Transcript from an interview with Stefan W. Hell

Interview with Stefan W. Hell on 6 December 2014, during the Nobel Week in Stockholm, Sweden.

Could you deescribe your Nobel Prize-awarded work in simple terms?

Stefan Hell: I discovered that a light microscope can see sharper pictures that we believed in the 20th century, more than 100 years. This is important because light microscopy is the only way by which you can look into transparent things, important things such as cells, living cells or tissue. And the fluorescence light microscope that I invented allows you to see details that you couldn’t see before. But the basic discovery was that in the 20th century, before I made my work, people believed that you have to separate things if you looked into the microscope if you want to see them separately, if you want to see the details, by focusing the light very sharply. But what I discovered is that you can overcome this barrier by making the molecules, that we look at, distinct different. If the molecules are different you can see things separately and you can tear them apart. That was the discovery, that has led now to microscopes that are not limited by the focusing of light anymore, but you can see things at much greater detail because the separation of things is done by the molecules.

At what point did you realize your work was a breakthrough?

Stefan Hell: There were many points, it wasn’t just a single point. First of all, you have to get the idea that you can do something rather like light microscope because people believe that this would not be possible, and it was fully accepted in the 20th century. So, I think the first point was when I had this kind of conviction evolving in me that there must be a way to do something about this diffraction barrier, as it is called. Then I was convinced continuing and then the second big event was when I had the first concrete idea. Actually, I had when I was a post-doc in Åbo in Finland, when I realised that you can separate fluorescence molecules that are closer together than this 200 nanometer barrier but turning them on and off, playing with the brightness of them. I discovered that you can use a phenomenon, but it is called stimulated emission and this phenomenon stimulated emission does nothing but keep molecules dark, shuts the molecules off. So, I used this phenomenon of stimulated emission to shut molecules off, turn them off to see that they break one. This was the second really important event in this journey.

The third important event was when I realised that this is doable, you can really do it in practice. This phenomenon of turning off really works the way I anticipated. The fourth event was when we got the first pictures that demonstrated  – yes, you can see details in much much smaller scales because you can keep things dark and if you have two things that you cannot separate normally, because they hit at the same time with a big blob of light, you turned this one off to see this one and the you turn this one off to see that one. And that was, as it turned out, to be fundamental discovery and with that you can see now, in principal, down to the molecular scale and in practise now we are about 20 nano meters, 30 nano meters, but it is clear that the resolution will increase further and further if you perfect this state transition is a technical term of going for a brighter dark state or between two different states.

What brought you to science?

Stefan Hell: It is fascination for what I am doing. It’s also … I am very much attracted to understanding things at a fundamental level. So, if I cannot break down things to very very simple phenomenon, so I can explain it to everyone, I feel that something is missing, I have not got the point. It is deeply rooted in my heart if this is true or not, for science in general, that is questionable, but that is my attitude. When I was a student, I spent hours over a certain phenomenon, sometimes days, just to understand at the really bottom, at the very basics and before I hadn’t grasped it, I didn’t stop. It is part of my personality and I have realised that my way of thinking about the problem with diffraction barrier is definitely correct. Of course, I had many people surrounding me at that time saying that this is not going to lead anywhere. But I had thought so much about the principles and also about protect the flaws, I always thought Could there be a flaw?, Could there be a flaw?

Could there be a flaw because I didn’t go out public saying – I thinking all the times of flaws, but that is what I did. I realised that I had ruled out flaws, conceptual flaws, and the only problem remaining was technical. It is very important to understand that you have separate or distinguish conceptual flaws and technical flaws. The conceptual flaws they probably are going to stay, you cannot overcome them. But technical problems you can overcome over time with development, technology progresses, there are better detectors, better lasers and so on. That is not a flaw, that is a technical shortcoming and this you can solve. I realised that my concept doesn’t have a conceptional flaw, so conceptually it is definitely working. I could easily stand up and say I am convinced that this I going to work because the problem that you are talking about are not conceptual, they are not for the metal they are technical so there will be metal detectors, will be better and so on. Eventually it will work and that kept me going.

Who is your role model, and why?

Stefan Hell: I didn’t have explicitly a role model some say scientist that I wanted to be like that person. I think this is also part of the success story, because you have to find your own way. It is very important that you do something from the bottom of your own heart and you find yourself in what you do and the work.  But of course, I admire scientists who had come up with fundamental and interesting ideas, with new ideas. Clearly to some extent, Einstein has always been a role model in a way of course, there is no comparison with him. He was unique. But seeing things differently, not caring about conventions, these are elements in his attitude of course that should be role models for all of us scientists and they are of course. But I also have great admiration for people like Richard Feynman. I read his book and also his biographies and when I was a student, I found him very inspiring, his attitude. He explained quantum mechanics in his own way and that was really great because it gave you some insights and that led him to do it in a new way of coming up with new things, quantum electrodynamics. These are role models in a way, but of course I have to do my own thing and I have to do it very much in my own way.

What are you future plans?

Stefan Hell: I definitely will continue because it is kind of part of my personality, if you like, so I am still attracted hearing discoveries, seeing things from a different angle, yes, I think it is kind of, how shall I put it, a kind of commitment saying no. But after I got the prize, I felt, maybe at some point I have to think about something else, open text books again and check out what else is there that people believe and has been repeated many times, many times, many times and everyone believes it. Maybe it is not the end of it or maybe something important has been missed out. I think it is very interesting to see how science works, this in retrospect, I didn’t expect it honestly. A lot of it is perception, I couldn’t have imagined that, so sometimes people and science perceive things in a wrong way and just taking a different angle and explaining things or sorting out things from a different angle – all of a sudden can open new aspects that were totally unanticipated and this is so important.

I think it is important to go back again and say okay now we have this phenomenon, we have this thing, but we have to take a different angle, maybe a different way of looking at it. Still, it has to be of valued one, no doubt, but taking a different angle is so important. I think, breaking the diffraction barrier is a fantastic example because, as I said, the the problem was that people saw, the scientists saw, you have to distinguish features, so to speak, by the focusing of light, the phenomenon of focusing of light and because they cannot focus light any better than a certain diameter you cannot do it. The breaking of the diffraction barrier happened because, I would back off and say oh, what do we have here, do we have to separate by the focusing of light or can we separate by the molecular states? Once we separated the molecular states, the focusing of light doesn’t matter or hardly matters. It is so important to understand, to just taking a different angle all of a sudden, make things look totally differently.

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