Stefan W. Hell, PhD, likes to get down to the fundamentals. As an undergraduate, he disliked hearing professors say, “If you do the maths, you’ll know why this is so.” He was convinced everything could be reduced to the simplest principles and spent hours, as he put it in his autobiography, “trying to distill concepts and phenomena down to their essence.”

No doubt that is partly why Hell latched so hard onto the idea of developing a way a microscope could more clearly see the fundamental parts of a cell, and spent years working on a solution, even though his idea was contrary to the accepted ideas of physics.

“He is very ambitious and has lots of energy; once he has an idea, he wants to pursue it and he wants to pursue it very completely and directly,” said Dr. Steffen J. Sahl, Hell’s colleague at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany.

Relatively early

That tenacity and curiosity earned Hell one of the three 2014 Nobel Prizes for chemistry, which were awarded to him and two American scientists “for the development of super-resolved fluorescence microscopy,” according to a press release from the Nobel Prize committee. The two others are Dr. W.E. Moerner and Dr. Eric Betzig; each worked independently.

“Many were surprised but extremely delighted and excited that this highest of honors came so relatively early,” said Sahl. “People widely felt that this was work of outstanding importance and significance – especially also because of its conceptual insight and implications, promising additional improvements to molecular microscopy in the years ahead – and that it definitely merited the Nobel. Stefan’s big experimental breakthrough demonstrations which clearly showed the feasibility to reach the few-nanometer resolution level came around the year 2005/2006.”

The University of Turku

The problem Hell had tackled was the accepted idea that there was a limit to the maximum resolution of traditional optical microscopy. In 1873, the microscopist Ernst Abbe stipulated that the maximum resolution of traditional optical microscopy could never become better than 0.2 micrometres, meaning that especially small items, such as parts of cells could not be seen clearly. Hell was able to devise the first viable concept for surpassing Abbe’s diffraction-limited resolution barrier in a light-focusing microscope.

“He was a young post-doc researcher and got the opportunity to work at the University of Turku, Finland,” according to Sahl. “There he got an idea one Saturday morning about how to radically overcome the refraction limit, and then he went on and pursued it for the next 20 years. His first demonstrations of the concept in experiment were published in 1999/2000, and the methods have since become incredibly powerful within a short space of time.”

Light microscopy is most important in the life sciences

The technology allows scientists to see not just cells, but molecules in sub-cellular compartments, even synapses between neurons in great detail. “Light microscopy is arguably most important in the life sciences,” Sahl explained. “You can mark molecules, focus light into living tissues…discern any type of protein or lipid also in living cells… things you cannot do with electron microscopes.”

Emigrated to Germany

Hell, who was born in Romania, became interested in science at a young age; American science fiction thrillers broadcast on Sundays helped to spur that interest, remembers Hell in his autobiography. He excelled in school and earned a coveted spot at the Nikolaus Lenau Lyceum in Timisoara, one of the best secondary schools in Romania, where he concentrated on math and physics.

But life under Dictator Nicolae Ceausescu was becoming more unsettled, and Hell and his parents applied for visas to emigrate to Germany, which were granted after two years, and they left the country in 1978. Once in Germany, he graduated early from high school and went on to attend Heidelberg University, where he earned his undergraduate and doctoral degrees in physics. From 1993 to 1996, he worked as a senior researcher at the University of Turku, Finland, where he developed the principle of STED microscopy, joining the Max Planck Institute in 1997 and remaining there since.

Nanoscope

The next step in this area of research for Hell and his group is to continually make the microscope faster over time, to subject cells to ever lower levels of light so that their observation is minimally- invasive, and to keep producing better and better 3D images. “Stefan’s lab recently was able to obtain images of neurons inside a living mouse brain with unprecedented levels of detail,” noted Sahl. “Using this kind of ‘nanoscope’, it should eventually be possible to observe how memories are formed at the molecular level.”

Info box

Name: Stefan W. Hell

Born: Dec. 23, 1962, Arad, Romania

Nationality: German

Family: Married, three children.

Position:  Director at the Max Planck Institute for Biophysical Chemistry, Department of NanoBiophotonics, Göttingen, Germany. Honorary professor of experimental physics at the University of Göttingen. Adjunct professor of physics at the University of Heidelberg

Director of the High Resolution Optical Microscopy Division at the German Cancer Research Center (DKFZ) in Heidelberg

Education: Diploma in Physics, University of Heidelberg, 1987, PhD in Physics, University of Heidelberg, 1990.

Other: Enjoys music, playing the saxophone, running

Published more than 250 original articles

Photo: Jenny Öhman