“God likes matter. He invented it” (C.S. Lewis): A talk by Kenneth Miller at the University of Maryland

On Thursday I came back to my office to find a ripped-down poster haphazardly taped to my door, announcing a talk Friday by Ken Miller--the author of popular books about evolution, such as this year’s Only a Theory. The culprits, a couple friends of mine in the department, had misunderstood Miller’s stand on evolution due to vague wording in the poster, and stuck it on my door to piss me off.

They didn’t know of course, that I just finished Only a Theory last week, loved it, had no idea Miller was coming to speak, and was overjoyed to be informed of it. Needless to say, they were annoyed that the guy wasn’t in fact a creationist, and I wasn’t in fact pissed off. The talk was wonderful though. He is as good of a speaker as he is a writer. I think he fills a very needed role in the evolution/creationist debates—as a Christian himself, he is able to speak directly to fears that evolution and theism are fundamentally incompatible. As Miller points out, people’s beef with evolution is not really scientific, it’s philosophical—the fear that evolution takes away our ability to be moral human beings with purpose in our lives.

His talk was basically a summary of OAT, but for those who haven’t had a chance to read it yet, I’ll outline the talk for you here.

He started off with an overview of all the legal challenges to evolution that have been cropping up within only the last four years: there have been two federal trials (outlined below) and two state elections (OH and KS) that hinged on questions of evolution. Anti-evolution measures were passed in six state legislatures during this period, and 44 states had local measures passed in counties or in individual communities.

At the federal level, there was the 2004 case in Cobb County, Georgia, where the school board decided to put warning labels on the inside of the local high school biology textbook (written by Miller, incidentally). The stickers read, “This textbook contains material on evolution. Evolution is a theory, not a fact, regarding the origin of living things. This material should be approached with an open mind, studied carefully and critically considered." Miller pointed out that the scientific definition of “theory” is not “we don’t really know,” and really a theory is of a higher order than a fact, since theories explain sets of facts. Additionally, he protested that the sticker conveys a false sense of certainty about all other fields of biology, and implies that, for instance, ecology and cell biology should not “be approached with an open mind, studied carefully [or] critically considered.” Kind of insulting to all biologists, really.

And then of course there was the famous Dover trial in 2005, for which he served as an expert witness for the side of science. In this case, the local school board was guided by the Discovery Institute’s booklet, “Intelligent Design in Public School Science Curricula: A Legal Guidebook,” and bought two sets of the Intelligent Design textbooks “Of Pandas and People” for the school library, as recommended by the booklet. The board also demanded that the biology teachers re-write their curricula to include intelligent design. They refused. The school board pushed back, demanding then that the teachers at least use an intelligent design lesson plan that the school board wrote for them. They refused. The school board finally asked the teachers to just read a statement to the class about the “weaknesses” of evolutionary theory and the teachers once more refused, forcing the school superintendent to come in and read the statement to the classes while the teachers stood outside. There was immediate protest from the community, of course, and a first amendment lawsuit was quickly filed against the Dover Area School District.

A group of scientists, including Miller, volunteered to serve as expert witnesses. Miller noted in his talk that despite ID proponents’ eagerness to subpoena “evolutionists” for a courtroom trial and force them to speak under oath, 5 of 8 ID witness volunteers dropped out of the case (including William Dembski, who wrote the document linked to in this paragraph).

The details of the ruling and the evidence is really quite fascinating, and you can find a thorough summary at Wikipedia along with a link to the judge’s decision. (The judge ruled, by the way, on the side of evolution.)

Miller then went on to outline just some of the purported evidence for Intelligent Design. In his talk on Friday, he just went over one major piece of the ID case—the “irreducible complexity” of the bacterial flagellum, but his book has many more, all of which he carefully considers and thoroughly destroys.

Michael Behe, one of the major ID theorists, defines irreducible complexity basically as the inability to produce a complex structure piece by piece while maintaining one function. For example, you couldn’t evolve a mousetrap because a mousetrap with only a couple of its parts is no longer a mousetrap—all of the parts are necessary for its mouse-catching function. The IDers say that the bacterial flagellum is an example of such an irreducibly complex structure, as it would not be able to function as a flagellum without any of its parts.

As Miller described in his talk and in OAT, the major problem with this argument is that it assumes that modern-day biological structures have evolved from earlier structures with similar functions. The fact is, as structures evolve, they often acquire radically new functions. (See my earlier post on the tryptophan operon for a biochemical example of this.) The same goes for the bacterial flagellum. It turns out that the base of the flagellum has incredible homology with another bacterial structure called a Type III Secretory System, used by bacteria to pump poisons. Additionally, other parts of the flagellum are made of a number of other proteins that exist elsewhere in the cell, performing other functions. So, unlike the predictions of the Irreducible Complexity argument, it is in fact possible to “take away” parts of a complex biological machine and have it still function—it’s just a different function.

At this point in the talk, Miller switched gears. He asked: well, if the best arguments the IDers can come up with don’t hold water, why is there such popular support for ID? He put a lot of emphasis on a quote from an NPR interview about evolution with former Sen. Rick Santorum, which I think is significant enough to reproduce here in its entirety:

"It has huge consequences for society. It's where we come from. Does man have a purpose? Is there a purpose for our lives? Or are we just simply the result of chance? If we are the result of chance, if we're simply a mistake of nature, then that puts a different moral demand on us. In fact, it doesn't put a moral demand on us."

Miller’s point was that Santorum--and approximately half of Americans--reject evolution because they see it as materialistic to a fault: denying souls, denying order, purpose, and meaning. Essentially, Miller argued, the design movement has forced science into a corner: out of opposition to the ID movement, scientists find themselves having to take the exact opposite position—that there is no design in the universe.

Miller argued the opposite: the universe has a design; it is the design of evolution. Basically, he said that evolution is an inherent, predictable property of life. It explores adaptive space in a predictable way, filling the same ecological niches with similar types of organisms. All organisms and biological structures do have a function, but it is a function that is driven by evolution. Miller went through several examples--such as the elegance of the genetic code, the specificity of proteins, the homology between different sorts of animals—-to illustrate this evolutionary “design.” He would probably note that the fact that I just put the word “design” in quotes in that last sentence is a sign that I am a scientist who has become afraid of the word because of its attachment to the anti-science ID movement. We, as the science-loving public, must reclaim that word, he argued. Regardless of our own beliefs about religion, we must show that the design of evolution does not mean our species and our lives are ruled only by chance and accident--we can still have purpose in our lives, and we are not "mistakes." Science’s derided materialism is its virtue, not its downfall, because it allows science to find natural explanations for natural phenomena. The ID movement was founded on an opposition to this materialism but Miller (like C.S. Lewis in the title of this post) argued that materialism shouldn’t frighten us, as a society, away from science. The scientific process cannot make claims about good and evil; this is society’s job as a whole. Science, and specifically evolution, Miller argued, will not make us immoral. It will only teach us about our place amongst the life on Earth, a place uniquely suited for us and our lives, each with its own unique purpose for the greater good.

Miller deftly answered the questions from the audience after his talk. This is obviously a man who has given many, many talks to diverse audiences, has heard every possible question, and has thought about all of them. His answers were eloquent and well-considered. If there were any IDers in the audience, they did not speak up in the Q&A period. As a friend and I discussed afterwards, they really wouldn’t have much to protest in the talk. Miller really covered all of the bases, and as a practicing Roman Catholic, could hardly be told that evolution is threatening to religion. If you haven’t yet read Only a Theory I suggest you pick it up at your local library. Not only does it thoroughly annihilate the ID position from every angle (useful reading for when you are forced to argue with a creationist) and discuss the larger anti-science implications of the anti-evolution movement, but it also provides a useful and much-needed perspective on the relationship between evolution and philosophical questions of morality and purpose. Read the book, and if you are lucky enough to see an announcement of a talk by Ken Miller, go and see him--and bring your friends.

Flip-Flopping Functions at the Drop of a (Leucine-Shaped) Hat

Conceptualizing evolutionary change is a difficult thing. If something has changed from A to B, and if A and B have drastically different forms or functions, it is often hard to envision the gradual changes that must have occurred between them. This difficulty is exacerbated if an intermediary form seems impossible, maladapted, or even just neutral. It’s easy to see how this conceptual difficulty might have led some people to reject evolution entirely.

However, a new paper in Nucleic Acids Research reminds us that intermediary forms are not always necessary in evolution. Resch and Striegl et al. [36(13):4390-4401] report a sudden switch in function in the evolution of a regulatory protein, which changes between two mutually exclusive modes of action with just one amino acid change. No conceptually impossible intermediate necessary!

Before I get into the paper, let me back up and go over some background you’ll need to understand it. The paper focuses on a bacterial repressor protein. In bacteria, repressor proteins stop transcription of a gene by binding to a certain spot in DNA, called the operator. Let me explain. Normally, for DNA’s information to be used, it first has to be transcribed into RNA by RNA polymerase. RNA polymerase binds to the DNA and travels along it, letting out a growing string of newly-transcribed RNA as it passes along. Before beginning to transcribe the actual gene in the DNA, however, the RNA polymerase must pass over the operator. If nothing is bound to the operator, the RNA polymerase can just continue on and complete the transcription. If, however, a repressor protein is bound to the operator, it physically blocks the RNA polymerase from passing, thus preventing the gene from being transcribed and “read.” (If you’re not a biology person and can’t picture this process blindfolded with your hands tied behind your back, check out this video.

There’s an added level of complexity when you consider what is regulating (controlling) the repressor. There are two completely opposite ways of doing this. One is through an inducer, which is a molecule that binds to a repressor, preventing it from binding to the operator. The second is through a co-repressor, which binds to the repressor, helping it bind to the operator. So, inducer → gene expression, co-repressor → no gene expression. Two totally different options. To illustrate, see the pictures and captions below:

This is a set of genes called the Lac Operon, which is regulated by a repressor and an inducer. Notice how the repressor (maroon oval) is always bound to the operator to prevent transcription, unless the inducer (blue oval) attaches to the repressor causing it to fall off and allowing transcription to occur.

This one is a picture of the Trp Operon, regulated by a repressor and a co-repressor. Normally, the repressor (U-shaped orange thingie) is not bound to the operator, and gene transcription occurs. However, when the co-repressor (blue hexagon+pentagon) is present, it binds to the repressor, allowing it to bind to the DNA, stopping transcription.

The take-home message from this is that repressor-mediated gene regulation can occur in two opposite ways: two things binding together to stop transcription, or two things binding together to allow transcription.

In the paper by Resch and Striegl et al., they describe how one regulator switched between the two opposites listed above in just one small evolutionary step. The regulator in question is called TetR, pictured below, bound to its operator on a strand of DNA:

TetR is involved in tetracycline resistance in bacteria. (Bacteria have a habit of quickly evolving resistance to whatever antibiotics we throw at them, and they’ve done particularly well with tetracycline—there is not just one but at least three different mechanisms for tetracycline resistance in bacteria. For an interesting review, check out this paper by Speer et al. from 1992. TetR works like the regulator in the Lac operon in the example above. Its normal position is to be bound to the DNA, preventing transcription of its tetracycline-resistance genes. Antibiotic resistance is often costly for bacteria, and they generally only activate their resistance when it’s needed. In this case, the resistance is needed when tetracycline is present in the environment. The tetracycline acts as the inducer, binding to TetR, which causes it to release from the DNA, allowing transcription of the resistance genes. When tetracycline is removed from the environment, TetR is able to bind to the DNA again.

The weird thing is, there’s several mutant versions of Tet-R (called revTet-R) that have exactly the opposite behavior. revTet-R cannot bind to DNA unless tetracycline is present, much like in the example of the Trp operon, above. In the mutant, tetracycline suddenly acts as a co-repressor, not an inducer. (This results in tetracycline in the environment turning off the tetracycline-resistance genes, and in the genes being on once tetracycline goes away.) Even weirder, one of these mutants is only one amino acid different than the sequence of the original Tet-R—the 17th leucine in the chain is replaced by a glycine. How could a change of just one measly amino acid in this large, complex protein change induce a completely opposite behavior from the one it originally possessed?

The authors and their team used a variety of biochemical procedures to answer this question. They raised the revTet-R mutant bacteria, broke open their cells, purified the contents to get out the revTet-R protein, broke it up, then sequenced the bits. Then they determined its three-dimensional structure with and without attachment to tetracycline.

Here’s a picture of the two molecules taken from the article, going through their processes of binding tetracycline and DNA, side-by side. The line drawings represent the overall structure of Tet-R and its variant. The left-most, vertical arrangement (A-C) is revTet-R, and the horizontal arrangement (D-F) is of Tet-R. The “effector” is tetracycline, and it binds to that little oval in the center of the egg-shaped part of the protein.

Let’s start with the standard Tet-R, images D-F. Notice that the helix α4 (the rectangle) functions like a pendulum, swinging up and tightening in the two ball shapes tight in close to the main egg-shape when tetracycline (the effector) is present. This prevents DNA from being able to fit into the binding site to attach. But in the absence of tetracycline, the pendulum swings down, opening up the binding site to DNA. However, in revTet-R, in the absence of tetracycline (A) the amino acid chains that are normally rolled up into two balls no longer want to bind up together. Instead, they are loose and free, and don’t make any of the three-dimensional structure necessary to bind DNA. The slight change in amino acid sequence in the mutant is enough to screw up the whole DNA binding apparatus. However, when tetracycline is bound in (B), all of a sudden everything tightens up, and the result looks a lot like (D): Tet-R with tetracycline. But, because of that amino acid substitution, the normally tightly-bound DNA binding site is not as tight as it usually is. This weakness allows DNA entry into the binding site even when tetracycline is attached, resulting in revTet-R to have an opposite action to Tet-R.

So from just one single amino acid change, this protein called Tet-R completely reverses its function, but through a completely different mechanism and set of conformational changes than it goes through normally. This just wows me with its level of specificity—with all the thousands of amino acids in this protein, just one change can screw everything up in such a drastic way. Not just to break it—which is easy—but actually to reverse it through a whole new mode of action. I’d imagine that creationist folks would say this is evidence of the delicacy of life, how everything is too fragile and precise to have arisen on its own without being designed. But I would argue that this incredible ability to change gears is evidence for the power of random change—how even if an organism’s environment suddenly does a 180, random mutation is sufficient to allow it to go with the flow and allowing the species to adapt in a radical manner to whatever its ecosystem can throw at it. Obviously in this case, a revTet-R mutant doesn’t seem very well-adapted to a bacterium’s normal environment. Turn off your tetracycline-resistant genes in the presence of tetracycline? (It was generated in a laboratory through random mutagenesis, not evolved naturally in the wild.) But it’s a great living analogy for the power of mutation to do crazy, seemingly-impossible things. Obviously evolution often occurs through slow steps and many intermediates, especially for larger, more complex organisms. But this paper shows that it doesn’t always have to happen that way.

Susan's Snazzy Arthropod of the Day: Mastotermes darwiniensis

I know some of my dear readers are less than fond of our termite friends, but as I'm pretty sure that my readership is still restricted to acquaintances in the U.S., you don't have to worry about it eating your house. It’s Mastotermes darwiniensis of Australia, the only extant member of the termite family Mastotermitidae. Apparently the common name is the Giant Northern Termite or the Darwin Termite. All the termite biologists I know, however, just call it by its genus name since that is pretty darn specific, it being such a phylogenetic loner.

The thing that makes Mastotermes so cool is its evolutionary significance. Upon its description a hundred or so years ago, it was the clue that made biologists pretty sure that termites are very closely related to cockroaches. This suspicion was confirmed last year with the first comprehensive phylogeny of roaches and termites using molecular data: In the roach family tree, termites are just one branching limb nestled in the tree, and Mastotermes is the branch closest to the roach trunk.
Below are pictures of a generic termite, Mastotermes side-by-side, with a generic cockroach right underneath.


You, a layperson, can easily see some of the striking similarities between Mastotermes and the cockroach. On the extended wings, do you see how Mastotermes and the cockroach both have that extra lobe coming out of the back end of the hindwing? That’s called the anal lobe. It’s found in all cockroaches, and no termites except for Mastotermes. The nerve patterns between Mastotermes and the cockroach are similar as well. Additionally, you can see the differences in the shield behind the head (called the pronotum, which covers the prothorax): on the generic termite it’s pretty small, but much larger in Mastotermes, as large as its head—much closer in size to the cockroach’s greatly expanded pronotum. You may also be able to infer from these drawings that Mastotermes is also quite a bit larger than other termites, closer in size to a roach. Other morphological similarities between Mastotermes and the cockroach that you’re not able to see in these drawings are the 5-segmented tarsi (feet) with pulvilli (adhesive pads), the ovipositor (egg-laying tube) in the females, the oothecae (egg masses), the row of spines along the tibiae (a leg segment), and possession of the same kind of gut microbiota. None of these features are shared by the other termites.

So it seems that both the morphological and molecular data point to Mastotermes representing a “transitional form” in termite evolution from a roach-like ancestor: i.e. it branched off early in termite evolution and still retains many of the ancestral cockroach characteristics. (Note: creationists commonly claim that no transitional forms exist, thus evolution is wrong—despite the overwhelming evidence. Next time you have to talk to one, remember Mastotermes.) Of course Mastotermes is a modern animal, and can’t be confused with the actual transitional form between roaches and termites that lived in the early Cretaceous or before. But since it seems to have kept many of those ancestral features, it’s a pretty good proxy in many respects.

As you probably know, termites are highly social creatures—they live in colonies of extended families where most individuals are altruistic and only a couple individuals reproduce. (Note that “social” in the context of evolutionary biology has a much more specialized meaning than it does in conventional speech.) Though some roaches live in simple family groups, none are truly social like the termites. So if we were interested in learning about the evolutionary steps in between family living in the roaches and true social (“eusocial”) behavior in the termites, it seems like Mastotermes would be the perfect place to look, because of its half-roach, half-termite appearance.

Wrong.

The odd thing about Mastotermes is that while it is morphologically primitive, and has not changed its physical appearance much in many millions of years, its behavior and social structure are highly complex, and as derived as the termites that have evolved most recently of all. Mastotermes builds huge underground nest structures that contain extensive gallery construction and tunnel excavation; it forages far afield from the nest, and has been known to damage structures over a hundred yards away from its colony. Full-grown colonies contain over a million individuals, with rigid caste structures and obligatory sterility for the worker forms. This is a lot like the most-derived, most-recently evolved termites, like the great mound-builders of Africa. In contrast, the most termite-like cockroach and the next-most-primitive termites after Mastotermes all live and eat inside one piece of rotting wood, have very flexible development, do not have obligatory sterility in the worker forms, build no galleries and no tunnels, and are have many fewer group members.

Mastotermes is thus a weird chimera of primitive morphology but derived behavior and development. If it were translated into, say, the primates, it would be a lemur with a big brain, language capabilities, and maybe a car. I think it’s a great example of the complexity of evolution, and shows how even within a single species vastly different evolutionary paths can be taken in different areas of one genome.

The Scala Naturae and Evolution

People often have misconceptions about the process of evolutionary change. I find that one of them is often that evolution is sort of a giant ladder. Life is arranged on this ladder in order of primitive to advanced, with each organism in its place. As evolution progresses, organisms can step up, reaching greater heights of perfection and complexity, climbing until at last, the pinnacle of human perfection is reached. This idea of evolutionary change actually has very deep roots, back to at least the Middle Ages.

The great chain of being, or scala naturae, was a medieval philosophical concept that was the basis of thinking about the order in the world for much of western history. In the great chain of being, all living things are organized from most perfect, at the top, to least perfect, at the bottom, in a continual series of gradations. Of course, God is above everything. Below God is the King, below the King are the lords, and so on. Eventually the chain reaches the last serf, and starts down into the animals. Every animal is ranked according to medieval man’s idea of its nobility, its complexity, and its usefulness to man. Lions and tigers and the like are at the top, ladybugs are above flies, oaks are above the demonic yews, and snakes are at the very bottom of all animals. All of these are then in turn above the minerals. Once microorganisms (animalcules) were discovered by Antony van Leeowenhoek in 1683 (in the plaque of an old man’s teeth), they fit perfectly in that gap between animals and minerals.

Once evolution was accepted by the mainstream scientific community, these ingrained ideas of “the order of nature” became the unconscious basis for the evolutionary ordering of life. The scala naturae was originally meant to be a fixed chain, with each thing’s place immovable, but with minor adjustments the same idea could be read as a ladder instead, a progression through time. And of course, who is at top, but man. Sean Nee has a great article about this in the journal Nature [435: 429] from 2005. He writes how any published phylogeny that includes humans inevitably will place humans at the top of the tree, even when they could correctly be placed in some other ordering. This isn’t coincidental. If you still have your high school or middle school biology textbooks lying around, take a look at them. You’ll notice how they will start out their discussions of living things with viruses and bacteria and other single-celled things, progress through plants perhaps, into insects and squirmy things, through reptiles and birds, and finally into the mammals, with the very last section being about human evolution: the pinnacle, the peak of God’s creation evolutionary history. It’s very deeply engrained in our cultural psyche.

This view of evolution and nature, obviously, is flawed. With this sort of idea it’s natural to visualize a whole-organism progression; a collective complexifying of all the organism’s parts simultaneously. However, organisms are mosaics of derived and primitive features [spoiler warning, see next post!]; our own genome contains remnants of retroviruses; our mitochondria were originally free-living bacteria. Furthermore, plenty of “simple” organisms have immense super-powers that we, the apex organisms, can only dream about, like the ability to survive in environments with and without oxygen, like facultatively anaerobic bacteria. The erroneous view of a progressive ladder implies that “simple” modern organisms are somehow ancestral organisms simultaneously, leading to the “men from monkeys” fallacy of human evolution and the recent portrayal of the platypus genome as “a cross between a reptile's and a mammal’s.”

A much better view of evolutionary “progress,” one that at least gives us an idea of our true place in the universe, is one like this one. Notice the small insignificant little “Homo” down there on the bottom left of this branching bush. (Compare that tree to this one though, to see how the same sort of information can be flipped around to feed that old human ego some more. Why are animals at the top? Bacteria are the ecologically dominant life-form, after all.) Or perhaps a web would be better, to show the interlinking of life: fungi and algae, joining to form lichen; retroviruses and humans, our genomes inextricably intertwined. Or perhaps the map could be of just one single organism, color-coded, labeled, showing the differential evolution of all the various parts—the parts that have slowed down their development, the parts that have gone off into something totally novel, the parts that happen to be very similar to its relatives.

Perhaps the reason why so many people have trouble accepting evolution is that they still have these ingrained ideas about it, based on the centuries old scala naturae. If you really start to look around at the world, nature doesn’t seem to fit such a rigid view, such a strict, ordered progression. If this is how people think of evolution, no wonder they reject it. If we are able to recognize these deeply embedded cultural preconceptions in our own minds, it would go a long way in helping us embrace the odd complexity of the world, the riotous transformations over evolutionary time, and our own place—a small side branch, nestled among the apes and the protists and the dandelions, a great vantage point from which to watch evolution unfold around us.

Score One More for Evolution--Magical Disappearing Fish Eyes

OK PEOPLE. Evolution is a fact. The details are up for grabs--that's how science goes. The book of Genesis, the seven days, the whole shebang, is an allegory, ok?
Now, can we just get over it and stop being stupid jerks and ruining kids' science educations? Really.

So we all know that deep down in dark caves lives oodles of weird animals without eyes. You've got your blind shrimp, your blind isopod, your blind salamander, and your blind fishy friend, the charismatic Astyanax jordani, the subject of a big huffy fit courtesy Casey Luskin at the Discovery Institute.

Luskin's argument is that loss-of-function mutations--i.e. mutations which occur randomly, screwing up a functioning gene so it "breaks"--are not contrary to the idea of intelligent design. The idea seems to be that God created something a certain way, and then something in our imperfect, corrupted world caused some oops to happen in the DNA that messed up God's perfect design. Ignoring the flaws in that argument for a moment (If that were so, and loss-of-function mutations were just unfortunate mistakes, how would they get fixed in a population? Could it be--gasp! natural selection??), let's examine Luskin's claim briefly.

He claims that the only thing that "Darwinism" (what a bad, incorrect term) cannot explain is gain-of-function, when an organism actually acquires a new trait.

Unfortunately for him, this loss-of-function in Astyanax jordani is actually a GAIN-of-function: a developmental gene called sonic hedgehog is actually upregulated, which increases skin sensitivity (beneficial to cave life, no?) while having the side-effect of disrupting eye development. PZ Myers has a great discussion of the flaws in Luskin's "argument" and the details of how A. jordani lost its eyes over at the Panda's Thumb.

Take that, Discovery Institute.