I like this hypothesis

But we have to be clear that it is only a hypothesis at this point. I was reading about domestication syndrome (DS) — selecting animals for domestication has a whole collection of secondary traits that come along for the ride, in addition to tameness. We are selecting for animals that tolerate the presence of humans, but in addition, we get these other traits, like floppy ears, patchy coat color, shortened faces, etc.; the best known work in this area is by Belyaev (YouTube documentary to get you up to speed) who selected silver foxes for domesticity, and got friendly foxes who also had all these other differences from their wilder brethren. Similar changes have been seen in rats and mink, so it seems to be a mammalian characteristic that all these differences are somehow linked. Here’s a handy list of the changes in domestication syndrome.

List of traits modified in the “domestication syndrome” in mammals

Trait Animal species Location/source
Depigmentation (especially white patches, brown regions) Mouse, rat, guinea pig, rabbit, dog, cat, fox, mink, ferret, pig, reindeer, sheep, goat, cattle, horse, camel, alpaca, and
Cranial and trunk
Floppy ears Rabbit, dog, fox, pig, sheep, goat, cattle, and donkey Cranial
Reduced ears Rat, dog, cat, ferret, camel, alpaca, and guanaco Cranial
Shorter muzzles Mouse, dog, cat, fox, pig, sheep, goat, and cattle Cranial
Smaller teeth Mouse, dog, and pig Cranial
Docility All domesticated species Cranial
Smaller brain or cranial capacity Rat, guinea pig, gerbil, rabbit, pig, sheep, goat, cattle, yak, llama, camel, horse, donkey, ferret, cat, dog, and mink Cranial
Reproductive cycles (more frequent estrous cycles) Mouse, rat, gerbil, dog, cat, fox, goat, and guanaco Cranial and trunk (HPG axis)
Neotenous (juvenile) behavior Mouse, dog, fox, and bonobo Cranial
Curly tails Dog, fox, and pig Trunk

(Hah, reduced brain size. I have a cat, I believe it.)

We have a very good idea of the proximate cause of tameness: the animals have reduced adrenal glands, which means their stress response is reduced, they’re generally less fearful, and they are more open, in early life at least, to socialization. But why can’t genetic mutations that reduce the size of the adrenal gland occur without also changing the floppiness of the ears? There isn’t an obvious physiological link between the two, or other traits in that list.

One idea is that there is a Genetic Regulatory Network (GRN). A GRN is a set of genes that mutually regulate each other’s expression, and may be controlled by the same set of signals. Imagine a lazily wired house in which the lights in the kitchen and the living room are on the same circuit, so you use one switch to turn them both on and off. Or perhaps you’ve cleverly wired in a simple motion sensor, so that when you trip the living room light, the changing shadows concidentally trigger the kitchen light too. Everything is tangled together in interacting patterns of connectivity, so you often get unexpected results from single inputs. The mammalian GRN works, though, so it’s been easier to keep it for a few tens of millions of years, rather than rewiring everything and risking breaking something.

More evidence that there’s a network involved is the fact that these domestication changes can happen incredibly rapidly — Belyaev was getting distinctive behaviors with only decades of selective breeding. What that means is that we’re not dealing with the sudden emergence of mutations of large effect, but with many subtle variations of multiple genes that are being brought together by recombination. This also makes sense. Rather than gross changes that change the entire GRN, what you are doing is tapping into small differences in a number of genes that individually have little or no effect, but together modify the target organ. So in order to change the size of an adrenal gland, you gather together an existing mutation that makes a tiny change in the size while also making ears floppier, and another one that also makes a tiny change in size while also shortening the snout, and another that makes a tiny change while modifying pigment cells.

That’s a very nice general explanation, but in order to advance our understanding we need something a little more specific. What genes? What links all these traits together?

Wilkins and his colleagues have suggested an obvious starting point: it’s all neural crest. Neural crest cells (NCCs) are an early population of migrating cells that infiltrate many tissues in the embryo — they form pigment cells, contribute to craniofacial cartilages, supporting cells for the nervous system, and just generally are found in precisely the places where we see the effects of domestication. So one reasonable hypothesis is that when you’re selecting for domestication, you’re actually selecting for reduced adrenal glands, which is most easily achieved by selecting for retarded or reduced or misdirected NCC migration or increased NCC apoptosis (multiple possible causes!), which has multiple effects.


In a nutshell, we suggest that initial selection for tameness leads to reduction of neural-crest-derived tissues of behavioral relevance, via multiple preexisting genetic variants that affect neural crest cell numbers at the final sites, and that this neural crest hypofunction produces, as an unselected byproduct, the morphological changes in pigmentation, jaws, teeth, ears, etc. exhibited in the DS. The hypothesized neural crest cell deficits in the DS could be produced via three routes: reduced numbers of original NCC formed, lesser migratory capabilities of NCC and consequently lower numbers at the final sites, or decreased proliferation of these cells at those sites. We suspect, however, that migration defects are particularly important. In this view, the characteristic DS phenotypes shown in parts of the body that are relatively distant from the sites of NCC origination, such as the face, limb extremities, tail, and belly midline, reflect lower probabilities of NCC reaching those sites in the requisite numbers. The stochastic, individual-to-individual variability in these pigmentation patterns is consistent with this idea.

They document all the phenotypic changes associated with domestication, and strongly correlate them with neural crest mechanisms. It’s a mostly convincing case … my major reservation is that because NCCs are ubiquitous and contribute to so many tissues, it’s a little bit like pointing at a dog and predicting that its features are a product of cells. It’s a very general hypothesis. But then they also discuss experiments, such as neural crest ablations or genetic neurocristopathies that directly modify the same processes involved in domestication syndrome. So it is a bit helpful to narrow the field from “all cells” to “this unique set of cells”.

I have a similar reservation about their list of genes that are candidates for the GRN — they list a lot of very familiar genes (PAX and SOX families, GDNF, RTKs) that are all broadly influential transcription factors and signaling molecules. Again, it helps to have a list of candidates, it’s a starting point, but in an interacting network, I’d be more interested in a summary of connections between them than in scattered points in the genome.

You need a diagram to summarize this hypothesis, and here it is, featuring the important distinction between selected and unselected traits.


I do have one question that wasn’t discussed in the paper, and would be interesting to answer with better genetic data. We talk about domestication syndrome as if it all goes one way: wild predator becomes more tolerant of humans. But it seems to me that it’s a two-way process of selection, and humans also had to be less stressed out and tolerant of sharing a space with an animal that would like to eat them, or compete with them for resources. Are humans self-domesticated apes? Were we selected for reduced neural crest input? If we figured out the changes in genes involved in domestication, it would be cool to look at dogs and cats and foxes, and then turn the lens around and ask if we experienced similar changes in our evolution.

Wilkins AS, Wrangham, RW and Fitch WT (2014) The “Domestication Syndrome” in Mammals: A Unified Explanation Based on Neural Crest Cell Behavior and Genetics. Genetics 197(3):795-808.

They don’t understand allometry!

I think the engineers are just trying to wind me up, again. Joe Felsenstein tackles a paper published in an applied physics journal that redefines evolution and tries to claim that changes in aircraft design are a good model for evolution. It’s a terrible premise, but also, the execution is awful.

But permit me a curmudgeonly point: This paper would have been rejected in any evolutionary biology journal. Most of its central citations to biological allometry are to 1980s papers on allometry that failed to take the the phylogeny of the organisms into account. The points plotted in those old papers are thus not independently sampled, a requirement of the statistics used. (More precisely, their error residuals are correlated). Furthermore, cultural artifacts such as airplanes do not necessarily have a phylogeny, as they can borrow features from each other in massive “horizontal meme transfer”. In either case, phylogeny or genealogical network, statistical analysis requires us to understand whether the points plotted are independent.

The paper has impressive graphs that seem to show trends. But looking more closely we notice that neither axis is actually time. If I interpreted the graphs as trends, I would conclude that birds are getting bigger and bigger, and that nobody is introducing new models of small airplanes.

And they really do redefine evolution.

Evolution means a flow organization (design) that changes over time.

I’m going to redefine bridge construction as gluing together lots of matchsticks. Hire me, everyone, to help fix your infrastructure problems! I can probably underbid everyone!

But it’s just kind of amazing that they’ve defined evolution without any mention of populations or shifting allele frequencies or any of the processes (which don’t include design) that lead to changes in genotype, or even a recognition of how these processes derive from a core unity and lead to diversity. Design done did it.

My big gripe is that they got this paper published that is all about allometry with scarcely any understanding of the concept. Here’s the abstract of The evolution of airplanes.

The prevailing view is that we cannot witness biological evolution because it occurred on a time scale immensely greater than our lifetime. Here, we show that we can witness evolution in our lifetime by watching the evolution of the flying human-and-machine species: the airplane. We document this evolution, and we also predict it based on a physics principle: the constructal law. We show that the airplanes must obey theoretical allometric rules that unite them with the birds and other animals. For example, the larger airplanes are faster, more efficient as vehicles, and have greater range. The engine mass is proportional to the body size: this scaling is analogous to animal design, where the mass of the motive organs (muscle, heart, lung) is proportional to the body size. Large or small, airplanes exhibit a proportionality between wing span and fuselage length, and between fuel load and body size. The animal-design counterparts of these features are evident. The view that emerges is that the evolution phenomenon is broader than biological evolution. The evolution of technology, river basins, and animal design is one phenomenon, and it belongs in physics.

Isn’t it cute how they claim biology as a small subset of physics? Blech.

But they only address a very narrow part of allometry. There is a functional constraint on form: you won’t survive if you have a human-sized body and a mouse-sized heart; if you scale the diameter of your legs linearly with your height, you won’t be able to walk; for a given metabolic rate and mass, you need a certain amount of respiratory surface area. That’s interesting stuff to a physiologist, but it’s also purely defined by necessity.

A developmental biologist might be more interested in how the relative sizes of different body parts change over time. Again, relative growth rates of different parts of your body are not linearly related; imagine being six feet tall with the same proportions as a baby. There are regulatory constraints on development that impose different rates in different areas.

But these guys are talking about evolution and allometry…and they treat it as a simple function of physics, where you need an engine of size X to propel a plane of size Y. Then how come every animal of the same size don’t look identical? Why doesn’t every passenger plane that carries a certain number of customers look the same (well, they do kind of blur together for me, but I’m sure any aerospace aficionado can tell me about all the differences between Boeing and Airbus. But many of these differences in animals are a result of inherited patterns, and phylogeny is essential to understand them.

For example, here’s a plot of brain mass relative to body mass (yeah, ugh, “lower” and “higher” vertebrates; let’s call them anamniotes and amniotes instead).


Notice that there are two lines drawn. Both show an upward trend, with a slope that’s proportional to the 2/3 power of the body size (that N2/3 shows up a lot in allometric growth plots). But given a fish (an anamniote, or “lower” vertebrate) and a mammal (an amniote, or “higher”) of exactly the same body mass, the mammal will have a relatively and absolutely much larger brain.

Explain that, engineer, with nothing but algebra and no concern about phylogenetic relationships. It takes more to understand evolution than physics alone, and you have to take into account history, environment, inherited properties, selection, and chance as important parameters.

Oh, well, I’ve learned that physics must be really simple. I can design a plane from the ground up if I simply postulate a spherical 747. Ha ha, all those fools getting engineering degrees when they could just bring in a clever biologist to solve all their trivial little problems.

Closure on the Obokata/STAP affair

I’ve been following the story of stimulus-triggered acquisition of pluripotency (STAP) cells with considerable interest, and there’s a good reason for that: from the very beginning, it contradicted how I’d always thought about cell states, and if it were true, I’d have to rethink a lot of things, which was vexing. But on the other hand, empirical results always trump mental models, so if the results held up, there was no question but that I’d have to go through that uncomfortable process of reorganizing my preconceptions. It would be OK, though, because there’d be a great prize at the end.

Well, it turns out that I don’t have to reboot my brain after all, because now that all the flailing about is over, STAP is a product of sloppiness and fakery, and is dead.

So here’s the controversy, and why I found it vexatious. We want to be able to specify cell states; in particular, we’d love to be able to take any cell from the human body, tickle it with a few specific signals, and see it throw away all of its historical constraints and become a different cell type altogether. In particular, the Holy Grail is to find the right combination of switches to cause any cell to become a pluripotent stem cell — the kind of cell we can then induce to become any other cell type we might need.

We know this can’t be impossible, and is probably even fairly simple, because we know that cells can do this already (well, to some degree; your body accomplishes this task by setting aside reserve populations of stem cells. It’s also likely that some cell types are so tightly locked in by the process of differentiation that their state is not reversible). The idea is that we just need to find the right combination of signals/genes — the right kind of key — and we can unlock the cell, and make it open to additional inductions that will allow us to manipulate it.

We have some idea of the shape of the key. Yamanaka identified four genes, Oct4, Sox2, cMyc, and Klf4, that when activated, switched cells into a pluripotent state, making induced pluripotent stem cells, or iPS cells. It works. The handicap right now is that we only have a kind of brute force method of switching those genes on, and two of them are oncogenic, so it’s as if we’ve got a rather clumsy key that opens the lock, but also damages it in unfortunate ways. The resolution to that problem, though, was learning how to finesse the genes — we need to figure out how to more delicately switch on the necessary genes by a way other than bluntly transfecting cells with copies of the genes that are always on.

Then along came Haruko Obokata, an investigator in Japan who announced that she could induce stem cells with simple, generic stress, such as by exposing them to acid or physically pushing on the cells. It was like saying she didn’t need a specific key, all you needed to do was shake the lock really hard, and it would spontaneously pop open. What, really? That just seems too simple. It would be phenomenally awesome if true, but it seemed unlikely. But then, I remember this one lab I worked in where all the publicly popular drugs, like ketamine, were kept locked in a drawer to which only the PI had a key…but the countertop wasn’t secured to the bench, so if you knew about it, you could just lift the top and get easy access. It was a backdoor to the goodies that was so stupid you couldn’t believe it existed, but it did.

Could it be that cells similarly had a stupid weakness that could be so easily exploited? The short answer is no; read the whole article by David Cyranoski.

But the paper1 that set out the fundamental technique was soon shot full of holes. There was plagiarized text in the article. Figures showed signs of manipulation, and some images were identical or nearly identical to those used later in the same paper and elsewhere to represent different experiments. More damning were genetic analyses that strongly suggested the cells were not what they were purported to be. And although deriving STAP cells was advertised as simple and straightforward, no one has yet been able to repeat the experiment.

Within the space of six months, Obokata was found guilty of misconduct by her institution; well-respected scientists, including RIKEN head Ryoji Noyori, bowed their heads in apology; and both papers were retracted. In the end, the evidence for STAP cells seemed so flimsy that observers began to ask where were the extra precautions and the ‘extraordinary proof’ that had been promised post-Hwang.

It sure would have been nice to have a simple technique for generating stem cells, but I have to confess to being a bit relieved. There’s the vindication of prior thinking and the value of incrementally improving our stem cell protocols, of course, but also, I’d personally rather that it weren’t trivial to switch my cells to a de-differentiated pluripotent state — that’s a recipe for easy cancer generation, too. It is somehow reassuring to think that evolution has shaped multi-cellular organisms to be somewhat resistant to spontaneously going all stem-celly under stress.

Marco Rubio is already Gish-Galloping

Marco Rubio is still staggering over charges that he’s a science denialist on climate change. He has discovered a familiar way to deal with it: distraction. Ask him about climate change, and he babbles about abortion.

Here’s what I always get a kick out of, and it shows you the hypocrisy. All these people always wag their finger at me about science and settled science. Let me give you a bit of settled science that they’ll never admit to. The science is settled, it’s not even a consensus, it is a unanimity, that human life beings at conception. So I hope the next time someone wags their finger about science, they’ll ask one of these leaders on the left: ‘Do you agree with the consensus of scientists that say that human life begins at conception?’ I’d like to see someone ask that question.

This is only settled science if you get all your science information from the preacher on scienticianology at your local fundagelical Church of the One True American Jesus. Let’s take that phrase “human life begins at conception” apart.

What do you mean by “life begins”? Was there some step between your parents and you where there was a dead cell? Life is continuous — there hasn’t been a transition from non-life to life for about 4 billion years. So, yes, I’d agree that the zygote is a living cell, but so were the sperm and egg that fused to generate it, and so were the blast cells that were precursors to it, and so were the zygotes that developed into your parents. We can trace that life all the way back to early progenotes with limited autonomy drifting in Archean seas, to self-perpetuating chemical reactions occurring in porous rocks in the deep ocean rifts. It’s all been alive, so this is a distinction without meaning.

What about “human”? It’s a human zygote, we’d all agree; but it’s also human sperm and human ovum. You can pluck a hair from my head and determine with a few tests that it’s a human hair; you can take a blood sample from me and check a few antigens and determine that it is human blood; you can similarly swab a bit of saliva or earwax or tears from me, and analyze its biochemistry and find that it is specifically human spit or earwax or tears. That we can tag something with the adjective “human” does not in any way imply that my earwax deserves all the protections and privileges of a full human being. “Human zygote” imposes as much ethical obligation on me as “human spit”.

And don’t even try to pull that BS about a unique, novel genetic individual being created at conception. One of the key properties of meiosis is a genetic reshuffling of alleles by random assortment of the parental chromosomes and recombination by crossing over — every sperm and egg is genetically unique as well, and we spew those profligately with no remorse. Conception just adds another level of semi-random rearrangement of a random assortment of genes that were made during oogenesis and spermatogenesis.

So what are we left with? An obvious attempt at distortion or incomprehension in which the common modifier “human” is used as an absolute signifier for sociological and historical and psychological of an entity as being a complete member of a higher level community. It’s a lie cloaked in ambiguous language.

And of course, at the end of that dissection, we’re still left with the fact that Rubio is dead wrong on climate change and threw out this whole line of argument to distract us from the point that Marco Rubio is an idiot.

It didn’t work.

Epigenetics ain’t magic

I just got a notice of an Epigenetics Conference in Portland, Oregon. It made me cringe. It’s infuriating because epigenetics is actually a very important concept in development, but there’s this terrible misperception among the public that it’s a magical shortcut for evolution. I was also a bit primed for it by the mention of epigenetics on Larry Moran’s blog.

The Humanists of Greater Portland™ is supporting the 2014 Epigenetics Conference being held on Saturday 5 April 2014. Epigenetics is a relatively new field of science that looks at how the environment affects one’s genetic make up. In former times, it was thought that it took generations to change one’s genetic make up but studies now suggest it can happen over a matter of weeks or months. What one eats, their environment, their activities etc. all can alter ones genetic make up and this can greatly affect one’s health. Even the environment of the mother can affect the genetic make up of the baby in the womb.

No, it’s not new. Conrad Waddington coined the term “epigenetics” in the early 1940s. He was explaining how development is modulated by gene regulation, and that there is a multigenerational pattern of restriction of cell fates within a lineage…and that’s a concept that’s at least as old as Wilhelm Roux.

It’s broader than just environmental effects. We can talk about epigenetic modification within an embryo, as a consequence of a clocklike sequence of switches, for instance. It really is a well-known, long studied developmental process.

It does not change the “genetic makeup”. Epigenetics affects the expression of genes without modifying any sequence information. Thinking that it represents rapid evolutionary change is the major misconception that leads people to think the timing is somehow radical. It isn’t. A mutation changes the “genetic makeup” of a cell — for realz — in a fraction of a second. Get up and run a lap around the room, and you’ll get a rapid change in your physiological state in a fraction of a minute. Move from your flatland home to Denver (or vice versa) and you’ll get long term changes to the constitution of your blood in a matter of weeks. None of these represent a revolution in how we think about evolution.

You want to greatly affect your health, quickly? Don’t drink any water for a day. Or drink a couple of Big Gulps worth of sugar water. That’ll have about the same effect on evolution as epigenetic modulation.

Fortunately, it’s just the general blurb for the conference that set my teeth on edge. The descriptions of the presentations sound much more focused and of reasonable and appropriate scope. It should be informative. But please, pop culture summaries of epigenetics make PZ cry.

Some people are thinking I’m denying any role for epigenetics in evolution. No — it’s just not the role some less informed people think it is. What epigenetic modification does is broaden the range of phenotypes produced by a given genotype, allowing more genetic variation to persist in the population. That surely does have some effect on evolution, but it’s somewhat more indirect than the Lamarckian mode pop culture assigns to it.

It’s one thing that allows genetic assimilation to occur, for instance. But if you think people misunderstand epigenetics, just wait until you hear what they say about genetic assimilation.

If you’re still baffled, I wrote up an introduction to epigenetics a while back. I’ve also got a couple of examples of genetic assimilation.

An atheist can be pro-life only by lying about the science

Hemant Mehta let an anti-choice atheist romp about and make her secular pro-life argument, but since he thinks it’s important to give a forum to bullshit but doesn’t think it’s important enough to criticize, I guess I have to. It’s by Kristine Kruszelnicki, president of Pro-Life Humanist, and we’ve dealt with her before; she’s the one who debated Matt Dillahunty in 2012, and lost miserably. She acknowledges that right at the beginning of her post, and then proceeds to make the same stupid argument.

Before we address the question of bodily autonomy in pregnancy, let’s meet the second player. What does science tell us that the preborn are? To be clear, science doesn’t define personhood. It never could. When I debated Matt Dillahunty on the issue of abortion at the 2012 Texas Freethought Convention, I’m afraid that as a first-time debater I really wasn’t clear enough on this point — and was consequently accused of trying to obtain rights from science. Science can’t tell us whether it’s wrong to rape women, torture children, enslave black people, or which physical traits should or should not matter when it comes to determining personhood. Science may be able to measure suffering in living creatures, but it can’t tell us why or if their suffering should matter.

Notice what she’s doing here. She recognizes that she totally got skewered on her claim that Science says abortion is wrong, so she’s nominally distancing herself from making moral claims with science. But guess what her very next sentence is?

However, science can tell us who among us belongs to the human species.

She’s doing it again. She’s claiming that science justifies her position.

She is at least aware that the right of women to autonomy is an extremely strong argument against her position — it’s how Dillahunty slammed her in the debate — and the entire post is about how she gets around that tricky problem of denying women control of their own bodies. Her solution? Simply decree by fiat, with the stamp of approval of her version of science, that the fetus and the woman have fully equal status as human beings, and that all discussion has to grant the fetus every privilege we do the woman.

If the fetus is not a human being with his/her own bodily rights, it’s true that infringing on a woman’s body by placing restrictions on her medical options is always a gross injustice and a violation. On the other hand, if we are talking about two human beings who should each be entitled to their own bodily rights, in the unique situation that is pregnancy, we aren’t justified in following the route of might-makes-right simply because we can.

At least this time, she didn’t sprinkle photos of bloody fetus parts in her post, and she avoided the most egregiously absurd elements of her position. This is my summary of what she said at the debate:

She made it clear that she opposes a whole gamut of basic rights: birth control methods that prevent implantation are wrong, because that’s just like strangling or starving a baby; no abortion in cases of rape or incest, because the baby doesn’t deserve punishment; she did allow for abortion in cases that threaten the life of the mother at times before fetal viability, simply because in that case two fully human lives would be lost.

She sounds like a very liberal Catholic atheist.

But that’s the entirety of her argument, both in that piece and on the pro-life atheist web site: the fetus is fully human from the moment of conception, and science says so.

When it comes to normal human reproduction, sperm and ovum merge to form a new whole. They cease to exist individually and become a new substance that is not the mother and not the father but a new body altogether, one that is also human and has the inherent capacity to develop through all stages of development.

When we talk about rights and personhood, we leave the realm of science for that of philosophy and ethics. History is ripe with examples of real biological human beings whose societies arbitrarily decided they didn’t qualify as equals, on account of criteria deemed morally relevant. At one point (and still, in many ways, today), it was skin color, gender, and ethnic background. Now, we can add to that list consciousness, sentience, and viability. We haven’t evolved so fast in 50 years as to be immune from tribalistic us vs. them thinking. If science defines a fetus as a biological member of our species, is it possible that our society is just as wrong in denying them personhood?

What happens when both a woman and her developing fetus are regarded as human beings entitled to personhood and bodily rights? Any way you cut it, their rights are always going to conflict (at least until womb transfers become a reality). So what’s the reasonable response? It could start by treating both parties at conflict as if they were equal human beings.

You get the idea. If she repeats that the conceptus becomes fully human at the instant of fertilization, and that science says so, over and over, we surely must be persuaded that she’s right, and we have to concede that she’s making an entirely secular argument, because SCIENCE. Unfortunately for her, she’s not actually using SCIENCE, but has mistaken BULLSHIT for science.

Let me tell you what science actually says about this subject.

Science has determined that development is a process of epigenesis; that is, that it involves a progressive unfolding and emergence of new attributes, not present at conception, that manifest gradually by interactions within the field of developing cells and with the external environment. The conceptus is not equal to the adult. It is not a preformed human requiring only time and growth to adulthood; developmental biologists are entirely aware of the distinction between proliferation and growth, and differentiation. So science actually says the opposite of what Kruszelnicki claims. It says that the fetus is distinct from the adult.

Of course, science also has to concede that because there is a continuum of transformation from conception to adulthood, it can’t draw an arbitrary line and say that at Time Point X, the fetus has acquired enough of the properties of the adult form that it should be now regarded as having all the rights of a member of society. That’s a matter for law and convention. But we already implicitly recognize that there is a pattern of change over time; children do not have all the same privileges as adults. Third trimester fetuses have fewer still. First trimester embryos? Even less. We all understand without even thinking about it that there is a progressive pattern to human development.

But what about this claim that science can tell us who among us belongs to the human species?

First question I have is…which species concept are you using? There are a lot of them, you know; I daresay we might be able to find a few, that when inappropriately and too literally applied, would define away my status as a human, which simply wouldn’t do. There are also a lot of non-scientific or pseudo-scientific definitions of what constitutes a human that have been historically abused. Were the Nazis being scientific when they defined sub-species of humans and classed Jews, Gypsies, and Africans as something less than fully human? What, exactly, is Kruszelnicki’s “scientific” definition of human, that she’s using so definitively to declare a fetus as completely human?

She doesn’t say. She can’t say. She’s not applying a scientific test, but a traditional and colloquial one, which she’s then claiming by implication as synonymous with an unstated scientific definition. That’s dishonest and more than a little annoying.

Reading between the lines on her horrible little website, I’m guessing that she’s using a trivial and excessively reductive definition of human: it’s human by descent. The cells come from the division of human cells, so it is by definition not a monkey or a llama or a beetle cell, it’s a human cell.

Of course, that’s not enough: by that definition, sperm and eggs would be fully human, and women would be committing murder every time they menstruate, and men would be committing genocide every time they ejaculate. So she has a patch to work around that:

There is no such species as “sperm” or “ovum”. Sperm and ovum are not distinct unique organisms. They are in fact complex specialized cells belonging to the larger organism, namely the male and female from which they came. In other words, they are, like skin cells and blood cells, alive and bearing human DNA but nonetheless parts of another human being, even when mobile like the sperm.

There is no such species as “man” or “woman” either; we can always find some characteristic of an individual to distinguish them from a species (well hey, just the fact that they are an individual is enough). Her waffling about the status of sperm and ovum is ridiculous; I can give you species definitions that would recognize haploid gametes as fully human. If your restriction is simply that one is a complex, specialized cell belonging to the larger organism, well gosh, the zygote fits that, too! A fertilized egg is not a generic human cell: it is incredibly specialized and complex.

I can’t help but notice that multicellularity isn’t part of her definition of “human”. Nor does it include any craniate characters, like having a notochord or a brain or branchial arches. There are a lot of scientific definitions of our species that the zygote fails!

If we’re going to emphasize the “not part of a human being” aspect of her fuzzy definition, then we have another problem. If you pooped this morning, that turd contained shed human epithelial cells, now swimming free. I could actually say, with full scientific accuracy, that that was a human turd. Why aren’t you giving it full legal protection?

She has an escape clause for that, too.

Sperm and ovum lose their individual identity and their function as sperm and ovum once they have merged. Instead of being parts carrying 23 chromosomes from two different human beings, the unification and merging of their chromosome pairs has now created a new whole with a new set of chromosomes and a cellular structure that now contains the inherent capacity to grow and develop itself through all stages of human development. This of course is something that neither sperm nor ovum parts had the inherent capacity to do on their own. It’s something that only whole human beings can do.

Oh. So here’s her full definition of a fully human being: it is a totipotent cell with the capacity to develop into a human being. Alas, her last sentence is wrong. Whole human beings cannot do that. It means I am not human, only a few small bits of me can aspire (in vain! I’m done with that) to someday fuse with another haploid cell and briefly become fully human, in the few days of happy cleavage before their cells become committed to specialized fates, which then are not fully human.

The only logical scientific conclusion one can make from Kruszelnicki’s hopeless definition is that blastocysts are fully human, but people are not.

Which actually doesn’t surprise me at all, and fits quite well with what I hear from the fetus-worshippers.

As I said before, there certainly are secular arguments for all kinds of nonsense — “secular” is not a synonym for “good”. We have to do more than simply accept arguments because they don’t mention gods, we also have to apply logical, reasonable philosophical and scientific filters to those secular arguments. The one obvious conclusion from any examination of these so-called “pro-life” arguments is that they are sloppy and dishonest, and not deserving of recognition by reasonable secular people.

Being atheist is not enough. One of the implications of an absence of gods is that revelation is invalid, and that we have to rely on reason and evidence to draw conclusions…and further, I would add, that we have to define values that we consistently and rationally apply, and we have to assess whether our methods appropriately serve those values. I choose to value the equality of a community of living, fully-born human beings, and when irrational superstitious attachment to status of a blastocyst compromises the autonomy and worth of members of that community, I choose to reject that belief. It helps quite a bit, though, that the “pro-life” position is so incoherent and anti-scientific.

Another take: even if you accept Kruszelnicki’s premise that a conceptus is “fully human” (I don’t), her argument doesn’t work and was dismantled over 40 years ago.

Pathways to sex

I was talking about sex and nothing but sex all last week in genetics, which is far less titillating than it sounds. My focus was entirely on operational genetics, that is, how autosomal inheritance vs inheritance of factors on sex chromosomes differ, and I only hinted at how sex is not inherited as a simple mendelian trait, as we’re always tempted to assume, but is actually the product of a whole elaborate chain of epistatic interactions. I’m always tempted in this class to go full-blown rabid developmental geneticist on them and do nothing but talk about interactions between genes, but I manage to restrain myself every time — we have a curriculum and a focus for this course, and it’s basic transmission genetics, and I struggle to get general concepts across before indulgence in my specific interests. Stick to the lesson plan! Try not to break everyone’s brain yet!

But a fellow can dream, right?

Anyway, before paring everything down to the reasonable content I can give in a third year course, I brush up on the literature and take notes and track down background and details that I won’t actually dump on the students (fellow professors know this phenomenon: you have to work to keep well ahead of the students, because they really don’t need to start thinking they’re smarter than you are). But I can dump my notes on you. You don’t have to take a test on it and get a good grade, and you won’t pester me about whether this will actually be on the test, and you won’t start crying if I overwhelm you with really cool stuff. (If any of my students run across this, no, the content of this article will not be on any test. Don’t panic. Go to grad school where this will all be much more relevant.)

Onward. Here’s my abbreviated summary of the epistatic interactions in making boys and girls.

The earliest step in gonad development is the formation of the urogenital ridge from intermediate mesoderm, a thickening on the outside of the mesonephros (early kidney), under the influence of transcription factors Emx2, Wt1 (Wilms tumor 1), Lhx9, and Sf1 (steroidogenic factor 1). Even in the earliest stages, multiple genes interact to generate the tissue! The urogenital ridge is going to form only the somatic tissue of the gonad; the actual germ cells (the cells that will form the gametes, sperm and ova) arise much, much earlier, in the epiblast of the embryo at a primitive streak stage, and then migrate through the mesenteries of the gut to populate the urogenital ridge independently, shortly after it forms.

At this point, this organ is called the bipotential gonad — it is identical in males and females. Two genes, Fgf9 and Wnt4, teeter in a balanced antagonistic relationship — Wnt4 suppresses Fgf9, and Fgf9 suppresses Wnt4 — in the bipotential gonad, and anything that might tip the balance between them will trigger development of one sex or the other. A mutation that breaks Fgf9, for instance, gives Wnt4 an edge, and the gonad will develop into an ovary; a mutation that breaks Wnt4 will let Fgf9 dominate the relationship, and the gonad will develop into a testis (with a note of caution: the changes will initiate differentiation into one gonad or the other, but there are other steps downstream that can also vary). These two molecules may be the universal regulators of the sex of the gonad in animals: fruit flies also use Fgf and Wnt genes to regulate development of their gonads.

But the key to the genetic symmetry-breaking of selecting Fgf9 and Wnt4 varies greatly in animals. Some use incubation temperature to bias expression one way or the other; birds have a poorly understood set of factors that may require heterodimerization between two different proteins produced on the Z and W chromosomes to induce ovaries; mammals have a unique gene, Sry, not found in other vertebrates, that is located on the Y chromosome and tilts the balance towards testis differentiation.

Sry may be unique to mammals, but it didn’t come out of nowhere. Sry contains a motif called the HMG (high mobility group) box, which is a conserved DNA binding domain. There are approximately 20 proteins related to Sry in humans, all given the name SOX, for SRY-related HMG box (I know, molecular biologists seem to be really reaching for acronyms nowadays). SOX genes are found in all eukaryotes, and seem to play important roles in cell and organ differentiation in insects, nematodes, and vertebrates. Sry is simply the member of the family that has been tagged to regulate gonad development in mammals.

If a copy of Sry is present in the organism, which is usually only the case in XY or male mammals, expression of the gene produces a DNA binding protein that has one primary target: a gene called SOX9 (they’re cousins!). In mice, Sry is switched on only transiently, long enough to activate SOX9, which then acts as a transcription factor for itself, maintaining expression of SOX9 for the life of the gonad. Humans keep Sry turned on permanently as well, but there’s no evidence yet that it actually does anything important after activating SOX9; it may be that human males neglect to hit the off switch.

SOX9 binds to a number of genes, among them, Fgf9. Remember Fgf9? The masculinizing factor in antagonism to the feminizing factor Wnt4? This tips the teeter-totter to favor expression of Fgf9 over Wnt4, leading to the differentiation of a testis from the bipotential gonad.

So far, then, we’ve got a nice little Rube Goldberg machine and an epistatic pathway. Sf1/Wt1 and other early genes induce the formation of a urogenital ridge and an ambiguous gonad; Sry upregulates Sox9 which upregulates Fgf9 which suppresses Wnt4, turning off the ovarian pathway and turning on the testis pathway.

But wait, we’re not done! Sry/SOX9 are expressed specifically in a subset of cells of the male gonad, the prospective Sertoli cells. If you recall your reproductive physiology, Sertoli cells are a kind of ‘nurse’ cell of the testis; they’re responsible for nourishing developing sperm cells. They also have signaling functions. The Sertoli cells produce AMH, or anti-Müllerian Hormone, which is responsible for causing the female ducts of the reproductive system to degenerate in males (if you don’t remember the difference between Müllerian and Wolffian and that array of tubes that get selected for survival in the different sexes, here’s a refresher). Defects in the AMH system lead to persistent female ducts: you get males with partial ovaries and undescended testicles. So just having the Sry chain is not enough, there are downstream genes that have to dismantle incipient female structures and promote mature properties of the gonad.

As the gonad differentiates, it also induces another set of cells, the embryonic Leydig cells. We have to distinguish embryonic Leydig cells, because they represent another transient population that will do their job in the embryo, then gradually die off to be replaced by a new population of adult Leydig cells at puberty. The primary function of Leydig cells is the production of testosterone and other androgens. The embryo gets a brief dose of testosterone early that initiates masculinization of various tissues, which then fades (fortunately; no beards and pubic hair for baby boys) to resurge in adolescence, triggering development of secondary sexual characteristics. Embryonic testosterone is the signal that maintains the Wolffian duct system. No testosterone, and the Wolffian ducts degenerate.

Just to complicate matters, while testosterone is the signal that regulates the male ducts, testosterone must be converted to dihydrotestosterone (DHT), the signal that regulates development of the external genitalia. Defects in the enzyme responsible for this conversion can lead to individuals with male internal plumbing, including testes, but female external genitalia. Sex isn’t all or nothing, but a whole series of switches!

By now, if you’re paying attention, you may have noticed a decidedly male bias in this description. I’ve been talking about a bipotential gonad that is flipped into a male mode by the presence of a single switch, and sometimes, especially in the older literature, you’ll find that development of the female gonad is treated as the default: ovaries are what you get if you lack the special magical trigger of the Y chromosome. This is not correct. The ovaries are also the product of an elaborate series of molecular decisions; I think it’s just that they Y chromosome and the Sry gene just provided a convenient genetic handle to break into the system, and really, scientists usually favor the easy tool to get in.

One key difference between the testis and ovary is the inclusion of germ cells. The testis simply doesn’t care; if the germ line, the precursors to sperm, is not present, the male gonad goes ahead and builds cords of Sertoli cells with Leydig cells differentiating in the interstitial space, makes the whole dang structure of the testicle, pumping out testosterone as if all is well, but contains no cells to make sperm — so it’s reproductively useless, but hormonally and physiologically active. The ovary is different. If no germ line populates it, the ovarian follicle cells (the homolog to the Sertoli cells) do not differentiate. If germ cells are lost from the tissue only later, the follicles degenerate.

Ovaries require a signal from the germ line to develop normally. One element of that signal seems to be factors associated with cells in meiosis. The female germ line cells are on a very strict meiotic clock, beginning the divisions to produce haploid egg cells in the embryo, even as they populate the gonad. These oocytes produce a signal, Figα (factor in germ line a) that recruits ovarian cells to produce follicles. The male gonad has to actively repress meiosis in the embryonic germ line to inhibit this signaling; male germ cells are restricted to only mitotic divisions until puberty.

Even before Figα signaling becomes important, there are other factors uniquely expressed in the prospective ovary that shape its development. In particular, Wnt4 induces the expression of another gene, Foxl2, that is critical for formation of the ovarian follicle. The pathways involved in ovarian development are not as well understood as those in testis development, but it’s quite clear that there is a chain of specific genetic/molecular interactions involved in the generation of both organs.

Wait, you say, you need a diagram! You can’t grasp all this without an illustration! Here’s a nice one: I particularly like that cauliflower-shaped explosion of looping arrows early in the testis pathway.

The molecular and genetic events in mammalian sex determination. The bipotential genital ridge is established by genes including Sf1 and Wt1, the early expression of which might also initiate that of Sox9 in both sexes. b-catenin can begin to accumulate as a response to Rspo1–Wnt4 signaling at this stage. In XX supporting cell precursors, b-catenin levels could accumulate sufficiently to repress SOX9 activity, either through direct protein interactions leading to mutual destruction, as seen during cartilage development, or by a direct effect on Sox9 transcription. However, in XY supporting cell precursors, increasing levels of SF1 activate Sry expression and then SRY, together with SF1, boosts Sox9 expression. Once SOX9 levels reach a critical threshold, several positive regulatory loops are initiated, including autoregulation of its own expression and formation of feed-forward loops via FGF9 or PGD2 signaling. If SRY activity is weak, low or late, it fails to boost Sox9 expression before b-catenin levels accumulate sufficiently to shut it down. At later stages, FOXL2 increases, which might help, perhaps in concert with ERs, to maintain granulosa (follicle) cell differentiation by repressing Sox9 expression. In the testis, SOX9 promotes the testis pathway, including Amh activation, and it also probably represses ovarian genes, including Wnt4 and Foxl2. However, any mechanism that increases Sox9 expression sufficiently will trigger Sertoli cell development, even in the absence of SRY.

The molecular and genetic events in mammalian sex determination. The bipotential genital ridge is established by genes including Sf1 and Wt1, the early expression of which might also initiate that of Sox9 in both sexes. b-catenin can begin to accumulate as a response to Rspo1–Wnt4 signaling at this stage. In XX supporting cell precursors, b-catenin levels could accumulate sufficiently to repress SOX9 activity, either through direct protein interactions leading to mutual destruction, as seen during cartilage development, or by a direct effect on Sox9 transcription. However, in XY supporting cell precursors, increasing levels of SF1 activate Sry expression and then SRY, together with SF1, boosts Sox9 expression. Once SOX9 levels reach a critical threshold, several positive regulatory loops are initiated, including autoregulation of its own expression and formation of feed-forward loops via FGF9 or PGD2 signaling. If SRY activity is weak, low or late, it fails to boost Sox9 expression before b-catenin levels accumulate sufficiently to shut it down. At later stages, FOXL2 increases, which might help, perhaps in concert with ERs, to maintain granulosa (follicle) cell differentiation by repressing Sox9 expression. In the testis, SOX9 promotes the testis pathway, including Amh activation, and it also probably represses ovarian genes, including Wnt4 and Foxl2. However, any mechanism that increases Sox9 expression sufficiently will trigger Sertoli cell development, even in the absence of SRY.

So that’s what I didn’t tell my genetics students this time around. Maybe I’ll work it into my developmental biology course, instead.

Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, Poulat F, Behringer RR, Lovell-Badge R, Capel B. (2006) Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol 4(6):e187

Ross AJ, Capel B. (2005) Signaling at the crossroads of gonad development. Trends Endocrinol Metab. 16(1):19-25.

Sekido R, Lovell-Badge R (2009) Sex determination and SRY: down to a wink and a nudge? Trends Genet. 25(1):19-29.

Sim H, Argentaro A, Harley VR (2008) Boys, girls and shuttling of SRY and SOX9. Trends Endocrinol Metab. 19(6):213-22.

Yao H H-C (2005) The pathway to femaleness: current knowledge on embryonic
development of the ovary. Molecular and Cellular Endocrinology 230:87–93.

The reification of the gene

Razib Khan poked me on twitter yesterday on the topic of David Dobbs’ controversial article, which I’ve already discussed (I liked it). I’m in the minority here; Jerry Coyne has two rebuttals, and Richard Dawkins himself has replied. There has also been a lot of pushback in the comments here. I think they all miss the mark, and represent an attempt to shoehorn everything into an established, successful research program, without acknowledging any of the inadequacies of genetic reductionism.

Before I continue, let’s get one thing clear: I am saying that understanding genes is fundamental, important, and productive, but it is not sufficient to explain evolution, development, or cell biology.

But what the hell do we mean by a “gene”? Sure, it’s a transcribed sequence in the genome that produces a functional product; it’s activity is dependent to a significant degree on the sequence of nucleotides within it, and we can identify similar genes in multiple lineages, and analyze variations both as a measure of evolutionary history and often, adaptive function. This is great stuff that keeps science careers humming just figuring it out at that level. Again, I’m not dissing that level of analysis, nor do I think it is trivial.

However, I look at it as a cell and developmental biologist, and there’s so much more. That gene’s transcriptional state is going to depend on the histones that enfold it and the enzymes that may have modified it; it’s going to depend on its genetic neighborhood and other genes around it; it’s not just sitting there, doing its own thing solo. And you will cry out, but those are just products of other genes, histone genes and methylation enzymes and DNA binding proteins, and their sequences of nucleotides! And I will agree, but there’s nothing “just” about it. Expression of each of those genes is dependent on their histones and methylation state. And further, those properties are contingent on the history and environment of the cell — you can’t describe the state of the first gene by reciting the sequences of all of those other genes.

Furthermore, the state of that gene is dependent on activators and repressors, enhancer and silencer sequences. And once again, I will be told that those are just genetic sequences and we can compile all those patterns, no problem. And I will say again, the sequence is not sufficient: you also need to know the history of all the interlinked bits and pieces. What activators and repressors are present is simply not derivable from the genes alone.

And I can go further and point out that once the gene is transcribed, the RNA may be spliced (sometimes alternatively) and edited, processed thoroughly, and be subject to yet more opportunities for control. I will be told again that those processes are ultimately a product of genes, and I will say in vain…but you don’t account for all the cellular and environmental events with sequence information!

And then that RNA is exported to the cytoplasm, where it encounters other micro RNAs and finds itself in a rich and complex environment, competing with other gene products for translation, while also being turned over by enzymes that are breaking it down.

Yes, it is in an environment full of gene products. You know my objection by now.

And then it is translated into protein at some rate regulated by other factors in the cell (yeah, gene products in many cases), and it is chaperoned and transported and methylated and acetylated and glycosylated and ubiquitinated and phosphorylated, and assembled into protein complexes with all these other gene products, and its behavior will depend on signals and the phosphorylation etc. state of other proteins, and I will freely and happily stipulate that you can trace many of those events back to other genes, and that they respond in interesting ways to changes in the sequences of those genes.

But I will also rudely tell you that we don’t understand the process yet. Knowing the genes is not enough.

It’s as if we’re looking at a single point on a hologram and describing it in detail, and making guesses about its contribution to the whole, but failing to signify the importance of the diffraction patterns at every point in the image to our perception of the whole. And further, we wave off any criticism that demands a more holistic perspective by saying that those other points? They’re just like the point I’m studying. Once I understand this one, we’ll know what’s going on with the others.

That’s the peril of a historically successful, productive research program. We get locked in to a model; there is the appeal of being able to use solid, established protocols to gather lots of publishable data, and to keep on doing it over and over. It’s real information, and useful, but it also propagates the illusion of comprehension. We are not motivated to step away from the busy, churning machine of data gathering and rethink our theories.

We forget that our theories are purely human constructs designed to help us simplify and make sense of a complex universe, and most seriously we fail to see how our theories shape our interpretation of the data…and they shape what data we look for! That’s my objection to the model of evolution in The Selfish Gene: it sure is useful, too useful, and there are looming barriers to our understanding of biology that are going to require another Dawkins to disseminate.

Let me try to explain with a metaphor — always a dangerous thing, but especially dangerous because I’m going to use a computer metaphor, and those things always grip people’s brains a little bit too hard.

In the early days of home computing, we had these boxes where the input to memory was direct: you’d manually step through the addresses, and then there was a set of switches on the front that you’d use to toggle the bits at that location on and off. When a program was running, you’d see the lights blinking on and off as the processor stepped through each instruction. Later, we had other tools: I recall tinkering with antique 8-bit computers by opening them up and clipping voltmeters or an oscilloscope to pins on the memory board and watching bits changing during execution. Then as the tools got better, we had monitors/debuggers we could run that would step-trace and display the contents of memory locations. Or you could pick any memory location and instantly change the value stored there.

That’s where we’re at in biology right now, staring at the blinking lights of the genome. We can look at a location in the genome — a gene — and we can compare how the data stored there changes over developmental or evolutionary time. There’s no mistaking that it is real and interesting information, but it tells us about as much about how the whole organism works and changes as having a readout that displays the number stored at x03A574DC on our iPhone will tell us how iOS works. Maybe it’s useful; maybe there’s a number stored there that tells you something about the time, or the version, or if you set it to zero it causes the phone to reboot, but let’s not pretend that we know much about what the machine is actually doing. We’re looking at it from the wrong perspective to figure that out.

You could, after all, describe the operation of a computer by cataloging the state of all of its memory bits in each clock cycle. You might see patterns. You might infer the presence of interesting and significant bits, and you could even experimentally tweak them and see what happens. Is that the best way to understand how it works? I’d say you’re missing a whole ‘nother conceptual level that would do a better job of explaining it.

Only we lack that theory that would help us understand that level right now. It’s fine to keep step-tracing the genome right now, and maybe that will provide the insight some bright mind will need to come up with a higher order explanation, but let’s not elide the fact that we don’t have it yet. Maybe we should step back and look for it.

Higher order thinking

The one thing you must read today is David Dobbs’ Die, Selfish Gene, Die. It’s good to see genetic accommodation getting more attention, but I’m already seeing pushback from people who don’t quite get the concept, and think it’s some kind of Lamarckian heresy.

It’s maybe a bit much to ask that the gene-centric view of evolution die; it’s still useful. By comparison, for instance, it’s a bit like Mendel and modern genetics (I’ll avoid the overworked comparison of Newton and Einstein.) You need to understand simple Mendelian genetics — it gives you a foundation in the logic of inheritance, and teaches you a few basic rules. But once you start looking at real patterns of inheritance of most traits, you discover that it doesn’t work. Very few traits work as Mendel described, and one serious concern is that we tend to select for genes to study that behave in comprehensible ways.

And every geneticist knows this. Mendel was shown to have got some things wrong within a decade of his rediscovery: Mendel’s Law of Independent Assortment, for instance, simply does not hold for linked genes, and further, linkage turns out to hold important evolutionary implications. But I still teach about independent assortment in my genetics course. Why? Because you need to understand how to interpret deviations from the simple rules; it’s an “a-ha!” moment when you comprehend how Morgan and Sturtevant saw the significance of departures from Mendel’s laws.

Most of genetics seems to be about laying a foundation, and then breaking it to take a step beyond. Teaching it is a kind of torture, where you keep pushing the students to master some basic idea, and then once they’ve got it, you test them by showing them all the exceptions, and then announcing, “But hey! Here’s this cool explanation that tells you what you know is wrong, but there’s some really great and powerful ideas beyond that.”

That’s what’s fun about genetics: compounding a series of revelations until the students’ brains break, usually right around the end of the term. Over the years I’ve learned, too. Undergraduate genetics students usually collapse in defeat once I introduce epistatic interactions — the idea that the phenotype produced by an allele at one locus is dependent on the alleles present at other loci — but it’s always great to see the few students who fully grasp the idea and see how powerful it is (future developmental biologists identified!).

And that’s how I see the gene-centric view: absolutely essential. You must understand Mendel, and Fisher, and Wright, and Hamilton, and Williams, and once you’ve mastered that toolkit, you can start looking at the real world and seeing all the cases where it’s deficient, and develop new tools that let you see deeper. The new idea that Dobb’s describes, and that is actually fairly popular with many developmental biologists, is that phenotype comes first: that organisms are fairly plastic in response to the environment in ways that can’t be simplified to pure genetic determinism, and that the genes lag behind, acting to consolidate and make more robust adaptive responses.

I’ve written about genetic assimilation/accommodation before, and have given one lovely example of phenotypic change occurring faster than the generation of new mutants can explain. It’s always baffled me about the response to those ideas: most people resist, and try to reduce them to good old familiar genes. It’s a bit like watching students wrestle with epistatic modulation of gene expression when all they understand is Mendel, and rather than try to grasp a different way of looking at the problem, they instead invent clouds of simple Mendelian factors that bring in multi-step discrete variations. They can make the evidence fit the theory — just add more epicycles!

I’m seeing the same responses to Dobbs’ article — it’s still all just genes at the bottom of it, ain’t it? Oh, sure, but the interesting parts are the interactions, not the subunits. We need to take the next step and build tools to study networks of genes, rather than reducing everything to the genes themselves.

Sexy T-rex meets lecherous creationist

Charlie Stross has written a story, A Bird in Hand, which rather pushes a few boundaries. It’s about dinosaurs and sodomy, as the author’s backstory explains. And as everyone knows, every story is improved by adding one or the other of dinosaurs and sodomy, so it can’t help but be even better if you add both.

A note of caution, though: Charlie is really, really good at spinning out all the latest scientific buzzwords and deep molecular biological concepts into an extraordinarily plausible-sounding mechanism for rapidly recreating a dinosaur — it’s much, much better than Crichton’s painfully silly and superficial dino-blood-from-mosquitoes-spliced-with-frog-DNA BS — but I was a bit hung up on poking holes in it. It won’t be quite that easy, and it rather glibly elides all the trans-acting variations that have arisen in 70 million years and the magnitude of the developmental changes. But still, if we ever do manage to rebuild a quasi-dinosaur from avian stock, that’ll be sort of the approach that will be taken, I suspect. Just amplify the difficulty a few thousand fold.

Also, it’s way too technical to survive in the movie treatment.