Mary’s Monday Metazoan: What? Females aren’t beautiful for me?

bluecrabfemale

That female crab doesn’t make herself gorgeous for the males of her species, it seems — sometimes a lady just has to look good.

Contrary to expectation, the model shows that winning the romantic interest of picky males is not enough to explain how desirable feminine features become widespread — even when better-looking females are more likely to land a good catch.

The results of their mathematical approach support other research suggesting that female beauty doesn’t evolve just to win mates.

Instead, traits such as the dance fly’s frilly legs or the blue crab’s red-tipped claws may help their bearers compete for other resources, such as social status or protection from predators. The results are consistent with an idea called the “social selection” hypothesis, first proposed three decades ago by theoretical biologist Mary Jane West-Eberhard of the Smithsonian Tropical Research Institute.

Impossible. They might consider other resources than access to my magnificent manliness to be valuable? Heresy.

It’s Flyday

I don’t have any classes today, so I catch up on my custodial work. That means I’m going to spend a few hours scrubbing fly bottles: bottles caked with medium the consistency of slimy oatmeal, full of maggots, with dead flies scattered around like raisins.

May not have an appetite tonight.

Ah, the glamor of the scientific life…

Not enough hours in the day

farsidequestions

Yikes. I have been buried in work — we’ve just begun a week of interviews for job candidates, and I’m on the search committee, so I’ve been tied up all last night, all day today, and this evening. And what time hasn’t been occupied in service work has been involved in preparing for tomorrow’s ecological development class.

The big project tomorrow is a critical analysis of Richard Lewontin’s The Triple Helix. It’s a short book, but it’s packed to the gills with concepts they may not have encountered before…and most importantly, concepts they may not have questioned before. So I had to put together a framework for discussion. I’ll let you read it, too, although it’s not going to be very useful unless you’ve read the book as well.

The book is only 3 meaty chapters long with a concluding summary. I’m trying to provoke some arguments with these questions.


I. Gene and Organism

Lewontin complains about metaphors: what’s wrong with the DNA as blueprint metaphor?

We have a bias in our language. The word “development” implies an “unrolling” of a program. Is that a good explanation of the process?

We talked about preformation vs epigenesis on the first day. I told you that preformation is an untenable explanation, but Lewontin argues that preformation has won. How?

He explains that there is a deep difference between transformational vs variational change. Explain.

Brenner, p10: he claimed that with the complete sequence of DNA, he could compute the organism. What’s wrong with that statement?

Similarly, Gilbert, p11: with the genomic sequence, we will know what it means to be human. Do you believe it.

He gives several examples of complicating “transformations”:
p19: Explain phototropism, geotropism
p21: What are norms of reaction

Contrast fig 1.8 (p 29), Jensen’s IQ model, with 1.6 (p25), Drosophila viability as a function of temperature. What’s the obvious flaw with Jensen’s hypotheses?

Leads up to fig 1.10 — what are all these different theoretical patterns? Can you explain what each one means?

II. Organism and Environment

Adaptation and fitness…what are they? What’s wrong with the idea of an organism “fitting” to an environment?

p44: “Adaptive explanations have both a forward and a backward form”. Explain what he means.

What’s the problem with these modes of explanation? See discussion of Orians & Pearson results for an explanation.

p47: “the organism is the object of evolutionary forces”. Is this reasonable?

Lewontin says the concept of construction best captures the process of evolution. Explain.

He objects to the search for life on Mars for what reasons? (not that he thinks we shouldn’t look, but that he thinks the methods are wrong)

p54: “If one wants to know what the environment of an organism is, one must ask the organism.” How did he arrive at that conclusion?

p57-58: Explain Van Valen’s “Red Queen hypothesis”. Why is it somehow different from what Lewontin proposes?

p68: “Save the Environment!” But “the environment” does not exist to be saved. Is Lewontin a (shock, horror) an anti-environmentalist? What is the point he is making in his conclusion?

III. Parts and Wholes, Causes and Effects

A critique of the analytical, reductionist examination of the organism as a machine. This is generally how we teach biology; Lewontin argues that much of it is invalid. How would you alternatively expect biology to be taught?

p74: What are the current failures of that analytic approach? (with the understanding that that approach might still succeed, with enough time and data).

p77: What is the problem of the development of the human chin? What is the “error of arbitrary aggregation”?

p81: “Only a quasi-religious commitment to the belief that everything in the world has a purpose would lead us to provide a functional explanation for fingerprint ridges or eyebrows or patches of hair on men’s chests.” Does finding a functional explanation for any of those things invalidate the criticism? Why or why not?

Explain Tables 3.1 and 3.2. What do they tell us about the relationship between fitness and genetics when more than one gene is involved?

p90: When you see the variation in ceratopsian horns, how do you personally try to explain it? What is your default explanation?

p96: What are the “acute problems” in genetics? How much of it is a genuine problem with the scientific approach vs. attempts to shoehorn our explanations into simplistic causal models?

Lewontin gets political in the last page of this section, blaming environmental problems on “an anarchic scheme of production that was developed by industrial capitalism and adopted by industrial socialism”. What do you think?

IV. Directions in the study of biology

Lewontin admits that he’s been negative and strongly critical in the earlier parts of the text, so he has a brief epilogue in which he tries to advocate for some positive directions we can take. What are some ideas you might have?


It’s entirely possible we’ll only get two or three questions in, if we get argumentative, and that’s OK!

Of pigs and people

chimeras

Calm down, people. Nobody is making human-pig hybrids, even if the news is making a big deal about it. To be honest, I’m not even very impressed with the utility of the experiment, although it is interesting and technically accomplished. It’s being touted as a step in developing pigs with human-derived organs for transplants, and no, I just don’t see it.

The experiments involve xenografts in the blastocyst; that is, they take pluripotent stem cells from one organism, and inject them into the embryos of a different species at a very early stage of development, when the embryo is a hollow ball of cells with an inner cell mass that will eventually become the fetus proper. Then they look for incorporation of the injected cells into the embryo.

It doesn’t always work. The inner cell mass doesn’t necessarily accept these alien cells, or the injected cells don’t thrive in this unusual environment, so you might do the injections, implant the resultant hybrids, and when you open up the host days or weeks later, your injected cells are all gone. It is non-trivial to get this to work, so what they’ve accomplished is technically impressive.

It was a lot of work, too. They injected 2,181 pig blastocysts with human pluripotent stem cells, cultured them in vitro for a few days, and had 2075 embryos that were then implanted in masses of 40-50 embryos into host pigs (which implies that many would be expected to be lost), and collected 186 embryos about 4 weeks later. This is a good yield — I’ve done experiments with much lower rates of success — but the real question is whether any of the human cells were incorporated into the pig embryos.

It worked! They got incorporation of human cells into the pig embryos. Unfortunately, there are a few problems: one is that the embryos with incorporated human cells were significantly retarded in their growth. This ought to be expected; just the timing of development for the two kinds of cells will be out of sync, so I’d actually have expected even greater problems. It’s promising that they got incorporation at all. The other problem is that the incorporation was very low: 0.001% of the embryo’s cells were human. Uh, that’s not very good. If you’re trying to generate organs grown in pigs that have exclusively human antigens, even 99.9% human isn’t going to be good enough — it’s going to trigger an immune response when transplanted.

None of these cells made up the majority of cells in any organ, even; the experiment doesn’t really test the feasibility of accomplishing that, and I suspect that trying to increase the percentage of human cells is going to also increase the incompatibilities and lead to greater and greater rates of developmental failure. They do have some interesting ideas for increasing the rates, though. If the host pig cells are transgenically modified to make them unable to make a pancreas, for instance, any pancreas in the pig would have to be derived from human cells. It would still be infiltrated with pig-derived nerves and blood vessels and connective tissue, though, so that’s insufficient to create a transplant-ready organ.

As pure basic research, it’s a good experiment, and I’ll be interested to see how much further it can go — if nothing else, it’s going to expose evolutionary disparities in development between different mammalian species. The head investigator has an appropriate perspective on it, I think:

Scientific American: So this is very, very basic biology?

JCIB: So I feel that there has been a little bit of exaggeration of where we could go with this now. If you look on the Internet you see images of chimeras between human and animal. And I feel that that’s a little bit of exaggeration. It’s true that it works very nicely between rat and mouse — just this experimental protocol that I am telling you. It’s only a couple of months ago that we have been able to put human cells into another animal. In this case in a mouse and realized that they can differentiate in the three germ layers. The three germ layers are the mesoderm, ectoderm and endoderm that will give rise to the more than 250 different cell types. So that’s a major accomplishment I will say. But from there, dreaming that they will generate a functional structure, I think we’re going to need time and a lot of luck.
So we need to go for a lot of basic research still. It’s my own feeling, of course. There are other people who think that tomorrow we are going to create human organs. And I wish that I am wrong and they are right, but I think it will take time.

Yes! It’s basic research, which is a grand and worthy thing. It’s too bad so much of the press coverage can only grasp it in terms of making organs for human transplantation — I doubt that this approach will ever work for that, but will instead teach us more about development and evolution and molecular biology.

The second week of ecological developmental biology

limbdevelopment

I’m trying to do weekly assessments of how my new class is going…and also to have a regular record of concerns and successes so I can remind myself of what not to do next time I teach the course. We’re wrapping up a rapid survey of a few developmental systems just to expose them to some of the concepts of the field first; last week we blitzed through early polarity formation and gastrulation. This week we covered neural tube formation and neural crest on Tuesday, and this morning it was limb formation and craniofacial development.

One of my concerns is that it’s really easy for me to dominate the class hour. Yeah, just trigger me with a few phrases like apical ectodermal ridge, progress zone, and zone of polarizing activity, wind me up, and I’ll happily talk about cool experiments and nifty results for a few hours, my eyes glazing over as I forget that those students are there. That’s bad. I have to slap myself out of that habit. And as I mentioned last week, it’s not helping that it’s 8am and the students eyes are a bit glazed over, and I’m concerned about drawing them out to talk more. My ideal class would be one where I just help answer questions for the entire period.

I’m happy to say that, while they aren’t quite at that point yet, the students are warming up and I’ve been getting a few sharp questions, including some that I was unable to answer, which always leaves me overjoyed. Challenging stuff! It’s the best!

It also helped that the last half of today was something completely different: I gave them a short review paper that was rather densely technical on craniofacial development. I warned them that I was throwing them into the deep end of the pool to start with, so we struggled our way through all the acronyms and unexplained syndromes and weird little genes. We puzzled out the molecular basics for common developmental problems, like cleft palate, and more exotic and severe ones like Bartsocas-Papas syndrome (if you read the paper, you might not want to follow up by googling the syndromes, because you’ll encounter lots of tragic children). I learned a few things myself, like how common ribosomopathies are in these craniofacial disorders — there are genes like TCOF1 which produce proteins that act specifically in the nucleolar regions to regulate ribosome expression in specific tissues, and haploinsufficency leads to all kinds of failures in cell migration and differentiation.

I got even more questions. That’s good — I wasn’t looking forward to a semester of talking at nodding heads. I’m beginning to relax a little now.

Next week will be even more of a shock. I won’t be leading the discussions at all — I’ll be the one sitting back and answering questions. Tuesday will be student-led reviews of the stages of human embryonic development, with discussions of clinical correlates. Each student has been assigned a tiny snippet of the sequence to explain to us. Thursday they all have to explain The Triple Helix to me. Next week is all about student engagement!

The first week of Ecological Developmental biology

dogtired

We’re off to a slow start in my brand new course, largely because I’m in the awkward phase of trying to catch everyone up on the basics before we plunge into the deeper waters, but also because the 8am scheduling is not good for inspiring interaction. Maybe it wasn’t the best decision to begin with a crash course in introductory concepts in developmental biology, because it’s encouraging the students to think that I’m going to do nothing but pour knowledge into their brains, but I’m at a loss to know how to get right into the primary literature without making sure they’re comfortable with the terminology and ideas of the discipline first.

The theme of the first week really was fundamental: polarity. How does a single-celled zygote figure out which end goes up? The students had to read a few chapters from the Gilbert developmental biology text (which is free online, at least in the 6th edition, which is good enough for a quick summary), specifically the chapter on anterior/posterior polarity (which is almost entirely about Drosophila, I added a fair number of examples from Ciona and echinoderms), and the chapter on the organizer in amphibians. That covered a good range, from an organism in which the orientation is pre-specified by maternal RNA (flies) to a case where it’s determined by an environmental interaction — the sperm entry point followed by a cortical rotation reaction (frogs). I also added a bit about mammals, where the decision by the blastula cells to form inner cell mass vs. extra-embryonic membranes is basically a chance event, biased by location in the cluster of early cells.

In all of the examples, though, the key point is that the decisions are not determined exclusively genetically, whatever that would mean, but are contingent on interactions between genes and cytoplasm, which also has structure and pattern, and that that structure may also be influenced by the external environment.

It was fun and familiar to me, but again I’m concerned that when I do most of the work, I’m encouraging passivity in the students. That role is continuing this week, when I give them the stories of neural tube and limb development, as examples of later organ systems that rely on complex interactions. The third week, though, I completely turn the tables on them: they’ve got some reading assignments for that week, and have to do short presentations in class. I’m just going to sit back and ask questions, and hope I don’t get bleary-eyed silence in response.

In my notes for what to do next time I teach this course:

  • Lobby for a better course time. 8am is too damn early for young men and women, even if it is just fine for us oldsters who don’t sleep as much and get up early anyway.

  • This section is a prime candidate for a flipped classroom approach — I could make some short videos ahead of time that they need to watch in their homes, with an accompanying set of questions that they’ll have to discuss in class. The problem there is that in-class responsiveness is one of their weaknesses right now.

  • Later in the course we’ll be trying some different pedagogical approaches: watch for what works best with this group, and maybe revise our crash course section to use that.