Stefan Hell: Biophysics’ determined lateral thinker
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- Stefan Hell’s discoveries have turned the world of physics on its head, and he’s now hoping that biomedical scientists will start a revolution on the basis of his work. Quelle: Ansgar Pudenz/Deutscher Zukunftspreis
01.12.2006 -
Stefan Hell has always felt perfectly happy to break ranks. The physicist at the Max-Planck Institute for Biophysical Chemistry in Göttingen, Germany, has made a career out of looking where others have not though to look – and in the process repeatedly unearthing highly valuable finds. This ability to think laterally has brought its rewards: In 2002 Hell revealed a new type of optical microscope, with which living cells could be observed with undreamt-of sharpness, and, in doing so, demolished a previously unquestioned physical law. For this work, Hell was presented with the German Future Prize, presented by German Federal President Horst Köhler at a ceremony on 23rd November.
"Nobody believed that the so-called ‘Abbe’s law’ could be overcome", remembers Hell. It was thought to be a given that anything smaller than 200 nanometers - 250 times the width of a human hair - would appear blurred if viewed with an optical microscope. This limit was discovered approximately 130 years ago by the German physicist Ernst Abbe from Jena and, until Hell’s achievements, had thought to be an insurmountable hurdle. Every child will learn this at school: Light spreads as a wave and will bend if you try to focus it on a single point. This point becomes a spot of light of half the width of the wavelength – at most the exact figure of 200 nanometers.
Rascal pushes the diffraction envelope
For decades, this area of physics was defined by a lack of progress. Instead, the electron microscope emerged as a magnifier of choice, because, as particles, electrons have a much shorter wavelength and scientists can therefore use them to bring out much sharper details. "The only problem is that the electron microscope requires a vacuum, and if it’s a cell you’re observing, it will soon be a dead cell", explains Hell. For those seeking to observe living processes, they were naturally limited by the available technology. Even the development of the fluorescence microscope, which uses bright marker molecules to allow the observation of individual procedures in the cell, was unable to break the 200nm barrier. Nevertheless, this procedure is today part of the standard repertoire of every biomedical scientist, being the only way to observe certain proteins in living cells. However, decades passed and nobody tackled the resolution limit.. "The physicists had given up on the issue whereas the biologists who were confronted with it were out of their depth, as it was essentially seen as a physical barrier", says Hell, summarizing the problem. For Hell, on the other hand, tackling this sort of difficult issue had always been a source of fun. Indeed, this particular scientist, who, as a child, had taken nothing at face value and had later bombarded his physics professors with the question “why?”, was intent on proving to the mainstream that the diffraction limit could be cracked. "I felt intuitively that this hadn’t been fully thought through" he remembers, then admitting: "It’s the rascal in me."
Abbe’s law was considered to be insurmountable, until Stefan Hell dared himself to crack it. Source: German future Prize
It all began with his doctoral thesis at the University of Heidelberg, under physics professor Siegfried Hunklinger, one of the joint founders of the ‘Heidelberg instruments’ company, a forerunner to today's Leica Mircosystems. At that time, as a young postgraduate student, Hell spend a lot of time at the company and, step by step, he began to reconsider the standard approach to fluorescence microscopy. Ultimately, in 1990, on his own initiative, he developed and patented the so-called 4Pi-Microscopy – his first step towards the later breakthrough to come. With this, he already succeeded in illuminating three-dimensional cell structures four times more clearly than was previously possible with conventional methods. "After my doctorate I began to peddle my invention", says Hell. The German Research Foundation (DFG) eventually gave him a scholarship, with which he was able to work at the European Molecular-biological Laboratory (EMBL), but without his own laboratory he could not pursue his idea as determinately as he would have liked. In order to test his approach, expensive laser apparatus was required which wasn’t available in every laboratory - but lateral thinkers never had it easy in university and academic structures at that time. "If you came up with an original idea, which had not been discovered and promoted by a professor, then you weren’t going to fit in", says Hell today. Through a Finnish colleague in Heidelberg, he eventually succeeded in finding a professor in Finland, who offered Hell the needed space in his laboratory at the University of Turku. In 1993, with an additional scholarship from the Finnish Academy, Hell moved north and developed his own working group in the medical physics department.
Discovery brings the German back home from Finland
One Saturday morning – whilst buried deep in a physics book - the central idea behind STED microscopy flashed up in Hell’s imagination. STED stands for STimulated Emission Depletion, and is a completely new kind of fluorescence microscopy. Two rays light up the living cell sample: one to provoke fluorescence and one to prevent fluorescence. By skillfully overlapping these two jets, it is possible to increase the resolution, nearly at will. "In principle, up to the size of a single molecule is possible, thus disproving Abbe’s law", says Hell of his groundbreaking invention.
Hell’s creation will arrive on the market next year. Source: German future Prize
In the mid 90's, Tom Jovin, the then acting Director of the Max-Planck Institute for Biophysical Chemistry in Göttingen, became aware of Hell’s breakthrough. Soon after, in 1997, following a six-month stay in Oxford and his Habilitation at the University of Heidelberg, Hell moved back to Germany. The Max-Planck Institution had offered him the opportunity to lead an independent working group in Göttingen. "I could hardly believe it. To be offered such a position, overnight, from such a renowned institution. It was a salvation", remembers Hell, referring to the budget constraints which he had experienced in Finland. After arriving at Germany, the physicist was also boosted with funding from the German Federal Ministry for Education and Research (BMBF), which supported his project within the framework of the ‘Laser 2000’ program.
First STED microscope awaits market entrance
In 2002, Hell presented his new microscope to the professional world (Physical Review Letters, 22 April 2002). In the same year the Max-Planck Institution granted the license for the manufacturing of the microscope to the optical company Leica Microsystems. At that time, Hell was the only one who could operate the self-built microscope. Since then, the technology has been greatly developed and could be on the market as soon as next year- for a price of somewhere between 800,000 and 1 million Euros. As far as Hell is concerned, his invention could also bring about revolutions in other areas. The physicist sees much potential in this technology, particularly in disease research or medicine development. "If we can see more clearly how a medicine affects a cell, then many animal experiments would be unnecessary and development time enormously shortened", he says.
With the STED procedures (right) the insides of nerve cells can be pictured much more clearly. Source: MPI for Biophysical Chemistry
Entirely new perspectives in basic research are also conceivable, as an initial cooperation with Max-Planck neurobiological scientists has already shown. Together with the Leibniz winner and Goettinger MPI colleague Reinhard Jahn, Hell is granting science the ability to see more clearly, for example surprising details in nerve cell signal transmission. In August, Hell was able to refine the technology to such an extent that a resolution of 15 nanometers is now possible (PNAS, 1 August 2006), opening the door yet further into the cellular nano-cosmos.
Research efforts rewarded with the Future Prize
With the awarding of the 250,000 German Future Prize, presented by Federal President Horst Köhler at a ceremony on 23 November, Hell has been rewarded for his many years of work. Now, the father of twins has just one more wish: “To see STED, or a similar technology, available for every basic medical research laboratory so that it could radically alter the depth of knowledge. Then, I would be able to feel that I had really done something.”
More information about Stefan Hell can be found on the German Future Prize website: www.deutscher-zukunftspreis.de
