N.zyme Interview: prof. Robert Huber

Profesor Robert Huber pochodzi z Monachium. Jako dziecko zmagał się  z trudnościami II Wojny Światowej. Swoją edukację rozpoczął wstępując do humanistycznego Karls-Gymnasium, jednocześnie poświęcając dużo czasu na rozwijanie pasji związanych z naukami ścisłymi. Pnąc się po szczeblach edukacji, zawsze był pilnym i zaangażowanym uczniem, studentem oraz badaczem. Szczególne zainteresowanie krystalografią wyznaczyło drogę jego kariery naukowej. 

Jak sam mówi, krystalografia była ciągle rozwijającą się metodą analityczną, pozwalającą na poznanie wielu interesujących struktur chemicznych. Pośród licznych zbadanych cząsteczek, to wyjaśnienie budowy centrum reakcji fotosyntetycznej stało się podstawą do wyróżnienia w 1988 profesora Roberta Hubera wraz z Johannem Deisenhoferem i Hartmutem Michelem Nagrodą Nobla w dziedzinie chemii.

Wywiad odbył się 22. kwietnia (poniedziałek) na Wydziale Biochemii, Biofizyki i Biotechnologii Uniwersytetu Jagiellońskiego z udziałem obecnych na sali studentów.

N.zyme: How did you spend your days so far in Cracow?

R.H.:  I had a help from professor Holak, who was my city guide on Saturday evening when I came from Warsaw. Yesterday, we walk around  the Old Town, had a guided tour of Wawel Castle, saw many exhibits… I like the city really, really much. It has an Italian flare which is due to the architects mainly responsible for building up the city and also due to lucky effect that it was not destroyed during war time.

N.zyme: We would like to ask you an obligatory question: Which city is better- Warsaw or Cracow? We are kind of rivals…

R.H.: In Warsaw I had a day when I visited universities and research institutions where I gave lectures. There were much smaller lecture rooms but crowded, students were sitting on the floor. I had one morning to visit Warsaw with accompanying professor and his students. They were very nice. The old part of the city is reconstructed but they have done it very well. I like it too, but it is not comparable with medieval city of Cracow. Here everything is original with some restorations but not reconstructions; one can feel the difference.

N.zyme:  We know that you were only eight when War ended. Did this early years’ experience somehow affected you, your life and your research?

R.H.: I grew up as a war child: I was born in 1937, war started in 1939 and I lived in Munich. Then, in 1945, war ended and Munich was a ruins, as unordered as Warsaw was. Left no stone unturned on the road.  Well, when I’m asked to speak to students about  ‘how did I become a scientist?’ (it was even one of my lecture which I gave in Warsaw) than I begin with a slide with picture of Munich in 1945, headed:  Ruinen- Jahre (‘year of ruin’, editor’s note). Well, did anybody visit Munich?

From room: Ewa! (laugh)

R.H.: So, there was a view of two towers in Munich. It was actually the only thing that hardly left… But when economy improved, they started reconstruction. Very gently, they did the best they could do, making it as it had been before the war. When you now visit Munich,  then you see how it was. Beautiful. The last slide that I showed to students was the picture of Munich in front of the mountains.

It of course affected my career. During the war there was no primary school, I learned reading and writing with the help of my parents. I learned easily, I should say. Then I went to the only gymnasium in Munich- humanistic gymnasium, where I learned Greek and Latin, but for some reasons, which i don’t know, I began to love chemistry and read it from the books. I started to study chemistry at the university and then crystallography came. It had to do with my frequent mountain climbing excursions and searching for minerals. It was quite clear, that I would do my Master’s on crystallography. It was a lucky decision because it was a time when protein crystallography was born. This field was not developed at all. Was more or less just being recognized as an analytical tool, but there were no instruments and no methods. I was lucky in sense that I was working in the field where everything was new and you made a discovery every day. It was pure luck. Then, I had big successes, I taught students and I was given an opportunity to have my own group. I decided to start protein crystallography, what was successful, too. Then,  there was again luck that I had an offer of professorship in Basel and at the same time the director position in Max-Planck Society. So, I stayed in Munich, was born in Munich, went to school in Munich, studied in Munich, became director in Munich…

Professor Holak: Everything around forty-five kilometres! (laugh)

R.H.: Yes, I’ve never left except that! Of course, it is not true. I have to tell that what I do after my retirement is that I’m visiting professorships in many places in the world, so I spend most of my time in England, Spain, Korea, China.

N.zyme: You say that there were no significant breakthroughs causing your decisions to study chemistry or to focus on crystallography. Were those decisions rather spontaneous?

R.H.: My love for crystallography had to do with my mountain climbing excursions and it was quite clear that the only  way to understand crystals found there is by doing crystallography. I asked a chemist at the technical university to become my mentor. His name was doctor Hoppe. I joined his research group focused on crystallography, which, as I already mentioned, was not really developed at that time. I built instruments, cameras, wrote computer programs, but even computers weren’t  really available. Just right after first computer had become available, I wrote computer programs to use new methods to study the mechanism of photosynthesis, but they were basic operations in crystallography. At that time, work, I would say, was based on physics, mathematics and a little bit of chemistry. Only with the development of the tools, focus moved to chemical problems. Later, with protein crystallography it moved to biological problems, but always with crystallography as a  powerful tool.

The first chemical problem during my thesis, work as a post doc, was ‘a very large, small molecule’. Unknown molecule. I would like to excess my respond a little bit on it.

Development of insects is very different from development of mammalian species. They grow to certain size limited by their cuticula. For the next stage of development they have to shed the cuticula, then develop and grow a new one. How this process was signalled was unknown. Two famous biochemist in Munich worked on this problem. One was Peter Karlson, known as an author of biochemistry textbook (Zarys biochemii, editor’s note), the other one was Adolf Butenandt who discovered the human sexual hormone and received Nobel Prize in 1939. They worked on the problem such- are there hormones in insects? What is the regulation of this complex developmental processes? They worked on Bombyx mori – silk moth, simply because it was available in big quantities. They isolated a substance that leads to molting, using many kilograms of silk moths during very difficult assay. Should I tell you how the assay was done? Can you imagine? I didn’t do it by myself, but it was interesting.

This molecule called ‘ecdysone’ (ekduo is from Greek, meaning ‘emerging’) is produced in the heads of larvae. If you want to isolate substance, you have to study its biological activity. In order to avoid natural ecdysone and to signal molting they had to strangulate these larvae, then inject substance into their bodies, checking if the molting is up.

Look at the assays made nowadays…

This is how, I would say, heroic people isolated substance in quantity which I could crystallize. Analytical tools at that time were very different from what is available now. Molecular weight was the first question. They did it by ebullioscopy. Hands up who knows what it is (laughing). Normally, don’t ask people physics…

You dissolve the substance in solution and measure the boiling or freezing point, which are changed depending on the number of added molecules. You know that about what you bathing in, and measure increase or decrease of the point. Differences are tiny. One can count the number of molecules. In this case they did an error. They came up with the molecular weight which I found hard to be true. They hit carbon, hydrogen, oxygen analyses, they made a decomposition- heated up to see the fragments and came up with a suggestion that it may be a naphthalene- two fused six-member rings and some substitutes. But the molecular weight was wrong. So, I crystallized this molecule. Without any detailed analysis, you can get molecular weight, because you measure the unit cell and you know just by taking a diffraction pattern, measuring the distances of the reflections, density of the crystal, and from the symmetry of it, you know how many molecules there is. You can count them very precisely. I found out the molecular weight and compared with what ‘nobeled’ Butenandt found and established. I did not believe myself. I repeated this very simple experiment many times and it became clear, that I was right. Continual deduction found out that ecdysone was a steroid. Close related to the human sexual hormone. Hence, insects have a molecule that is related to human molecules, later analyses of protein crystallography showed that insects and bacterial proteins are also related to human.

Question from the audience: In your opinion, what would be the next new achievement in protein crystallography?

N.zyme: Thank you very much for this conversation.

Wszyscy opuściliśmy salę śmiejąc się z priorytetu jaki otrzymał obiad 🙂