Antibodies and Awards

Lunchtime: on the fifth floor of the Institute of Biology Prof. Dr. Michael Reth invites me to dine with him. The Freiburg immunologist serves rice and vegetables with meatballs, offering a touch of soya sauce and sweet Bavarian mustard with it. The Asian-Bavarian fusion food tastes superb, but Reth fends off compliments, “No comparison with the Asian cuisine I’ve just been able to sample in New York.” However Reth did not cross the Atlantic for the cooking. New York was the conclusion of a journey that took the native Düsseldorfer first of all to Washington: in May 2019 he was the first scientist from the University of Freiburg to be elected a member of the USA’s National Academy of Sciences (NAS).

What conditions cause the immune system to activate? This is the question at the heart of Michael Reth’s research. Photo: Sebastian Kaulitzki/stock.adobe.com

The National Academy of Sciences is an illustrious honorable society of leading international scientists, with a rich tradition stretching back to its foundation by U.S. President Abraham Lincoln. “You meet luminaries from every field,” Reth describes his impressions of the annual meeting. “I found the encounters and lectures extremely stimulating.” In Germany there are only two immunologists who have been awarded the honor of membership of this academy. Klaus Rajewsky, professor emeritus at the University of Cologne, has been a member of the NAS since 1994. And now Reth – who wrote his dissertation under Rajewsky – joins him. “I have a lot to be grateful to him for,” says Reth about his doctoral supervisor, who he came to originally more by chance. “I went to Cologne because I wanted to study ecology there. I wanted to do nothing less than save the world.”

But Reth did not like the fact that in Cologne studying ecology meant first of all studying beetles, “Back then, I couldn’t associate beetles with the imminent environmental catastrophe.” He soon found a more exciting group, the one headed by Rajewsky: immunology. “And our immune system is of course a kind of ecosystem,” Reth traces the line back to his original motivation. Eventually, he dedicated his entire career to the immune system – or more precisely to the question: What causes this system to activate? What conditions need to be met so that an organism produces antibodies that protect people from germs?

How signals occur

Reth’s research focuses on signal generation and the signaling processes in lymphocytes, a sub-group of white blood corpuscles. At the end of the 1980s he was the first researcher to be able to describe the signal subunits of the antigen receptor on B-cells – these are the only cells that form antibodies. Later, Reth and his team succeeded in the first identification of an important protein, one that is decisive for the ‘differentiation’ of B-cells: during the development of the cells it functions like a kind of gene that suppresses the tumor. This work enabled significant insights into the occurrence of leukemia in children.

Reth’s research brought him many honors and awards: in 1988 he received the Heinz Maier-Leibnitz Prize and in 1995 the renowned Gottfried Wilhelm Leibniz Prize from the German Research Foundation (DFG). In 2014 this was followed by the Paul Ehrlich- and Ludwig Darmstaedter Prize – the most prestigious award in German medical science.

Michael Reth is one of just two immunologists in Germany who have been elected members of the National Academy of Sciences. Photo: National Academy of Sciences

Professorship, teaching degree programs, Cluster of Excellence

“Three people were important to my professional career in Germany and the USA,” the biologist recalls. In the USA it was Prof. Dr. Frederick Alt, under whom Reth worked as a postdoc. In Germany, alongside his doctoral supervisor Rajewsky, he names the Nobel laureate Prof. Dr. Georges Köhler, Director of Freiburg’s Max Planck Institute of Immunobiology and Epigenetics (MPI -IE), “He drew me to Freiburg. In 1989 I became group leader at MPI.” This productive cooperation ended in 1995 with Köhler’s premature death. Before that, however, he encouraged Reth to apply for the new post of Professor of Immunology at the University of Freiburg, which Reth took up in 1996.

“That was quite a change, because then I no longer just had to research, but also develop a degree program and organize teaching for immunology.” He also had to link up immunology at the Faculty of Medicine and with the University Medical Center. “I think we’ve been quite successful. But then I’ve always had excellent students,” says Reth. Some of his former team have since become professors themselves. Reth’s research into signaling and experience in building up immunology at the Faculty of Biology later helped him with the foundation of the interdisciplinary Cluster of Excellence BIOSS – Centre for Biological Signalling Studies, where he is the speaker.

Sensational news fell on deaf ears

In 2000 the biologist and his team made an astonishing discovery: until this point people had assumed that receptors were chaotically distributed across the cell surface, in other words random. But the work group’s data revealed something else, that is, a complex organization of the receptors in the nano range. “It’s a sensation,” Reth told his team, “it will be a real bombshell.”

But when the immunologist presented the results of this research at a conference, nothing happened. “The possibility that receptors and biological membranes are organized in the nano range just didn’t fit in with thinking at that time and was simply ignored,” he says. It was his Galileo moment: a major scientific discovery that no one acknowledged. Reth says he was astounded. “Fortunately, we have a Ministry of Science in Germany that enables long-term funding. So we were able to continue our research.” Ultimately it was confirmed. “It only took 18 years,” he says and smiles.

Nano world of immune cells

The fact that he persisted despite all the opposition is one of the reasons for his inclusion in the NAS, Reth believes. But he isn’t the slightest bit angry. Rather, he expresses an understanding for colleagues who did not want to accept his thesis for so long, “The organization of the receptors can only be studied at nano level, 100-times beyond the resolution of an optical microscope. In those days there was hardly any technology for researching nano ranges of cell membranes.”

Today, there are several new methods for ‘illuminating’ the nano range. Michael Reth is convinced that this technology will ensure even greater advances in his discipline, “We are on a journey of discovery into the nano world of immune cells, can understand the regulation and activation of these cells far better with this, and potentially prevent diseases of the immune system.”

Mathias Heybrock