Autobiography Stefan Hell

be overcome. He had sent the manuscript to three experts in near-field optics -
among others a famous one in the USA - and only one of them had replied - not
favourably. It would all have to be demonstrated experimentally befbre making
such claims, he said. When he realised my despair and that I didn’t really have the
means to do that, he advised me to go back to Professor Hunklinger’s laboratoiy so
that he submits an application to the DFG on my behalf I was terribly disappoin-
ted about the German academic System.
Today, it’s perhaps hard to understand, but the 1990s were not particularly
receptive to the notion of obtaining nanometre scale resolution in a lens-based mi-
croscope. This can be readily concluded from the fact that no laboratoiy had tried
STED, although I had advocated the concept with much passion. In my opinion,
there were two reasons for this. First, near-field optical microscopy seemed the
way to go at the time, including for the life Sciences. The other reason was even
weightier: since the discovery of the diffraction limit in the 19th Century, concepts
had repeatedly been proposed to overcome it, but ultimately none of them really
worked, or got beyond a factor of two. So it was therefore natural not to take STED
and related ideas seriously either.
However, I was convinced that this time it will work. My reasons were simple:
STED differed from other concepts in that it relied on separating features via the
molecular States of the sample, rather than on tackling diffraction itself. But even
more important, I could not find a basic physical oversight in my concept - in
contrast to all of the ones reported until then. If problems were encountered in the
realization, they would only be technical, not conceptual in nature, which meant
that they could be overcome through development. In principle, with the right
transitions, one can transfer fluorophores between two States, such as a bright and
a dark state, as one likes. When the molecule is in a dark state, that doesn’t mean
that (fluorescence) signal is lost; it simply isn’t produced. In other words, you can
discern adjacent features by keeping some of their molecules silent without losing
anything, exccpt recording time. If some signal is nevertheless lost, that is not due
to the approach, but to the fact that something eise takes place as well - something
that is outside the conceptual framework. By discriminating against that, one can
make the concept work. This insight gave me the courage to carry on with the
development.
However, a first research proposal submitted in 1995 to a European grant
agency with a view to implementing STED was rejected. A Marie Curie individual
postdoctoral stipend came through at the last minute. In this precarious Situation,
Prof. Soini advised me to license my 1990 privately owned patent for the double-
lens microscope (alias the 4Pi) to a Company in Turku, Wallac Oy, in exchange
for research funding. The company’s CEO agreed to transfer 100,000 dollars to
a university account. To this day, I believe that compassion played a role. Those
funds were crucial, because they bought me time for an incredibly fortunate event

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