Nobelist Roger Kornberg: "If there is any one subject an educated person should know, that is chemistry"

Roger Kornberg received the 2006 Nobel Prize in Chemistry for figuring out the atomic-level details of the process of transcription, that foundational aspect of life that frees up the message in DNA and allows it to work its magic through messenger RNA. 

Following the announcement of the prize, Kornberg had a remarkable exchange with an interviewer in Stockholm when the interviewer asked him whether the work he was doing could rightly be classified as 'structural biology' or something else. In the process he offered a supreme paean to chemistry as the central science.

“The fact remains as I said that the boundaries have blurred, but what is more is that the work that we do in the structural biology department is in some places done in departments of chemistry and in other places done in departments of biology.  

Beyond that I might add that in my personal view chemistry is really the queen of the sciences; chemistry is the common ground for all scientific investigations. So our best hope of applying physical principles for the world around us is at the level of chemistry. Our best hope of understanding the biological organism and ultimately the form and function of the human body is at the level of chemistry. I have said before and I would repeat that if there is any one subject that an educated person should know in the world that is chemistry.”

As if this glowing praise was not enough, Kornberg further elaborated on his view of the necessity of chemistry when the interviewer asked him about what kind of preparation he expects potential students and postdocs in his lab to have.

"I have a very straightforward answer to your question. The one thing I look for is chemistry. People come to my lab from a background in biology, they come from a background in physics, and the question I always ask is about their training in chemistry; if they have studied chemistry then what chemistry did they study and how well did they do it. 

If someone comes along who has studied physical and organic chemistry and have been good at it, then I know they will fit in well, that they will succeed in what we do…absent that I’m doubtful…if they’re a biologist they must have done chemistry, if they’re a physicist then they must at least show an aptitude for chemistry."

Kornberg's superlative leanings toward chemistry may seem excessive but he makes an excellent point. His statement that our best hope of applying physical principles for the world around us is at the level of chemistry succinctly captures the emergent nature of chemical science that frees it from its underpinnings in physics. DNA is composed of quarks, but you cannot understand its principal properties like base pairing and hydrogen bonding at the level of quarks. You can only understand them - both philosophically and practically - only at the molecular level, only at the level of molecular orbitals and electronegativity.

The central science of chemistry reigns over biology, over applied physics, over astronomy, over engineering, but it often works its subtle but powerful influence through the shadows. Like the spacetime of general relativity it simply is everywhere.

Ahmed Zewail and the challenges of intercultural chemistry

A few days ago I was reading the fine biography of the Caltech chemist Ahmed Zewail who won the 1999 Nobel Prize in chemistry for his wonderful work on laser femtosecond spectroscopy which allows us to literally peer into the secret lives of molecules.

The book and the associated Nobel Prize website biography are instructive because they document in fond detail the inculturation of a highly talented and aspiring immigrant in the United States - an experience that has been shared by hundreds of millions of people since the founding of the Republic.

As Zewail details however, applying deeply ingrained, familiar-as-day cultural quirks in a new environment is not always successful.

"Arriving in the States, I had the feeling of being thrown into an ocean. The ocean was full of knowledge, culture, and opportunities, and the choice was clear: I could either learn to swim or sink. The culture was foreign, the language was difficult, but my hopes were high. I did not speak or write English fluently, and I did not know much about western culture in general, or American culture in particular. 

I remember a "cultural incident" that opened my eyes to the new traditions I was experiencing right after settling in Philadelphia. In Egypt, as boys, we used to kid each other by saying "I'll kill you", and good friends often said such phrases jokingly. I became friends with a sympathetic American graduate student, and, at one point, jokingly said "I'll kill you". I immediately noticed his reserve and coolness, perhaps worrying that a fellow from the Middle East might actually do it!"

I morosely wonder how this kind of a friendly retort might go down worse today in a post-9/11 world where fear of perceived entities continues to be sold to us by politicians and the media with copious mass appeal; I wonder if someone would be bull-headed enough to ignore such cultural differences and go straight to the authorities. Along the same lines I wonder how those famed World War 2 European emigre scientists, arriving here by the boatloads from openly fascist countries, might have fared in 2014.

I ardently hope their experiences would have been the same; no exaggerated fear of anything real or perceived comes anywhere close enough to deny this country the kind of immensely enriching experiences and dominance in science and other fields that amazingly talented immigrants like Zewail, Fermi, Weisskopf and Chargas have brought.

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

Image: Nobelprize.org

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!

Updated #chemnobel odds for tomorrow

So today's physics Nobel Prize was awarded to three physicists who worked on blue LEDs, devices that make light bulbs glow brighter and last longer than normal ones. It's a well-deserved recognition, really one for a physics-based invention rather than for a fundamental discovery (as an aside, it's worth noting how much the invention owes to the chemistry of gallium nitride semiconductors). The last time an invention was recognized was when the prize was given out for CCDs in 2009.

However I think the prize also casts some serious doubt on a lot of predictions that Thomson Reuters and others have been making for tomorrow's chemistry award. It's certainly not unheard of for prizes in two disciplines to be awarded for the same field of study (for instance chemistry and medicine often trail each other in the context of crystal structures of important proteins) and I haven't really done an exhaustive study of how often this has happened before, but I would guess that the odds of it are pretty low.

If nothing else, today's blue LED prize almost certainly means that one of the most popular predictions for tomorrow (and Thomson Reuters's choice) - that for Ching Tang's work on organic LEDs - will have to be tossed out of the window for now. It seems extremely unlikely for two kinds of LEDs to be awarded two different prizes in the same year.

Today's recognition is not just a recognition of materials science but even more so of energy. That might mean that some of the energy-based prize predictions for tomorrow may also be off the mark. Thus, the odds for awarding a prize for Li-ion batteries or for dye injected solar cells may sadly have worsened.

Since both materials and energy are no longer looking that great in my book, I now have a revised set of predictions. In light of today's development I think that the chances for other kinds of chemistry might now be higher. So I am now bumping up my predictions for biochemistry (click chemistry, nuclear receptors, chemical biology - eg. Stuart Schreiber) and also adding a prediction for polymers (especially ATRP) which I missed earlier. Single molecule spectroscopy (Moerner etc.)  and electron transfer in proteins and biomolecules (Gray, Barton etc.) also stand a good chance now.

Chemists, time to break out the pitchforks: A biologist may "steal" "our" Nobel once again...

Chemistry Nobel Prizes and second acts

While having a discussion about Barry Sharpless with a fellow chemist the following random question occurred to me: How many chemists have contributed at least one significant piece of work to science after winning the Nobel Prize? Sharpless himself invented click chemistry after being recognized for asymmetric synthesis.

After winning the prize many laureates bask in the sunlight and cut down significantly on research. Some use their newfound celebrity status to advance educational or social causes. Others can disappear from the world of science altogether. But a select few plough on as if they had never won the prize and the names of these persistent souls should be more widely known. 

A couple of examples spring to mind. At the top of the list should be the man who continued to do research that turned out to be so important that he shared another Nobel Prize for it: Fred Sanger, who got his first Nobel Prize for protein sequencing and the second for DNA sequencing.

R. B. Woodward must also join Fred Sanger at the top. Although technically he won just one Nobel Prize he would have undoubtedly won another (for the Woodward-Hoffmann rules) had he been alive (and cut down on the scotch and cigarettes) and was probably a candidate for a third (ferrocene and organometallic chemistry).

But we can find examples much further back. Ernest Rutherford received an anomalous 1908 prize in chemistry instead of physics, but after winning it he continued to churn out Nobel Prize-winning students and pathbreaking discoveries, including the demonstration of artificial or induced radioactivity. Harold Urey received a prize in 1934 for his discovery of deuterium, but he contributed at least partially to the founding of origins of life chemistry with Stanley Kubrick (ok it's Miller, huge typo, but I am going to let this stay; I can only surmise that I was fantasizing about a Kubrick movie titled "2001 A Space Odyssey: RNA World Edition") in the 50s. In this context Manfred Eigen is another interesting example; after being recognized for methods to study fast reactions in 1967, Eigen embarked on an origins of life career and among other things came up with the idea of "hypercycles".

Interestingly, Linus Pauling who is widely considered the greatest chemist of the twentieth century had exhausted his quota of important chemical discoveries by the time he won the Nobel Prize in 1954. Until then he had already revolutionized the theory of chemical bonding, proposed the alpha helix and beta sheet structures in proteins and had contributed a host of other important ideas ranging from rules for predicting the structure of minerals to proposals about the mechanism of action of antibodies and enzymes. Pauling continued to do interesting work scientific after this, but most of his attention was focused on arms disarmament for which he won the peace prize in 1962. For the rest of his life Pauling was occupied partly with interesting scientific projects and partly with controversial medical projects. Nothing that he did came close to his accomplishments before winning the prize, although given the magnitude of those accomplishments I guess we can cut him some slack.

I don't have an exhaustive list here but I doubt if there's many more names to add here. Doing one piece of significant science in your life seems hard enough so perhaps it's unrealistic to expect two. And yet there are a few hardy souls who achieve this.