The role of epigenetic software in researching rheumatism

Steffen Gay is spending several months in Berlin as a BIH Visiting Professor to conduct a clinical study on patient responses to different rheumatism medications at the Charité. During his stay in Berlin, the Leipzig-born scientist, who trained at the Max Planck Institute in Munich-Martinsried, told us what brought him back to Germany after over 40 years abroad.  

Professor Gay, when one looks at your career, places with recent historical associations come up again and again. What sort of things have you experienced there?

In the days of communist East Germany, I grew up in the Erzgebirge mountains and studied medicine in Leipzig. Together with my wife, who also studied medicine, we both continued our training in Munich. There, I did research into connective tissue diseases. In connection with that, I was able to determine the distribution of the structural proteins in collagens in different human tissues, using fluorescence-marked antibodies. But also, I always wanted to go to America. As there was interest in my technology over there, I was subsequently awarded a scholarship grant by the German Research Foundation to introduce this fluorescence technology in Birmingham, Alabama. Birmingham does remind one of racial issues and the Ku Klux Klan, which was very active there. However, the research at the University of Alabama (UAB) was excellent, under the outstanding leadership of J. Claude Bennet (who, incidentally, also helped to build up the German Rheumatism Research Center here in Berlin), which is why we spent so many years of our scientific career there – 20 to be precise. In particular, the governor of the time, George Wallace, expanded heart surgery and the cancer center, so that the Clinical Immunology/Rheumatology Department of the UAB became one of the largest worldwide.

You now work in Switzerland. What lured you away from the USA and back to Europe?

22 years ago, I was offered the chance to become the director of a research center as Professor of Experimental Rheumatology in Zurich. I found the field of epigenetics particularly fascinating. An interesting job opportunity also opened up for my wife in Switzerland and we followed the call. 

Could you explain what epigenetics is in layman’s terms?

Our DNA is packaged in chromosomes and wound around tiny balls, otherwise it would be about two meters long. Only two per cent of it is  used: the rest was long termed  “junk DNA”. Today, we know that genes are turned on and off. These regulatory processes are called epigenetics. Our current knowledge largely consists of studies that state which gene is associated with which disease. We don’t know precisely how that specific disease is triggered. Each gene has a kind of traction engine, called a “promoter”. If methyl and acetyl groups attach themselves to these, no further other substances can attach to switch on the gene. There are about two million such switches in the human body for methyl groups alone, and if those aren’t working, you fall ill. I’m often asked whether regulation is therefore more important than genetics. It’s similar to asking whether the hardware or the software in a computer is more important...