World's Fair

A next step beyond believing in it (or any well established theory — e.g. Evolution) is to ask: do you like it? (and here I’m talking about the real thing, we’ll deal with the television show later).

Einstein didn’t like it. So much so he made his self-proclaimed “biggest mistake” trying to work around it.

Over on Oscillator, Christina quotes a great line from the biography of Barbara McClintock:

“Good science cannot proceed without a deep emotional investment on the part of the scientist. It is that emotional investment that provides the motivating force for the endless hours of intense, often grueling labor.”

So, does the way you approach the science change depending on whether you like (love, hate) the theory or model on which you are working?

In my own work in biophysics, I thought of a couple of examples:

I really like the theory that changes in heat capacity (delta-Cp) during the association of different biological molecules can be directly related to the surface area change involved in the reaction, and particularly the non-polar surface area of interaction. This theory says that if you measure the delta-Cp, you can predict the surface area of interaction between two proteins, or between a protein and a piece of DNA that it binds to. And vice-versa –measure the interaction surface and you can directly predict the heat capacity. I like this theory because it is one of the few times that it has seemed that one might have a simple and direct way to relate a thermodynamic quantity to a bio-molecular quantity. Yet, my lab’s own work, along with the work of many other laboratories, have shown that this correlation doesn’t really hold, especially for protein-DNA interactions. So I really like it, but sadly I have to tell it that we cannot be friends anymore. (Note: many labs still “believe” it — this is a very active research area in biological physics.)

Another example: I don’t particularly like the two-state theory of protein folding-unfolding. This basically states that when a protein folds into its native state, it is essentially an all or nothing process — that there are few or no intermediates, it just jumps from a wiggly piece of spaghetti into the complex structure you see in textbooks. We know the situation is more complex for most larger proteins, but many smaller proteins follow this model, at least thermodynamically, very very well. My lab has also done work in this area, and every experiment we do supports the two-state theory for the particular proteins we work with. I don’t hate the two-state model, I just think it sounds too much like magic or like the double-slit experiment — it just doesn’t seem mechanically sound, yet experiments keep verifying it.

These are only two examples, but it’s interesting to think about a multi-dimensional map of the science we work on with questions like: what do you believe in? what to you know? what do you like? what do you dislike? And how does this all effect your work?

Comments

  1. #1 Matthew Ptman
    January 16, 2010

    This may be the most important self analytical test for scientists. We are all inspired by and imprisoned by our beliefs in particular theories. The inspiration can allow us to spend those hours mentioned above, but the imprisonment can lock us in a cage of lonely misunderstanding. The truly great scientist is most inspired not by a particular theory, but by discoveries, rather they are the original idea or not. I do know a lot of people like this. An example is the LHC, where most physicists I know say they will be even more pleased if the Higgs is not discovered, even though the theory they work on predicts it. That happiness comes with the humility that there is more to be explored and discovered.

  2. #2 Grant
    January 16, 2010

    As you say, sound introspection is a critical part of science, or any sound reasoning.

    I’m interested in protein-DNA interactions myself. Naïvely (i.e. with a mere few seconds thinking about it!), I’d have thought that a relationship between changes in heat capacity and interaction surface area would hold better when both interacting molecular are relatively rigid—? (I’m thinking of the energy cost of deformation as a confounding factor, DNA isn’t terribly rigid, etc.)

    (Just idle Sunday thoughts procrastinating from what I really ought to be doing…)

  3. #3 Grant
    January 16, 2010

    ‘molecules’ for ‘molecular’. Sigh.

  4. #4 Rosie Redfield
    January 16, 2010

    Actually DNA is quite rigid on the size scale of single proteins – it has a persistence length of about 50 nm, and even modest bending needs quite a few strong DNA-protein interactions.

  5. #5 Grant
    January 16, 2010

    Rosie, I’m thinking on a smaller scale, local twisting, local roll, etc. Ditto for proteins. Both the interaction surface and the local structures change on interacting.

    (Maybe that’s a smaller scale than Vince is considering, in which my comment might be moot.)

  6. #6 Vince LiCata
    January 18, 2010

    Hi Grant and Rosie,

    A lot of the current work is on movement and heat capacity is on two different scales: 1) rigid body association versus induced fit, which seems to be what Grant is mostly talking about: here there are a few labs that say that when you do not find a delta-Cp—surface area correlation, it is because you have not correctly calculated surface area because the induced fit is causing you to over or underestimate it, or because all the surface area information is not well reflected in available crystal structures due to missing or poorly resolved areas of structural data. 2) A theory gaining momentum more recently is that delta-Cp is actually more correlated to changes in micro-vibrational freedom at the molecular interfaces (a much smaller scale effect). A problem, from my perspective, with #1 is that it mostly just says the correlation is right and your measurement was wrong. #2 is still being formulated, and a few labs are working to get good empirical backing for it.

  7. #7 Jim Thomerson
    January 23, 2010

    Finding things you expect gives a certain warm feeling, but real excitement comes with discovering things you did not expect.

  8. #8 theresnoonehere
    January 31, 2010

    A long time ago when I was in my undergrad, I first started learning about quantum mechanics and general relativity. My first reaction to both of them was very different. Both theories hit my belief-o-meter just fine, but although I liked the mathematics used in QM, I never really liked the theory itself. Unfortunately, to me (and this is entirely personal taste – therefore, an opinion), QM has always seemed like a patch-job that just never fit together like GR managed to.

    What was really frustrating was that I wanted to like QM, because, well, I find the whole topic just so damn interesting, but it always ended up like one of those relationships that never quite meshes, no matter how much the two of you try.

    When I got into grad school and started with more GR and also quantum field theory, the same original feelings never went away. This influenced my research and anything in the land of high-energy physics just managed to disappear entirely. Ultimately, it meant that I ended up going into mathematics and the physics side of my life faded away. OTOH, it also ended up sparking a ten-year fascination with knots, topology, difference and differential equations, and their impact on biological systems. Go figure :-)

  9. #9 Buffoon
    February 5, 2010

    As a self-contained explanation of the origin of the universe? No, I hate it.

    As a starting point of our local universe in a larger undefined situation? Love it.

  10. #10 cristine837
    February 8, 2010

    I haven’t watch these types of funnier shows before..Every thing you have watched in the TV series is similar i mean mostly all series have a same story but it is not like that..This is a great intelligent sitcom.Even I recommend it to everyone.I have a site where you can easily watch The Big Bang Theory episodes to just visiting given link..Even this site has also a fine picture gallery..and the site is http://thebigbangtheory.edogo.com/
    Have fun Guys!!!!

  11. #11 drew pierce
    September 19, 2010

    Its my favorite TV show and I like to watch hilarious shows and this show contain all the ingredients to make it more interesting.

  12. #12 adsense hack
    February 5, 2011

    What was really frustrating was that I wanted to like QM, because, well, I find the whole topic just so damn interesting, but it always ended up like one of those relationships that never quite meshes, no matter how much the two of you try.

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