Small and Very Far Away

As Father Ted might have explained it to Dougal, this one is very small:



but that one is far away.


Mars (NASA)

And yet it is the distant planet and not the nearby atom that seems to excite the greatest interest in the public mind. I blame Carl Sagan. And bloody Brian Cox. And a dozen other popularisers of science (that git Simon Singh springs to mind) who have done such a fantastic job of bringing the solar system and the rest of the glimmering cosmos into our homes and into our heads. How come the same attention isn’t lavished on atoms and the wondrous things that can be made from them — molecules. I spend my life on molecules but I’m not sure other people are interested.

I was struck by the criminal inattention paid to molecules as I tried out Cmol, a nifty program that allows interactive display of their structures on the iPad (and the iPhone). As a professional structural biologist I make my living by figuring out what protein molecules look like and spend a lot of time looking at them. It seemed to me a no-brainer that someone clever would come up with a decent app to let me view my precious molecules on a glossy Apple tablet.

Well Helen Ginn is someone clever and her Cmol app is pretty damn good. It might need a couple of developmental tweaks (which she’s told me are in the works) but the program is already relatively powerful. I’d say it’s on the verge of being a serious professional tool. It certainly beats the only other contender, Molecules, into a cocked and poorly rendered hat.

In Cmol I can view structures that I’m currently working on or download any molecule that is available from the Protein DataBank (PDB), the free public depository of biomolecular structures (proteins, DNA and RNA). There are then a variety of ways that I can select and represent different portions of the structure. In the example below — a picture of the albumin protein found in your blood serum — I am showing the bonds between protein atoms as sticks coloured by atom-type: oxygens are red, nitrogens blue, carbons grey and sulphurs yellow; the atoms of the fatty acid molecules that albumin carts around your body are represented as coloured spheres using the same colour code. It’s a complex image but I hope you can get some sense of how it might be deciphered.

Human serum albumin on Cmol

The real success of Cmol is the way the program levers the interactive capabilities of the iPad. With one finger you can rotate the molecule, with two you can move it across the screen or zoom in. The view may be two-dimensional but the interaction — the hand-eye coordination — makes the encounter truly immersive. It is almost as good as using 3D goggles, which we wear in the lab for heavy-duty structural work.

Now that’s all very well for me and for other structural biologists but few outside our monkish, molecular discipline can access this lovely experience. For many biologists and biochemists, never mind the public at large, the idea of downloading and displaying a PDB file — the structure of a protein molecule, say — is about as conceivable as parsnips on Pluto. Despite some laudable efforts, such as the PDBwiki, the complexity of these structures and the abstruse coding of PDB files hides them from view.

For the general public, apart from the iconic image of the DNA double-helix, I suspect there is little grasp of the molecular intricacy that sustains life, and therefore no feel for the subject. The molecular question simply doesn’t arise and that is a disappointment to me. The starry universe out there is familiar to many people, but there is a whole universe inside every living thing on Earth that, sadly unknown to most, seethes with as much variety and wonder as the contents of the night sky.

Paradoxically, the big stuff that is so far away is much more familiar than the small stuff — the molecules — of which we are made.

But there’s no paradox. Sagan, Cox, Singh and their ilk have helped us to befriend the universe by revealing our connection to it. That supernova might be light years away but it was just such an explosion that created the elements that made us and our home planet. The fascination with the possibility of life on other worlds is fuelled by the dreadful excitement of how that would change our conception of ourselves.

And so it should be with molecules. Is it intrinsically more difficult to tell the story of the multitudinous building blocks of the living cells of our bodies? I don’t believe it; or don’t want to. After all, the connection is obvious, even if it is too often blindingly so. But I know from experience that making the connection to the reader is not easy. To tell a gripping molecular tale, you probably have to work at least as hard as Father Ted.

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54 Responses to Small and Very Far Away

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  2. cromercrox says:



    Well, what else did you expect at 3:49 am?

  3. cromercrox says:

    But srsly, what molecules need is a champion. So why not you? You’re doing it already.

  4. Steve Caplan says:

    Three cheers for the micro over the macro! While the universe at large is fascinating, for me I think the atomic level is far more interesting. Through a wonderful collaboration with an NMR spectroscopist and his lab, these past few years have opened up new horizons for me, and led to what I think are some of our most interesting and important findings. After “we” had solved the structure of the protein domain we were working on, I sat for hours and hours playing with the 3D structure on one of the computer programs that opens PDB files, trying to figure out what all the various functions did, and enjoying every minute. I can definitely understand what draws researchers to structural biology.

    • Stephen says:

      Lucky you, Steve! However, like you (and despite my injured tone) I like the macro as much as the micro.

      But would you have had the know-how or the inclination to look at a pdb file if you hadn’t teamed up with your NMR spectroscopist friend?

  5. steffi suhr says:

    But Stepen – and I hate sounding like I’m promoting the project I work for (well, not really) – if you ask me, the molecular world is about to move very much into the foreground with XFEL facilities popping up around the world and the possibilities and ways of imaging the buggers increasing exponentially… so don’t despair, your time will come…

    • Stephen says:

      Why are you hesitant to promote such an amazing project? For shame! (And I did catch sight of those Nature papers last week. Just haven’t yet had a chance to read them properly.)

      And I’m not really in despair. Adam Rutherford has a new series — Genome — coming soon to BBC. I have high hopes for that.

      • cromercrox says:

        Actually, I pimped this post to Adam …

        • Stephen says:

          Thanks Henry. Actually, the post was in part inspired by a chat I had with Adam R recently in which we bemoaned the latitude offered to mathematicians and physicists to put across their science on TV. Maybe that was unfair – but I have the feeling that (as discussed with Richard below), the difference is due to a lack of useful reference points for the uninitiated. Those blasted molecules are so damn small that no-one has any personal experience of them. But of course, it is a matter of creating an imaginative connection.

  6. rpg says:

    And don’t forget the Large Hardon Collider.

    I think part of the problem is that people can grasp the concept of space and planets—science fiction has been on about for 100 years and more. But atoms… they don’t really exist anyway. You can’t see them. You can’t ‘see’ proteins—that’s why we draw cartoons.

    There’s no feel for molecular intricacy because there’s nothing to relate it to. An atom doesn’t look like that ball—it looks like nothing at all (albeit moving very very fast)—and though I like mucking around with protein structures as much as Stephen, I’m under no illusion they are anything other than convenient models. Proteins and DNA aren’t made up of balls or ribbons or sticks or anything that makes any sort of intuitive sense.

    • Chris says:

      I think RPG is right in what he said with regards to people finding it easier to look outwards than inwards. As soon as we get to the micro scale, as beautiful as it is, it requires more money and better technology. What is easily visible to the naked eye and then through cheap optical enhancement via binocular and telescope is far more accessible to the everyday public, than a microscope that can show you molecular structure and DNA proteins.

      I love both the micro and macro and I wouldn’t say that people are un-aware of atom’s, molecules, dna. From what I remember of school biology and chemistry covered this pretty well, well enough to the point that most would have some idea of what you are talking about. More so than those who still don’t understand that our sun is a just another star, or that we live in a galaxy of billions of stars and that’s one of billions of galaxies. some of which you can point out and observe yourself.

      One would almost be correct in saying that the macro world is far more accessible. This doesn’t mean it’s any less important. One of the side effects of this is that people who learn about the macro, get led down the path of learning the micro elements that made us what we are….so they are one and the same lol.

      • Stephen says:

        Chris, I think that’s what we call a circular argument — though in this case it’s really quite effective! 😉

        I agree that most people have a passing acquaintance with the existence of atoms. But beyond DNA, what molecules might people have heard of? DO they know the structure of any common drugs (aspirin? ibuprofen?) or even one protein? I suspect most have no idea that drugs often act by sticking to proteins. There is work to be done.

  7. stephenemoss says:

    Stephen – Molecular structures are endlessly fascinating, but perhaps more difficult to explain to a lay audience than the cosmos. We can all look at a computer-generated rendering of the solar system and even a young child can figure out what’s going on, but the molecular structure you depict – with all the balls and sticks – is not so readily understood. But I agree with cromercrox, there can be no better person than you to champion the cause of the atomic world. Why not submit a programme outline to the BBC?

  8. Chris Hainey says:

    That would be an ecumenical matter

  9. Stephen says:

    @RIchard – I know what you mean about the lack of a mental hinterland. That’s why I’ve always struggled to talk about this stuff in pubs. And it was an issue for me during the I’m a scientist competition because it was hard to relate the science that I do to the kids. But as you and I and Steve Caplan and Stephen Moss above have discovered – there is endless fascination to be had with these blessed molecule thingys.

    @Stephen – Nice of you to say so — I’m certainly going to try to write more on the subject. As for TV, I’d settle for an episode of Father Ted (or maybe The IT Crowd) devoted to molecules…

  10. peeceedee says:

    This brings to mind David Phillips talking about the structure and mechansim of lysozyme on an Open University TV programme. So long ago that I think it was in black and white (showing my age there on both counts – OU-TV / B&W). I also was given for safe keeping by an early-retiring enzyomology lecturer a canister of film, and a VHS recording of the same, which is supposedly Max Perutz’s early animation of oxygen binding to h(a)emaglobin. I have not confirmed this but I remember being in awe of it when shown by MF himself at a lecture he gave when I was a student in Oxford. People really should be interested in how antibiotics work, why tamiflu might not save us from an evolving avian flu, how the DNA in chromosome ends might not be a double helix… Looking forward to seeing Steve present the Lennard-Jones potential and the hydrophobic effect on prime-time!

  11. Rory J says:

    Perhaps instead of attacking those who have brought cosmology to the masses you should think of how to make molecular physics exciting and take it into the mainstream. I am currently being lectured in atomic and molecular physics by Jason Crain at Edinburgh and his enthusiasm really rubs off. It is a fascinating subject area and the public could do with more exposure to it. I reckon the lay reader/viewer is often grabbed by strange ideas out of direct reach. For example, every time I have explained the basics of quantum mechanics (very generally) to a friend they have been very intrigued.

    What Cox et al. have done for cosmology is truly fantastic and I believe it would be equally fantastic to do the same for condensed matter. Get thee to the BBC.

  12. Stephen says:

    @peeceedee – Snap. I never had the pleasure of being lectured by Perutz but it was my introduction to his work on haemoglobin that sold me on structural biology.

    The hydrophobic effect on prime time, eh? Easy. I’ll need cats. Lots of cats.

    @Rory J – I’m sure you know my ‘attack’ was tongue-in-cheek. And of course it was only ever motivated by envy at the collective communicative talents of Cox, Singh, Sagan etc. 😉 I agree totally that the public probably has an appetite for weird ideas — including the strange molecular components of life and their idiosyncratic interactions. My aim (shared with others no doubt) will be to sell them a bit harder.

  13. Much as I love space, I am always fascinated by the stuff, molecules, atoms, etc that makes up that space.
    Here in the UK, the bbc has had quite a few television programs detailing atoms and molecules. Albeit on BBC4 a satellite only channel, and not on prime time.
    Molecules do need a better champion, but unfortunately, the people who watch such science programs on tv, want something pretty to look at, or they switch off.
    I’m currently studying physics and want to complete modules in quantum mechanics. I have studied quite a bit of the astro side of physics, if you do that, then wonders of the solar system, for example, is the picture ABC books, that teach kids the alphabet (Yes I know its intention, and it was a good one, however it was too dumbed down in my honest opinion). With molecules and atoms, you have to have a more educated viewer, and tv stations don’t like doing that, certainly not British ones. They don’t want to “patronise” people, or more aptly to make people realise they are actually uneducated, which is why the schedules are full of trash programming an amoeba could probably understand.
    I wish television would be more educated, I think stations are so afraid of political correctness and ratings, they forget that the television could be used as a potential learning tool, attracting more people to science, or similar career pathways.
    Great post.

    • Stephen says:

      Many interesting points Rhiannon – many of which came up at a panel discussion recently at the Free Word Centre, which involved Adam Rutherford, Marcus du Sautoy, Ben Goldacre and Liz Bonnin (actually – there’s a Little Atoms podcast of it – the Free Word special event – 30-1-11).

      I won’t rehearse the whole thing here. I share some of your frustrations but an important point to bear in mind is that ‘the public’ is a very heterogenous entity and contains many subgroups who want different things. At present, TV doesn’t do a bad job of catering to that – the more popular stuff is on BBC1/2 while perhaps more challenging material (e.g. Jim Al-Khalili’s “Atom” series) can be found on BBC4.

      I agree there’s a tendency to fill the screen with pretty pictures – perhaps that’s needed because there are so many competing demands on our attention now (twitter, facebook, youtube, lolcats…). I was struck when watching “The Ascent of Man” — made in the ’70s — by how much time Jacob Bronowski was given to stand and talk to camera. He was still mesmerising though I doubt he’d be given that freedom now.

      • John the Plumber says:

        O.K. forget the rump steak – just start at a pretty rump. – T.V always aims at the lowest common denominator – probably me.

        • John the Plumber says:

          Is it that we are all famliar with the language of the galactic large, having learnt from Jules Verne, Dan Dare and Luke Skywalker. Knowing the language, then we are easilly sold the dreams. With little experience of the language of microbiology has the average punter – yours truly – nowhere to hang his hat.

          My favourite door into the micro is the orange dust specks found scattered on spiders webs. Touch the web and the dust (baby spiders) runs home. I find quite awesome that each dust speck has eight little legs and a brain that says panic – run off home – and knows the way home. To delve into the molecules of protein sugar and amino acid – each molecule a couple of hundred atoms long – into the cell srtucture – DNA RNA – enzymes hormones – what collosal number of atoms make this incredibly complex speck of dust?

  14. Jamie says:

    It’s not just molecular structure that is hard to appreciate, it’s also the dynamics. All of my work is computer simulation, so I make a lot of movies of atoms. You wouldn’t believe how much the individual atoms wobble about, even at room temperature.

  15. Stephen says:

    Don’t get me started on dynamics – a crystallographer’s nightmare since this washes away the structure from our electron density maps…!

    Seriously though Jamie, it’s a very important point about macromolecular structure. I’ll make sure to mention it to the producer… 😉

    • Jamie says:

      Ah, then you know exactly how much the atoms wobble! But I was surprised the first time I made a movie of a simulation.

      It’s also an awesome teaching tool. I used something similar to Cmol to show molecular movies during an ‘intro to simulation’ course I was teaching. As I turned down the temperature, the disordered liquid crystallised into perfect close-packed order, and the students’ faces lit up 🙂

      • Stephen says:

        Movies or animation can be a very powerful tool. I use them in presentations — particularly in cases where we have the structure of a protein in two different conformations, which allows you to calculate the ‘morph’. This can reveal features that you just don’t notice by flicking back and forth between 2 images.

  16. astrologerthe says:

    Perhaps this might be of interest

  17. ricardipus says:

    ^what RPG said. We can see planets but we can’t see atoms. But further than that, in order to “see”, or at least get a feel for, atoms and molecules, you need a lot of training and some pretty fancy and expensive equipment. If you’re interested in planets (and I know that you know this well, Stephen), and you want to see them better, you can use binoculars. Spend a bit more money and you can buy a telescope. Spend more and you can buy a *better* telescope. All without any need for higher education. There’s no real parallel for looking at atom-sized things, although you can certainly go in that direction by buying microscopes.

    • Stephen says:

      For sure – the X-ray (or NMR) gear is still a bit pricey. But not only that, because many of the tools that we use to probe molecular structure are indirect – running a protein through a gel for example. It makes for a rather schematic outcome and one that you can only really ‘see’ if you have a mental image of what is happening in the analytical process. But the challenge is to imagine a way out of that maze of assumptions so that we can invite the uninitiated in…

  18. Adam Rutherford says:

    yep, Stephen and I did chat about this briefly before the call of beer was heard. Here are some thoughts:

    From a director’s point of view, after the idea itself, the next most important question you have to ask is “what do I show?” Part of the language of TV is that the audience have expectations about what they will be looking at (which evolve, and as I mentioned to Stephen, the Ascent of Man would not be filmed like that today; that’s not a statement about dumbing down or slipping standards, just that tastes change). Films have a pace which is determined in the edit, and the speed of cuts is determined by the mood of what you’re trying to say. When doing interviews or talking heads, there are few occasions when you can simply hold the frame on someone’s face for more than 30 seconds (unless they are extraordinarily attractive), so we need cut-away shots, and that means close ups, or tea drinking or looking thoughtful etc. So:

    Problem 1: What do you show? In my next series, Genome, we’ve had a nightmare with this question because, as you know, almost all biology is molecular, which means minute quantities of colourless liquids. Non-natural history biology is a fucker to film. Attenborough has animals to look at, Brian has planets, Alice Roberts has bones. Jim’s programmes are about things so abstract, they can show anything. I’ve got colourless liquids.

    There really isn’t that much biology on telly. There is a tonne of natural history, which whilst being rooted in evolution, doesn’t tend to reflect the actual workings of the majority of the science that occurs in the world, i.e. molecular biology. My meagre contribution to the BBC output is a small attempt to correct that.

    Problem 2: This is specific to Genome, and genetics in general. I think that people in general come with a whole load of preconceptions about biology and genes n stuff, because these are familiar terms, and because genes are things that we all have etc. The fact that geneticists don’t know what most of the genome is doing means that a lot of the process of making this film has been correcting fallacies (the final film won’t be like that, as that makes for a different type of film). In Physics and Astronomy, most of the concepts are so abstract or impressive that there’s a wow factor, which means you can get away with less explanation. But, in my experience, talk about genetics, and everyone’s got an opinion. That means the battles are different. Filming Genome has been one of the hardest intellectual challenges I’ve faced. Trying to get complex ideas as simple as possible and as visual as possible has been exhausting. We explained recombination in one Ep1 and Sanger sequencing in Ep2 with playing cards, which I think works, even if it is grossly simplified.

    So, you can rely on the beautiful 3D animations of someone like Drew Berry, but tonally, from a story telling pov that conveys a very specific look and feel, which will probably not gel with the style of the programme (which, a LOT of thought goes into; which should be invisible). Any suggestions are welcome.

    • Stephen says:

      Many thanks Adam – a really insightful comment. (For anyone who doesn’t know Drew Berry’s work, try here — he’s a bit of a legend in molecular animation.)

      You’ve obviously thought a lot more about these issues than most. I agree that one would certainly have to mix things up. Even I couldn’t watch a molecular animation for more than a few minutes at a time. As with any film, the most important element is the story (The Phantom Menance might look fantastic but it’s still shite).

      The story is obviously influenced by what is known and what one can show (which is the lesser limitation these days) but remains the key element. To engage the viewer I guess any molecular narrative needs to start with the viewer — an interesting bodily function or the progress of a disease. But a historical progression could also be a good way to go; there were plenty of rivalries in the development of molecular and structural biology as I recall.

      Plenty of scope for experimentation I would have thought… will definitely reflect some more on this.

  19. Matt says:

    Brilliant post, Stephen.

    I agree with Adam in that the molecular is difficult to film/represent on screen. However, I don’t know that this is the biggest problem with talking the language of molecules.

    I think that one aspect that chemistry, in general, is missing is an overarching humanities-based theme. In astronomy and particle physics, along with the stated research, there is the implied relationship with the question, “Where do we come from?” The search for distant planets and solar systems screams, “Are we alone in this world?” The LHC, which would seem to have the same issues as the molecular world, is championed for its search for the physics that led the universe into existence. The physics-plugging crew have done a great job making us notice this relationship. Biology also takes advantage of its natural balance with issues of the humanities. Evolution (everything leads back to evolution, right) IS the question of how did we come to this place as we are.

    Molecular sciences in general, I think, have really failed to take this approach. Part of the problem is that the science is tremendously broad. Most people will view physics as dealing with astronomy and particles, and most would view biology as being evolution. The fields have been branded. Not so for the molecular world. Now, we could go the way of physics and biology and tout the search for the chemical origins of life. This I think could be part of a solution. But, I think it is an artifice. As a chemist, I see those working in our field as artisans. Some are artists, making the most beautifully intricate molecules or protein structures just because they can. Others make molecules to be functional. And there are those of us who see both beauty and function in what we do. We need to find new ways to convince people to be engaged/immersed/not-sure-of-the-right-phrase-here in the beauty and artistry of what we do.

    Of course, this is just one way at it, and likely there are better.
    -Just a humble chemist’s opinion

  20. Stephen says:

    Thanks Matt – very interesting analysis. I agree there’s a deficit in the presentation of the molecular science to a wider audience but surely the opportunities for connecting with human life are legion? Evolution – at bottom – is a molecular process. And one of the most amazing features of our genetics is the ongoing repair work that happens every second to keep our genomes intact.

    As for chemists, with all these house-building and home improvement shows on the telly, surely there is an appetite for construction and a way to present a compelling story of chemical synthesis? We all take pills from time to time – how are they made?

    I wonder if we have been too inhibited by the jargon that comes with chemistry and biochemistry? As you say, perhaps we’re just a bit behind the curve compared to physicists and mathematicians.

  21. Helen says:

    Really? Wow. I’m not sure I agree that the molecular level is intrinsically less interesting than cosmology. As someone who’s far more excited by the mini than the massive (and no I’m not a structural biologist!), I feel that ‘what are we made of and why’ is every bit as fascinating and humanity-defining a question as any the cosmos can come up with. I suspect that they’ve thus far just had the monopoly on dramatic imagery, but with advances in imaging and visualization, this needn’t be true anymore. Get on to those producers Stephen!

    • Stephen says:

      I totally agree, Helen. I didn’t intend to suggest the micro was in any way less interesting – just that it had received less attention. I’ll call the producer… 😉

  22. Cath@VWXYNot? says:

    Stephen, when you get your BBC programme, I INSIST that the small / far away joke be used within the first two minutes.

  23. Helen says:

    I think I stumbled over my wording! I probably meant something like ‘harder to present as an interesting narrative’ which I definitely don’t think it is. Let us know the broadcast date…

    • Stephen says:

      Ah – well I’m not sure I agree entirely with that. I believe it can be done but suspect there is some difficulty. Otherwise why the imbalance in coverage – not just on TV, but in books and other media? Now that I think if it, I wonder what is the molecular content of a magazine like New Scientist?

      But maybe I’m neglecting whole swathes of work. Very happy to be corrected.

  24. Bob Arthur says:

    Prof Cox gave an excellent insight in his LHC Ted talk, demonstrating the extremes that our scientists have reached; IIRC he stated that if the Universe were the size of Montana, Montana would be the size of the particles being slammed together in the LHC, yet we as a species have a not inconsiderable (though [thankfully?] far from complete) understanding of processes at both ends of that scale.

    It’s utterly mind boggling to try to comprehend these scales, but the rewards for trying are so beautiful that it’s no wonder the good professor goes around with a semi-permanent grin on his face 😉

    • Bob Arthur says:

      Forgot to mention that I am also fascinated by the smaller end of the scale, and as a pure maths graduate have been so inspired by what I’ve seen, heard and read about the work at the LHC that I’ve embarked on a (possibly futile) challenge: teach myself enough physics to properly appreciate what a Higgs boson really is, before the LHC finds one.

      Whether or not I win the “race”, I’m thoroughly enjoying the work so far.

      • Stephen says:

        Thanks for your comment Bob – sorry for not responding sooner. I’m not quite sure I follow the Montana metaphor – I guess I’ll have to track down that TED talk.

        Best of luck with your maths challenge – that’s quite a goal you’ve set yourself.

        • Bob Arthur says:

          Oops! Turns out it was Monterey, not Montana. My bad. Essentially he was saying that that the step down in size from that of the observable universe to that of Monterey is roughly equivalent to the step down from the size of Monterey to that of some of the fundamental particles in the Standard Model; so the fact that we’ve discovered any of these at all is amazing in and of itself.

  25. peeceedee says:

    Just got this in my twitter timeline:

    RT @MarcusduSautoy: Off to Imperial College to do some structural biology with Stephen Matthews. Even in biology shape matters. #bbccode

    Protein NMR on TV later this year?

    • Stephen says:

      Sorry to disappoint but I understand that Steve — who’s been known to do a bit of crystallography these days — is planning to show off the X-ray & crystallisation kit. I think symmetry is what the good professor is after…

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