hodgkin at a meeting in Cold Spring Harbor. Hodgkin and Huxley had just published their famous papers on the mechanism of nerve impulse conduction. Their voltage clamp experiments had revealed the voltage- and time-dependency of the Na+ and K+ conductance in the axon membrane; the ’H-H’ equations gave a quantitative description of the mechanism underlying the nerve impulse. Still, it was not known how the opening of the ion channels in the axon membrane came about. Frankenhaeuser and Hodgkin decided to test the hypothesis that Ca2+ acts as a ’plug in the hole’ that controls the conductance. This idea originated from the knowledge that the Ca2+ concentration of the external medium influenced excitability. Voltage clamp experiments were again performed on the squid giant axon at the Marine Biological Laboratory in Plymouth. They found that changes in Ca2+ concentration shifted the voltage dependency of the ion conductances – as predicted by the hypothesis – but the effect was not large enough. Nevertheless, the findings about the Ca mechanism were of great importance and this paper has been highly cited.

Hodgkin and Huxley had clarified the mechanism of impulse generation in squid axons. But vertebrate myelinated nerve fibres have a different structure. Huxley and Stämpfli had shown that impulse propagation in myelinated fibres is saltatory. But which ionic currents underlie the nerve impulse at the node? In order to answer this, a method was required that allowed voltage clamp of the isolated nerve fibre. After several false starts, and when Bernhard was near despair, he finally managed to get the method to work. Using negative feedback, the longitudinal currents could be controlled and the membrane potential recorded. This was decisive for allowing control of the membrane potential with yet another feed-back amplifier and obtaining a voltage-clamp system. With the new method in hand, Bernhard made a thorough analysis of the nodal ionic currents and discovered many similarities with the squid axon membrane, but also some interesting differences. Bernhard was one of the pioneers in computer simulation of biological processes and managed, together with Andrew Huxley, to recreate a nodal action potential using his experimental data and advanced programming.

One aim at the onset of the voltage-clamp experiments on the node was to try to resolve ’quanta’ in the recorded ionic currents. The node is especially suitable for this approach because of the very restricted membrane area. Bernhard did not quite reach his goal, but his method of noise analysis was of a pioneering kind.

Bernhard had a position as researcher at the Swedish Medical Research Council between 1963 and 1965, was Professor in Physiology at the University of Umeå 1965–67, and succeeded Granit as Professor in Neurophysiology at the Karolinska Institutet and as Director of the Nobel Institute for Neurophysiology in 1967 until his retirement in 1981. A characteristic of Bernard as a scientist was his aim at perfection. He could spend many weeks, even months, at refining a technique: it was all or nothing – he would never engage in mediocre science. Bernhard is author of 49 publications listed in PubMed and contributed to at least equally as many as supervisor. For him it was natural to share his vast knowledge generously and to work with the manuscripts of pupils and colleagues.

I remember Bernhard as extremely knowledgeable about electronics: from the beginning in the laboratory he constructed his own equipment – very much the British style. He also designed a large part of the electronic equipment for other people in the department. He was very generous with his knowledge and put together a lab programme for us beginners to increase our understanding of the mysteries of electronics. Bernhard had many collaborators (post-docs) from other countries as well as a number of Swedish PhD students (including myself) of which he took very good care.

Questions about the threat to the environment were something that engaged Bernhard at an early stage. He was an ardent (and very well-informed) opponent of nuclear power and was politically active in the debate in Sweden which raged in the 1970s. He was also very concerned about phosphate eutrophication and the risk of lack of oxygen in the Baltic, as well as the use of pesticides such as DDT and PCB. Bernhard was in fact one of the pioneers in environmental science, which is now such a hot topic.

Bernhard was not only generous with his knowledge in mathematics and electronics, but also generous outside the lab. Many of us remember his summer parties at his house in Saltsjöbaden, southwest of Stockholm, close to the water, where the whole department was invited. Not far from his house, his beloved Dulcibella, a relatively big sailing boat, was moored. Some of us PhD students were recruited as crew onboard Dulcibella and sailed with Bernhard in the Åland archipelago where he tried (with mixed results) to teach us navigation and seamanship.

The starting point of this portrait of Bernhard was a photo-collage, made by some of his pupils just before his retirement. The collage was given to Arne Wallhorn, a well-known engraver and famous for his miniature engravings for postage stamps. He made a large steel engraving and, from the steel block, a limited number of prints were made. The artist has been playing a little when drawing the voltage clamp circuit and it is up to the reader to discover the error – no prizes given!

References

Dodge FA & Frankenhaeuser B (1958). Membrane currents in isolated frog nerve fibre under voltage clamp conditions. J Physiol 143, 76–90.

Frankenhaeuser B (1963). A quantitative description of potassium currents in myelinated nerve fibres of Xenopus laevis. J Physiol 169, 424–430.

Frankenhaeuser B & Huxley AF (1963). The action potential in the myelinated nerve fibre computed on the basis of voltage clamp data. J Physiol 171, 302–315.