„I was on a quest to find meaning in a chaotic world“
After his doctorate, Joachim Frank went to the USA with a scholarship and decided to stay there. Since 2008 he has been Professor of Biochemistry and Molecular Biophysics at Columbia University. For his groundbreaking work on the development of cryo-electron microscopy he received the Nobel Prize in Chemistry together with Jacques Dubochet and Richard Henderson in 2017.
In this interview, he talks about his childhood in bombed-out Siegen, why he stuck with his research idea despite the obstacles he faced and the magical moments he experienced during the Nobel Prize award ceremony.
He thought that there was no money in it (laughs). He asked me: “Where are you going to work as a physicist? How will you earn money?” He looked into it and asked acquaintances if there really was an economic footing, if one could make a living as a physicist. Finally I was able to convince him and was allowed to go to Freiburg to study. But overall my parents have always supported and encouraged me.
Has your interest in Natural Sciences already been apparent when you were a child?
Even as an eight-year-old I spent a large part of my time in the cubbyhole. That was the area under the porch of my parents’ house which briefly served as a pigsty after the war. Here I would tinker around, build shelves, fill little empty bottles of bitter with all kinds of reagents, which I mixed to quench my boundless curiosity: How does carbide react with water, how is it possible for a metal like zinc to completely vanish in acid, why does hot coal excrete a flammable gas? Later on, I also started to tinker around with the radio. And as for theory: my parents’ house had an incredible treasure in their living room: the twenty-volume Meyers Encyclopedia from 1905, each volume consisting of 1,000 pages. Ever since I could read, I was leafing through these books. I found nothing unusual about my hours of research, after all, as a child you have no idea what is normal or unusual.
When you were little, you experienced the destruction of war. What influence did these events have on you?
They had an immense impact. When I was three and a half years old, I saw a house in my hometown go up in flames. In February 1943 our house was hit by firebombs, the roof was destroyed and we had to move. When the war was over, we children used to play in the rubble. I remember finding copper pipes and bakelite fittings – and a large family of young pink mice. Everything was wonderfully fascinating, only I wasn’t allowed to say anything about it at the dinner table (laughs). But a desire to create order began to emerge within me. I was on a quest to find meaning in a chaotic world. And in the end, this search could only be satisfied by living a life in science.
You started studying Physics in Freiburg and moved to Munich after your intermediate examination, initially to LMU. When did you develop an interest in Electron Microscopy?
My supervisor at LMU was an experienced electron microscopist, and I was interested in the technology. I wrote my diploma thesis on the interactions of electrons with metal, i.e. the backscattering of electrons on liquid gold. It was a very long and challenging project in terms of experiments. This brought me into contact with electron scattering for the first time. So after my diploma I finally found my way to Professor Walter Hoppe at TUM. I had researched who in Munich could teach me more about the topic and already at that time he was known as an expert in the field. So I knocked on his door and he accepted me as a student.
It sounds so simple.
To be honest, as a student who didn’t have a clue about anything, the entire thing almost gave me a heart attack (laughs). You have an appointment with a professor who will listen to you for a minute and then gives you different projects to choose from. Later I found out that the project that Walter Hoppe gave me was actually impossible. It just wasn’t realistic.
Did Professor Hoppe know that it was impossible?
No, I don’t think so. Back then, as a researcher of X-ray crystallography, he himself was a newcomer to Electron Microscopy. He had a lot of very good theoretical ideas, but not much practical experience yet. There was hardly anyone who had worked on image processing before. I developed many of my ideas in complete contrast to my mentor’s research. I was convinced that the way he approached the problem was completely wrong. We had many discussions about it, but also about Hoppe’s leadership style. He was a very authoritarian person and was leading the group accordingly. That was in the late sixties, when everyone was sensitive to authority. I constantly questioned his authority – in all kinds of areas.
Was he able to appreciate that?
Concerning his leadership style, not at all (laughs). But he did acknowledge the inventive contributions I made. When I wrote my first article about my research, I wanted to name Hoppe as the leading author. But he crossed out his name and said, “This is all your work.” At that time, that was very unusual. My first paper authored by just me.
In 1970 you submitted your dissertation and immediately afterwards you went to the USA. Tell us how this came about?
I was lucky enough to get a Harkness Fellowship. That was great because it gave me unconditional funding for two years, no matter where in the USA I went. In total, I did research in three different laboratories in the USA and met a number of PhD students who later became leaders in this field.
Actually quite the opposite. For me it was almost liberating. I felt Germany was suffocating. That was due to the authoritarian way things were organized here. One of the main reasons was also the Hitler regime and the way it had poisoned the language. In my spare time I like to write. In German I always had the feeling that I had to avoid certain expressions. It was liberating to be able to express myself in a different language.
Is your command of the English language that good?
Already in school I had a very good feel for language. After a few years in the USA I wrote all my texts in English. Some time later I started to write my non-scientific texts, such as short stories in English, too. I took an evening course with Pulitzer Prize winner William Kennedy, who encouraged me a lot on this path.
Most of the research you received the Nobel Prize for was done during your time in Albany.
Yes, the first eleven years were mainly concerned with the development of the mathematical and computational foundation for the single-particle method. It means that we used image processing methods to make electron microscopic images sharper and that we combined two-dimensional electron microscopic images in such a way that they produced a three-dimensional image. However, this was frustrating at times: some journals did not accept our articles and the scientific community was rather skeptical.
What kept you from giving up?
Well, there were some people who encouraged me to continue. Also, we have been making steady progress in the research group and have put out some very good publications.
Would you call yourself a self-confident person?
I am more of a loner. I often felt that I did not really belong. There were times when I doubted that my scientific career would ever be successful and thought I had nothing to contribute. This is probably something that every scientist is familiar with. But this feeling can be quite frightening. But then better times came along: We contributed key findings on the representation of ribosomes, which were highly acclaimed. We were able to represent the ribosomes in their different functional stages and different conformations, which was not possible with other methods. However, the resolution was not better than ten angstrom, which is a very small unit of length. In 2000 there was a breakthrough in my field, when X-ray crystallography was able to achieve a much better resolution in the representation of ribosomes. It was three angstrom, close to atomic resolution. If there had ever been something like a race between cryo-electron microscopy and X-ray crystallography, it now seemed that the race was over and X-ray crystallography had “won”. It seemed like we no longer had a chance to catch up here.
But that wasn’t the end of it.
For the next ten years we used X-ray crystallography models to interpret reconstructions from cyro-electron microscopy, but we never had better results than five angstrom. This changed in the years from 2012 to 2017: After the introduction of single electron detection cameras, the methods I had developed suddenly attained a resolution of three angstrom or more. A revolution, because my method also made the different stages and functionalities of biomolecules visible. So you get much more information than before. Many laboratories that had previously worked with X-ray crystallography now switched to single-particle cryo-electron microscopy. As a result, our research became the focus of interest.
On October the 4th 2017 at 5:18 New York time your phone rang. What went through your head?
I was torn from my sleep in the middle of the night. But of course I knew that the Nobel Prizes in Chemistry would be announced on October the 4th. I suspected that this call had to be from Stockholm. At just after seven, the first reporters were already waiting in our lobby to take pictures. A former postdoc called me: He had been up all night, convinced that we would win the Nobel Prize this year. I knew that from now on my life would change.
You travelled to Stockholm for the Nobel Prize award ceremony. What do you remember most?
There were many magical moments. When the Nobel Prize is awarded, the Festival of Lucia – the Festival of Lights – is taking place in Sweden. One morning there was a knock on our hotel room door. We were still in bed and a group of girls in white dresses with candles in their hands came running into the room and started singing. Then we were served breakfast in bed. An incredible experience.
You once said in an interview that thanks to the Nobel Prize you no longer have to write survey papers. Has anything else changed?
Yes, that truly is a great liberty. I hate writing survey papers. They are annoying and very time consuming. In addition, I now have much more creative freedom: I no longer have to worry about the profitability of my research and I get a lot of recognition. In addition, my conversation partners no longer interrupt me or at least a lot less than before (laughs).
Joachim Frank wurde in Weidenau, einem heutigen Stadtteil von Siegen, geboren. Nach dem Vordiplom in Freiburg graduierte er an der Ludwig-Maximilians-Universität München zum Diplom-Physiker. 1970 wurde Joachim Frank bei dem Elektronenmikroskopie-Pionier Prof. Walter Hoppe an der TUM mit einer Arbeit zu elektronenmikroskopischen Aufnahmen hoher Auflösung mit Bilddifferenz- und Rekonstruktionsverfahren promoviert. Als Postdoktorand arbeitete er am California Institute of Technology, an der University of California, Berkeley und an der Cornell University.
Von 1972 an war Frank Forschungsassistent am Max-Planck-Institut für Biochemie, ab 1973 Forschungsgruppenleiter an der University of Cambridge. Seit 1975 ist Frank am Wadsworth Center, New York State Department of Health (University at Albany, The State University of New York) tätig. Seit 1997 hat Frank zusätzlich eine Forschungsprofessur für Zellbiologie an der New York University inne und seit 2008 die Professur für Biochemie, molekulare Biophysik und Biowissenschaften an der Columbia University.
Joachim Frank leistete wesentliche Beiträge zur Kryo-Elektronenmikroskopie von Einzelmolekülen und konnte mit dadurch ermöglichten elektronenmikroskopischen Aufnahmen wesentlich zur Aufklärung der Struktur und Funktion von Ribosomen beitragen. 2017 wurde ihm gemeinsam mit Jacques Dubochet und Richard Henderson der Nobelpreis für Chemie zugesprochen. Joachim Frank ist verheiratet und hat zwei Kinder.