Field of Science

The 2014 Nobel Prize in Chemistry and tool-driven scientific revolutions

Last year I wrote a post detailing the views of historian Peter Galison and physicist Freeman Dyson of science as being as much of a tool-driven revolution as an idea-driven one. Now here's a great instance of that tool-driven paradigm change: this year's Nobel prize for chemistry which was awarded to Eric Betzig, Stefan Hell and W. E. Moerner for single molecular techniques, especially single molecule fluorescence microscopy and spectroscopy. The prize has been awarded for a set of techniques - and technological developments - rather than for a groundbreaking idea. But these techniques have led to ideas which hold enormous promise for the future. The recognition thus reflects how ideas and tools feed off of each other in science.

Moerner seems to have been an obvious choice on several people's lists for years while Hell and Betzig seem to have largely escaped attention. 

Here's what the three prizewinners did, in a nutshell:
Two separate principles are rewarded. One enables the method stimulated emission depletion (STED) microscopy, developed by Stefan Hell in 2000. Two laser beams are utilized; one stimulates fluorescent molecules to glow, another cancels out all fluorescence except for that in a nanometre-sized volume. Scanning over the sample, nanometre for nanometre, yields an image with a resolution better than Abbe’s stipulated limit. 
Eric Betzig and William Moerner, working separately, laid the foundation for the second method, single-molecule microscopy. The method relies upon the possibility to turn the fluorescence of individual molecules on and off. Scientists image the same area multiple times, letting just a few interspersed molecules glow each time. Superimposing these images yields a dense super-image resolved at the nanolevel. In 2006 Eric Betzig utilized this method for the first time.
The whole suite of single molecule techniques have huge implications for imaging, tracking and tagging molecules of all kinds, but especially so in biology. The importance of fluorescence and spectroscopy for biology have been recognized for years (as exemplified by the Nobel Prize in 2008 and 2002 for instance) but today's prize brings those techniques together and applies them to individual molecules. The prize is not only eminently well-deserved but heralds several prizes of this sort in the future as these techniques are applied to important and promising areas like neuroscience and drug discovery. In addition it is a truly interdisciplinary recognition bringing together physics, chemistry and biology. Which means that everyone should celebrate (or complain...).

There are a few interesting tidbits associated with the three scientists and their work. It seems like both Hell and Betzig were sort of in the wilderness when they made their original pioneering contributions. Hell was working in Finland, away from the mainstream research centers when he had the idea for beating the diffraction limit. And in a trend that's more common than we think, his 2000 paper on STED was rejected by Science and Nature and accepted in PNAS.

Betzig's story is especially interesting: He left academia in 1996 and worked at his father's machine tool company for several years, developing hydraulic technology which was commercially unsuccessful. But the single molecule fluorescence bug had bitten him too hard to let go, so through a series of ventures - one of which involved building a single molecule instrument with a friend in the friend's living room - he gradually returned back to academia, settling in at the Janelia Research Farm Campus in Virginia. My suspicion is that those years dabbling in technology and industry were exactly what enabled Betzig to develop his engineering acumen and apply it to building the right tools.

It's also interesting to note that both Betzig and Moerner made their original pioneering discoveries in industry - Moerner when he was working at IBM in San Jose and Betzig when he was working in his own private company. I think their stories send a clear message that interesting ideas - and especially their implementation - come quickest when good pure science collides with the kind of good engineering and practical expertise that one is exposed to in industrial settings. I think the 2014 chemistry Nobel Prize recognizes engineering as much as science and this makes it an especially important example of a tool-driven scientific revolution.

In any case, an eminently well-deserved prize with implications that are just starting to be realized and which will undoubtedly scale many new horizons in the future. Congratulations to the three prizewinners!


  1. The field of super-resolution imaging points to the interdisciplinary nature of chemistry, and science in general. The field relied on developments in physics and optics (e.g. Moerner's and Betzig's work on single molecule detection and Hell's work on stiumlated emission depletion), development of new chemical probes (e.g. work on photoswitchable fluorescent proteins by Jennifer Lippincott-Scwartz and photoswitchable organic dyes by Xiaowei Zhuang), and the technique has been hugely important in addressing a number of fundamental biological questions from the spatial organization of components in bacteria to the inner workings of the brain.

    This is an unfortunate case where the limit of only three Nobelists per prize excludes worthy individuals from recognition. All three are definitely worthy of the honor (though Moerner more for his contributions to single molecule imaging and spectroscopy, not necessarily to super-resolution imaging). For example, Betzig published his super-resolution imaging method simultaneously with two other groups, those of Xiaowei Zhuang and Sam Hess. Jennifer Lippincott-Schwartz also has contributed to a lot to the field through her work with photoswitchable fluorescent proteins, a requirement for Betzig's method (she was a co-author on Betzig's key 2006 paper). Mats Gustafsson, who sadly passed away a few years ago, was another key pioneer in the field through his work on structured illumination microscopy, and would have been another worthy of recognition.

    1. Thanks for that summary. I agree that Hess, Zhuang and Gustafsson both made important contributions. As usual the Nobel Prize reveals both people who deserve it and got it and those who didn't.

  2. "science as being as much of a tool-driven revolution as an idea-driven one"

    Yes, yes! Emphatically YES!
    …and experiments using those tools and the ideas that are ‘driven’ from that work.

    Another Nobel for work using lasers. Remember when some prominent physicists, including some Nobel Prize winners, told Townes his maser would not work? Microwave amplification! Before the Second World War microwaves could not be generated until a new device was created, the cavity magnetron, and the world changed. That device was dumped into the laps of US scientists working on radar by the British desperate to get high quality radar into production at the outset of WW II. How much has physics and chemistry and biology benefited by new tools using microwaves? Willis Lamb was working on radar during the war. The discovery of the Lamb shift propelled physics forward immediately after the war. The almost never mentioned Shelter Island Conference following the war had tremendous benefits for QED theory. Microwave spectroscopy has benefited all areas of science including astronomy. Microwaves gave us the first amplification by stimulated emission of radiation. Townes builds the first optical laser, a solution in search of a problem, and now we have more Nobels awarded for new tools using lasers. What a magnificent journey!

    Great article Ash!

    1. Ah, Shelter Island. I have been planning to write a post on its impact on physics for a while now. I should get started. Thanks. Lasers and microwaves are indeed great examples of tool-driven revolutions, especially in astronomy.

  3. I suppose one might have hoped for a more spectroscopy-oriented prize (Orrit & Xie, perhaps with Moerner), but it could be worse. What gets me is that my off-hand joke from a while back (about whether people would whine and moan about a p.chem-slanted Prize being applied physics) actually came true.

    I mean, there was a line of discussion a while back of chemistry Laureates not even being recognizable as chemists of any sort (MDs, or in a med school, etc.) Now, Moerner is a professor of chemistry at Stanford, and Hell is a group leader at the MPI for Biophysical Chemistry. (Betzig...well, can't win them all.) It almost seems like the chemistry e-discussion community wants to exclude healthy swaths of the current chemistry community since they're not quite "real chemists" under a constantly changing definition.


    1. I always think of Max Planck's quote in such cases; at one point the old generation (us) will perish and a new one will arise, one which will feel completely at home with these interdisciplinary developments. Nobody seemed to complain when Ernst got the prize for what were essentially methodological developments. Even Rutherford and Joliot-Curie won the chemistry prize, so the recognition of the grounding of chemistry in physics goes back a long way indeed.

    2. I read somewhere that the physics prize is considered by the Nobel Academy to be a bit more prestigious than the chemistry prize (or all other science awards). For that reason I have always considered Rutherford’s placement in the chemistry category as a bit of a snub or at least an indication that the Academy did not value the work he was doing as much as they valued the development of color photography (Lippmann won the physics prize the same year), primarily a chemistry experiment.

      Rutherford’s citation reads, "For his investigations into the disintegration of the elements, and the chemistry of radioactive substances." Well, the disintegration mentioned involves a change in the nucleus, a new component of the atom, and the identification of the primary types of radioactive decay. While it took some creative chemistry and physics to identify the alpha particle his work was much more about the physical nature of radioactive elements and understanding the fundamental nature of matter, especially when compared with color photography.

      M Tucker

    3. Agreed. I think the chemistry prize made more sense for the Joliot-Curies and Hahn than it did for Rutherford. Especially for Hahn since his and Strassman's work involved chemical sleuthing more than anything else (this is documented in Rhodes for instance).

  4. "The prize has been awarded for a set of techniques - and technological developments - rather than for a groundbreaking idea."

    Since it is unlikely that we will have many groundbreaking ideas or theories in the near future (and we haven't had many in the last a few decades), I now think that many of the people that I had considered as candidates do not have much chance to win the prize unless the prize is given for some kind of life-time achievement. But, then who deserves and why? That's hard to evaluate at least for me.


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