Friday, 29 April 2011

I see London, I see France, I see…Drosophila’s internal structure

This isn't going to be a long, lengthy post, but rather a short note on an interesting paper just published in Frontiers in Systems Neuroscience, detailing a neat advancement in ultramicroscopy.

As you probably already know, Drosophila is perhaps the most commonly used model organism in genetics. When a geneticist used Drosophila for a genetic screen, he generates mutants and then scans the progeny for particular desired phenotypes. For instance, if you're interested in a gene involved in the development of limbs, you'd generate mutants and then look for ones that have mutated legs. External phenotypes like this are pretty easy to observe, even without a microscope, but it's a bit harder when it comes to internal structures. What if your gene of interest is involved in forming the gut, or a particular set of muscles? One way you could go about observing internal structures would be to dissect your flies, but this has its limitations – it requires good manual dexterity, and has the added risk of tearing, ripping or otherwise mutilating your specimen. You could use in situ staining or florescence microscopy, but what you end up with is a flat 2-dimensional image that might not reveal all the details that would be present in three dimensions. Using a confocal microscope will give you good resolution, but generally use high magnifications that will not allow you to view your whole specimen at once. The paper by Jährling et al details a technique using ultramicroscopy that allows for an entire 3D reconstruction of a specimen, complete will internal structures visualized in situ.

The basic procedure goes like this: they began by "chemically clearing" their specimens – that is, using a series of chemical washes and incubations, they removed almost all colour from their specimens. They were left with flies which were nearly transparent. This would allow the internal structures to be visualized. The specimens were then mounted on an ultramicroscope, and using a laser, they took a series of 597 images, beginning at the top and moving down through the vertical plane. Once the images had been taken, they used specialized software to layer the images on top of one another to reconstruct a 3-dimensonal model. Since the flies were transparent, the model allowed for the visualization of internal structures as well as the specimen's surface. Using this technique, you can easily visualize internal structures that might be of interest to you without ever having to dissect your specimen or rely on 2-dimensional imaging techniques.

This technique really becomes powerful when coupled with fluorescent microscopy. Imagine you're convinced that your gene of interest plays a role in the development of the fly's gut. Attach GFP to a gut-specific promoter, insert the construct into your flies and then image them. What you'd get is a perfect 3D model of the fly's gut, easily distinguishable from surrounding tissue. Any phenotypic effects would be easy to observe! Using this technique, you could easily, quickly (the authors state that it takes about 30 minutes from start to finish) and reliably visualize any internal structure you wish. Pretty cool, no?
Jährling N, Becker K, Schönbauer C, Schnorrer F and Dodt H-U (2010). Three-dimensional reconstruction and segmentation of intact Drosophila by ultramicroscopy. Front. Syst. Neurosci. 4:1. doi: 10.3389/neuro.06.001.2010

Saturday, 23 April 2011

A lame argument about laminin.

It would seem that debunking Youtube creationists has become a hobby of mine. This week, I present a fellow by the name of MyGhettoGospel (I guess Jesus was into gangsta rap), who, for the sake of brevity, I'll refer to as MGG henceforth. MGG believes that biology can prove that the Bible is true, and presents his argument in the video below.

His argument is as follows: the Bible tells us that God "holds everything together"1. If it were not for God, he claims, everything would simply fall apart and the universe would be devoid of any sort of structure - and this includes people. Luckily for us, MGG says, biology provides evidence that this is indeed the case. The cells in our bodies are held together by adhesion molecules. One class of these molecules are laminins (or 'laminin's' as MGG seems to prefer). And, Great Scott, these molecules look like crosses. MGG has a picture and everything! What else could this be but the indelible mark of the Creator? A sound theological argument. Too bad it isnt reality.

MGG's argument falls apart for a variety of reasons. The first, and probably the biggest flaw in his argument is that laminin  doesn't actually look like a cross. In his video, MGG states "If you look up laminins in any scientific medical piece of literature, this [the cross shape] is what you will see'. Well, I called MGG's bluff on this one and took a brief perusal through the literature. Here is an image taken from Denzer et al (1998)2:

Look much like a cross to you? Maybe, if it were constructed by a carpenter in a drunken stupor.  How about this image from Beck, Hunter and Engel (1990)3:

Nope, still not a cross. I guess the literature does not support MGG's argument as strongly as he thinks.   His error is in mistaking diagrams of laminin, like the one he presents, for the molecule's actual physical appearance. Diagrams of any molecular structure are stylistic representations. They are always drawn in a way that makes it easy to understand the basic structure of  a molecule - where the domains are in relation to one another, how many peptide chains comprise the molecule and how they are linked together, for instance. They are not meant to be taken as representing precisely what the molecule looks like. There is always some creative liberty taken when designing a diagram. Laminin does not have a rigid cruciform structure. It resembles a cross only vaguely.

This vague cross-like shape shouldn't be in any way surprising to start with. A cross shape is very simple; it's just two lines running perpendicular to one another. Given the number of different types of proteins in the body and the variety of conformations that they can take on, it would be incredible if there weren't any proteins that resembled crosses. It can easily occur naturally and randomly. Imagine tossing toothpicks across a table. Given enough toothpicks, you're bound to find some that fall to form a cross. Would anyone argue that God had a role in this? I guess Divine Toothpicks aren't marketable.

But even if laminin did take on a rigid shape, who is to say that it depicts a cross? It could look like many things. Rotate it 90° and it looks like a dagger. I think you'd be hard pressed to find anyone who would claim this is a molecular representation of a Sikh's kirpan, and therefore Sikhism is the one true religion. The cross argument is equally absurd.

Another reason why MGG's argument is bunk is that it takes for granted the shape of Jesus' execution device as a cross. The shape of the cross has been branded into the public conscience for centuries but there is little historical reason for this. Implements for crucifixion took a variety of shapes. Writing 75 CE, the Roman historian Josephus commented that crucifixion was done in a variety of ways4. Indeed, crucifixion was sometimes done using wooden devices shaped like a T, like a Y or even like an X, as well as using the familiar cross shape. Is there any reason to believe that Jesus was crucified on a cross? Surprisingly, no. The word used in the Bible to describe Jesus' execution implement, in the original Greek, was "σταυρός" (stauros). This is translated as "upright stake" or "wooden post", indicating that he was nailed to a simple, single upright beam (known as a crux simplex). Plutarch and Lucian describe the stauros as having the form of the Greek letter Tau, or T. Neither of these interpretations can be taken as meaning a cross. So if Jesus being crucified on a cross is of dubious nature, so too is the laminin argument. If Jesus actually died on a simple wooden pole, then a cruciform molecule has no significance.

MGG's argument is also problematic theologically. The structure of laminin predates the supposed crucifixion of Christ by many millions of years. Even by Creationist standards, the crucifixion did not occur until thousands of years after Creation. Why would God decide to use a design based on the cross, then? Did he have foreknowledge that Jesus was to be crucified? This would indicate that Jesus was destined to die on the cross for mans' sins. And if Jesus was destined to die on the cross, then mankind was destined to sin. This sort of deterministic implication is at odds with the rest of theology, which claims that God gave man free will and that sin is a choice. MGG's argument implicates the opposite. Which is it, MGG? You can't have it both ways.

In essence, MGG's argument fails. Not only does laminin not resemble a cross, but even if it did, it wouldn't make any sense to interpret it as as sign from a Creator. Creationists, please stop polluting molecular biology with your nonsense. Besides, we all know who really holds us all together.


1. "The Son is the image of the invisible God, the firstborn over all creation.  For in him all things were created: things in heaven and on earth, visible and invisible, whether thrones or powers or rulers or authorities; all things have been created through him and for him.  He is before all things, and in him all things hold together" Collosians 1:15-17

2. Alain J. Denzer et al. Electron microscopic structure of agrin and mapping of its binding site in laminin-1 . The EMBO Journal (1998) 17, 335–343, doi:10.1093/emboj/17.2.335

3. Konrad Beck, Irene Hunter, and Jürgen Engel . Structure and function of laminin: anatomy of a multidomain glycoprotein . The FASEB Journal . 4(2), 2148-2160

4. Josephus, Wars of The Jews, 5.11.1

Wednesday, 6 April 2011

DNA and the Case of the Bad Metaphor: Now with 100% more Creationist Smackdown!

I love DNA. It is a wonderfully complex molecule and the mechanisms whereby genetic information is stored and accessed is fascinating; and yet, at the same time, the basic premise by which is works - the "central dogma" of molecular biology - is beautifully simple. There is little wonder why DNA has caught the eye of the public in a way that few other biological compounds have. This fascination with DNA has necessitated trying to explain the concepts underlying genetics to the public. Therein lies a problem for scientists and science journalists: how to convey the intricate and often confusing workings of science in a way that is both interesting and easy to understand for the layperson. The one tool brandished about the most is the metaphor. Unfortunately, the metaphor can be dangerous, and there is no better example of this than those metaphors used to explain DNA. Two unfortunate metaphors for DNA have been devised: the idea that DNA functions as a "blueprint" and the idea that DNA functions like a "computer code".

The 'blueprint' metaphor is especially poor. Consider what a blueprint is, exactly. It is a scale schematic used to represent a structure. If you have a blueprint of a hotel, you have a schematic of how to build that hotel. The blueprint tells you everything you need to know - how high the ceilings are, how long each wall is, how many steps are in each flight of stairs. Furthermore, you know that 1 inch on the blueprint represents, say, 1 meter in the actual hotel. From the blueprints, you can precisely construct the hotel. But there is more to a blueprint than this. The information conveyed in a blueprint works both ways - you can use a blueprint to construct a hotel, and from a fully constructed hotel, you can derive a blueprint. If a wall in the hotel is 3m in length, you can draw a wall on the blueprint 3 inches long. The information is reversible. You can go from blueprint to structure and from structure to blueprint.

This is where the analogy with DNA fails. DNA does not work as a blueprint because the information is not reversible. DNA does contain information necessary to construct an organism, but if you examine a fully formed organism, you cannot reconstruct the original DNA sequence. You cannot measure the length of a nose or determine the colour of an eye, and then write out the specific sequence needed to create these features. This is a very important aspect of a blueprint, and DNA does not meet this requirement. Rather, DNA acts more like a recipe. A recipe tells you what ingredients you need and in what manner to combine them in order to create a pie. But if you have a pie, you cannot examine it, even in the most minute of detail, and work out the exact recipe that was used. The information contained in a recipe is not reversible, just as the information spelled out by our genes is not reversible.

The 'computer code' metaphor is also a poor one, for multiple reasons (this particular analogy was popularized by Discovery Institute lackey Stephen C. Meyer). The way a computer code works is that the exact sequence of the code - the precise order of the binary 1s and 0s - spells out exactly what operations the computer must perform. But in genetics, the sequence is only part of the picture. Just as important are genetic regulatory networks - which genes are turned on at what times and in combination with which other genes. Phenotypes are not simply the result of particular gene sequences but the result of specific gene-gene (or gene network-gene network) interactions.

But DNA bears little relation to a "code" in a more fundamental way. Consider exactly what a "code" is. A code is a system of arbitrary symbols used to represent  ideas and objects. In a sense, language itself is a "code"; the symbol "dog" represents that furry tetrapod with a waggly tail, for example. In a code, the symbols themselves have no inherent meaning. The letter "d" is meaningless by itself, as are the letters "o" and "g". It is only in combination that they derive meaning, and their meaning is derived from the idea that they represent. Furthermore, they only have meaning because we give them meaning. "Dog" is merely the label we apply to Fido; in a universe without sentient beings, "dog" would be meaningless. DNA does not fit this description at all. DNA is not arbitrary in any way; each letter of the genetic "code" is an actual biological compound. ACCGTCGA might be the gene for determining how long your toe hair is, but unlike a code, A, C, T and G each have their own non-arbitrary meaning. And this meaning exists independently of human sentience - the sequence of nucleotides does not have meaning only because we give it meaning. It would have meaning even if humans didn't exist at all.

What DNA is, is a polymeric chemical that follows a dynamic chemical process, governed by universal physical rules. It is only a "code" in the same sense that nuclear fusion is a "code" for how stars produce light

So why am I taking the time to mention these things? The reason is because both these weak metaphors have been abused time and time again by creationists (and particularly the Intellignent Design IDiots). Just recently, the video below was posted to Youtube by Nephilimfree, who you may recall from my last blog post (to which he made no attempt to refute, despite having been made aware of my critique - something that should probably come as no surprise to anyone, given the tendency for creationists to retreat with tail planted firmly between their legs when presented with cold, hard, scientific fact). This latest video does not appear to be made by Nephy himself (though he gives no credit to the video's creator), but is nonetheless filled to the brim with that Nephy-brand distortion of science. While it is significantly shorter than his last few 14-minute diatribes, it might still result in significant impairment to your mental faculties, so watch at your own risk.

The video wastes no time in misleading the viewer, tossing out the "blueprint" metaphor 39 seconds in: "DNA contains the blueprint of all life and is by far the densest information storage mechanism known in the universe".  For reasons stated above, we know this metaphor is misleading at best and deceptive at worst. But it continues: "The program code and design of such an incredible system indicated a supremely intelligent designer".

Now, a claim like that one is pretty bold, and would require pretty strong evidence to rationally accept it as fact. So what kind of evidence does the video provide? The answer, really, is "none". It immediately cuts to clips of creationist talking heads (Ken Ham, Dave Hunt, and the like) who reiterate one point: "DNA is a code, and codes are information, which only comes from intelligence". Yet, at no point do they present one shred of evidence for why this is the case. They expect the viewer to simply take what they say as being true. Here we have a major distinction between science and creationism - any scientific claim will be backed up by evidence and cite sources explaining why the claim is true, whereas creationism makes assertions which they simply expect you to believe.

The video proceeds to give some details of DNA - it is self-replicating, has error-correction mechanisms ("there are special proteins called enzymes...making repairs" announces Frank Sherwin - a statement that could only be more generic had he said "there are chemicals that do stuff"), etc. But throughout, a unifying theme is repeated - "these things are complex and only God can produce complexity". But again, they provide no reason why we should believe this is true. Perhaps it is left up to our imagination.

What the video boils down to is that creationists make two claims about DNA: 1) that DNA is a "code", and 2) information/complexity (via the genetic code) can only come from an intelligent designer. Both these claims are really nonsense.

Calling DNA a "code", as explained above, is simply incorrect. DNA is not a code in any sense of the word. But let's assume for a moment, that DNA is a code written by God. If this were the case, then God could definitely benefit from taking an introductory computer programming course. God seems to be an awful coder. DNA is very error prone, and the code is regularly mistranslated and copied incorrectly. Different organisms have similar functions, but use different coding sequences. Some organisms contain the code for functions they don't even use, and the majority of code in any given organism is completely non-coding! For an all powerful supreme being, his code is awfully amateurish.

The argument that "information and complexity can only come from intelligence" is also absurd. To begin with, whenever creationists fling around the term "information" they never define what it is they mean by the term. "Information" can mean different things in different contexts. To a creationist, information is some amorphous concept, never, or only vaguely, defined. The idea that "information" cannot be arranged by nature is also silly. Consider the following situation. A friend says to you, "The sun has to have been created by an intelligent creator. There is no other way to explain sunlight." "Don't be silly," you retort. "The sun is a burning ball of hydrogen which emits energy with wavelengths in the visible spectrum." Unfazed, your friend replies, "That is nonsense. Consider the sources of light we have here on Earth. We only ever see light from light bulbs. Light bulbs do not arise naturally! They are the produce of man made design. We never see light occurring naturally. The sun has to have been intelligently designed. Chemicals cannot just come together and "randomly" create light!". Such an argument is not unlike that creationists use to explain genetic information. They claim that genetic information has to have been designed because information does not arise spontaneously; but the claim that information does not arise spontaneously assumes that genetic information was designed! Once again, a creationist argument is little more than tautology.

In the end, the argument presented in Nephy's little video can basically be paraphrased as "Look at DNA! Look at it! Isn't it complex?! And look at cells! They are soooooo complex!", and then baselessly ascribing that complexity to God. This is, of course, patently untrue. There are many examples of complexity arising through completely naturalistic mechanisms. Snowflakes are a perfect example of this. Do creationists really think that their God spends time making each individual snowflake? What about crystals? Pour some sugar into hot water and suspend a string in it, and before long, you have beautiful and complex crystalline growth. This is an entirely natural process - complexity without the intelligence.

Complexity is not the hallmark of design. DNA is not a blueprint nor is it a computer code. And once again, Nephilimfree is not correct.