A clearer view of biological cells

This year’s Nobel Prize in Chemistry was awarded for advances in a high-resolution microscopy. One of the laureates, William Moerner, has a connection to ETH Zurich.

Enlarged view: Nobelpreisträger Chemie 2014
The winners of the 2014 Nobel Prize in Chemistry: Stefan Hell, William Moerner and Eric Betzig (from left to right). (Photo: Keystone)

Eric Betzig from the Howard Hughes Medical Institute, Stefan Hell, Director of the Max Planck Institute for Biophysical Chemistry in Göttingen, and William Moerner, Professor at Stanford University, were awarded this year’s Nobel Prize in Chemistry. In awarding the prize, the Nobel Committee recognises the scientists for their contributions to high-resolution light microscopy.

One of the laureates also has a connection to ETH Zurich: William Moerner was a visiting professor here for one year in 1993/94. Urs Wild, now Professor Emeritus of Physical Chemistry at ETH Zurich, first met him when they worked together at the IBM research centre in San Jose, California, and invited him to Zurich for a research fellowship. “Moerner was already an outstanding researcher at IBM. He struck me as someone who worked in an original and experimentally and intellectually demanding manner,” says Wild today.

Research topic at the ETH

Moerner’s year at ETH was his first post as a researcher and lecturer at a university. “This was an important period for him  by making the transition from industry to a university career,” says Wild, who remains in contact with Moerner to this day. During his stay at ETH (and previously at IBM), Moerner worked on making individual molecules microscopically visible. At that early stage, their goal was to examine how individual molecules behaved photochemically, such as their brightness, says Wild. Moerner and Wild published four joint research papers on the topic during this time.

Enlarged view: William Moerner
William Moerner at a science conference organised by ETH at Monte Verità in 1992. (Photo: permission granted)
Enlarged view: Abbildung Forschungspublikation
A single fluorescent molecule (top left) on a 100 x 100 micrometre surface. Image from a 1994 research publication by Moerner and Wild. (Source: Plakhotnik T et al. Chimia 84: 31-32)

In subsequent research, Moerner and many other researchers, including Betzig and Hell, contributed towards the development of sophisticated light microscopy systems that are now able to see living samples, such as cells, at high resolution. The three Nobel-winning scientists worked independently: Moerner and Betzig on the same technology and Hell on another.

Ten times the resolution

Although it is possible to produce higher resolution images using electron microscopy than with light microscopy, the samples must be fixed chemically or by other means. Living cells therefore cannot be examined. The Nobel Prize has been awarded for work that has helped to increase the resolution of light microscopy by approximately 10 times in comparison to previous systems.

The latest generation of light microscopes are also available at the Scientific Center for Optical and Electron Microscopy (ScopeM) at ETH Zurich. The first was brought in two years ago, and a second device, which works with a different technology, was added a month ago. Researchers at ETH use the devices mainly for cell biology work, as it allows them to see inside cells at a high resolution.

Award for the entire field

“The prize is a recognition for the entire field of light microscopy,” says Gábor Csúcs, technical director of light microscopy at ScopeM. “Light microscopy was severely limited for many years and the differences in resolution in comparison with electron microscopy were huge.” Thanks to the work of this year’s Nobel Prize winners, the differences have been drastically reduced.

In contrast to some earlier Nobel Prizes, this year’s Nobel Prize in Chemistry does not honour an actual discovery, but rather the development of a method, explains Csúcs. Super-resolution light microscopy has been now in use for some years, but typically in combination with other measurement techniques. To his knowledge, until today there is no high-impact cell biology work published that relies on super-resolution light microscopy alone.

“Outstanding scientists”

Csúcs has met Betzig and Hell at scientific conferences, and both have also spoken at seminars at ETH Zurich on several occasions. “They are outstanding scientists,” says Csúcs. He recalls speaking to Betzig and describes him as a very funny person, but also as someone who cares first and foremost about scientific discoveries. “I had the impression that he places little value on fame and awards, so I’m curious to see how he reacts to the Nobel Prize.”

“All three winners have played an important role in the development of high-resolution light microscopy,” says Csúcs. But they are not the only influential scientists in this field of research and the decision by the Nobel Committee to honour these three is likely to generate some discussion within the scientific community. In total, currently three super-resolution light microscopy techniques are in frequent use, but the three winners represent only two: STED microscopy (Stimulated Emission Depletion) and localisation microscopy. The third technique, SIM (Structured Illumination Microscopy), is just as important today, says Csúcs, yet its developers were not recognised by this year’s Nobel Prize.

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