W.E. Moerner is really the father of single-molecule spectroscopy. It’s not surprising that a prize for single molecules went to him. His early work laid the foundation for single-molecule photophysics that made PALM-type super-resolution possible.
Also, most people don’t realize that almost all the early cryogenic single-molecule imaging resolved molecules that were closer than the diffraction limit. At temperatures near absolute zero, the spectral linewidths get super narrow. This means that any one laser wavelength excites only a fraction of the dyes in a crystal; dyes in different parts of the solid experience slightly different nano environments, and their spectral properties are different. This is called inhomogeneous broadening. By tuning the wavelength of a dye laser, Moerner and others were able to excite different dyes at different times, all within one diffraction-limited laser spot. That was routinely done, and many of the early single-molecule images were actually plots of intensity, with distance on one axis (moving the laser spot) and wavelength on the other (changing the laser color).
Fluorescence excitation spectra for pentacene in p-terphenyl at 1.5 K measured with a tunable dye laser of line width ∼3 MHz. The laser detuning frequency is referenced to the line center at 592.321 nm. (a) Broad scan of the inhomogeneously broadened line; all the sharp features are repeatable structure. (b) Expansion of 2 GHz spectral range showing several single molecules. (c) Low-power scan of a single molecule at 592.407 nm showing the lifetime-limited width of 7.8 MHz and a Lorentzian fit. [From: Moerner, W. E. J. Phys. Chem. B 2002, 106, 910– 927.]
[From: Ambrose, W. P. and Moerner, W. E. Nature 1991, 349, 225– 227]
Eric Betzig contributed to single-molecule spectroscopy early on, imaging single molecules at room temperature with near-field super-resolution microscopy (Betzig 1993) and proposing an early variant of PALM super-resolution imaging back in the 1990s (Betzig 1995). (His proposal was realized at cryogenic temperatures by van Oijen in 1998.) After that, he left science and worked at his father’s tool factory.
When Betzig heard about the development of GFPs that could be easily photoswitched on and off, he realized that these could be applied to his super-resolution concept he proposed a decade earlier (Betzig 1995). So he built a super-resolution microscope in his friend’s living room and published the first PALM paper in 2006. It should be noted that Xiaowei Zhuang and Sam Hess each independently published similar super-resolution methods in 2006 (Betzig 2006; Hess 2006; Rust 2006).
[From: Betzig 1995]
Stefan Hell has a very interesting story. After proposing STED microscopy in the 1990s (Hell 1994), he worked for years with little funding and almost no support or recognition. A decade later he got his STED microscope producing super-resolution images and now he’s a huge force in the field.
It goes without saying that there were many others who contributed to the field of super-resolution and single-molecule imaging (Yanagida, Webb, Zhuang, Hess, Gustafsson, Lippincott-Schwartz, Zare, Vale, Orrit, Rigler, Xie, Cremer, Baer…) and many people will probably be disappointed. But is hard to argue that these three were not deserving and I congratulate them!
Also, Ash at Curious Wavefunction has a great summary. See my post from 2006 on super-resolution methods. And my single-molecule timeline (please excuse any omissions: it is impossible to include everyone!). And remember when the Simpsons predicted W.E. to win?
And full disclosure: W.E. was my PhD advisor. :)
Ambrose, W. P. and Moerner, W. E. Nature 1991, 349, 225– 227.
Betzig E and Chichester RJ (1993) Single molecules observed by near-field scanning optical microscopy. Science 262:1422-1425.
Hell SW and Wichman J (1994) Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion-microscopy. Opt. Lett. 19:780-782.
Hess, S. T., Girirajan, T. P. K. and Mason, M. D. Biophys. J. 2006, 91, 4258–4272
Rust, M. J., Bates, M. and Zhuang, X. Nat. Methods 2006, 3, 793– 795
van Oijen AM, Kohler J, Schmidt J, Muller M and Brakenhoff GJ (1998) 3-Dimensional super-resolution by spectrally selective imaging. Chem. Phys. Lett. 292:183–187.
Time for 2014 Nobel Prize predictions. Actually, it’s a little early, but with Lasker Prize announcements, I just couldn’t wait. Here’s my track record:
- 2008: I said that it was obvious that Roger Tsien would win.
- 2009: I didn’t make a prediction
- 2010: I included Suzuki and Heck in my predictions.
- 2011: I failed miserably.
- 2012: I included Kobilka and GPCRs among my six predictions.
- 2013: I (and everyone else) correctly predicted that Higgs would win.
So here are my 2014 predictions:
Chemistry: Nanotechnology: Alivisatos, Whitesides, Lieber
Medicine: DNA/blotting: Southern, Jefferys, Burnette
Physics: Cloaking/nonlinear optics: Pendry, Harris
Peace: Ebola: Médecins Sans Frontières
Other and past predictions:
Biomolecular motors: Vale, Sheetz, Spudich, Brady
Unfolded protein response: Walter, Mori
Soft lithography and microfluidics: Whitesides, Quake
Chaperonins: Horwich, Hartl, Lindquist, Ellis
Polymers: Frechet, Matyjaszewski, Wang, Willson
Electrochemistry/bioinorganic: Bard, Gray, Lippard
Single-molecule spectroscopy: Moerner, Orrit
Solar: Grätzel, Nocera
DNA synthesis: Caruthers
Next-gen sequencing: Webb, Craighead, Klenerman, Church …
Super-resolution optical microscopy: Betzig, Hell, Zhuang, Hess
NMR and membranes:
Electron Transfer in DNA/Electrochemical DNA Damage Sensors: Barton, Giese, Schuster
Pd-catalyzed Alkyne/Alkene Coupling and Atom-Economy: Trost
Nuclear hormone receptors: Chambon, Evans, Jensen, O’Malley
Two-photon microscopy: Webb, Denk, Strickler
DNA microarrays: Brown
The Pill: Djerassi
T-cell receptor: Allison, Reinherz, Kappler, Marrack
Suggestions from others:
Quantum dots: Brus
Lithium-ion batteries: Goodenough, Whittingham, Yoshino
Optogenetics: Deisseroth, Zemelman, Miesenböck, Isacoff
Does anyone else love ACS’s ActiveView PDF viewer for reading PDFs and seeing reference? And Nature’s ReadCube, too. Great stuff.
Of course, after I scan the ActiveView, I still download the old-fashioned PDF and use Papers (or Mendeley) to read and manage my library.
Well, I predicted G-protein coupled receptors (GPCRs) and Brian Kobilka, but not Robert Lefkowitz. Congrats to both!
GPCRs are cell-surface receptors that translate signal from an extracellular ligand to a G-protein, a molecular “switch” turned on and off by GTP. (The discovery of the G-protein was awarded the 1994 Nobel in Medicine). GPCRs are very important in a variety of signaling in the human body, and most modern drugs target GPCRs.
Kobilka and Lefkowitz first had inklings of the structure of GPCRs in the 80s, when they began isolating and purifying the β2-adrenergic receptor (βAR). They eventually realized that the protein had seven transmembrane helices; to their surprise, that hinted at a very similar structure to rhodopsin—the component in the eye responsible for detecting light—another GPCR. This discovery implied that all the receptors that couple to G-proteins might have a conserved structure! Over the last few decades, Kobilka, Lefkowitz, and others have produced a bunch of structures for GPCRs, which should aid in future drug design.
I think it’s fascinating is that Kobilka was a postdoc with Lefkowitz many years ago. I wonder how often it happens that both the professor and a student/postdoc share a Nobel? Of course, Kobilka has performed enough work during his independent career to earn a Nobel, but I still think it’s cool that he won the award with his former professor. I’m not sure why Stevens or Palczewski were not also included in the prize, but it seems that the committee (given only three available slots, of course) stuck to the early discoveries that lead to the GPCR structures.
And I must discuss the concern from many corners that this is not “chemistry.” Why did it not win the medicine prize, instead? Well, I don’t know. It certainly could have won the prize in the medicine category, because of GPCR’s huge role in medicine! But the Nobel Committee seems to often place protein structures into the chemistry category [Update: see this great history]. I think that is reasonable: the task of isolating, purifying, crystallizing, and determining the structure of a protein is basically biochemistry, not medicine. And many of the individuals in the lab performing the tasks are probably chemists and biochemists. Maybe the lab isn’t located in a chemistry building, but neither is the lab that I work in, and I am certainly a chemist performing chemistry. (Well, right now I’m blogging.) I continue to think that these type of discoveries being labeled “chemistry” is great for the field of chemistry. Maybe I feel this way because I don’t perform “traditional” chemistry synthesizing small organic molecules. My research has spanned polymer physics, spectroscopy, optics, and cell biology. But I have applied my skills and knowledge of a physical chemist to all those sciences. As I said in my interview with Slate.com (where I did not predict GPCRs):
The line between chemistry and other fields (especially biology) is often blurred, and that’s a wonderful thing; but this fact sometimes results in a chemistry Nobel Prize being awarded for a decidedly biological discovery (like the 2009 prize for the structure of the ribosome). This may be exacerbated by the fact that the physiology or medicine prize tends to go to things directly related to health, and the chemistry prize often is used to cover the more basic biological science feats. Personally, I think it is a testament to the central position the field of chemistry holds in the Venn diagram of science.
Biology is the next frontier for the physical sciences! There is so much to learn about how biomolecule, cells, and organisms work. Let’s embrace biology’s commingling with chemistry with all our hearts!
You can read more about GPCRs here:
Other bloggy commentary here:
I’ve always warned against the Precautionary Principle, mainly because it has a fatal flaw: no one applies the same principle to the alternatives. The Precautionary Principle assumes a product (or medicine or technology) is harmful until it is proven to be safe, instead of the other way around. This sounds nice, but the problem is that it doesn’t take into account the dangers of the alternative products (or medicines or technologies). That is, at least how most consumers apply the principle.
I warned against this when the BPA kerfuffle emerged. Many people started to get concerned about bisphenol A, which is a monomer for polycarbonate used in many plastic bottles. Some BPA can leach from the plastic into food or liquids, and there has been some evidence that it may mimic hormones in the human body and may have negative health effects especially in children. So everyone started banning BPA bottles and switching to other materials. The main alternative is “BPA-free” plastics. When this happened, I asked, “But what are those plastics made of??”
Basically, everyone switched over from a known product (polycarbonate) that might have some deleterious effects, to a proprietary polymer (Eastman’s Tritan) that we knew nothing about. And everyone felt safe.
But what if Tritan is a thousand times more dangerous? What if the glass bottles that some people switched to leaches lead (although I doubt many parents are giving their kids crystal to drink out of)? What if those steel water bottles put chromium into your water? (The aluminum ones like Sigg are coated with a plastic, anyway.) It doesn’t really make tons of sense to throw away your old water bottles to buy brand new ones that have a new, proprietary plastic that can leach new, unknown chemicals into your water.
C&E News has a story about Eastman’s Tritan and it’s possible health dangers. We should all throw away our new water bottles and start drinking out of another unknown material so another company can make billions off of our fears. Or just start drinking directly from the faucet.
The only correct application of the Precautionary Principle is to have someone measure the safety of all the materials used to make water bottles and baby sippy cups and weigh the dangers against each other. Maybe Eastman should pay for that. ;)
(That said, I must admit that I drink out of glass, a coffee mug made in China, and a steel water bottle. Who knows what I have in my body.)
Thanks for the tip, Chemjobber.
Wow, it’s already Nobel season! ChemBark and the Curious Wavefunction already have predictions. My 2010 Nobel predictions are here (and, of course, the Simpsons had their own last year). I don’t have too much to add to my 2010 predictions; instead, I’m going to put my chips all in and give just one prediction for each category.
Physics: Moerner, for single-molecule spectroscopy
Chemistry: Matyjaszewski, for polymer synthesis
Medicine: Djerassi, for The Pill
Peace: Twitter, for liberating Egypt
Literature: Twitter, for making literature shorter
Before the Spring meeting has even started? This is not cool.
It’s almost impossible to actually find out, but the deadline for submitting an abstract to the ACS Fall meeting in Denver has already passed. This is how I tried to find out:
First, I went to the ACS website, and clicked on the “Meetings” tab. The Fall 2011 meeting isn’t even listed there (see screenshot on the left). OK, that’s silly.
Next, I searched “deadline” from the ACS homepage and clicked on the top link, “Events & Deadlines.” That brings me to the Events & Deadlines page. Where the Denver meeting doesn’t even have a link. The Anaheim meeting’s link is live, but you can’t click on the Denver meeting. OK, maybe that means the deadline is so far away that you don’t need to worry about it. Wrong. Apparently, the Events & Deadlines page is only for past deadlines. Why have a deadlines page only for past deadlines?!? Wouldn’t future deadlines be a bit more helpful? I guess, the “Events & Deadlines” page is more a shrine to the deadlines you’ve already missed, not intended to help you meet future deadlines.
OK, let’s try going directly to the Denver meeting homepage. Not a lot of info there. But it turns out that, if you click on the symposia link, you’ll find that many of the deadlines have already passed!!! And the Spring meeting hasn’t even started yet! (There’s also this strange PDF I found somewhere on the ACS website; it list different deadlines.)
That really, really sucks. I feel like, with all the stupid emails I get from ACS every day, I’d have seen this deadline coming. I suppose it’s all my own fault: I should have been paying attention. But I figured that the deadline for the next meeting wouldn’t be before the current meeting starts. And I do blame the ACS website: I’ve been looking at the “meetings” tab for info on Denver, but it isn’t even there yet.
My suggestion: Why doesn’t ACS have one deadline for all the divisions, have it after the current meeting is finished, and actually announce that deadline on their webpage?
I am annoyed.
Some profs at UCSF have concerns about the radiation dose of backscatter scanners, specifically that all the energy is deposited in the skin instead of being spread throughout the entire body. So the dose is concentrated in time and volume. Basically, it sounds like TSA hasn’t done enough safety testing on these machines.
I would like to see a risk analysis of the probability of the screening causing cancer vs. the reduced threat of airline passengers dying from terrorism. The problem is that all these are very low probability events.
Anyway, this is my response to the entire fiasco: http://www.youtube.com/watch?v=wRpWnK6Rg3E
Hmmm. IVF but no The Pill. (Actually, I think that would have been a good split prize for Medicine. Would have been a big FU to the Vatican, though.)
Scotch tape graphene won the physics prize. Weird. Graphene is very new and basically unapplied as yet. But the Nobels are supposed to go to discoveries, and pulling graphene off of graphite with Scotch tape is a discovery.
And it was cross-coupling for chemistry (our #16 prediction): Heck, Negishi, and Suzuki. Oops, we mispredicted Sonogashira. I don’t know enough about organic reactions to know if this was the right move, but most folks are saying Negishi deserved it.
Congrats to all these well-deserving laureates! Hearts out to all those who were hoping for the prize this year, and didn’t get the call. (Especially Sonogashira, who must be pretty bummed right now…)
Read Paul’s liveblogging of the announcement.
Now just waiting for Twitter to win the Peace prize!
UPDATE: A guide to reporters by Chemjobber.
Some revealing letters of Francis Crick have been found—mostly to Maurice Wilkins—and they discuss Rosalind Franklin. Here are some of the excerpts that I found interesting. For instance, this letter from Wilkins to Watson and Crick after they proposed the double-helix model:
My dear Francis,
I gather you have got the coordinates of your model or some worked out. Do you think we could have a copy of what you have?
The crystalline data is clearing up nicely. To think that Rosie had all the 3D data for 9 months & wouldn’t fit a helix to it and there was I taking her word for it that the data was anti-helical. Christ.
We have redone a lot of the 3D more accurately on mouse & will need all the extra accuracy for dealing with some of the finer points.
Regards & to Odile too.
P.S. I think I have a flat.
But “Rosie” had been focusing on the A structure of DNA, which generated clearer crystal diffraction pattern images. Unfortunately for her, crystalline DNA-A wasn’t helical. Crick agreed when he eventually saw her data:
This is the first time I have had an opportunity for a detailed study of the picture of Structure A, and I must say I am glad I didn’t see it earlier, as it would have worried me considerably.
All in all, it sounds like Franklin was generally unfriendly to her colleagues (and competitors). Wilkins wrote to Crick of Franlkin’s leaving King’s College:
I hope the smoke of witchcraft will soon be getting out of our eyes.
It sounds like her colleagues didn’t like her too much. But there was friction from the beginning: Wilkins thought that Franklin was going to work for him … or at least they would work together on DNA … and Franklin had been told that she would work independently. What a mess.
I feel bad for Franklin having to deal with these sexist jerks. Watson and Crick were probably the most annoying, because they didn’t do any experiments; instead, they’d listen to Franklin (and others) present their data, then run off and make a model. Annoying. Intellectual thievery almost. (And Watson and Crick admit as much, referring to it as “burglary” in one of their letters.)
But on the other hand, it seems Franklin made some serious mistakes interpreting her data and was quite abrasive. No angels here. No devils (or witches?) either.
I suspect that if everyone had worked together and been friendly, Watson and Crick would have proposed the correct structure much earlier. Not only that, but I think Franklin would have been given more credit by the boys. But that’s just my speculation. I just know that I’d prefer to collaborate with folks than fight with them.
Phew. That was a long wait. Since 1995.
But the wait wasn’t really worth it. NRC released basically a gimungous table of data, and didn’t actually give departments rankings. I don’t have time to wade through all this data. Someone needs to tell me that my department(s) are better than Harvard.
To make things worse, their spreadsheet doesn’t work on MS Excel 2008 on Mac (only on 2004). Maybe I’ll update sometime if I can wade through the data. In the meantime, see if your school has posted its own analysis. (Berkeley has. It looks like Stanford is still in the process of manipulating the data to make themselves look awesome.)
Here are the top chemistry programs (ranked on research activity):
And programs containing the word “biophysic”:
So there. You can go make your own tables. I find this very confusing.
UPDATE: Not surprisingly, there are some serious errors being found in the piles and piles of numbers being released by the NRC ranking. And come to think of it, since when does Stanford chemistry have 50 faculty members??? Something is very wrong…
NRC should just list schools according to the US News and World Report rankings and keep their data hidden. jk.
This was on The Simpsons last night:
(the screenshot is from 1 min 22 sec on Hulu)
I may update my predictions to reflect the venerated opinions of cartoon writers.
By the way, seeing my PhD advisor and a member of my dissertation committee listed on The Simpsons feels really strange.
(My/our real predictions are here.)
In previous years, I’ve awarded Edsel-Nobels, which no one really cared about. Maybe this is the year I’ll make predictions for the actual Nobel. Paul at Chembark already started his predictions, and everyone else will be buzzing about it soon enough.
In no particular order (and without much forethought):
- Solar: Grätzel
- Super-resolution optical microscopy: Betzig, Hell, Zhuang, Hess
- Cloaking: Pendry
- Birth control: Djerassi
- Laser-induced fluorescence: Zare
- Inorganic: Gray, Lippard
- Single-molecule spectroscopy: Moerner, Orrit, Rigler, Xie
- Chaperonins and protein folding: Horwich, Hartl, Lindquist, Ellis
- DNA fingerprinting: Jefferys
- Electrochemistry: Bard, Nocera
- Polymer synthesis: Matyjaszewski, Wang
- NMR and membranes: McConnell
- Discovery of kinesin: Sheetz, Vale, Brady
- Nano: Whitesides
- Peace: Twitter
- Cross-coupling: Suzuki, Heck, Sonogashira
- Electron Transfer in DNA/Electrochemical DNA Damage Sensors: Barton, Giese, Schuster
- Pd-catalyzed Alkyne/Alkene Coupling and Atom-Economy: Trost
- Nuclear hormone receptors: Chambon, Evans, Jensen, O’Malley
- Two-photon microscopy: Webb, Denk, Strickler
- DNA microarrays: Brown
- NLO: Harris (as predicted by The Simpsons)
So there. The only one I’m confident about it Twitter.
Please feel free to add more in the comments. I will probably continue to update this…
UPDATE: Paul now has updated odds. Very impressive. He’s put a lot more thought into this than I. I’ve added cross-coupling to the list. Additions are in italics.
UPDATE: Can you name all the Chemistry Nobel winners?
UPDATE: Thompson has released their predictions.
Senators McCain and Coburn (who is a physician!) released a political report complaining about stupid stimulus projects. Now, it’s not surprising that Republicans are calling for cutting science funding and mocking silly-sounding science, so of course there are several science programs funded by stimulus money that this report calls out. Here are a couple:
“A Better Way to Freeze Rat DNA”
[S]cientists at the University of Missouri received stimulus funds “to develop freezing protocols for epididymal rat sperm which would allow reconstitution of genetics by using standard artificial insemination and in-vitro fertilization methods.” The scientists note that “[o]ver the last few years, our laboratory has generated ample amount of data related with optimal sperm handling.
“Reducing Menopausal Hot Flashes Through Yoga”
“Weather Predictions for Other Planets”
“In a time when jobs are hard to come by, several high school and college students have gotten federal funding to inspire their scientific curiosity.”
OK OK, I understand that some of these seem silly, but when Senators start mocking scientific programs without acknowledging the broader context, those Senators come across as ignorant and foolish. The rat DNA one is especially annoying: Hehe, it says sperm! What, do they get middle-schoolers to write this stuff?
We could make any scientific project sounds silly if we wanted: Scientists try to send light down a tiny glass tube; federal government spending billions to develop satellites that will see where your phone is; some nut is trying to make a horseless carriage.
The point of gov’t stimulus is to get money flowing and jumpstart the economy. Most economists acknowledge that Federal spending has a significant multiplier effect, so spending money on construction projects, scientific research, and infrastructure isn’t really that silly. I can understand how some would question how studying rat DNA could make any money flow back into the economy, but those people would be forgetting about scientific-supply companies like Nalgene (originally of Rochester NY), ThermoFisher (of Waltham MA), Invitrogen (of Carlsbad CA), Sigma-Aldrich (St. Louis MO), etc. I’m sure those and many other companies that employ Americans are very happy about stimulus money going to scientific research!
Still, I do agree that these spending projects should not be beyond reproach. I’m not convinced that science funding is always the most efficient approach to stimulating a national economy in the short run. We should check up on our stimulus funding and try to measure how well each project is benefitting American taxpayers. But what McCain and Coburn have done is lazy—and ignorant. Instead of mocking science because it involves sperm or yoga (or even both), step up and take a mature approach to critiquing our spending policies!