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Buffeted by the winds of chance: why a cell is like a casino

Category: CreationismMolecular BiologyNeurobiologyScience
Posted on: February 3, 2008 2:37 PM, by PZ Myers

Many of you have already seen the gorgeous video below: it's a spectacularly beautiful animation of the activity in a cell.

I like it, and it's a useful illustration, but … there's something fundamental that it gets completely wrong. So today I'm not going to praise it, I'm going to criticize it. It's a substantial criticism, too, one that means I wouldn't show this video in my classes without spending more time explaining the error than it takes to show it.

Here's the central problem: molecules don't behave that way. What is portrayed is wonderfully precise movement; it looks like the molecules are all directed, purposeful, and smooth. Take for instance the behavior of kinesin, that stalk-like molecule seen marching in a stately way down a tubule, with two "feet" in alternating step, towing a large vesicle. That's not how it moves! We have experiments in which kinesin is tagged — it's towing a fluorescent sphere — and far from a steady march, what it does is take one step forward, two steps forward, one step back, two steps forward, one back, one forward … it jitters. On average it progresses in one direction, but moment by moment it's a shivery little dance. Similarly, the movie shows the monomers of tubulin zooming in to assemble a microtubule. No! What it should show is a wobbly cloud of monomers bouncing about, and when one bumps into an appropriate place in the polymer, then it locks down. I made this same criticism in my review of Mark Haw's excellent book, Middle World, which does get it right. For purposes of drama and minimizing complexity and confusion, though, the animators of that video have stripped out one of the most essential properties of systems at that scale: noise, variability, and the stochastic nature of chemical interactions.

That's particularly unfortunate, because it is the seeming purposefulness of the activity of the cell that has made that clip so popular with creationists. It fits with their naive notions of directed activity at every level of the cell, and of their denial of the central role of chance in chemistry and biology. It allows them to say ridiculous things like this:

Well, I am a biochemist and biochemistry studies molecular basis of life. And in the past 50 years, science has discovered that at the very foundation of life there are sophisticated molecular machines, which do the work in the cell. I mean, literally, there are real machines inside everybody's cells and this is what they are called by all biologists who work in the field, molecular machines. They're little trucks and busses that run around the cell that take supplies from one end of the cell to the other. They're little traffic signals to regulate the flow. They're sign posts to tell them when they get to the right destination. They're little outboard motors that allow some cells to swim. If you look at the parts of these, they're remarkably like the machineries that we use in our everyday world.

That's Michael Behe, a biochemist. Biochemists should know better. There's a reason modern biology programs are inseparable from a foundation in chemistry — that's where our students are supposed to get a good foundation in ideas like equilibria and thermodynamics and the properties of molecules. I use that quote all the time in my lectures on creationism because it is such a perfect example of failing to understand a scientific concept. It's also hilarious because Behe doesn't seem to understand the meaning of the word "literally".

I am not a biochemist, but even I understand the idea. I have had a little bit of training in neuroscience, though, so let me illustrate the real noisiness of the cell with an example that is familiar to me, the properties of ion channels.

Neuroscientists have a technique that allows them to examine the behavior of single molecules, called patch clamp, illustrated below.

chnl_patch.gif

What's done here is that you use a fine glass microelectrode with a tiny polished tip, and you press it against the cell, ideally in such a way that a single channel protein is isolated. Then the voltage of the cell is modified with another electrode, and the current through the patch is measured with the patch electrode. That is, if the channel is open, charged ions can flow through it — a current — and the electronics attached to the electrode will report back the fractions of an ampere moving across the membrane. If the channel is closed, no ions can move, no current will be generated, and 0 amps will be measured. It's difficult in practice, but easy to describe and understand. We have a senseitive tool for measuring the state of a single pore in a membrane, whether it is open or closed or some state in-between.

Here's what the results look like.

chnl_open_closed.gif

Time is recorded along the horizontal axis, and current along the vertical. When the channel is closed, the current is 0; when it is open, it jumps up to a tiny, fixed value. There is a quantal nature to the current flow at this level, as a single channel allows a fixed number of ions to move through it per unit time, just as opening a faucet tap allows only a certain volume of water to flow. We can see that the transition state for an ion channel between open and closed is very brief; it flicks open and closed quickly. (By the way, the blue trace below the dark one is an idealized version, with the electrical noise removed.)

But now look at the whole trace, from beginning to end. Is the channel open or closed during the period of recording? You should answer that it's both — sometimes open, sometimes closed. Like the kinesin molecule I described above, it's jittery.

This is where the simple answers break down. The channel itself seems to be binary, either open or closed, but when we look over time and ask how it affects the cell, we see both states represented in our recording. The binary condition is actually translated into a kind of analog representation — we ask, "how often is it open relative to being closed?" As shown below, when we say it's closed, we mean that most of the time it is in the closed state, but you can see that it also flicks open occasionally. When we say it's open, we mean it is in the open state most of the time, as shown in the bottom trace, but yes, it still flicks shut now and then.

chnl_state.gif

This particular channel is voltage gated. That means that its permeability, whether it is open or closed, is regulated by the voltage across the cell membrane. When the voltage is positive, it should open; when it is negative, it should close. What we actually see is that the single channel is jiggling open and shut all the time, and that changing the voltage in a positive direction simply shifts the likelihood of it being open to a greater and greater value. We can plot the average behavior as a predictable increase in permeability even though the instantaneous behavior is either fully open or fully closed. The permeability of a channel is actually a measure of the probability that it will be open.

chnl_perm.gif

From many small chance events, one can still get a predictable aggregate behavior. At a larger scale, triggering a small voltage change across a membrane causes a predictable inward pulse of sodium as many channels open. Watch a single channel, you see it is open with greater likelihood at the start of the voltage shift; record 3 at once, and they sum nicely at the beginning; record dozens or the thousands in the whole cell, and smooth curve emerges.

chnl_avg.gif

This is what bugs me about the "Inner Life of a Cell" video. They're portraying the behavior of single molecules, and the movie has them dancing a slow waltz, steadily moving through fixed patterns. It should look more like a mosh pit filled with meth addicts; real chemistry doesn't direct single molecules, it shifts overall equilibria so that the random activity of single cells has certain probabilities of throwing them off a thermodynamic cliff into a new state. Those kinesin "feet" should have been pitter-pattering all over the place, occasionally falling into a more stable position that led them in a particular direction — what was needed was a portrayal of a hyperkinetic ratchet. Anyone who uses a microscope or looks at the activity of small numbers of molecules or studies thermodynamics and reaction equilibria (like, say, a chemist or biochemist) ought to be familiar with the stochastic properties of the world on such a small scale.

The closest example on a macro scale that I can think of is a casino. People go in and out of a casino, and they engage in many small probabilistic events. Some people win big, some lose big, and all states in between are represented…but the house always has its small, advantageous odds in its favor. They don't shake down the crowd deterministically and demand a cut from each, instead what they have done is basically tipped the the reaction equilibrium gently to favor the transfer from one state — your pocket — to another state — their bank. From the aggregate kinetics of a great many transactions with only a tiny edge in one way, they have constructed a powerful and reliable siphon hose to draw off your money. (I suspect that's also one, perhaps unconscious, reason why gambling establishments are fanatical about keeping out people with even a hint of a successful gambling system; it doesn't take much of a shift in the percentages to reverse the flow in their money siphon.)

If you watch single individuals in the casino, rather than the rising total profits for the whole institution, you wouldn't see a smooth and steady drain of money, though. Over long periods of time the trend would appear, but moment-by-moment? No. You'd see a herky-jerky random pattern of wins and losses.

And that's what I would want to see portrayed in my ideal version of an animation of the chemistry inside a cell: not a ballet, a jostling mob on an uneven floor. Show me more noise and chaos.


By the way, I've always wondered if chemists might have a better resistance to the temptations of gambling than people who are less familiar with the mathematical properties of reaction equilibria. I know I find it impossible to gamble any more — visions of reaction kinetics run through my head when I see chips on a table, and I see bankruptcy and ruin at the thought of miniscule odds against me amplified by prolonged trials. Small numbers have the potential for great power, as the casino owners all happily know.

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Comments

#1

Posted by: Fedor Steeman | February 3, 2008 2:56 PM

I am really glad someone points this out so strongly like you do, PZ, because you are right: Portraying the cell's innards as some finely tuned clockwork is exactly what the creationists can, will and do abuse. I have been using the same argument (of the cell's chaotic nature) against a creationist writer in my native country (the Netherlands), who, amongst other things, illustrates topoisomerase this way. He then makes it seem as if enzymes are as complex and finely tuned as industrial robots!! Unbelievable...

I wish there were some videos that show the chaotic nature of enzymes somewhere... That would help cutting through the smoke screen whipped up by these people.

#2

Posted by: dzho | February 3, 2008 2:57 PM

This is a great post, and I like the casino analogy.
Here in this Southern state are many creationists who don't see the irony of funding their schools with an 'Education Lottery'. How much time the schools spend on probability I don't know.

#3

Posted by: spudbeach | February 3, 2008 3:03 PM

Bravo! Thanks for a great explanation of the very small. Things really are different at the atomic/molecular level, where chance is real driving force.

As to chemists not liking casinos, I can't say, but I can say that statisticians hate going to them. It doesn't matter what the system, the more you play, the more you bet, the more you're likely to lose, until it becomes a near certainty. Sitting down and computing the odds of coming out ahead sure does ram that lesson home.

#4

Posted by: Dan | February 3, 2008 3:07 PM

It's not unconscious. Casinos know very well that they'll get cleaned out if they let people with a system play. If you want to make money, you have to make sure they don't know you're making money.

Also: fascinating about cells.

#5

Posted by: don kane | February 3, 2008 3:11 PM

Funny, that was my first thought too, those subunit streaming like lemmings towards the MT or actin fibers.

The other thing is that i don't think the cytoplasm is that "empty" looking; it should be more like a really crowded theater, only in 3D.

#6

Posted by: Moses | February 3, 2008 3:14 PM

You know, I know what you mean. Whenever my wife is preparing a poster or a paper, she makes do a pre-peer review for clarity and, sometimes, has me watch cell migration or inner-cell movements, etc. It's definitely not a linear process.

#7

Posted by: Bob | February 3, 2008 3:18 PM

...and the movie has them dancing a slow waltz, steadily moving through fixed patterns. It should look more like a mosh pit filled with meth addicts...

YES! Excellent.

#8

Posted by: Susan B. | February 3, 2008 3:18 PM

It's too bad, too. The video is meant to evoke wonder and awe at the amazing complexity of what happens inside the cell, and yet I for one find it all the more amazing that out of the chaos of individual molecules, these large scale patterns can actually emerge.

#9

Posted by: John T. | February 3, 2008 3:25 PM

I have wondered if I believe in a Creator, should I be called a Creationist? I mean the way it is used on this site it is as a derogatory expression. I have no clue on all the complexity of life development in the universe and I make no claim that anyone should believe what I believe. Yet in every fiber of my being I sense that I have been created by something greater than myself. Will I be able to prove it to anyone. It seems not. But I also know with all the new knowledge we develop about the universe, there is yet a person out here who can tell me what started it all. Lots of great ideas, but no absolutes. So we continue to guess, both educated and non. Let the mud slinging begin lol.

#10

Posted by: Andy James | February 3, 2008 3:25 PM

Yummy math, chemistry, and biology all on a Sunday's afternoon.

You could attend church your entire life and never learn as much as one could by this single article.

Thanks!

#11

Posted by: Steven | February 3, 2008 3:25 PM

Hey PZ,

You linked to my YouTube account. I feel all giddy inside(could be the Indian curry).

:-D

I agree with everything you said above.

Also, atoms don't actually look link cue balls.

#12

Posted by: Pete | February 3, 2008 3:30 PM

A very good point.
There are some very nice molecular dynamics movies from Jack Szostak's lab that give more of a flavor of what you're asking...
http://genetics.mgh.harvard.edu/szostakweb/movies.html

There are of course lots of other movies like this around (search youtube for "molecular dynamics" - lots of enzymatic action there), but I recently heard him speak about artificial life, and it was very cool.

#13

Posted by: Sven DiMilo | February 3, 2008 3:31 PM

For what it's worth, the scientists behind the video are well aware of this limitation. From an interview with Rob Lue:

But the videos aren't meant to be completely realistic simulations, right?

You don't want to simulate all aspects of reality, because reality is, in some ways, far too complex. If we showed the high density and full motion of the macromolecules and events in the cell, you wouldn't be able to see specific events.

So what we do is in between a diagram that you would see in a review paper and a high-end simulation that attempts to show every physical aspect. Our animations bring together key pieces of scientific data with the goal of communicating a specific point. If something is not relevant to that point, one can decide to not show it.

We're also working on detailed annotations that will be presented with each animation and will explain what we're showing and why we chose to show one thing and not something else. It will link up to the actual science: the multitude of papers used in the making of the animation. I think this is necessary for these animations.

#14

Posted by: James Brennan | February 3, 2008 3:31 PM

I'm not a biochemist, or even a chemist, but that was the first thing I noticed in the video. (My background is physics, so I understand stochastic behavior.) However, the filmmakers really had no choice. It would not be a very instructive video if everything looked like an angry swarm of hornets. They had to filter out the noise for clarity, but it is still important to point out that fact.

#15

Posted by: Owlmirror | February 3, 2008 3:43 PM

Whenever I see the creationist argument about machine parts (if left alone, will not spontaneously self-assemble; in fact, they won't even move), I keep thinking, "But that's not how things work at the scale of atoms and molecules!"

This makes it clear how things are different. It's a good thing to point at, next time the question comes up.

PS: Kinesin (in the video) looks adorably goofy.

#16

Posted by: PZ Myers | February 3, 2008 3:43 PM

And Don, you know that even if you look at the scale of single cells, their migration paths are all over the place. We always simplify.


I know the makers know the movie is a great simplification, too. I think they simplified away an important concept that I think budding biologists need to grasp. As it is, it accomplishes its job of making audiences go "Ooooo" very well, but it needs a little something else to counter the misconception creationists are taking away from it.

#17

Posted by: Pierre | February 3, 2008 3:45 PM

As a test, I watched the video BEFORE I read your 'negative' comments on it. Trying to predict what you would say. While I watched, I was thinking that "the mechanisms seem much too directed, much too predictable". Yes, I used the word "directed" too. I'm proud I noticed the same thing you did.

Other things I noticed: "there's too much free space, molecules should be a lot more crowded in the cell", but I also admitted that then nothing would be visible because the video would have no depth of perspective. Also, at that scale, objects don't really have a 'color'. Visible photons have wavelengths much larger than the molecules that are shown there, I suspect.

#18

Posted by: inkadu | February 3, 2008 3:50 PM

Creationist machines are funny things. They must drive cars that weave left and right, on and off the road, but drive straight when you look at the average trajectory. It's not their fault they're such terrible drivers -- it's just how intelligently designed machines work. And when a creationist slows his car down, what he is really doing is accelerating AND braking simultaneously but that, on average, the car is braking more than it is accelerating.

Yep. Those creationist sure know how machines work all right -- right down to the molecular level.

#19

Posted by: Speck | February 3, 2008 3:51 PM

The first of these visualizations does a fairly decent job of capturing some of the stochastic nature of the process. http://www.youtube.com/watch?v=E8NHcQesYl8 The second video is a bit deterministic, but then again, it does do a pretty good job of showing the different polymerases and helicase working together to duplicate the DNA strand.

#20

Posted by: jb | February 3, 2008 3:55 PM

I'm a chemist - I don't gamble. But that's more from knowledge of statistics learned from courses in thermodynamics, statistical mechanics, quantum dynamics, and good ol' physical chemistry, rather than reaction kinetics. But they're certainly all related. I'm not sure how many of the chemists in my department gamble, but the staff sure loves to go to Tahoe and Reno every so often!

We have a machinist on our staff who even has a poster for a Behe talk on campus posted over his desk.

Great post, PZ, but I won't forward it to the machinist - I need him to do things for me every so often....

#21

Posted by: Joe D | February 3, 2008 4:04 PM

I saw that one a few weeks ago and was thinking the same. Took me until the cytoskeleton construction to notice it. Looks like a whirlpool sucking everything in, with a neat little spiral motion.

#22

Posted by: Louise Van Court | February 3, 2008 4:07 PM

Whether these processes and reactions happen in a herky-jerky chaotic manner or in a smooth and orchestrated way it is absolutely astounding the amount of "work" that is occurring all at once in a cell. Show the current animations to students if you want them to get excited about biology and biochemistry.

#23

Posted by: Matt LaCrosse | February 3, 2008 4:14 PM

Nice post PZ. That answers some of my questions regarding cell complexity and randomness.

#24

Posted by: trrll | February 3, 2008 4:26 PM

Excellent article, and it points out the very thing that troubled me most about the video. I particularly appreciated your use of single channel kinetics to illustrate your point. I still remember when the first single channel recordings were presented at a Society for Neuroscience meeting--it was the first time I'd ever seen a standing ovation in the middle of a scientific presentation. Of course, everybody already knew that the function of ion channels was stochastic--Katz and colleagues had already shown this by fluctuation analysis. But to actually see it was for a neuroscientist a bit like seeing an atom.

In my experience, the most difficult thing for people to grasp--the one furthest from everyday experience--is how stochastic cellular functions are. There is a fundamental misconception--one that we hear all the time from ID/creationists that random mechanisms cannot create order. And as they say this, inside the cells throughout their body, the random, Brownian jiggling of molecules makes it possible for them to walk, talk, and think.

Of course, I understand why they made the choices they did. The function of proteins inside the cell is not like the stately movement of sea creatures under the ocean--it is more like Grand Central Station at rush hour. If they really displayed proteins moving about the cytoplasm with realistic concentration and velocity (which would be necessary to convey why these stochastic mechanisms work), you wouldn't be able to tell what was going on; it would look like you were in the middle of a huge, dense swarm of bees. Still, I winced when I saw the tubulin monomers being magically attracted to the growing microtubule, rather than bouncing around haphazardly until they happened to randomly collide with the end of the growing tubule.

The casino is a pretty good analogy. I can't think of a better one. The problem is that the average person doesn't get to experience a casino from the point of view of the management, with all those random wins and losses averaging out to add to the bottom line, just the way the kinesin molecule's halting, one step back, two steps forward progress gradually moves its burden along the microtubule.

#25

Posted by: Anon | February 3, 2008 4:31 PM

This one is my favorite video of this sort of thing: Definitely shows the chaos.

http://video.google.com/videoplay?docid=-2657697036715872139

#26

Posted by: trrll | February 3, 2008 4:32 PM

It's not unconscious. Casinos know very well that they'll get cleaned out if they let people with a system play. If you want to make money, you have to make sure they don't know you're making money

Actually, this is not true. Casinos love systems, because there is no system that will keep you from losing money when the odds are against you. And people who think they have a system take more risks. The sole exception is blackjack--a game where the rules were already locked into place by tradition by the time it was realized that the odds are actually with a player who is paying close attention to what cards have been played (so they kick you out if they catch you paying too much attention).

#27

Posted by: Escuerd | February 3, 2008 4:38 PM

Thank you PZ, for introducing me to the casino analogy. I'm also not a biochemist, but it has always bothered me that many introductory biology textbooks that are filled with diagrams outlining biochemical processes don't emphasize that these are in fact stochastic events, not discrete, deterministic stages.

I understand how this eases the introductory presentation, but always felt that it gave the wrong impression to students who were seeing it for the first time.

As for casinos, it's funny, but they don't even have to skew the odds on any game in their favor. Even if the expected absolute gain or loss for any customer were zero, the casino will still take in more money than it gives out. This is because the probability that the gambler will have run out of money (and hence had to stop playing) at some point after a given number of trials is much greater than this happening for the casino.

So even in a "fair" game the odds are stacked against you.

#28

Posted by: DiscoveredJoys | February 3, 2008 4:41 PM

Thanks PZ, although I was vaguely aware of the stochastic nature of the cell processes I hadn't thought of them as clearly as you explained it.

Similarly I have always taken the analogy of 'the brain is like a *digital* computer' with a huge pinch of salt. While there are clearly electrochemical signals flowing (which result in me scratching my nose when I feel an itch) there are lots of other chemical events happening outside and inside the neurons which can modify the end to end processes.

I just wish I could think of a better analogy for the brain - historically the most complex human designed mechanisms of the time (water in tubes, clockwork, tiny creatures, humors, spirits) have been pressed into use. The map is still not the terrain though.

#29

Posted by: Escuerd | February 3, 2008 4:46 PM

@ #25:

I remember a math student commenting on that video:

"I learned that the body is a magical place filled with hippies."

#30

Posted by: David Marjanović, OM | February 3, 2008 4:47 PM

I have wondered if I believe in a Creator, should I be called a Creationist?

Depends on if you intrude into the affairs of science. I wouldn't call John Paul II a creationist -- he believed the body had evolved and the soul was created; the existence of a soul in the first place is an untestable and probably useless hypothesis.

Yet in every fiber of my being I sense that I have been created by something greater than myself.

You don't. You believe -- you don't sense. :-)

Will I be able to prove it to anyone. It seems not.

Relax. Science cannot prove, only disprove.

But I also know with all the new knowledge we develop about the universe, there is yet a person out here who can tell me what started it all.

Yep, but we're working on it.

Lots of great ideas, but no absolutes.

Does it logically follow from this that the absolute "Yet in every fiber of my being I sense that I have been created by something greater than myself." must therefore be right?

"Only the Sith deal in absolutes." -- Obi-Wan Kenobi

#31

Posted by: Colugo | February 3, 2008 4:52 PM

The noise of the system is responsible for much of its robusticity and adaptability.

#32

Posted by: Penny | February 3, 2008 5:01 PM

Thanks, that was one of the most interesting things I read for a while. I wouldn't have thought about noise in molecular processes, but it seems perfectly natural now you mention it.

I was going to say that another thing creationists seem unable to do is distinguish between a model and a literal representation. Having watched the video, I think it falls more into the class of fine art than model. I wouldn't have watched it and imagined that the inside of a cell really looked like that. I doubt whether the colour, textures, space/object relationships are realistic either. Anyway, with my high school biology, I can only recognise a few of the most familiar molecules and processes. In the absence of commentary this animation has no ability to educate me! It's poetic, beautiful, quite anthropomorphised and evokes a general sense of wonder that anything that small can do so much.

#33

Posted by: Carlie | February 3, 2008 5:03 PM

What do you think of the DNAi videos? They are still pretty clean and "directed", but at least they have some amount of jittering of the individual molecules.

#34

Posted by: Nina | February 3, 2008 5:09 PM

"They're portraying the behavior of single molecules, and the movie has them dancing a slow waltz, steadily moving through fixed patterns. It should look more like a mosh pit filled with meth addicts-"

I absolutely love it.

#35

Posted by: Mrs Tilton | February 3, 2008 5:23 PM

You know what, though? If you turn off the sound controller in the YouTube box and instead watch the video accompanied by Stiff Little Finger's Inflammable Material, you get a lot of that stochastic, chaotic element you think the video lacks.

#36

Posted by: June | February 3, 2008 5:35 PM

Come to think of it, doesn't the incredible complexity of living tissue argue more for Evolution than for Creation? An omnipotent creator would have made skin out of - well - skin! When a human watchmaker makes a gear out of brass, he mills it out of a single piece of brass. He does not take thousands of pieces and laboriously glue them together with layers of brass glue. If a human engineer wants to move blood through blood vessels, he puts in a simple inline pump; he does not concoct a ridiculous balloon animal like the human heart.

#37

Posted by: mcscience | February 3, 2008 5:43 PM

Great article, PZ. I can't add much about the behavior of the molecules that hasn't been said, so I'll just skip to the fact that I'm a chemist-turned science teacher who loves to gamble. However, I do it with full understanding of the odds against me. I just like playing the games, interacting with oddballs, and watching people. I only gamble on vacation, and take a fixed amount of money I expect to lose. If I win, cool, but I consider my losses the cost of some entertainment.

Also, I prefer to play poker, which is a different animal, since it's a game of skill against other players, rather than the house.

I know not everyone can do this, but I manage to gamble non-compulsively.

#38

Posted by: Shigella | February 3, 2008 6:15 PM

Love that cell video! My immunology professor actually used it to show us the bit with the TAM molecules on the outside of the cell linking to receptors on another (a T-cell, I think). I agree with the consensus that biology/biochem students should be introduced to the concept of stochastic interactions on the molecular level, though. I was never exposed to the concept of random voltage-gated Na+ channel fluctuations leading to an overall probability factor in human physiology class. It makes total sense, though. Thanks for the interesting lesson, PZ.

Isn't knowing that all this is mediated by chance and quantum mechanics rather than some incompetent Designer so much cooler?

#39

Posted by: Marcus Ranum | February 3, 2008 6:17 PM

Wow! That's cool and detailed information!! Now, if I become a creationist flack, instead of saying "I read Scientific American" I can say "I read PZ (Not Dr.) Myers blog!" Oh... Wait....

#40

Posted by: eric taylor | February 3, 2008 6:28 PM

i think the video is fine. all it takes is one look under a microscope to realize the chaotic nature of small objects.

If you're a biologist and have never looked at small stuff using a microscope what is wrong with you?

#41

Posted by: Jason S. Kong | February 3, 2008 6:51 PM

Since I'm fully aware of the single molecule work on Kinesin, FIONA, patch clamp, and since I do study those things everyday, I thought I would say that I still love the movie. The movie is fine for its purposes which is to describe the structure and function of proteins and other respective molecules. Yes, stochasticity needs to play a role, yes, we need to look at the events as if they were Markovian poisson processes - but just like how we go to conferences and give lectures, we want to tell a story that tells people why what we do is important.

Ever read how Sunney Xie begins one of his papers about horse racing and how that ties back to single molecule work? In the end, single molecule work is messy. The data typically sucks, isn't clear, and you're only lucky if you can get two state behavior most of the time. But if you can tell the story of structure and function from your messy data, then you're set. That's why Xie refers to the horses. And that's what the movie sets out to do and succeeds admirably. The story must be told amidst the noise.

The movie's great.

#42

Posted by: October Mermaid | February 3, 2008 7:17 PM

That's a really cool video, but I don't really know what I was seeing from one second to the next. I learned about cells and all, but I'm starting to wonder just how poor science education really IS in Texas. A lot of the things that people supposedly learned in school was never even covered, if I recall correctly. Now it feels like I'm playing catch-up just to get even that much of a working knowledge of biology.

#43

Posted by: lylebot | February 3, 2008 7:42 PM

Just wanted to speak up as someone who understands probability & statistics but enjoys going to casinos occasionally anyway. It's just another form of entertainment. The only difference between going to a casino rather than a bar or movie or concert, price-wise, is that the cost per hour varies depending on skill and luck, and sometimes they pay you.

#44

Posted by: Ba'al | February 3, 2008 7:48 PM

I am a patch clamper, and you are quite right about the stoachastic behavior of molecules. Intellectually I knew things behaved that way from the statistical mechanics portions of my classes in physical chemistry, but it wasn't until my own data showed it to me that I really internalized the concept.

That said, I think it would have made the animation difficult.

As for creationists, show them a brown stain in their underwear and they will see a weeping Virgin Mary, so there is not much you can do that will keep them from invoking design at everything they see.

#45

Posted by: Mark (Monty) Montague | February 3, 2008 7:54 PM

I agree with the criticism of the video, but I also think there's a trap here. Behe's arguments are flawed, but I think there is a tendency of people to throw the baby out with the bathwater in this regard: biological molecular machinery works because it produces biases in the chaos, like Maxwell's Demon. As they scale up to large numbers (as in the casino where the house wins in the aggregate) they do have "purposeful" behavior of a sort. This doesn't mean that they were "intelligently designed" or anything, but saying "wants to" or "prefers to" or "is designed to" is sometimes a useful shorthand for saying "was preferred by natural selection because introducing this bias to the statistical system provided a benefit that allowed the organism to survive and reproduce more successfully" or what-have-you. I've noticed that there are a lot of folks who comment here, and sometimes PZ is even prone to this, that put "this kind of thing is coopted and twisted by creationists" as a reason to fight against certain ways of thinking that seem common in actual scientists studying this stuff. While many scientists see teleology as something to be wary of, and antropomorphising even more so, it also can be good "shorthand" both to help explain and to help explore real biology. I forget if I've mentioned this before, but I very much enjoyed The Tinkerer's Accomplice by J. Scott Turner, and was dismayed to find on his web site that he has allied himself with some of the religious right ID folks, despite his declarations in his book that he is a staunch believer in Darwinian evolution. As far as I can tell, this is because some anti-creationists, rather than considering his books and talks, have protested his work as sort of 1984 thought-crime because he uses words like "design" and "intent" (although on close reading, he is careful to say that he means that (paraphrasing) evolved physiological systems that maintain homeostasis display elaborate systems that can be legitimately considered goal-directed for preserving certain homeostatic goals, and that frequently what starts as such a "Bernard Machine" system can be coopted by evolutionary forces to provide other benefits to the organism.

The conceptual "intention" or "intelligence" or "goal-directed" behavior that can be applied both in the casino analogy or Maxwell's demon sorts of things are similar, in that they imply that there is a bias in probability. I'm sitting in on a class right now that described that the occupancy of promoter sites is not so much influenced by how often a protein bumps into that part of the DNA, but rather by how likely it is to stick there... the dissociation rate goes way down for the protein and its favored site... as opposed to the way things are portrayed in the video, the enhancers are bumping into the DNA indiscriminately all the time, and just stick on the binding sites to activate. Of course, sometimes something funny is going on and the press feels obligated to say that DNA has telepathic superpowers (can it call squids to its aid like Aquaman?) So I obviously think this teleology viewpoint can be taken too far.

My side point here, though, is that I've found that as I've been reading Pharyngula and the comments from this crowd, there are often things that are at odds with what comes across when I talk with or read publications from other biology researchers I respect... none are anti-evolution at all, and generally consider any questioning of evolution as a foundational work to be some combination of foolish and grossly ignorant, but also not worth wasting time about, yet many do use shorthand like "designed" or "wants to" or what-have-you... and I even have a friend who received a grant from the Templeton Foundation for his evolution-related work, and he says that they have been very supportive of his work and have not pressured him in any way connected with giving him money (and he's been known to contribute to some of the "Celebrating Darwin's Anniversary" museum shows and the like.)

I've wandered rather aside from the topic of the original post here, but I've been trying in vague "ruffle the feathers" ways to point this out occasionally, and this rather got be on a roll: I think there's rather a danger when otherwise-respectable pro-evolution people have too much of an emotional response to the anti-evolution kooks, and become "culture wars zealots" to the point of bashing on "using politically incorrect language/framing/whatever" merely because people like Behe like to use similar jargon. To be perfectly honest, the chaos in the cells machinery and the effects of Brownian motion and such actually make the "tornado in the junkyard" an interesting analogy if it's used by people who have some understanding of the underlying scale, forces, biases, amplification factors and whatnot: it's evocative, if not pro-evolution newspeak, to say that the cell's biochemical systems are designed to use an entropy gradient and statistical ratchet-like behaviors to intentionally take the tornado-in-a-junkyard chaos and deliberately self-assemble into precise machinery that operates to meet the goal of contributing to the animal's survival and reproduction because it was designed to do that by the process of natural selection. Of course, I deliberately chose loaded words that creationists love to coopt and twist for that description, but someone who doesn't care about the culture wars and is just trying to explain things or think about things to a naive listener might easily choose that sort of language to better make their point. Praising PZ's "casino" language is fine, of course (it's a great analogy) but I think it's worth noting that one of these creationists could just as well say "even PZ Myers admits that a cell is like a casino, and everyone knows casinos don't just pop up in the desert, they have to have an architect who designs them, so clearly cells can't have arisen by a random process." Which I mention not because it's bad that PZ has used an analogy that creationists could twist and misrepresent, but because it seems like a lot of enthusiastic fans of the PZ/Dawkins mindset seem to like to eviscerate other people for doing that, and I think it alienates potential allies and gives fuel needlessly to the "Expelled" mentality. I certainly encourage everyone who would be interested in the topics of this blog to actually read Turner's The Tinkerer's Accomplice for its own merits (although I think his example of a squid that uses ammoniacal buoyancy control may be incorrect) and consider if it's good for the pro-science camp that he felt attacked for his choice of using the word "design" to the point where he does think that some of academia is being so anti-creationist that it's impinging on intellectual freedoms. I don't know the guy except through his books and web site, but he sure doesn't seem like a fool or a creationist to me... in fact, I think he has some great "thinking out of the box" ideas about a number of fields in biology viewed through a physiology-of-homeostasis lens, and was actively annoyed to read that he's gone to this camp (although he admits to a contrarian streak.)

#46

Posted by: Interrobang | February 3, 2008 7:54 PM

I'm not even a chemist or a biologist; I'm just a writer. That said, writing a forty-page distance-learning module on inferential statistics as they apply to occupational health and safety cured me of ever wanting to gamble again. That still doesn't stop me from thinking wistfully of what I'd do if I had the kinds of sums they advertise on the lottery signs.

/exeunt, whistling "If I Had a Million Dollars"

#47

Posted by: Ba'al | February 3, 2008 7:59 PM

Minor correction to your post, almost pedantic, I'm sure. However.... The permeability of a channel refers to its properties at allowing ions to move ONCE IT IS OPEN. (There is stochasticity there, too, but at a much much faster time scale. Permeation properties of pores are often described by something called Eyring rate theory, which generates a blizzard of rate constants, which are also probabilities of some sort at a fundamental level).

It is the CONDUCTANCE of a channel that is a probability in the sense that you meant (a function of voltage, ligand binding, etc.). There is no simple model-independent relationship between permeability and conductance.

#48

Posted by: Stuart Ritchie | February 3, 2008 8:03 PM

Aha! Thanks for this, PZ! I was arguing with an ID creationist (I know, I know, I really shouldn't bother) last week and he started rolling out all this stuff about molecular machines - I wasn't sure how to respond (not being a biologist in any way, shape or form), but your casino analogy is perfect!

#49

Posted by: Marcus Ranum | February 3, 2008 8:05 PM

I'm already a bit uncomfortable about the awareness that I'm a meat robot, but the idea of being a meat robot that is directed by billions of mosh-pits of meth-fuelled .. ah....!

It all makes me feel so - squishy.

#50

Posted by: Sven DiMilo | February 3, 2008 8:15 PM

Worth mentioning that if you want to know what's going on in the video, there is a longer, pedantically narrated version available here.

#51

Posted by: Mick | February 3, 2008 8:17 PM

--------------------------------------
Quote: John T.

Yet in every fiber of my being I sense that I have been created by something greater than myself.
--------------------------------------

People can believe all sorts of stuff with every fibre of their being, and it can still be totally wrong. It's no indication of truth whatsoever. No doubt some Pacific island Cargo Cultists believed with every fibre of their being that fashioning radios out of lumps of wood and lengths of vine would allow them to call down a delivery of supplies from the sky gods, but that didn't make it true. And it's not just other people's instincts which are fallible, we are all susceptible to believing nonsense if we don't examine those beliefs carefully.

Of course we can speculate about possibilities, but putting faith in unsupported hypotheses is asking for trouble, especially when they are so similar to those religious beliefs which we know contradict our knowledge of reality.

#52

Posted by: holbach | February 3, 2008 8:35 PM

Though the videos and PZ's description are not my discipline, we can all remark so heartfully and with
awesome admiration; isn't SCIENCE the wonder of it all!
The insane religious morons have no inkling that all this
came about without their freaking non-existent god. Damn,
doesn't that just piss the shit right out of them!

#53

Posted by: Robster, FCD | February 3, 2008 8:48 PM

Actually, I use it to teach cell biology to students for exactly this reason. To point out that it is useful to think in smooth flowcharts, with the understanding that YEAH! SACK HIM! it is always a false image GO GIANTS! that only makes you think you understand what is going on. Only when you HO YEAH! FIRST DOWN! get rid of the random noise do you get a useful message.

#54

Posted by: rubberband | February 3, 2008 9:37 PM

Like others, I watched before reading to find 'the error.' I hate to admit that I could not readily identify some of the processes, but I did note that what looked like an attempt at DNA replication didn't start with pre-existing strands(not to mention the omission of lagging strands and Okazaki fragments) and thought I had it. Alas.
To my credit, I noted in passing that everything looked too 'perfect,' but shrugged that off as being a necessity of illustrating the aggregate action. I teach introductory Biology at a High School (my freshmen are only 14 & 15 year olds!)so I can completely understand why Bio texts and vids are simplified in this way. I really appreciate this post however, because I didn't realize the fundamental misunderstanding that gets communicated each time I teach a process this way. From now on I will make it a point to emphasize the chaos, too!

#55

Posted by: katie | February 3, 2008 9:52 PM

This what I think a lot of people get wrong about evolution too. Even if a particular trait is helpful...it's helpful -on average-. Not for every individual, every time. Probability plays a role.

I have to admit, when I build an energetic model (I study the evolution of cold tolerance strategies in insects), I build them based on individuals because that's where selection happens. But, when I get a particular answer in a particular situation, I don't think it applies to -all- individuals. It identifies a selection pressure: the average direction, with all the associated noise.

#56

Posted by: Brian Macker | February 3, 2008 10:27 PM

Exactly, that was my first reaction to the film. "Why aren't the molecules bouncing around randomly?"

#57

Posted by: Skeptic8 | February 3, 2008 10:36 PM

PZ; Docere, that is to say Teacher.
The Casino illustration of the practical concept is priceless! Please spread it about.
The gent who 'goes for the show' and has a loss limit is already accounted for in the Casino books. If we were legion they'd cut back on the talent. I'm sure he's had a companion, a bit overwhelmed by the glitz and the libations exclaim, "Oh, you've won! WHAT! You're walkin' away! You could have a 'winnin streak'. The polite answer is, "They just paid for the drinks". Don't take her by the 'galley slaves' workin' at the slot machines. The devotees of Fortuna outnumber those of Yah; mebbe they should organize some temples in each community.

#58

Posted by: Epikt | February 3, 2008 11:23 PM

James Brennan:


However, the filmmakers really had no choice. It would not be a very instructive video if everything looked like an angry swarm of hornets. They had to filter out the noise for clarity, but it is still important to point out that fact.

[nerdflag]
Yes, and it isn't just that the "random" motion obscures what's going on. The shapes of typical intermolecular interaction potentials, and typical thermal velocities, determine the timescale you have to use to get stable molecular dynamics trajectories, and it's on the order of femtoseconds (which is one reason why nobody uses MD to model continental drift). Often (though I don't know about cases involving these really huge molecules with lots of internal degrees of freedom) the things you're interested in (e.g. diffusive events in solids) happen on a much longer timescale, so that most of the time your MD simulation just sits there without doing anything interesting. In other words, if you want to get the thermal motions really right, often you'll never get around to seeing so-called infrequent events. Kinetic Monte Carlo, and accelerated dynamics methods can deal with longer timescales.
[/nerdflag]

You kind of need to look at these visualizations as impressionist paintings of what's really going on.

#59

Posted by: B McManus | February 3, 2008 11:28 PM

The most elegant explanation I've seen of biomolecular dynamics is a delightful little book by Howard Berg called _Random Walks in Biology_. Berg derives, from first principles wherever possible, the actual statistics pertaining to movement of macromolecules, among other statistical things related to biology. I had so much fun reading it. I press it on all the other biologists I know, because it's a lot of fun, it will leave just about anyone with a clearer conception of molecular dynamics, and it's only about 90 pages.

#60

Posted by: cm | February 4, 2008 12:22 AM

Either I misunderstand, I am wrong, or #27 is wrong about the casino odds bit.

#61

Posted by: Scott de B. | February 4, 2008 12:43 AM

For those wanting explanations of what is depicted in the video, look at this site:

http://multimedia.mcb.harvard.edu/media.html

#62

Posted by: Bob O'H | February 4, 2008 12:58 AM

Oh, PZ, stop whinging and do something. Put your own commentary over the top, strip out the titles and replace it with something more appropriate to your message, and then take it with you as you go lecturing around the country.

Get the message out!

Bob

#63

Posted by: H. Humbert | February 4, 2008 1:34 AM

It's almost like Behe sees the inside of a cell as that fancifully complex and functioning Metropolis the cover of his box of sea monkeys promised, but never quite seemed to deliver. Behe is a disappointed child who grew up from dolls only so far as imaginary friends.

#64

Posted by: Corey | February 4, 2008 2:30 AM

I'm a biochemist.
In at least one of my undergrad courses I was shown this video, and I don't think it was emphasized enough at the time that "molecules don't behave this way".
However, that message was clear at many other points.
Which bothers me with respect to Behe. He advertises himself as a biochemist, but misses so many important biochemistry fundamentals.

#65

Posted by: Carpworld | February 4, 2008 4:59 AM

Best.Post.Evar.

#66

Posted by: Shawn Wilkinson | February 4, 2008 7:42 AM

I admit that I have tasted the casion on my 21st birthday. Like one person commented, a casino can be looked at as another avenue of entertainment. Expensive in some respect, but for losing only $100, I got to drink and eat as much as I want AND stay in a fancy-pants hotel room at the resort.

It's an experience I'll never forget. But, I know I won't be back anytime soon...maybe when I retire in 40-60 years?

But back to the main point, I think I commented on something like this similarly on either this blog or ERV's. The movie is "incorrect" if it was attempting precision and accuracy. However, from its makers, the movie was attempting neither but a perspective.

And, this is probably a result of misfortune in the secondary education process, but how many people would have the background for an intro biology class on Brownian motion or any other form of stochastic processes? I was never formally introduced to them myself in a lecture setting but forced myself to read the monographs and relevent texts to capture the necessay elements.

So, yeah. A rant, but I think people understand what I'm saying?

#67

Posted by: Jim Hollister | February 4, 2008 9:10 AM

Nicely put. It's important to get across that functionality that is "good enough" is sufficient. The actual behavior of kinesin is a strong argument against Intelligent Design. Why would an Intelligent Designer, particularly an omnipotent one, craft kinesin so that it marches two steps forward and one step back?

#68

Posted by: zer0 | February 4, 2008 11:27 AM

Wait... I was told there was no science on this blog. W T F

#69

Posted by: David Marjanović, OM | February 4, 2008 11:36 AM

Comment 36 says it.

------------------

Docere, that is to say Teacher.

No, it means "to teach" (verb in the infinitive). To say "teacher", you need magister... or doctor.

#70

Posted by: lazybratsche | February 4, 2008 12:10 PM

I'm a bit late to this, but here's my favorite collection of molecular biology animations: http://www.wehi.edu.au/education/wehi-tv/dna/index.html

One of which was already linked to as a youtube video, but here are the rest. These, probably better than any other animations I see, capture the stochastic nature at the core of these processes. And, as a bit of trivia, one of these clips was used in the background of a Doctor Who episode.

#71

Posted by: William | February 4, 2008 1:45 PM

This is one of the important points I try to hit whenever I teach probability: just because an experiment is random doesn't mean there aren't trends. Your progression from one channel to the whole cell ion current is a great example: the jitters get smaller and smaller, until there's this lovely smooth curve. You can show, without any more than freshman calculus, how as the number of trials gets big the variance gets extremely small compared to the total, so the bell curve becomes a "spike," which gets sharper and sharper. Sharply-defined data emerge from random events. And the best example really is thermodynamics: there isn't much more random than the motion of molecules in a gas (the words gas and chaos are related!), which are bouncing around in all different directions with an enormous spread of energies. Umpteen quadrillions of them collide with the bulb of a thermometer over the course of a second. But the average total energy they transmit varies so little a cheap thermometer in the air can give you fast readings to the hundredths of degrees.

#72

Posted by: Leon | February 4, 2008 3:50 PM

It's also hilarious because Behe doesn't seem to understand the meaning of the word "literally".
Not to mention that he doesn't seem to understand the difference between "they are" (they're) and "there are" (there're).
#73

Posted by: melior | February 4, 2008 6:40 PM

That's such a great explanation, I can tell you've given it a few times. :)

#74

Posted by: Leon | February 4, 2008 8:00 PM

lol! Not with this one specifically, but this type of error, yeah. It's distressingly (and increasingly) common for people to make these kinds of mistakes, and if no one points it out when it happens, the trend will never reverse.

Not that I'm going to reverse a trend in a language by myself, but I can at least make a contribution.

#75

Posted by: chuck goecke | February 4, 2008 9:41 PM

One other thing, besides the lack of brownian movement and random jitteryness of the molecules is the lack of the water molecules that would be surrounding all these larger molecules like swarms of bees. They'd bee (sic.)sticking to some, more than others, and positively repelled by some molecules, or parts of molecules. I like the casino model, but with it absolutely filled with bees. Wouldn't make a very good video though.
chuck

#76

Posted by: PZ Myers | February 4, 2008 9:46 PM

Actually, no, I've never given this before. This one came to me as I was lying in bed Sunday morning, about 5am, thinking it was too early to get up but that my brain needed something to do. My brain often tells me it needs to play a game or it's going to go stir-crazy trapped up there in that bony vault, and most often what it wants to do is review old data and theory.

I keep telling it that the trophy wife is right there and there are other stimulating activities to consider, but no, this time revisiting the stochastic properties of chemistry was what it wanted to do.What can I say? It's in charge.

#77

Posted by: thwaite | February 5, 2008 4:22 PM

PZ, #76 wrote: What can I say? It's in charge.
...and here's your theme song (and mine), lyrics from Laurie Anderson's album Strange Angels: Baby Doll, which opens I don't know about your brain- but mine is really bossy...

--
Mark Montague, #45 - thanks for the notes on Tinkerer's Accomplice. That book caught my eye at the library the other day and now I'm definitely motivated to make time. It'd be interesting to see more discussion here.

#78

Posted by: Anil | February 6, 2008 1:37 AM

how about them kasinos, are them intelligently designed, or evolved from somethin or both?

#79

Posted by: Alex Tolley | March 26, 2008 1:31 PM

I understand your concern, but the real noise in the system does make understanding more difficult. From your casino example, it would be very difficult for an observer to understand that he casino is making money by observing the players. Only the aggregate data would show a noisy but rising casino bank balance and declining bank balances of the punters.

The noisier the system, the larger the sample data has to be to observe the underlying results.

In the case of bio-molecules, all the biochemical diagrams in text books are simplistic and the video just extends that trend. I'm not so against the simplicity as long as one understands that it is only a representation that clarifies some of the mechanisms.

#80

Posted by: Ichthyic Author Profile Page | October 19, 2010 10:35 PM

SPAM SPAM SPAM SPAM

wonderful spam.

HTML commands: <i>italic</i>, <b>bold</b>, <a href="url">link</a>, <blockquote>quote</blockquote>

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