Commemoration by Edward De Robertis

Günter Blobel was a cell biologist born 81 years ago in Silesia, eastern Germany, now part of Poland. He had a colourful life. He had an idyllic childhood during the Second World War – his village was untouched by the war – and he had to move ahead of the Red Army at the age of 8. For the first time he saw his first large city in Dresden, where he greatly admired the architecture of the Frauenkirche, that’s the Church of the Virgin, and a few days later, staying with relatives thirty kilometres away, saw the sky light up with fire during the fire bombing of Dresden, so clearly you could read the newspaper under the fire of Dresden. Impressed by this, later he used his Nobel Prize in 1999 as the seed money for a foundation for the reconstruction of the Dresden Frauenkirche and the synagogue there. That’s the colourful part.

The most interesting part of Blobel’s life is his science, because it provides an example of the epistemology of biology, how do we do biology. In the 19th century, French physiologist Claude Bernard published a book on the introduction to experimental medicine. I once gave a whole talk here on that, and how, in experimental biology, we construct an idea in our minds, and then we test it by experiments. So Blobel, who studied medicine in West Germany and then did a PhD in Wisconsin, ended up in the laboratory of George Palade, who was member of this Academy, at Rockefeller. And Palade had discovered that secreted proteins go to the endoplasmic reticulum to be secreted, while other proteins are not, and so he wanted to know, how is it that some proteins go to the secreted pathway and others do not. And there, in the lab of Palade, he teamed up with a young assistant professor called David Sabatini and they produced a hypothesis of how this might work, in their own minds. David Sabatini was a graduate student of my father in Argentina, and now we have his son, sitting right there. So they came up with an idea without any proof, so this was very much resistant, and their idea was the signal hypothesis. They said maybe the way the proteins go into the endoplasmic reticulum is because there is something in the messenger RNA, in the protein, a signal in the beginning of the protein that is going to tell the ribosome using a signal recognition particle, so the beginning of the protein will have a signal that will bind it to the membrane of the endoplasmic reticulum so that it can be secreted in the microsomes. So ribosomes have a small sub-unit and a large sub-unit so this one starts first, and they actually produced this, there will be a signal in the beginning of the protein that will put it out of the endoplasmic reticulum.

This was in 1971 but they had no evidence for this. Now Sabatini had discovered that there was a channel in the large sub-unit of the ribosome that protected the nascent peptide from degradation, and then he had also found that the large sub-unit binds first to the membranes. Except for that there was no evidence, so this was very much resisted and criticised, and Blobel kept on working on this until in 1975 he could publish two papers with Dobberstein, reconstructing the system in-vitro by adding ribosomes and membranes and messenger RNA and showing that it is the property of the messenger RNA which will lead the protein inside the membranes and make it resistant to protease. 

Now this is an example of how you can come up with an idea and prove it only five years later, and it proved to be correct, and so this is the famous signal hypothesis, and in recognition of this he got the Nobel Prize in 1999. He was a great cell biologist in the school of Palade, who was here in this Academy too.