Born the son of an engineer in 1960, Eric Betzig grew up during the ‘space race’ and dreamt of being an astronaut, telling his parents he would be a millionaire and Nobel Prize winner by the age of 40. He may never have reached space, but his other dream came true, albeit the Nobel came 14 years later than predicted.
Betzig shared the prize with fellow American William E. Moerner and Romanian-German Stefan W. Hell for revolutionising science through the development of super-resolved fluorescence to exceed the accepted limits of traditional optical microscopy, set down in 1873 by Ernst Abbe who stipulated the maximum resolution could never be better than 0.2 micrometres. By using new techniques to break that barrier, the three Laureates created nanoscopy – allowing molecules to be examined inside living cells. Betzig almost missed his chance at glory, however, having dropped out of academia for several years, and ended up building his prize-winning device in his friend’s living room.
(Robert) Eric Betzig was born in Ann Arbor, Michigan, in January 1960 and is the brother of social historian Laura Betzig. He attended Ann Arbor Pioneer High School and studied physics at the California Institute of Technology, gaining his BSc in 1983 before going on to study applied and engineering physics at Cornell University in New York, earning his MSc in 1985 and PhD in 1988.
After receiving his doctorate, Betzig joined the semiconductor physics research department at AT&T Bell Laboratories in New Jersey. By the early 1990s he was exploring near-field microscopy, in which the light ray is emitted from a thin probe a few nanometres from the sample. This improves on Abbe’s limit and reduces light damage to the whole sample but has too short a range to see structures below the cell’s surface. In 1989, Moerner had become the first person to detect the light absorption of a single molecule. Betzig then replicated this feat at room temperature instead of near absolute zero, allowing practical study of biological molecules. He further theorised that if molecules glowed with different colours, such as red, yellow and green, a microscope could create one image per colour and superimpose them to form one image far better than Abbe’s diffraction limit. At the time, however, there seemed no way to generate these molecular optical properties.
In 1995, feeling he had done all he could, Betzig resigned his post and accepted his father’s offer of a career in the family engineering company, where he developed Flexible Adaptive Servohydraulic Technology (FAST) to speed up production line machinery.
However, the desire to crack Abbe’s limit was still strong. Betzig teamed up with former Bell colleague Harald Hess and, hearing from Mike Davidson’ at Florida State University about photoactivated fluorescent proteins, the two set out in 2005 to implement his super-resolution idea from a decade before, using stochastic photoactivation instead of colour to isolate the molecules. After building the microscope in Hess’ living room, the two moved the instrument to the lab of Jennifer Lippincott-Schwartz and the National Institutes of Health. Using weak pulses of light, the device activates fluorescence from a few proteins at a time without killing the cells (as electron microscopy does) or disturbing their biological processes, and after many such rounds of activation and imaging, the measured positions of all molecules builds the super-resolution image Betzig anticipated.
The following year, Betzig and Hess were both hired at the Howard Hughes Medical Institute’s Janelia Research campus in Ashburn, Virginia, where Betzig lives with his Chinese-born wife, Ji Na, whom he met at Janelia, and their two children.
The PALM method is now helping scientists form greater understanding particularly of biological processes, but Betzig has already moved on. His latest creation, the lattice light-sheet microscope, generates a sheet of light, made up of an array of lower-power Bessel laser beams, that come in from the side of the sample and harm it less than one solid cone of light.
He explains, simply: “An engineer can always make improvements to a microscope.”