For scientists, perhaps the single most useful tool in the laboratory is the microscope. With it, the minute world of cells and organisms can be explored, often providing answers to how diseases are spread or life itself works.
Since 1873, however, it was thought that optical microscopes had a natural limit. German microscopist Ernst Abbe calculated that, as they rely on light to work, no microscope could discern individual objects less than 200 nanometres apart, equivalent to half a light wavelength.
Abbe’s equation is quite literally set in stone, in Jena, Germany, and one might think that 200nm (a nanometre is one millionth of a millimetre) would be ample until you realise that so much of biochemistry in particular happens inside individual cells, by enzyme machines and other structures that are closer to 5-10 nm in size.
Electron microscopes, using electrons instead of light waves, can map objects nanometre by nano-metre, but cannot be used on living tissue. The 2014 Nobel Prize for chemistry was therefore awarded to three men who found a way to work around Abbe’s limit, using molecules and their fluorescence. In Germany, Stefan Hell used lasers to stimulate fluorescent molecules in tiny regions to build up compound images. In the US Eric Betzig came up with similar ideas based on single-molecule microscopy, which was first demonstrated by William Moerner in the early 1990s. The scheme involves turning the fluorescence of individual molecules on and off. Scientists scan the same area several times, allowing just a few molecules to glow each time, like light bulbs randomly spaced along a string. Merging the positions of these molecules produces a ‘super-image’ resolved at the nanolevel. This more focussed approach allows greater understanding of molecular and cellular behaviour, such as how diseases can develop. Betzig demonstrated a working microscope in 2006, but it was Moerner who was the first to isolate an individual molecule with light for spectroscopic analysis many years before.
William Esco (known as W.E.) Moerner was born in June, 1953, at Parks Air Force Base in Pleasanton, California, and grew up in San Antonio, Texas, where he attended Thomas Jefferson High School and took part in many activities, both at school and with the scouts.
He gained degrees in physics, electrical engineering and mathematics at Washington University in St Louis, finally graduating in 1975 and moving to Cornell University, New York, for his MSc (1978 and PhD (1982) in physics.
Moerner worked at IBM’s research centre in San Jose, California, from 1981, rising to project leader from 1989-95. It was there, in 1989, that he became the first person to measure the light absorption of a single molecule. Previously, scientists had to take an ‘average’ impression of vast numbers of molecules in a sample but Moerner, working with his postdoctoral associate Lothar Kador, performed absorption spectroscopy on a low concentration of pentacene hydrocarbon molecules in an organic crystal and chilled to near absolute zero, which enabled them to use a finely-tuned laser to pick out individual molecules. Observing individuals showed that many “march to different drummers,” and quickly the ability to optically switch a single molecule was demonstrated.
This breakthrough inspired many others, including Eric Betzig, who replicated Moerner’s feat at room temperature and theorised about the possibilities of a fluorescent imaging microscope, but in 1995 he started a prolonged break from research.
That same year Moerner became the Distinguished Chair in Physical Chemistry at the University of California in San Diego. There he met Roger Tsien, who in 1997 was working on his own Nobel-winning project, the isolation of green fluorescent protein (GFP) from a jellyfish, and coaxing it to fluoresce in a range of colours. It could also be linked to other proteins to reveal their position within a cell. Moerner found that one variant of GFP could be turned on and off like a light by stimulating it with certain wavelengths of light, a critical property used later by Betzig’s microscope. By dispersing these proteins in a gel solution he was able to detect their individual glow with an optical microscope.
In 1998 Moerner moved to Stanford University, California, where he continues his pursuits as Harry S. Mosher Chair in physical chemistry and applied physics with single molecules. He lives with his wife Sharon, with whom he has one son, Daniel.