That’s Random!  A Look at Viral Self-Assembly

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April 8, 2010

"The BioLogos Forum" frequently features essays from The BioLogos Foundation's leaders and Senior Fellows. Please note the views expressed here are those of the author, not necessarily of The BioLogos Foundation. You can read more about what we believe here.

Today's entry was written by Kathryn Applegate. Kathryn Applegate is Program Director at The BioLogos Foundation. She received her PhD in computational cell biology at The Scripps Research Institute in La Jolla, Calif. At Scripps, she developed computer vision software tools for analyzing the cell's infrastructure, the cytoskeleton.

That’s Random!  A Look at Viral Self-Assembly

You hear it all the time: “That’s so random!” When used by people of my generation, the word “random” can simply mean “cool” or “surprising.” Or it can mean something like “disconnected,” as in the phrase, “I had a random thought” (which returns 189,000 hits on Google, by the way—random!).

Despite this usage, most of us know that randomness has something to do with probability, and that it often implies a lack of conscious intentionality. But what do mathematicians and scientists mean when they say something is random? Can a random process lead to an ordered, even predictable outcome? Is there evidence that God makes use of random processes to fulfill his creative purposes?

These are big questions, and we won’t address them all today. But I think randomness is an important topic to cover for two reasons: 1) it is integral to many processes in biology (and math, physics, chemistry, etc.), and 2) it is commonly misunderstood to be incompatible with Christianity.

As I said above, most of us know that randomness has something to do with probability. If you pick a card “at random” from a shuffled deck, you have a small probability of drawing an ace (4 out of 52, or a 7.7% chance). If you flip a coin, you have an equal probability of getting heads or tails.

Randomness also seems to imply a lack of intentionality or purposefulness. After all, you might hope for an ace when you draw a card, but you can’t choose one on purpose. You might call heads when you flip a coin, but you can’t know beforehand what the outcome will be. Thus the outcome is indeterminate, but is it purposeless? Not necessarily. Indeterminacy simply means the result cannot be predicted from the outset.

It should be noted that indeterminacy does not imply that God does not have foreknowledge of future events. Christians ought not to be uncomfortable with the idea of God interacting with his creation through chance. We often describe a seemingly-random (i.e. unplanned by us) sequence of events as being “providential,” or planned by God. A good introduction to the way divine action could drive physical processes can be found in this Question.

In biology, it is very hard or impossible to calculate precise probabilities for most processes, so when we say a process is random, we typically mean it is extremely unpredictable. Eventually we will discuss randomness within biological evolution, but first we must consider some simpler processes, like the self-assembly of a virus.

Viruses are remarkably efficient entities. Coiled tightly within a protein-based shell is a small amount of DNA needed for self-replication. The shell, called a capsid, is made of many repeating protein subunits and is therefore highly symmetrical (see figure). Important biomedical insights have certainly been gleaned from structural studies of viruses, but viruses also teach us about the emergence of order from non-order.

The virus life cycle has four main steps: 1) enter a host cell, 2) hijack the cell’s replication and translation machinery to make many copies of itself, 3) assemble into many virus particles, and 4) exit the cell to invade another host.

When I first learned about this process, I found it very hard to believe it just “happens.” The idea that a bunch of molecules bumping into each other inside a crowded cell could spontaneously assembly into a fully-functional virus seemed a bit far-fetched. Many viral capsids have over 100 protein subunits that must interact with each other in just the right way, or it won’t work. Surely there must be something driving this process, right?

There is! Random motion. I had to see it to believe it. I distinctly remember sitting in class during my first year of graduate school when the professor demonstrated self-assembly of a virus using a 3D model as shown in the following video. In less than 30 seconds, you can watch a jumbled heap of proteins become a beautifully ordered structure.

As the narrator explains, sub-assemblies form and break apart en route to the most stable structure, the full capsid. As the sub-assemblies begin to form, further associations with free subunits become more favorable and as a result occur rapidly, while the final steps may take considerably longer. While the subunits in the model are rigid, in reality the proteins take on multiple conformations, allowing the capsid to “breathe.”

Amazing as it is, the system we just considered—one virus capsid in a jar—is pretty simple. One wonders how self-assembly can happen in a crowded cell, where there are countless other molecules diffusing around, potentially getting in the way. We can’t directly see how it happens in a cell, but we can reconstitute the process in a test tube using different combinations of constituent molecules.

Consider two viruses, where each protein subunit in one virus is the mirror image of the corresponding subunit in the other. Putting the two viruses together by hand would be pretty tricky, because the constituent parts look so similar. But random motion can do the job in short order:

From this model, we can see clearly, in real-time, how distinct complex structures can arise from their parts randomly interacting with one another. Many large viruses also use special scaffolding proteins to assist in the assembly process, and some even use their own genomes as a scaffold. In addition, two closely-related viruses that happen to infect the same cell can exchange parts to create a new virus. This is one way viruses can evolve quickly to evade the host’s immune system.

Here we have seen how viruses demonstrate a principle inherent in God’s world—that order can emerge out of chaos from random processes. In my next post, we will look at some other biological processes that make use of—rather, depend on—randomness. This will set the stage for us to see that such processes can not only assemble a structure within seconds or minutes, but also generate complex, information-bearing molecules over billions of years. Even though the freedom inherent in nature sometimes produces unintelligently-designed structures (like viruses, which can kill us), we see that God has made, and continues to oversee by his providence, a good creation that, at least in part, is capable of creating itself.

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Charlie - #9101

April 8th 2010

Kathryn,

You ended with “Even though the freedom inherent in nature sometimes produces unintelligently-designed structures (like viruses, which can kill us), we see that God has made, and continues to oversee by his providence, a good creation that, at least in part, is capable of creating itself.”

So you say that the virus is an unintelligently-designed structure but then you say right after that, that God has made a good creation.  Are you not contradicting yourself in the same sentence?

You also said “It should be noted that indeterminacy does not imply that God does not have foreknowledge of future events.”

Don’t you think it’s important to also say that indeterminacy has no support for the notion that God does have the foreknowledge of future events (or of God’s existance for that matter)?  Like you said, indeterminacy basically just shows us we don’t know the outcome.  How can we create a conclusion or correlation based of something “random”?  I personally don’t get how randomness supports or refutes a religious conclusion.  It seems off scope.

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Mike Gene - #9109

April 8th 2010

Hi Kathryn,

Very nice posting.  And I loved the videos.  You write, “It should be noted that indeterminacy does not imply that God does not have foreknowledge of future events. Christians ought not to be uncomfortable with the idea of God interacting with his creation through chance. We often describe a seemingly-random (i.e. unplanned by us) sequence of events as being “providential,” or planned by God.”

True.  The best example of this would be our own existence.  Each of us exist because of the chance union of a particular sperm and a particular egg.  As far as I know, no Christians feel the need to find some mechanism that ensures the right sperm is guided to the egg.

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whoschad - #9110

April 8th 2010

I’ve always had trouble in thinking that anything with God could be considered ‘random’.

Don’t we just say things are ‘random’ simply because we don’t have all the information? Computers can’t generate random numbers. There’s an algorithm that produces a random seeming number, but if we knew all the variables, we would have been able to determine the outcome beforehand.

Likewise with the examples of randomness at the beginning of the post: Picking a card or flipping a coin. If we TRULY had access to all the variables, is it really random? If we knew the strength, direction, velocity, wind, or whatever other factor involved, before the coin flip, wouldn’t we know what MUST happen? It’s not like a particular set of molecules could decide to bounce off each other in a different direction because they felt like it. If we knew all the variables, you couldn’t call it random.

This is why it’s hard for me to think that anything could truly be called random - especially for God. I’m quite certain that He isn’t bound by the Uncertainty Principle either.

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Mike Gene - #9112

April 8th 2010

As far as self-assembly goes, it’s a brilliant strategy.  In their book on nanotechnology, Mark and Daniel Ratner outline several methods of constructing nanostructures and conclude that self-assembly holds the greatest potential The alternatives are nanoscale versions of bulldozing, rubber-stamping, and writing with an old fashioned dip pen, all of which restrict your output.  The only serious alternative to self-assembly is Drexler’s notion of an assembler, but that does not look feasible for many reasons.

Yet, in essence, cells do have an “assembler” – it’s called the ribosome.  But the assembly-aspect of the ribosome boils down to creating peptide bonds between amino acids.  It is the physico-chemical properties of the linked amino acids which then enable the chain to fold into the 3D conformations that in turn tap into the realm of self-assembly.  Outstanding. In this case, the assembler itself self-assembles (although the order of mixing becomes important).

Of course, self-assembly fits very comfortably within the hypothesis of front-loading.

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Bilbo - #9116

April 8th 2010

Hi Mike,

Since you’re around, and since this is sort of on topic, I thought I would ask about IFT and cilia.  Nick point out a paper that says (he says, I wasn’t even able to obtain the abstract) that cilia can assemble without the aid of IFT.  Do you know anything about it?

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Richard Colling - #9120

April 8th 2010

Kathryn,
Random is a term much misused and also misunderstood.  People of faith are sometimes uncomfortable with the idea that our very existence embodies an element of randomness and chaos (indeterminacy).  But this is simply the way life works.

Randomness, as commonly understood, is not necessarily a bad thing.  Even the random processes that are a part of our biochemistry, and evolution which jumbles, sorts and creates new genetic combinations, accomplish great good for life.  If we believe God is the creator, then these processes are simply a part of his process and plan to create, nurture and sustain life.
Rick

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Glen Davidson - #9121

April 8th 2010

So you say that the virus is an unintelligently-designed structure but then you say right after that, that God has made a good creation.  Are you not contradicting yourself in the same sentence?

Not necessarily.  One could say that capitalism is an unintelligently-designed system that is nonetheless good, arguably better than other economic systems.  Of course it’s not an exact analogy, because capitalism clearly has designed aspects, and, after the latest frauds, scams, and creeping disregard for good vs. bad risks, attempts at more design have been attempted.

One could enumerate any number of differences between capitalism and evolution, of course, including the lack of forethought in evolution (at least some still exists in capitalism), but my point is that freedom may be preferred because it allows processes to respond to contingencies. 

Glen Davidson
http://tinyurl.com/mxaa3p

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Glen Davidson - #9122

April 8th 2010

continuing #9121:

How this might relate to any god or God (who might be able to think through everything) is, I would think, something that could be questioned.  However, with our limited abilities, sometimes the “best” we can do for certain goals (although socialists might suppose other goals to be better ones) is to allow for relatively free development.  Hence I do not think that it is inevitable that something might be largely unintelligently produced, yet be counted a “good” system.

Glen Davidson
http://tinyurl.com/mxaa3p

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Glen Davidson - #9123

April 8th 2010

Oops, should have been:

Hence I do not think that it is inevitable that something might be largely unintelligently produced, yet not be counted as a “good” system.

Glen Davidson

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Kathryn Applegate - #9127

April 8th 2010

Hi Rick,

Thanks for your comment.  I very much enjoyed your book, “Random Designer” - it is a wonderful discussion on this topic of randomness and how God uses it to create.

Hi whoschad,

I agree with you that God isn’t *bound* by randomness or the Uncertainty Principle, but in some mysterious way, randomness is real and not just a limitation of our knowledge.  Quantum mechanics has turned up the most surprising things.  I only hesitate to write on them because of the strangeness of it all!  Feynman famously said, “I think I can safely say that nobody understands quantum mechanics.”

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Mike Gene - #9129

April 8th 2010

Hi Bilbo,

Plasmodium can synthesize a flagellum, but they lack all of the IFT genes.  This all makes for a very interesting rabbit hole that I can explore on my blog if you want.


Hi whoschad,

There’s an algorithm that produces a random seeming number, but if we knew all the variables, we would have been able to determine the outcome beforehand.

Keep in mind that God does not need to determine any outcome “beforehand,” as God is not constrained by time.

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Micah - #9144

April 8th 2010

Kathryn,

Not to put you on the spot, but do you have a working definition of “random?”  (Or anyone else?)

whoschad,

There’s a big gap between knowing all of the variables and knowing the outcome.  If I take a brown paper bag and pour into it 75 red and 25 blue M&Ms;, I can predict the probability of an outcome (or outcomes) because I know the variables, but I have way to determine the order of the outcome.  This example may be simplifying your comment too much, but it seems to be a relevant consideration.

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Mike Gene - #9151

April 8th 2010

Simon Conway Morris, whose views are very similar to mine, has a new paper that touches on the significance of self-organization:

It is also striking how in general the idea that primitive groups are simple, almost skeletal constructions in comparison to their descendants, is simply incorrect and in precursors as diverse as the last common ancestor of the eukaryotes or choanoflagellates we either infer or see an extraordinary degree of complexity. Rather than imagining that this arose by a series of conveniently cryptic prior stages, we may have to face the possibility that evolution involves what to us seem to be a baffling series of self-organizations.

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Micah - #9152

April 8th 2010

I should have revised that to say: “but I have no way to determine the order of the outcome”

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Bilbo - #9166

April 8th 2010

Hi Mike,

By all means, IFT to the rabbit hole!

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nancy - #9173

April 8th 2010

Wonderful kathryn and I am thrilled at your research project. I guess what I want to say to is particularly to Charlie. I don’t believe you can “prove” the existence of God through science nor can you disprove it. You can confirm what you (think ) know when you have come into a relationship with God, but God is Spirit and science is not.

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Gregory - #9192

April 9th 2010

Glen,

#9121

As a person with degrees in economics and sociology, the two fields which most closely study ‘capitalism,’ I can assure you that ‘capitalism’ is not ‘unintelligently designed.’ Saying so is a bad analogy because the vast majority of human-social actions are ‘intentional’ and ‘planned’. Sure, there are “unanticipated consequences of intentional social action” (Merton 1936), but that doesn’t outweigh the ‘reality’ of the power of human choice. In 21st c. we know this.

The challenge for this thread, which Kathryn raises as a biologist, which Rich echoes, another biologist, is limited to the sphere of ‘natural-physical science.’ Once one moves outside of that scientific realm into other scientific realms or into philosophy or theology, then choice, purpose, planning, destiny, teleology, etc. come into play more seriously.

Kathryn and Rich are *not* talking about ‘choices’. No, this cannot come into the topic they are addressing as biologists.

p.s. thanks Micah for asking the question to Kathryn of a working definition of ‘random’!

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hmm - #9225

April 9th 2010

Kathryn Applegate wrote:

“Even though the freedom inherent in nature sometimes produces unintelligently-designed structures (like viruses, which can kill us), we see that God has made, and continues to oversee by his providence, a good creation that, at least in part, is capable of creating itself.”

What does the term “UNintelligently-designed” mean?

Does it mean that designer (God) is unintelligent or that viruses are designed at all? Or does it mean just some form of scientism (God of the Gaps thinking)  where God could have acted only if any other explanation is not available. And if for something exists “natural” explanation, then it is supposed to be “done” by “nature”. And not by God.

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Rich - #11956

May 1st 2010

The formation of the spheres by the shuffling of magnetized parts is misleading, in two ways.

First of all, it’s greatly oversimplified in terms of what has to happen in macrovolution.

Second, information has been snuck into the model.  Look at the shapes of the pieces, and the relatively small number necessary to form a nice spherelike structure.  Yes, you can randomly slosh particles like that around, and get a regular shape, because simplicity and compatibilty have been built in by the modeller.  The people who designed the model didn’t spend decades trying out every odd shape to see what worked; there would have been literally millions of basic shapes that could not have produced such nice structures, or at least not until after thousands of years of shuffling.  The basic shapes have been cherry-picked, by reverse engineering, to be likely to achieve the desired result in a brief time.  This is not randomness, but intelligent design.  Random shuffling is merely the catalyst which eventually brings out the implict information.

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Roger A. Sawtelle - #27593

August 30th 2010

Kathryn,

I prefer a different definition of random, which is simply “without order.”  If a series of numbers chosen at random happens to be 12345, they are not random.  There are many other combinations, which must be rejected even if they were chosen at random.

Your preordered demo is not random.

Dawkins agrees that random means “without order.”  He also admits the probability of order coming out of disorder is impossible.  Have you have heard the old saw, “If a billion monkeys typed on a billion typewriters for a billion years, they would produce War and Peace?”  If you do the math you will quickly find that this is not possible. 

So instead of meeting randomness head on Dawkins wants to breakdown each aspect of evolution into very simple steps which are solved very gradually over millions of years.  That sounds more plausible, but still does not compute.  Disorder times disorder equals disorder.  If the universe is governed by orderly natural laws, how can anything truly be random?

The problem is that Dawkins, Dennett, and Monad maintain that the universe does not have purpose or order.  Certainly they do not speak for all evolutionists, but they say their conclusion is based on Darwin’s Theory.

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