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Stefan Hell – a Nobel Prize for a lateral thinker

Stefan Hell was awarded the Nobel Prize in Chemistry for the development of STED fluorescence microscopy which has made it possible to obtain optical images well below the optical diffraction limit. However, Hell does not really see himself as a developer. His passion is scientific principles, the identification of how things are connected and the exploration of new, uncharted paths.

Stefan Hell and his team from the German Cancer Research Center in Heidelberg. © DKFZ

On 8th October 2014, the Nobel Committee in Stockholm announced their decision to award physicist Stefan Walter Hell the 2014 Nobel Prize in Chemistry “for the development of super-resolved fluorescence microscopy”. For Professor Otmar Wiestler, Chairman and Scientific Director of the German Cancer Research Center (DKFZ) in Heidelberg, it was only a matter of time. Although Hell had previously been nominated on a number of occasions for the Nobel Prize, when he received the call from Stockholm he could not believe that he had actually won it. “At first, I thought it was a joke, but fortunately, I recognized the voice of Professor Mormark, who is the secretary of the Swedish Academy of Sciences,” said Hell in a hastily convened press conference.  

Professor Stefan Hell is a director at the Max Planck Institute for Biophysical Chemistry in Göttingen where he heads up the Department of NanoBiophotonics. He is also head of the Department of Optical Nanoscopy at the German Cancer Research Center in Heidelberg, where the methods he has developed are used in basic medical and biological research. The two university towns are delighted with Hell’s achievements and this award of the highest scientific distinction a researcher can ever receive.

Childhood and studies

Prof. Dr. Dr. h.c. mult. Stefan W. Hell. © Helmholtz Association

Stefan Hell was born in 1962 in Arad, Romania, in the Banat near the Hungarian border and spent his childhood in what was then a predominantly German-speaking village of Sântana. He attended a German primary school and later the Nikolaus Lenau Lyceum in Timişoara, where Herta Müller, the winner of the Nobel Prize in Literature in 2009, was a teacher. Hell attended special mathematics and physics classes. His mother, who was a teacher, and his father, an engineer, strongly encouraged and supported Hell’s talent for the natural sciences – partly for the purely practical reason that they were subjects that were less influenced by communist ideology than history and literature. His parents were convinced that science was the perfect choice and the basis for a career in any country. Back in the 1970s, many Banat Germans planned to leave Romania as soon as the opportunity arose.

In 1978, the family emigrated to West Germany where they settled in Ludwigshafen. The 15-year-old Stefan saw the family’s emigration as a kind of liberation. He loved being in a country where his mother tongue was spoken. At school, he was way ahead of his classmates in physics, biology and chemistry, and was best in his class in German. He was particularly interested in linguistics and etymology, the history of the origin of languages and how words were used in the different Germanic languages. 

Stefan Hell did his doctorate in the building shown in the photo. This building is the oldest part of what is now the Heidelberg Technology Park. © Heidelberg Technology Park

Finding out how things are connected was a similar driving force when he began studying physics at Heidelberg University in 1981. After receiving his diploma degree in 1987, Hell went on to do his doctorate at the University of Heidelberg. His thesis was entitled “Imaging of transparent microstructures in a confocal microscope”. Confocal microscopy was about to emerge as a new microscopy technique, as it had the advantage of suppressing light from above or below the focal plane and was thus able to scan the three-dimensional surface of an object with a focused laser beam. Confocal microscopes therefore have a far better depth resolution than standard microscopes. Hell used such a microscope to study semiconductor chips. His thesis supervisor, the solid-state physicist Siegfried Hunklinger, was the co-founder of Heidelberg Instruments, a start-up company developing confocal microscopes. Parts of the company were later acquired by Leica Microsystems, a well-known manufacturer of optical microscopes.

During his doctorate in the Heidelberg Technology Park, Hell was working on calculating focal light distributions when he came up with the idea of using two opposing objective lenses focused on the same geometrical location in order to increase the axial resolution of light microscopy. This would then enable scientists to obtain images of structures several times smaller than had previously been thought possible. He received his “summa cum laude” doctorate in physics in 1990 and subsequently worked as an independent inventor for a short period. During this time, he laid the foundations for a microscope which later became known as the 4Pi microscope and filed a patent using money he had been given by his grand-parents.

From 1991 to 1993, Hell worked in the Light Microscopy Group at the European Molecular Biology Laboratory (EMBL) in Heidelberg. Thanks to the support of Professor Reinhard Neumann and Professor Christoph Cremer from the Institute of Physics at the University of Heidelberg and a grant from the German Research Foundation (DFG), Hell was able to continue working on the improvement of the resolution of light microscopy. In 2004, Leica Microscystems placed the first commercial microscope based on Hell’s 4Pi technology on the market.

He’s never been a developer

Differences between a STED microscope and a confocal microscope in localizing amyloid precursor protein (APP) in mouse neurons. Cooperation with Dr. S. Klins at the Centre for Molecular Biology in Heidelberg. © DKFZ
Recalling the period when he was working on the improvement of microscopes, Hell thinks that the biologists probably saw him as someone who developed microscopes for them. However, he makes it clear that he has never seen himself as a developer. His passion is less technological progress and more basic research: while others might believe they have found the final answer, Hell will continue working to get to the heart of the matter. As defined by Ernst Abbe in his famous diffraction law of 1873, light microscopy is only able to resolve objects separated by a distance of no less than 200 nm, which equals half the wavelength of light. While it was generally believed that light microscopy had reached its limits, Hell hoped to be able to improve the resolving power of microscopes. He based his assumptions on the light-field distribution values which suggested that the material examined contained transitions of molecular states that could be discerned at a resolution far below Abbe’s diffraction barrier. However, he did not see any perspective in Germany and was looking for somewhere where he could continue his work on the resolving power of microscopes. With support from his colleague Pekka Hänninen from the European Molecular Biology Laboratory (EMBL), Hell gave a talk to an audience of reviewers from the Academy of Finland. He was offered a position as group leader at the University of Turku in the Department of Medical Physics led by Erkki Soini. In autumn 1993, he finally came up with a solution for overcoming the diffraction limit. The idea was to use selectively deactivating fluorophores to enhance the imaging. In the years that followed, Hell had to prove that “stimulated-emission-depletion fluorescence microscopy” (STED microscopy) was not just something that worked in theory, but also in practice.

Years of recognition

Since the physics behind the STED technology is correct, the initial scepticism of experts eventually gave way to recognition. In 1996, Hell received his habilitation in physics from the University of Heidelberg and was offered a position as group leader of an independent research group at the Max Planck Institute for Biophysical Chemistry in Göttingen. The move from Turku to Göttingen also marked the end of the period that he had to live on small grants. For his project on the high resolution of microscopes, Hell brought not only talented physicists with expertise in optics on board, but also established a chemistry group that was specifically focused on the development of microscopic dyes and a biology group that focused on the application of the new inventions. In 2002, Hell was able to present a microscope with a resolving power that was more than 10 times greater than that proposed by Abbe in 1873, making it possible to obtain images of structures ten times smaller than had ever been thought possible. The Max Planck Society granted Leica Microscope the license to construct Hell’s invention, and the first STED microscope was placed on the market in 2007. During the development of the microscope, Hell’s contacts from his student days in the Heidelberg Technology Park turned out to be very useful.

Despite numerous highly attractive job offers from Germany and abroad, Hell remained at the Göttingen-based Max Planck Institute for Biophysical Chemistry, where he became scientific member and a director in 2002. He established the Department of NanoBiophotonics and has since been able to enjoy the freedom to investigate anything he is interested in. He also became professor in the Heidelberg University Faculty of Physics and Astronomy and subsequently honorary professor in the Department of Experimental Physics at the University of Göttingen. In addition, he became the head of the Department of Optical Nanoscopy at the German Cancer Research Center (DKFZ) in Heidelberg where he continues to work on the application of STED microscopy in basic medical research.

Stefan Hell is a member and honorary member of prestigious scientific academies, holds an honorary doctorate from the Universities of Turku, Arad and Bucharest, and has received numerous awards, including the Leibniz Prize from the DFG, the Otto Hahn Prize, the Gothenburg Lise Meitner Prize, the Meyenburg Award, the Carus Medal of the Leopoldina, and finally, in September 2014, the 1-million-euro Kavli Prize for outstanding achievements in the nanosciences. However, the culmination of his career is the Nobel Prize in Chemistry which he will be awarded on 10th December in Stockholm, shortly before his 52nd birthday. The Royal Swedish Academy of Sciences decided to award the Nobel Prize in Chemistry for 2014 to Hell and the two American scientists Eric Betzig and William E. Moerner, who, independently of Hell, have laid the foundation for single-molecule microscopy and taken Abbe’s diffraction limit to a totally new dimension.

The highest distinction in science will continue to inspire his research into the nanometre range. It is still too early to make any statements about the enormous opportunities that live observation of molecular processes is likely to generate, especially in the field of life sciences. The DKFZ celebrated the award of the Nobel Prize in Chemistry to Professor Hell with a research group that will be named after him and receive financial support for five years. He will no doubt visit Heidelberg as often as he can, even though Göttingen has long been home to him. In addition to working at an institute of international standing, he lives – with his wife, who is a doctor at Göttingen University Hospital, his two nine-year-old twin boys and his daughter – in a beautiful flat with a stunning view across the city. Sometimes, he even has time for his hobby – playing the saxophone. In an interview with the newspaper Göttingen Tageblatt, Stefan Hell says that he found it difficult to get used to the weather in Göttingen. Having grown up in the Banat in the Hungarian Plain with its hot summers, he finds Göttingen too cool. Heidelberg is warmer, he says.

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