Goodbye Spring Break, hello Spring

It’s officially the first day of Spring. I looked outside to see if flowers had suddenly erupted, but it’s too early and too dark to see.

It’s also the end of our Spring Break, and I have to get back to work, although it’s not as if I took it easy this last week. I’m actually prepared! This is my agenda for the week:

  • Genetics: We’ve been working through chromosomal changes, and I’ve been a little concerned about some of the students not quite understanding what’s going on, so we’re going to spend the first half of class with me leading them through some visualization exercises. I’m going to give them some word problems and have them draw the answers — it should also be a gentle warm-up to the class. Then it’s all sex and mapping for a while.

  • Genetics lab: Our mapping experiment is done, we just have to collate the results and do the calculations. Simultaneously, we’re starting a new experiment, a complementation assay.

  • Ecological Development: Endocrine disruptors! That’s always a fun way to start your week. Even more fun: an exam! An oral exam! The last half of this week and the first half of next week are going to be dedicated to meeting one-on-one with students to grill them on general concepts.

  • Biological Communications: I don’t think I’ve mentioned it before, but I’m also teaching a course in science writing — this semester it’s more of an independent study sort of thing, where they’re supposed to be putting together a substantial term paper on a subject of their choice. So far, it’s been little stuff — come up with a topic, do the preliminary research, give me short writing samples to demonstrate that you’re actually working on it — but their first full rough draft is due this week, so I’m getting stacks of papers to grade over the coming weekend.

  • We also have a guest seminar this week from an immunologist, Amy Weinmann, who is going to talk to us about epigenetics and development, which will fit in just fine with my eco-devo course.

I’m actually all planned out for the next two or three weeks. I just have to do the actual work. At least I think I know what I’m doing.

Juggling flies, fish, and students all week long

farsidevet

Time for another reflection on my mundane week of teaching. I know this is unexciting, but I’m trying to be self-aware about what I’m doing in the class.

I’ve already summarized some of what I did this week: we explored the meaning of “epigenetics”, and I made a big push to get them to think critically about the papers we’re reading. They’re supposed to be developing a topic they’ll explore independently, so I’ve had them doing library work to find a line of research they find interesting, and master the skill of extracting the key questions the work is trying to address. I’ve got a small stack of short papers that I’m going to read this weekend and we’ll see how well they can do that.

We also discussed symbiotic interactions in development, and next week the topic is other environmental effects. They are getting much, much better at opening up and talking at the miserable hour of 8am.

The other regular highlight of my week is FlyDay, when I have to scrub dead maggots and pupae out of fly bottles. I had to postpone FlyDay this week! Yesterday I was scheduled to meet with students and parents visiting the university to confirm their plans to attend, and I was all spiffed up in a nice suit, which isn’t the best thing to wear when one is flicking bits of chitin and gooey medium around. I went in early this morning to scrub bottles and get them cooking in the autoclave.

By the way, at that student meeting I was the official biology representative, and although biology is currently the largest major on campus, almost no one stopped by to talk to me. It might have been my terrifying glare, or my sciencey reek, but no: it was because there was a separate table for the pre-professional programs (pre-med, pre-vet, pre-dental, etc.). This is a minor peeve of mine: this is not 19th century England. You do not graduate from your public school education and go straight into medical school — no, here in 21st century America you get a broad-based undergraduate education first, and then you apply to med school. You should be thinking about your liberal arts education first, and in a couple of years we’ll start coaching you on how to get into those professional programs.

Oh, well. They ignore me now, but I know that I’ll get my claws on most of them soon — they’ll want all those bio classes to prep them for the MCATs.

I should mention that I am teaching another course beyond ecological development — I’m teaching a lab course on transmission genetics. They’ve been doing crosses with flies all semester long, and we’re getting to an interesting point.

The first half semester we’re doing a mapping cross, using recombination to estimate the distances between a couple of genes on the X chromosome. We’re using flies that are mutant for eye color (white, w), wing length (miniature, m), and bristle morphology (forked, f), and I’ve also got a few groups mapping body color (yellow, y), wing veins (crossveinless, cv) and forked, f; the latter are doing a pilot test to see if I want to add that cross to our regular repertoire.

The way this works is that they are given wild type and triple mutant flies. I first have them raise a new generation of the purebred stock, simply to get a little practice in sexing flies and basic skills in growing them. So they first do these crosses:

♀w m f/w m f x ♂w m f/Y

which produces bottles full of homozygous white-eyed, miniature-winged, forked-bristled flies, and

♀w+ m+ f+/w+ m+ f+ x ♂w+ m+ f+/Y

which produces bottles full of homozygous wild type flies.

Then I have them do a reciprocal cross of flies from the two bottles. These are X-linked traits, so it matters which strain is the mother and which the father, and I want them to see that. That is, they cross wild type females to triple mutant males, like so:

♀w+ m+ f+/w+ m+ f+ x ♂w m f/Y,

which produces progeny that are all wild type, both male and female (they all inherit the dominant wild type allele at all loci from their mothers). After they’ve scored the flies from this cross, we dispose of them all and don’t think any further about them.

They also cross mutant females to wild type males, like this:

♀w m f/w m f x ♂w+ m+ f+/Y.

That has the useful result that all the sons inherit w m f from their mother and a Y chromosome from their father, so they all express the mutant phenotype. The daughters, however, are all heterozygous, inheriting the mutant alleles from their mother and a wild type chromosome from their father, so their genotype is:

♀w m f/w+ m+ f+

Now the fun begins. Meiotic recombination in those flies will rearrange the +’s and -‘s in those chromosomes with a frequency dependent on their distance from one another — you’ll get less recombination between genes that are close to one another.

This week, they completed the reciprocal cross and got their heterozygous females and mutant males. Yay! That worked. They are now setting up a test cross to assess recombination frequencies.

I just want to say that I think I planned everything perfectly. That test cross will be ready to score next week, which is the week before spring break, which means we’ll have the data for all the calculations before they leave, and when they get back, I’ll be able to lead them through all the theory. It also means I’ll be able to purge a lot of fly bottles and get them scrubbed up over the break (you can tell already that I have glamorous plans for my short vacation). Trust me, though, this is good — there have been semesters where, due to student error, the flies haven’t been ready, and then my spring break is spent maintaining 120 bottles of student flies.

It also means we can launch into the next experiment as soon as they get back: we’re going to do a complementation cross between two eye color mutants, brown eye (bw) and scarlet eye (st). If I’ve got this one all timed out correctly, we’ll be getting F2 results of crosses between heterozygotes for both loci a week before the end of classes.

Now you know. I choreograph fly sex for my convenience.

Next up, I have to choreograph my schedule. It turns out I have been summoned to Howard Hughes headquarters on 8 March and 18 April, which punch big holes in my planned lessons, and which I hadn’t accounted for in my syllabi. I’m going to have to juggle lectures and exams and rearrange the order of various things in a big way this coming week.

What the heckity-gosh-darn is epigenetics?

comfortable

Today in my class we talked for a while about epigenetics. I used it as an example of a term we’d encountered more than once in our ecological developmental biology course, but that has some complicated ambiguity and fuzziness that has led to all kinds of weird popular confusions about the subject. I was also using it as an example of critical analysis of a paper, as I discussed yesterday, and it was a lead-up to having the students discuss papers on relevant topics they were interested in — so we spent most of our time talking about other things.

But I’m going to talk now about just this one paper I read. You see, Larry Moran and I have been having this long-running disagreement about epigenetics — nothing hostile, just an occasional cocked eyebrow in each other’s direction — which you can see on display in this article by Larry on epigenetics, in which he disagrees with my definition of epigenetics, back in 2008. Here’s my definition:

Epigenetics is the study of heritable traits that are not dependent on the primary sequence of DNA.

And here’s the definition used in Gilbert’s text:

…molecular processes around DNA that regulate genome activity that are independent DNA sequence and are mitotically stable.

And here’s Larry’s objection:

Here’s the problem. If this is epigenetics then what’s the point? When I was growing up we had a perfectly good term for these phenomena—it was regulation of gene expression. Why is there a movement among animal developmental biologists to use “epigenetics” to refer to a well-understood phenomenon?

While I agree that “epigenetics” is a huge, broad, diverse category of phenomena, I think he’s overlooking a key point to claim it is synonymous with gene regulation. It is gene regulation that is heritable and mitotically stable. It’s still far too open-ended, but it’s not just any old example of gene regulation.

It’s also clear and consistent. Larry challenges us with eight instances of regulatory phenomena and asks which ones qualify as epigenetic. Easy. 1, 2, 6, 7, 8. Those are the ones where he specifically mentions multi-generational inheritance of a regulatory state. 3, 4, and 5 describe responses within a single cell in a single generation (5 is sneaky, though: Drosophila oocytes are having gene expression modified in ways that might be transmitted through multiple generations — it’s just that those cells are being loaded with bicoid RNA, not having their bicoid genes being set to a sex-specific state).

I am also comfortable with the idea that inheritance of the regulatory state of the lac operon is an example of epigenetics. It’s arguable whether that’s a useful category, but it does fit the definition.

So one approach that could be taken is to come up with a more specific or more practical definition.

Larry has a more recent article in which he agrees with a new paper by Deans and Maggert that tries to do exactly that. It also takes a much appreciated historical approach, giving the various definitions that have been wafting about since the 1930s. For instance, here’s Waddington’s ancient physiological definition:

the branch of biology that studies the causal interactions between genes and their products which bring the phenotype into being

Yes, I agree — that would simply be gene regulation nowadays. You can’t blame us wicked developmental biologists for promoting that one, though, because we don’t use it anymore.

Now we favor the Holliday definition:

the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail change in DNA sequence.

To me, “heritable” is the magic word that makes all the difference. This, however, is not enough for Deans and Maggert. They want to add more focus, often a good thing, and narrow the definition. I was not happy with their argument, and thought it poorly made, though. See if you can find what was objectionable in this section of their paper (I highlighted it to make it easy, an epigenetic modification that does not change the sequence of the letters in the text.)

We don’t feel that it is possible to reconcile Waddington’s focus on gene regulation with Holliday’s more specific criteria within one field and still maintain the level of clarity needed to produce a useful definition. The efforts to preserve a relationship between these two conceptualizations have been impaired by the fact that there are just too many phenomena, with too few mechanistic connections, to categorize into one field. Also, among the definitions that do maintain the requirement of heritability, we feel that many lack the detail to be functionally useful in directing the testing of specific hypotheses, particularly as it relates to the location or site (cytoplasm or nucleus) of epigenetic phenomena. To mitigate these shortcomings, we advocate defining epigenetics as “the study of phenomena and mechanisms that cause chromosome-bound, heritable changes to gene expression that are not dependent on changes to DNA sequence.”

We feel that this definition makes a strong distinction between gene regulation (Waddington’s definition) and epigenetic inheritance (Holliday’s definition), and also emphasizes that epigenetic phenomena must deal exclusively with chromosome-bound changes. By making these distinctions, we have efficiently separated expressional changes caused by cytoplasmic compounds, which are more closely tied to gene regulation, from those which occur on, or in close association to, the chromosome. Doing so makes the focus of the field much clearer and identifies epigenetic mechanisms more explicitly.

We feel that this definition touches on several important elements not encompassed by other definitions, yet commonly implied in most uses. To further explain the reasoning behind our definition, as well as its utility for improving epigenetic research, we would like to offer a clarification and a test.

Yeesh. I don’t feel that your personall feelings are a strong argument, and I cringed when I hit that page. At least edit it to remove the emphasis on your personal discomfort; just say that the old definitions lack detail, rather than that you feel they lack detail.

So let’s pull out their shiny new definition.

the study of phenomena and mechanisms that cause chromosome-bound, heritable changes to gene expression that are not dependent on changes to DNA sequence

Well. All this fuss for a single change, the addition of the phrase chromosome-bound. That’s it. I agree, it does narrow the topic, but it’s still covering an awful lot of territory. I’m not feelin’ it. I have the impression that the primary virtue of the new definition is that it reduces a class of phenomena to a subset that many people are comfortable studying already, and in part reinforces a gene-centered perspective on cellular behavior.

It also leaves me wondering…what about the inheritance of cytoplasmic or membrane-bound factors that induce consistent changes in gene expression in daughter cells? The gene regulation aspect may be mundane, but it’s the inheritance that is interesting. Under the Deans and Maggert definition, this is no longer under the umbrella of epigenetics — it’s something different for which we have no general name now.

It makes Larry happier, though.

I think this is a useful definition. Nobody cares if dividing E. coli cells inherit molecules of lac repressor and continue to repress the lac operon. That’s a trivial form of epigenetics that never posed a threat to our understanding of evolution.

That’s odd. I do care that the lac repressor is cytoplasmically inherited, but then my primary interests, in the most general form, would be in the patterns of stability and change in cellular properties, rather than the metabolism of sugar. Telling me that I should only pay attention to inherited proteins or methylation states that are directly bound to DNA seems arbitrary.

I also don’t consider “poses a threat to our understanding of evolution” to be a relevant criterion. I agree that lac repressors don’t challenge evolutionary theory, but neither do heritable histone modifications or methylation. I’m one of those people who think epigenetics (even under the old definition!) is important and interesting, but doesn’t affect evolutionary theory much at all.

Larry and I agree.

Methylation is trivial.

Well then, if inheritance of the lac operon is such a trivial form of epigenetics that it should be excluded from the definition, then we apparently need yet another definition that excludes the triviality of methylation.

Or, really, we should recognize that “trivial” is not a good reason to exclude something.

I will still second Larry’s argument that none of this stuff overthrows modern evolutionary theory in any way. It would require extremely persistent inheritance of an epigenetic state over many generations to have those kinds of repercussions.

(The Gilbert text does mention one significant effect: the toadflax plant, Linaria vulgaris, has a radically different flower morph, Peloria, that Linnaeus himself classified as a different species. As it turns out, they only differ in the methylation state of the cycloidea gene, but the DNA sequence is identical. This is a case of an epigenetic change persisting for hundreds of generations. It’s a rare case, though, and also…would still definitely fall under the Deans and Maggert definition.)

Ecological Development: Getting critical

far_side_good_hands

In class last week, we continued our discussion of developmental plasticity and began to talk about epigenetics, and in particular, the underlying molecular mechanisms for epigenetic inheritance. In addition, students had to discuss papers on plasticity that they’d researched. Some of the topics covered were: sneaker males and alternative reproductive strategies; aggression in dog breeds, how much is genetic and how much is training; temperature-dependent and behavior-dependent sex determination in reptiles and fish; and physiological responses to variations in gravity (someone has put pregnant rats in a centrifuge and looked at the effects of 2 gravities on development). It was all fun stuff, and I made the students do all the work. Perfect!

This week they have another assignment. There’s a common problem in student writing about science: they tend to describe what a paper says. That makes for very boring reading, I’m sorry to say — if I just wanted to know what was in the paper, I could read it myself, after all. So this week they’ve been asked to write a critical analysis of a science paper relevant to the course. This is a routine skill that needs to be cultivated and practiced.

What’s involved? You first have to identify a key question or assertion in the paper, or even in a short section of the paper, and ask yourself if the authors have adequately defended the claim. Even if you agree with the claim, and think it’s eminently reasonable, you have to approach it as a critic and try to tear it down.

I’m going to try to lead by example, so I have given them a couple of papers to read ahead of time. One is “Novelty and Innovation in the History of Life” by Douglas Erwin, which makes an argument that should be familiar to the students, because we’ve already talked about some of the concepts. Here’s the abstract:

The history of life as documented by the fossil record encompasses evolutionary diversifications at scales ranging from the Ediacaran–Cambrian explosion of animal life and the invasion of land by vascular plants, insects and vertebrates to the diversification of flowering plants over the past 100 million years and the radiation of horses. Morphological novelty and innovation has been a recurrent theme. The architects of the modern synthesis of evolutionary theory made three claims about evolutionary novelty and innovation: first, that all diversifications in the history of life represent adaptive radiations; second, that adaptive radiations are driven principally by ecological opportunity rather than by the supply of new morphological novelties, thus the primary questions about novelty and innovation focus on their ecological and evolutionary success; and third, that the rate of morphological divergence between taxa was more rapid early in the history of a clade but slowed over time as ecological opportunities declined. These claims have strongly influenced subsequent generations of evolutionary biologists, yet over the past two decades each has been challenged by data from the fossil record, by the results of comparative phylogenetic analyses and through insights from evolutionary developmental biology. Consequently a broader view of novelty and innovation is required. An outstanding issue for future work is identifying the circumstances associated with different styles of diversification and whether their frequency has changed through the history of life.

Let’s take that apart. Erwin is saying that there are some long-held assumptions in evolutionary biology that he is going to suggest are possibly invalid. Those assumptions are:

  1. Diversity is the product of adaptive radiations;

  2. Radiations are driven by ecological opportunities; and

  3. Most morphological variants emerge early, in the process of filling open niches.

He’s going to propose alternative processes.

  1. Initially non-adaptive variants are going to generate morphological diversity;

  2. Novel forms construct the niches that they will fill; and

  3. Variation is a constant event in a lineage.

I am predisposed to like those new perspectives, and I’m also biased by the evidence we’ve discussed in class, that ecology and development are in a constant state of reciprocal feedback. But rather than reporting and describing this paper as something that reinforces my views, I need to examine it critically. Does Erwin adequately support his claims? Are there significant questions he does not address? He’s also given us a list of sources of evidence that he’ll use to challenge orthodoxy: “the fossil record, by the results of comparative phylogenetic analyses and through insights from evolutionary developmental biology”. Does he succeed?

I’m just going to consider his first point, whether it is adaptive variation that drives radiations (lesson for students: focus. Better to do one thing well than 3 things poorly). His evidence in this section comes primarily from analysis of the fossil record, which is going to raise some objections.

Erwin does not deny the existence of adaptive radiations, and wisely begins by discussing known examples. He cites the work on Galapagos finches, where we have strong evidence of morphology being shaped by adaptive necessity. He also discusses cichlids, where variations in the environment have clearly played a role in, for instance, feeding adaptations. To then argue for alternative mechanisms using the fossil record is problematic: adaptive radiations are seen in cases where you’ve got close-up, fine-grained observations of single clades, but the evidence for adaptation fades when you use a more coarse-grained, less well-sampled method?

One piece of evidence presented is basically an absence-of-evidence argument. There is a lack of evidence of character displacement in the fossil record. Character displacement is the shift in morphology away from each other from two similar species competing in an overlapping range; it ought to be seen if two populations are adapting to avoid competition.

His argument that solutions to adaptive problems can exist for milllions of years without a radiation occurring is more interesting. He points to Anolis lizards in the Caribbean that converge on similar strategies when they evolve on different islands as an indication that the potential for particular morphologies is present in the species before they find themself with fresh opportunities on a new island. The carnivore fossil record shows a limited repertoire of optimal feeding strategies, which canids exploited repeatedly. Sea urchins have been evolving to follow similar feeding patterns repeatedly, as well.

It’s a somewhat frustrating argument, though. He’s trying to show that a radiation can’t have been driven by the acquisition of an adaptation if the adaptation had existed for long periods previously without a radiation. I can see the point, but one could argue that the radiation depended on both the prior potential in the organism and ecological circumstance, which is part of his second point…which makes point #1 and point #2 codependent on one another.

I’d have to say that I wasn’t entirely satisfied that he’d supported his first conclusion to my satisfaction. It’s also the case that he’s arguing that both adaptive and non-adaptive radiations occur, meaning it’s a quantitative question of which of the two is most important under what conditions, and he hasn’t done anything to measure that balance. I don’t reject the hypothesis, but I also don’t think the work has been done to confirm it — yet. He concludes the whole paper by predicting that gene regulatory networks are characterized by stability, so morphological novelties may be based on features established outside the core GRNs, and are thus more flexible. I don’t know. That’s definitely well outside anything you could figure out with fossils, so it’s going to require a different approach.

That’s how I’m going to talk about a paper I enjoyed with my students (and you Pharyngula readers think I’m harsh with my mere movie reviews). I’m also going to discuss a second paper on epigenetics that I didn’t care much for — the heart of the paper is a painful exercise in writing about how they feel about certain definitions of epigenetics which made me snarl — but I still think it made some valid points.

That’s really the purpose of the whole exercise. Stop treating science papers as holy writ that you can’t challenge; think critically about everything, and try to find logical holes that can be plugged with better evidence. That’s how science gets better and better. These are smart students and they just need to learn that they can actually disagree with Famous Scientists.

The real challenge, too, is that my plan is to talk about these examples for maybe 15 minutes, and then put the students into groups to discuss the papers they’ll have brought with them, trying to punch holes in them. It might be fun. It might be difficult and frustrating. As mentioned, one of the annoyances of student writing is that too often they think of it as reporting, describing what’s in it rather than engaging with the ideas with their very own brain and questioning what the paper says.

Hey, maybe I shouldn’t call it “reporting” since that’s also what journalists should be doing, but too often aren’t. Reciting summaries credulously shouldn’t be what either scientists or journalists do.


Erwin DH (2015) Novelty and Innovation in the History of Life. Curr Biol 5;25(19):R930-40.

The third and fourth week of ecological developmental biology

morningonthefarside

I’d intended to make these reflections on the progress of my new course in ecological development a weekly feature on the blog, and then I failed to post an update last week. Bad professor, very bad. My excuse, though, is that I’m on a job search committee, we had three interviews in the last week, and they’ve all been kicking my butt and leaving me exhausted at the end of the day. That’s a duty that’s also a lot of work for us academics: there’s the gay social whirl all of a sudden, the scrutiny we have to give to each candidate, and sitting through job talks. The stress can be enormous, too — not for the candidates, although I’m sure they’re feeling a little anxiety, but for us. In the dream search, you bring in two candidates who suck and third that is gloriously qualified and a joy to spend time with, because then the decision-making is easy. In this case, we got three marvelous candidates and I want to hire them all, and we have to pick one. Just one. We’re going to make that painful decision on Saturday, so while all the work is done, the agonizing has only just begun.

And meanwhile, classes go on!

Last week was assessment time. I’m also teaching our genetics course, and they got an exam…an exam they did pretty well on, with an average of 79%. It could be that this cohort of students is just generally brilliant (but all of our students are brilliant), or it could be that some changes I’ve made in this class have been effective. I’ve been concentrating on laying a solid foundation: we’ve gone over basic Mendelian genetics, something I remind them over and over that they should have already been thoroughly exposed to and so this should just be review, and I also remind them over and over that later it’s going to get much harder and that we’re going to spend almost the entire semester talking about exceptions to this simplistic Mendelian stuff, and if they don’t fully grok the basics they’re going to be so screwed. We’ve also been working on a probability and statistics toolbox that they’ll be using repeatedly throughout the term.

I may have scared them into studying hard. Not only did they get a higher average score than past years, but the range tightened up considerably. I’m trying to build a strong foundation here, because as Al Franken explained to the nation in the DeVos hearings, we care more about growth than an arbitrary standard of proficiency. Give ’em the basics so the weaker students have something to build on rather than floundering and falling apart on the first day, and keep nudging them upwards at every step in the class.

My ecological development course also took a turn. The first two weeks, you may recall, consisted of the traditional Old Bearded Guy standing at the front of the room Old-Bearded-Guysplaining developmental biology to them — again, trying to put everyone on a firm footing in the fundamentals. The next step is to coax them into student-splain stuff to me. This has been harder than it should be, because this is an 8-fucking-am course, and I’m not my perkiest, and the students aren’t either. Next time I teach an interactive course, I must insist that it be offered sometime in the mid-day. Either that or demand IV bags from the ceiling filled with caffeinated beverages and start the morning going to each desk and jabbing everyone into alertness with a needle in a vein.

Instead of intravenous drugs, though, my approach to jump-starting their brains and making them comfortable speaking was to force them to do presentations last Tuesday. Short presentations; I gave them copies of Langman’s Medical Embryology, used a deck of cards to randomly assign each of them a week of human development, and had them give five-minute summaries of what was happening then: they had a few questions to guide them, like show what the embryo looked like, say something about critical events in their week, and discuss clinical correlates. It was straightforward and didn’t require intense thought, so it was simply a way to get them all to say a bit in class, as well as introducing a topic that we’ll return to in, for instance, a later discussion of teratogenesis.

Last Thursday, they had to talk again (I am such a cruel tyrant). They’d been assigned to read Lewontin’s Triple Helix, and this day was dedicated to a critical assessment of the text. I gave them a set of questions about the book, and then sat back and let them tell me the answers.

That actually went fairly well, I think. It still takes some time for them to warm up and get a conversation going, but they’re a smart bunch and we got some good discussion. It went well enough that we didn’t finish, so we extended the review to this past Tuesday. We identified a central theme of the book as construction: organisms are assemble themselves in an environmental context, and they are continually modifying their environment. These cycles of self-referential feedback mean that you simply cannot define an organism from nothing but its genome. They’re getting it!

This morning, I twisted the game around on them a little more. We’re digging into Gilbert’s Ecological Developmental Biology text with chapter 1, on normal plasticity, and this time I gave them the assignment ahead of time to write down three questions that chapter inspired in them. We spent most of our time bouncing questions and answers back and forth, which is always fun. I ended the session by listing some of the questions that got some vigorous responses, and putting them on the board. They were:

  • Temperature-dependent sex determination in reptiles: are there reptile intersexes? How often? We also got a suggestion that we should look more into behavioral sex determination in fish.

  • Inheritance of behavior differences: what causes differences in aggression in dog breeds? Is it genetically determined, how much and what genes are involved? (I asked where they fell on the continuum of biases about pit bulls, whether they where inherently vicious and needed to be put down, vs. a maligned breed that has a bad reputation because they are abused. I was surprised: 100% of the class came down in the not-intrinsically-evil camp. Dang liberals!)

  • Sneaker and dominant males: How do these differences within a sex in a single species arise? We discussed rhinocerous beetles and cephalopods.

  • Gravity. How dependent is development on this pervasive influence of gravity? We talked about some clear examples, like how the chicken body axis is dependent on rotation, and that led to speculation about human development and plasticity in microgravity. What happens to bodies in space? Can human fetuses grow normally in space?

  • Epigenetics…there were some good questions about that, but I deferred them all, telling them that we’re going to spend a whole week on epigenetics, so let’s take it off the table temporarily.

That was a good start. Then I divvied up the students — they volunteered for what subject most interested them — and sent them off to the library with an assignment, to find papers to address their question, and come back next Tuesday prepared to explain what they learned to the whole class.

Brains full. We stopped there. I’m looking forward to learning what they find next week.

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.

I’m a little worried about teaching genetics

I start teaching my genetics class today, and usually I plunge right in to simple Mendelian genetics to get through the easy stuff quickly. I’m making a big change, though, for social and political reasons. In a country rife with neo-Nazis and racism, it’s a bad idea to encourage simplistic thinking about genetics — too many people know a little bit about Mendel’s pea plants (trust me, those traits were chosen for their discontinuous properties and apparent simplicity), a teeny-tiny bit about Darwin and selection, and turn that into sweeping pronouncements about the True Nature of Humanity, as understood by idiots. It’s embarrassing. So I’ve decided to start the genetics course with a little demonstration of humility. Think before you leap to conclusions about how genetics works!

This page on the myths of human genetics is extremely useful for that purpose, so we’re going to go through a few examples right there in the classroom, and show some of the data. There has been a historical tendency to shoehorn traits into a simple Mendelian model, and it’s easy to show that there are cases where that doesn’t work, at all.

We’re also going to take on that popular nonsense about finger lengths, which is just a classic example of overinterpreting tiny amounts of variation (which is still statistically significant!), and making grandiose claims about human nature as derived from a morphological feature. It’s little more than modern palmistry…I’ve even found a page on palmistry that just runs on at length about these ridiculous claims about personality derived from the length of your index finger. And then there’s Joseph Mercola, who claims that you can use finger length to predict your IQ, SAT scores, and of course, autism, in addition to your sexual preferences.

In the end, I’m going to give them a short list of basic intellectual and ethical ideas they ought to have when beginning a study of genetics.

  • Avoid value judgments. What is a flaw to one person might be a virtue to another.

  • Do not concatenate assumptions. An individual might have a particular trait, but it does not imply that they have another, and another, and another, creating a false picture from a single data point.

  • Genetics is a mighty fine hammer; it does not mean everything is a nail. In particular, individuals are the product of gene products interacting with each other and the environment. Don’t disregard one component at the expense of another!

  • Reductionism is essential for a beginning of understanding, but is not sufficient for a thorough understanding. We start simple because that’s what we’re sure of; but our purpose is to build a more accurate model on that foundation, that will inevitably be more complex.

  • We do not understand everything about heredity. An ethical culture refuses to stereotype people on the basis of limited knowledge…or worse, false knowledge.

  • Nullius in verba. Critically assess all claims.

On Monday we’ll review basic Mendelian genetics, which seems to be all students come out of high school knowing anything about (and even at that, they’ll make lots of mistakes). It just seems to me, though, that in the current political climate it is irresponsible to put off a discussion of the limitations of science and ethical concerns until the very end of the course.

How to read a scientific paper

If you’ve been wondering how the pros do it, here’s a guide to dissecting a science paper.

Don’t be intimidated: it’s a description for how to really take every detail of the paper apart, and it’s a rough outline of what I do before talking about a paper on the blog. But it’s also a little bit of overkill for most papers. I read a lot of papers, and I can’t possibly analyze them as thoroughly as that article prescribes, and I take shortcuts — often, the methods are the most boring part, and I’ll just skim over them rather than doing the thorough diagramming recommended. I’ll go back and cover them thoroughly if I find other parts of the paper provocative, though.

The other course I’m teaching this term is an independent writing course, though, in which the students have to produce a well-researched term paper. I’ll have to send them a note telling them to read this article now.

Just in time for my cancer class

In a few weeks, we’ll be having a discussion of the ethics of cancer research: what is a reasonable intervention in the case of a patient who has no hope of survival? And look at the interesting case that just appeared on my radar: two cancer surgeons who treated brain tumors by deliberately infecting them with bacteria.

Two UC Davis neurosurgeons who intentionally infected three brain-cancer patients with bowel bacteria have resigned their posts after the university found they had "deliberately circumvented" internal policies, "defied directives" from top leaders and sidestepped federal regulations, according to newly released university documents.

Dr. J. Paul Muizelaar, 66, the former head of the neurosurgery department, and his colleague, Dr. Rudolph J. Schrot, violated the university’s faculty code of conduct with their experimental work, one internal investigation concluded.

All three patients consented to the procedures in 2010 and 2011. Two of the patients died within weeks of their surgeries, while the other survived more than a year after being infected.

The premise behind their experimental procedure is probiotics, which immediately throws a warning on the play: there’s a lot of abuse of the concept out there.

Muizelaar and Schrot called their novel approach “probiotic intracranial therapy,” or the introduction of live bowel bacteria, Enterobacter aerogenes, directly into their patients’ brains or bone flaps. The doctors theorized that an infection might stimulate the patients’ immune systems and prolong their lives.

But there are some serious problems here. They didn’t have institutional review and approval of their procedure! That’s not a warning flag, it immediately calls the entire research into question and brings the ethics of the doctors under the microscope. You don’t get to do that.

And then there’s their logic. This is a disease with a median survival of 15 months. Their first patient died less than 6 weeks after the surgery, while the second lived for a year, which the report says “buoyed the doctors and seemed to bolster their theory”. That makes no sense at all — with so few trials they can’t possibly make that kind of assessment. Furthermore, their third patient died of sepsis.

At least it sounds like we’ll have something to talk about. That seems a paltry reward for three people’s deaths.

(via The Tree of Life)