Wednesday, 15 July 2015

The Hans Krebs Legacy lives on

I became aware of the connection between Sir Hans Krebs and Sheffield when I first walked underneath the glass panel that framed the iconic Krebs Cycle in Firth Court, the home of the then Department of Biochemistry (now the Department of Molecular Biology and Biotechnology). When I was asked yesterday to explain in around 60 seconds, the significance of his work and his connection with the University of Sheffield, I started asking myself some searching questions. In the end, on a mobile 'phone in my car, I tried to capture at least some of the the essence of what I believe to be an intellectual tour de force: the synthesis of a coherent explanation for the transformation of the food we eat (sugars fats etc), the air we breath and the water we drink, into the energy that propels life. Of course, like any piece of Science, the Krebs Cycle was preceded by great work (that of Emil Fischer, Otto Warburg, among others) and it was succeeded by the work of those who mapped the pathway of ATP production, culminating in Peter Mitchell's incredibly innovative chemiosmotic theory, with John Walker and Paul Boyer providing the molecular icing on the cake nearly fifty years later.

Lotte Lenya.jpgIn 2012, during a splendid symposium in honour of one of the greatest elder statesmen of British Biochemistry, Sir Frederick Gowland Hopkins, founding Professor of Biochemistry at the University of Cambridge (1914), I had the privilege to relate the story of Hans Krebs' journey from Berlin to Sheffield. From his rural experiences in Hildesheim as a young boy, through the trenches of World War I, Hans Krebs forged a path through medicine, before finding himself in the laboratory of Otto Heinrich Warburg, in Dahlem Berlin. Originally entitled the Kaiser Wilhelm Institute for Biology (today: the Max Planck Institute, where incidentally as a young academic at Sheffield I spent many enjoyable visits to talk DNA modification with Professor Thomas Trautner). It is hard to imagine what Dahlem-Berlin must have been like in the 1920s. Around the corner from Warburg and Krebs, Albert Einstein, Otto Hahn and Lise Meitner where shaking the foundations of Physics (and the Electron Microscope would be unveiled in the early 1930s by Ernst Ruska). The rarefied atmosphere of Dahlem where both Science and the Arts were undergoing a truly revolutionary upheaval. While Kurt Weill and Lotte Lenya (top right) created music together, bruised, post-Versailles German pride fuelled the emergence of National Socialism which soon led to the collapse of this short lived intellectual and cultural "mecca". 

Image result for warburg manometerIn July 1933, Hans Krebs was dismissed from his employment in Freiburg University, fresh from his elucidation of the first molecular "cycle" in Biology: the urea cycle. With the support of  Sir Frederick Gowland Hopkins, Krebs was soon in Cambridge, but only a year later, he found himself in Sheffield, where  there began a remarkable period of achievements: both personal and scientific. In his Science: using small conical flask, with a side arm, the Warburg manometer combined a mercury displacement tube, coupled to the above flask, calibrated with great precision using mls of mercury! Tissue slices would be mixed with substrates by tipping the side arm and the consequent evolution of gases were measured as the whole apparatus, mounted in a cylindrical shaking water bath, rattled away in the corner of the lab. Careful measurements, forensic observation, meticulous recording of inventories of compounds transformed, gases evolved, pH changes at carefully controlled temperatures, produced the data from which the Krebs Cycle was forged.

The recognition of patterns in data has the potential to transform a simple, phenomenon into something of universal significance. When Krebs (and his colleagues) began trying to reconcile their manometry data with that of others; he recognised something of great significance and the proposal of a cyclical pathway that we now call the Krebs Cycle. Earlier today, the Krebs family through his marriage married to Margaret Fieldhouse, and all of whom grew up in Sheffield, decided to auction the Nobel Medal, awarded to their father. With the £275 000, they intend to establish the Krebs Trust Fund, to support refugee scientists. This splendid legacy seems to me to be completely consistent with everything I have read or heard about the man. It will be extremely interesting to see how this initiative impacts on Science.

1 comment:

  1. A deeper reading into the first 20 years of Biochemistry from the last century, in particular the elucidation of glycolysis and muscle metabolism led me to the lactic acid cycle. I feel a revision coming on!