confocal microscope with epi-laser-illumination, stage scanning and photomultiplier tubes as detectors. The stage could move along the optical axis (z-axis), allowing optical serial sections. In 1979 Fred Brakenhoff and coworkers demonstrated that the theoretical advantages of optical sectioning and resolution improvement are indeed achievable in practice. In 1985 this group became the first to publish convincing images taken on a confocal microscope that were able to answer biological questions. Shortly after many more groups started using confocal microscopy to answer scientific questions that until then had remained a mystery due to technological limitations. In 1983 I. J. Cox and C. Sheppard from Oxford published the first work whereby a confocal microscope was controlled by a computer. The first commercial laser scanning microscope, the stage-scanner SOM-25 was offered by Oxford Optoelectronics (after several take-overs acquired by BioRad) starting in 1982. It was based on the design of the Oxford group. Starting 1985: Laser point scanners with beam scanning In the mid-1980s, William Bradshaw Amos and John Graham White and colleagues working at the Laboratory of Molecular Biology in Cambridge built the first confocal beam scanning microscope. The stage with the sample was not moving, instead the illumination spot was, allowing faster image acquisition: four images per second with 512 lines each. Hugely magnified intermediate images, due to a 1-2 meter long beam path, allowed the use of a conventional iris diaphragm as a ‘pinhole’, with diameters ~1 mm. First micrographs were taken with long-term exposure on film before a digital camera was added. A further improvement allowed zooming into the preparation for the first time. Zeiss, Leitz and Cambridge Instruments had no interest in a commercial production. The Medical Research Council (MRC) finally sponsored development of a prototype. The design was acquired by Bio-Rad, amended with computer control and commercialized as 'MRC 500'. The successor MRC 600 was later the basis for the development of the first two-photon-fluorescent microscope developed 1990 at Cornell University. Developments at the KTH Royal Institute of Technology in Stockholm around the same time led to a commercial CLSM distributed by the Swedish company Sarastro. The venture was acquired in 1990 by Molecular Dynamics, but the CLSM was eventually discontinued. In Germany, Heidelberg Instruments, founded in 1984, developed a CLSM, which was initially meant for industrial applications rather than biology. This instrument was taken over in 1990 by Leica Lasertechnik. Zeiss already had a non-confocal flying-spot laser