And if you can come up with more difficult ways to try to explain science – we could start some other awesome contests. Explain your Ph.D. in poetry. Design a dress or suit that explains your Ph.D. Knit your Ph.D. Origami your Ph.D. Puppet Theatre Your Ph.D. Stop-Motion Animate Your Ph.D. Ballon Animalize Your Ph.D. But until then…

Dance! Dance! Dance!

This performance art show is a unique blend of art and science – it conveys some of its information in some unusual and compelling ways: the costumes, the set, and all the props are made of discarded plastic – each costume is made of 100-300 plastic bags, one costume is made of about 300 plastic bottle caps, there’s a dragon made of about 3000 bags, and a tree made of plastic – yet we’re reminded that all the plastic on stage during the show only represents the amount of plastic Americans discard about every 100 milliseconds. One scene in the show personifies the Great Pacific Garbage Patch in a whirling dance…one scene involves a shaman ecstatically scrawling the structures of polyethylene, polypropylene, and polystyrene on a plastic screen…one scene depicts the flow of plastic through a bird’s body. Each scene in the show explores a different aspect of our relationship with plastic and mixes science with mysticism, animal instincts with consumerism, creation myths with post-apocalyptic evolution and the “new nature”. If we taught more science this way (just a little more of it, certainly not all of it) – we might change a lot of people’s attitude toward science, in the way that this whole show hopefully also changes its audience’s attitudes toward plastic.

The New Orleans Fringe Fest has nearly 80 total shows (30 juried plus 47 “Bring Your Own Venue” shows) and it likes to feature very oddball stuff (one of its own tag lines is “wild, weird, fresh original theater of all types”). Since almost the whole cast is from Baton Rouge, we (like many of the fringe shows) are shelling out a lot of our own money to finance staying in New Orleans for the duration of the festival and mounting the show (fringe fest shows around the world are all a labor of love – even after ticket sales, a fringe show typically costs the performers lots of money – even the famous Edinburgh Fringe Fest strongly reminds participants of this in their guidelines). To try to cover some of our expenses we’ve started a Kickstarter campaign – so if you are so inclined, please visit our SACRED WASTE Kickstarter page (only active for the next 3 weeks) and help us ease the financial burden of taking the show to the Fringe Festival.

(Photo by Max Trombly, showing the creator of the show, Bonny McDonald (left), and Jen LeBlanc (right).)

The study deals with quite a lot of rather detailed thermodynamics of DNA binding (free energy, enthalpy, entropy, heat capacity…) and looks for correlations between such thermodynamic measurements of binding and the functional behavior of a couple of similar DNA polymerases. DNA polymerases are the enzymes that replicate DNA. The strong correlation that we found was between entropy (ΔH) of binding and onset of functional replication activity. Or to state it another way:

As the temperature increases, the enthalpy of binding of the polymerases to DNA goes from positive (unfavorable = heat input required) to negative (favorable = heat released). Right at the temperature where the binding enthalpy switches from positive to negative, the replication activity of the polymerase effectively switches “on”. So, the polymerases bind to DNA quite fine at lower temperatures, but are effectively “shut off” functionally until after the temperature where the ΔH of binding switches from positive to negative. And this temperature is not the same for each polymerase – it is specific to the particular polymerase. This correlation is illustrated in the figure below:

So what does this mean?  We believe it means that the simple binding of an enzyme to DNA is not sufficient for that enzyme to carry out its catalytic function on the DNA, and that the balance of different types of binding energy (enthalpy versus entropy) may dictate when a bound enzyme is turned “off” versus turned “on”.  While this is the only set of DNA binding proteins where applicable overlapping binding and activity data have been compared, we hypothesize that this correlation may hold for many DNA-binding enzymes.

It is also interesting because a few other studies in some very different systems have also recently been finding that for some processes, following the enthalpy is much more important than following the free energy (ΔG) (the free energy is what biochemists “follow” for mechanistic clues 99% of the time).  We mention other examples in the paper, but a particularly interesting one is the finding that the efficacy of HIV protease inhibitors also tracks with enthalpy of binding, and not with the free energy of binding (Freire, Drug Discovery Today 13:19 (2008)).

So why does switching from positive to negative enthalpy effectively switch “on” the protein activity?  Good question, we’d love to know the answer.  We postulate a few possibilities in the paper – one of which being that maybe the catalytic reactions just need a little heat, and a negative binding enthalpy will release a little heat.

The data in our paper also speak to a longstanding concept in extremophile research: something called the concept of “corresponding states”.  This concept states that a protein from a thermophile (a high temperature organism) will function “normally” only at high temperatures.  According to the corresponding states theory, our thermophilic polymerase should not bind DNA at all at lower temperatures, and should not show “normal” nucleotide activity until quite high temperatures.  Our data show that neither of these “corresponding states” predictions is true, and suggest that the situation is somewhat more complicated than “heat up the protein and then it will behave like the lower temperature version of the protein”.  The corresponding states theory has been challenged by a few different studies over the past decade, but it turns out that for a variety of reasons it is actually difficult to get appropriate data to properly refine it.  It is one of those theories that must wait a little longer for experimental technology to catch up to it for it to be appropriately tested and refined.

As always, if would like a copy of the paper and you cannot get it free from the link above or your library, I will send you one.

Here is my understanding of how we are “supposed” to do it:  We walk into the astronomy summer camp group that we will be showing them to, and immediately give them a quiz on the content in the videos, THEN we show them the videos, then we give them the same exact quiz again.  For control groups, we are apparently supposed to swap out the videos for a standard talk that has the same content.  You then look at the gain from Test 1 to Test 2 for the 2 different groups.  I first heard about this “Test Them, Teach Them, then Test Them Again” strategy for education assessment only about a year and a half ago, or so – but I’ve been told that IT IS THE ABSOLUTE NORM.

When I first heard about this assessment strategy I went: huh?  When I describe the strategy to students who are working with me, they go: huh?  When I describe it to other biochemists, they go: huh?  But any education person I talk to says that this is the way it is done.  Clearly, however, the pre-test primes the audience for the information.  It just seems so odd that no-one has come up with a widely acceptable alternative to this pre-test/post-test approach.

I’ve been wondering if maybe this strategy is a way to avoid having to have large test pools.  It just seems that if you only gave tests after the videos, and your audience numbers were small, of course audience member variations in “prior knowledge” could totally skew the results.  But what if you test, say 150 kids after the videos and 150 kids after the “standard lecture” (no pre-test for either of them) – if you had randomly sorted the 300 into their 2 pools it just seems like any “prior-knowledge bias” of some audience members would be overwhelmed by the numbers.  If your difference between groups were small, you might have to worry – but if the difference is large and statistical, it seems it would be difficult to argue that too many people in one group had too much prior knowledge.

It just seems like either strategy has drawbacks, but for some reason educational assessment researchers have decided that priming people with which answers to look for (by giving them the pre-test) is okay, while risking the probability that some people will have prior knowledge is not okay. Every education researcher I have talked to this about has acknowledge that this is, in fact, one of the choices being made in designing assessment studies this way, but that everybody does it and everybody expects it.

Anyway, next week we are going to start doing some assessment, and I feel confident that we will be learning a lot more about assessment itself as we proceed.

Degradational is when the science or the scientists are depicted as evil or as the cause of problems – you know the type: Jurassic Park and such. Inspirational (which might need some subcategories) – is when there is science in a piece of art, but the science is just there as set decoration, or because a main character is a scientist, or because some minor plot points hinge on some sciencey-sounding mumbo-jumbo-speak that (supposedly) makes the audience feel that serious science has saved the day (or at least moved the plot forward incrementally). Inspirational SciArt is the bulk of what is out there – pushing 98% in my opinion (mostly because of a significant decrease in degradational SciArt, which used to occupy a sizable portion of what was out there).

In the minority, however, is informational SciArt. I am not talking about documentaries here – or Nova specials – they are clearly informational and have a lot of artistry to them, but in my opinion are in a different genre than SciArt. So what is informational SciArt: it is a play or a movie that stands on its own in terms of plot or character but at the same time has a LOT of real and accurate science in it (or culture of science – how scientists act and such). Can you think of many of these? Not many out there, eh. And many of the ones that are out there are medically oriented (because people can relate better to something medical – as opposed to say, something about neutrinos or identifying a new species of frog).  Movies like Contagion or Contact or Gorillas in the Mist or Awakenings, or October Sky, or And the Band Played On, or the classic 2001 – these are at least moving in the direction of informational SciArt – and they are definitely more than inspirational.  What sets these movies apart from “inspirational” ones?  The fact that you can walk away from these movies and actually have learned some real science (or science culture) – even among these, however, the amount of science information is wildly variant (and mostly on the lower side).  Think of “A Beautiful Mind” – is it informational because there is a 30 second recap of one of John Nash’s therories?  Or is it really more suitable for the “inspirational” category?

Why bring this up?  I feel that the informational SciArt category has long been in the minority and largely because the commercial side of the SciArt couple is afraid that audiences don’t want to see things with lots of real information in them – movies or plays.  Yet in day to day conversations, with scientists and non-scientists alike – I continually hear people say that they really enjoy learning new science through movies or television shows or even plays (although the fraction of informational SciArt plays is even lower than that for movies and television).  So why not trust that people want to pack some of their entertainment with science and let’s start seeing more informational SciArt – or at least information heavy SciArt.  When you see something labelled as SciArt – something funded by the Sloan Foundation or something in the Imagine Science Film Festival – both fantastic programs, but both of which support 98% inspirational SciArt – when you see SciArt – talk it up – did you learn any science from it?  If not – ask: would it have been improved or more interesting if there had been more hard science in it?  There is certainly a place for inspirational SciArt – art that intrigues and excites us about science – but there also needs to be more of a place for informational SciArt out there – at least more than 2%, which, in my opinion, is even an optimistic estimate of what is out there right now.

Daumantas has a relatively large lab group slotted into his multiple little rooms where they study a variety of biophysical questions centered on drug binding and protein stability. Daumantas uses changes in protein stability to assess drug binding, and is designing new chemical entities to bind to a variety of well known drug targets – but the lab is not just a drug screening operation, in fact the bulk of the lab publications are concerned with fundamental biophysics and biological thermodynamics.

Saulius Grazulis is also at the Institute for Biotechnology and is a resident crystallographer in the laboratory of Virginijus Siksnys. Saulius is one of those semi-autonomous scientists (mentioned above) within a faculty lab (the Institute labs also have more “normal” postdoc positions within each lab, but there are a large number of these semi-autonomous positions that are more similar to so-called Research Professor or Research Associate positions in the US). Saulius is an extremely energetic and curious guy who carries two different cell phones and rarely utters a sentence that does not contain a physical chemical concept. (Okay, he really does talk about normal things too – but he loves to talk shop and we probably talked pure biophysics for about 92% of the time I spent talking to him over three days.)

After giving a Thursday seminar in Vilnius, Daumantas and several of his lab members drove me to Kaunas (about 100 kilometers from Vilnius) for another seminar and for a meeting that was part of an effort that Daumantas is mounting to coalesce several of the smaller biophysical clubs and local societies in Lithuania into one big Lithuanian Biophysical Society. This meeting in Kaunas was supported by the US Biophysical Society, as part of its new Biophysical Society mini-grant program (thank you Biophysical Society!). About 40 different Lithuanian biophysicists from many different specialization areas met in a sort of futuristic round conference room that looked like a mini-version of the UN Security Council meeting room, with a table in the middle for refreshments.  Most of the proceedings were conducted in Lithuanian, but Saulius (the crystallographer mentioned above) kept me somewhat informed of what was going on. It seems that there are already many small biophysical clubs and consortiums in Lithuania (about 5-6 in all, some quite well established – which is rather impressive for a country that has a population roughly that of the state of Minnesota, and which has only been free from Soviet rule for under two decades). Coalescing these many different mini-societies into a more comprehensive national one will take a few more meetings and a few more discussions of logistics, but Saulius indicated that this meeting appeared to be a good start to that effort.

While in Kaunas, we also visited the laboratory of V.Arvydas Skeberkis in the Institute of Cardiology there in the Lithuanian Univ. of Health Sciences. Arvydas gave us a 40 minute long tour of the many small rooms in his lab, where he is doing things like transplanting stem cells into damaged heart tissue (in rabbits) and then measuring current, contraction, and gap junction behavior using fluorescent methods and patch clamp techniques. The fluorescence techniques he uses are really interesting: where he uses fluorescent dyes that react to changes in intracellular pH or electric potential. He also studies cellular nanotubes – not the tubular equivalent of a nanoparticle, but actual cellular membrane projections that some cells send out from their surface in order to make contact with other nearby (but physically separate) cells. His lab wants to know how the cell that originates the nanotube knows which direction to grow it in (it always grows in a strait line toward a nearby cell), and what the cells send through the nanotubes once contact is made.

All in all, at least from the few samples that I saw, biophysics in Lithuania is clearly a thriving and valued component of the biological research going on there.

Dear Victor,

I just saw the most recent portrayal of your exploits – the Nick Dear authored, Danny Boyle directed, broadcast version of the National Theatre play. What a masterpiece production – one of the best versions of your story I’ve ever seen – largely because of the intense focus on the interaction between you and “the monster”. And Danny Boyle as a director! Wow!  I, of course, love his film work (Slumdog Millionaire, The Beach, Trainspotting) – I mean, who doesn’t love Danny Boyle’s work? And two fantastic actors: Benedict Cumberbatch and Jonny Lee Miller – each getting to switch back and forth between playing you and the monster (I saw the version with Cumberbatch as you and Miller as the monster). Yes – it was/is a most fabulous and exciting production.

But, Victor, once again you’ve allowed yourself to be portrayed as a scumbucket. Once again, you’ve cast a stench over all scientists with your Faustian egomania and self-absorption. I mean, come on, the monster kills no less than five people in this production, including your own brother and your fiancé, and every single person who views this play comes out of the theater with more sympathy for the monster than for you. What does that say to you Victor? Well, obviously nothing.

Yes, yes, I know you didn’t write this version, or any of the others, but you do have some influence you know. You could have sat down with Nick Dear and/or Danny Boyle and let them know a few things. Such as:

1) Scientists don’t generally look down on their hometowns from mountaintops and shout out about how stupid everyone else in the world is. In fact, most scientists harbor a fair amount of self-doubt.

2) Most scientists would not abandon their own results/creations simply because they found them ugly. I mean, what is wrong with you Victor? You want the credit for being the world’s greatest genius (which you so vainly believe you are) and yet you cannot even look upon your own creation? Why not take the opportunity to reflect on how subtle the concept of human beauty is? How even small deviations from symmetry or shape or smoothness can cause someone to go from beautiful to hideous with very little actual change (think of Charlize Theron playing Aileen Wuornos in “Monster”). Sure, you can’t help being disgusted – but to abandon your creation? To leave him alone to die, just because you didn’t like the results? What a shit.

3) Victor – it gets really tiresome when every time someone asks you about your work you reply with something to the effect of: that the purpose of your work is to prove how smart you are. It especially happens over and over again in this play: Why did you create the monster? To prove you were a genius. Why did you want to create life? To demonstrate to everyone that you were smarter than them. Why would you agree to try to make a female creature? To help out your first creature? No. To test some of your theories further? No. To refine your bioengineering techniques further so that they might someday be used for medical advances? No. You decide to do it so you can show everyone that you are the greatest scientist in the world! I have known some scientists for whom self-aggrandizement does seem to be their overarching goal in doing science, but I’ve known many, many more for whom the reason to do science is to: solve the puzzle, unlock the secret, find something novel, figure out why something happens, become able to design a new function into an existing biosystem, attempt to cure a disease. Do none of these less self-centered goals appeal to you Victor? Or is it the writers, like Nick Dear, who have gotten you wrong all these years? Is it they who just don’t understand what a real scientist is like? Is it they who just don’t know how to write the story about your work without vilifying all of science through you? Or are you really such a piece of garbage?

I find it difficult to believe that one could not create a version of Victor Frankenstein that is at least as human as his own monster, and at least as much of a real scientist as the average graduate student. But I just don’t see it in most of the versions of your story, Victor. I’ve yet to see you as a conflicted Galileo, who desperately wants the truth to be known, but who also fears the consequences. I’ve yet to see you as a passionate Dian Fossey, who would sacrifice all for the benefit of your creations/charges. I’ve yet to see you as a J. Robert Oppenheimer, who knows he must touch the void, who knows his creation can go off in both extreme good and extremely evil directions, and who works the rest of his life to try to insure against the evil uses. No, with you it’s just all about Victor, all the time. Quite frankly, Frankenstein, I don’t even know why your monster gives you the time of day. In my opinion, Victor, especially as you’ve been portrayed in this play, you are a supreme bio-technician, but one who does not even begin to understand the implications of your own work, who cannot see past your own ego, and who most certainly I would not want to count as a fellow scientist. I thank goodness that you are, and always will be, a fictional character. I long for the day when you might become a less uni-dimensional one.

Love and kisses…

Kirby interviewed a large number of consultants and filmmakers for the book, and he makes it clear that the science consultant is just that: a consultant, someone who can give advice which is as often, or more often, discounted than it is utilized. He discusses the highly variable relationships with directors: some of whom hire science consultants seemingly solely for the purpose of ignoring every single piece of advice they offer, and some of whom rely heavily on science advisors to help them shape the drama, the story, the setting, and the characters. He emphasizes that there has not been a single science advisor in the history of film who has walked away from a film saying, “Ah, everything was accurate” – never, ever, ever. When the director does take accurate science seriously, the result is always a hybrid of real science and cringe-worthy gobbledygook. Probably one of Kirby’s most illuminating conclusions is when he notes that scientists often think there is a tension in film-making between the story/entertainment content and the science-accuracy content. Kirby says this is a myth that lives in the minds of scientists – there is no such tension between science and entertainment: entertainment issues always win: always. When the science enhances the entertainment or story, it gets included.

But all this is not to say that Kirby, or the many science-consultants he interviewed for the book, view science-consulting as futile or from a predominantly negative perspective. Quite the contrary – he sees science consulting as an effective way to get a variety of scientific concepts into the mainstream consciousness. And while he cautions that science in the movies, for some of the reasons described above, will never be fully accurate – that scientists should count any enhancement of science accuracy in the movies as successful. The realistic picture of science consulting that Kirby paints is tremendously useful to anyone considering doing paid or pro bono science consulting. If you have any need or desire for real creative control on a project, then science consulting is probably not for you – and you’d be best off working on your own “entertainment” projects, like an increasing number of scientists are doing. If, however, you want to experience the fun of working with the talented teams of people who put together both big and small budget films, and if you want to help make the world of cinema a little more science-savvy and a little less science-cringe-worthy, then science consulting can be quite enjoyable, and sometimes lucrative. As for how to become a science consultant: according to Kirby, this often involves google-induced phone calls from producers to unsuspecting scientists, but Kirby’s book also describes a number of different ways for scientists to try to purposefully get involved in this growing new form of science outreach.

Here at LSU we’ve been discussing almost the Exact Same Issue in the Honors College for the past few weeks and coming to the Exact Opposite Conclusion to CUNY. We are re-designing an Honors version of Introductory Biology for Non-majors – and everyone is on board with the need for an associated laboratory in the course – even though (get this): the lab is not even a General Education requirement at LSU. Doing some science experiments with your own hands completely changes your perspective on it — every scientist knows that — we don’t design expensive, staff-intensive, time draining, space-hogging teaching labs just for the fun of it – we design them because without them, you’re only getting part of the picture.

So, for commitment to educating our future non-scientist leaders in the basics of science, the score this week is: LSU: 1 and CUNY: 0. (of course in the competition for good nearby pizza, the score is the opposite, thus creating a stalemate at present). Sadly, however, outside of the Honors College, as noted above, LSU’s non science majors face some of the same incompleteness of their general science education, since labs are not part of the General Education requirements.

Not having some decent science literacy is a bit crippling for anyone who wants to be a future societal leader in any field. In the same way that not having some familiarity with foreign languages or art likewise makes for poorer scientists. And both situations make for poorer citizens.

Our lab’s contribution focuses on how the thermodynamics of binding of DNA polymerases different DNA structures might influence the balance between replication and repair in the cell. Yanling examined DNA molecules with normal replication start sites, along with DNA molecules with nicks and gaps between bases, and DNA molecules with mismatches near the polymerase binding site. One of the major questions was: do the “same” enzymes from two different organisms (in this case the Pol I DNA polymerases from E. coli and Thermus aquaticus) actually perform the “same” functions in the two different organisms? The thermodynamic results of this paper suggest that there are some serious differences between these two “homologous” enzymes, such that the E. coli enzyme is more advanced in being able to recognize different DNA structures.

The schematic below illustrates this in cartoon fashion by illustrating how Klentaq (from Thermus aquaticus) sees a primer-template (i.e. a “normal” replication start site) as being equal to a DNA with a gap in it. In contrast, Klenow (from E. coli) binds the primer-template DNA with much higher affinity than it binds the gapped DNA.

The paper compares the binding preferences among a large number of different DNA structures, and consistently finds that the E. coli enzyme is capable of distinguishing among all these DNAs (and binding to them with differing affinities), while the T. aquaticus enzyme sees and binds to almost every DNA exactly equivalently. We spend some time discussing how this might shift the balance between repair and replication in the two different organisms, and discussing how evolutionary time has made this enzyme more subtle and sophisticated in its DNA substrate choices.

As always, if your institution does not have access to the paper and you would like a copy, I will be happy to send you one.