You know who else was a great painter? Hitler.

Sorry for the excessive hyperbole, but I had to counter the sniveling sycophancy in this Fox News puff piece.

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They’re impressed that it took “only a month” to teach him to paint like that? It shows. He’s going to go down in history as a great artist? Judging by what is shown in that clip, this is a retired guy with a nice hobby. That’s about it. Good for him — at least he’s not ripping the hearts out of virgins and kicking puppies for a hobby like Dick Cheney — but come on, American Pravda, let’s not lay it on quite so thickly.

I think I’ve just been persuaded that MOOCs suck

I’m convinced. Physioproffe is right: MOOCs are a great big boondoggle. It wasn’t PP’s words (true as they are) that persuaded me, though — it’s that Thomas Friedman has endorsed them, in a godawful column complete with helpful discussion with his driver from the airport.

Just consider this claim:

We demand that plumbers and kindergarten teachers be certified to do what they do, but there is no requirement that college professors know how to teach. No more. The world of MOOCs is creating a competition that will force every professor to improve his or her pedagogy or face an online competitor.

Holy crap. Right now I’m in ‘competition’ with skilled colleagues who were selected for their position on the basis of their teaching skill — I’m evaluated in comparison with my peers. I’ve seen these MOOC-style lectures, and please please please, I would love to be assessed against some person whose interactions with students are entirely through a glass screen, in a format that favors linear lecturing, and considers email a marvelous way to communicate outside of class.

This is what Friedman considers an increase in competition for college teachers? I see a slackening and a reduction of standards…and what the administrators and mouth-breathing ignoramuses like Friedman see is a way to outsource and reduce the costs of the expensive part of an education…the part that is also the only real education component of the process.

What I taught today: heavy on the epistasis

Today we talked about gap genes and a little bit about pair rule genes in flies, and to introduce the topic I summarized genetic epistasis. Epistasis is a fancy word for the interactions between genes, and we’ve already discussed it on the simplest level. You can imagine that a gene A, when expressed, activates the expression of gene B. The arrow in this diagram? That’s epistasis.

epi1

So far, so simple. This could describe how bicoid activates zygotic hunchback for instance. But of course not all epistatic interactions are linear and one dimensional; often one transcription factor will turn on or repress multiple genes — so A might switch on genes B, C, and D.

epi2

But wait! Now there is the potential for all kinds of combinatorial interactions: maybe C has positive feedback back on A, and B activates D and C, and D activates B, and C represses B. There’s a whole mathematically bewildering world of possibility here.

epi3

And it gets worse and worse. B, C, and D could have downstream effects on other genes, like E, F, G, and H, and each of those interact with each other and can have feedback effects as well. It’s not at all uncommon to be taking apart the sequence of events of a developmental pathway and discover a whole tangled snarl of epistatic interactions that lead to complicated patterns of gene expression.

epi4

And that’s molecular geneticists and developmental biologists do: they try to tease apart the snarl, asking how each gene interacts with all the other genes in the system, working out the kind of genetic circuitry shown in those diagrams. Often the approach is take it one gene at a time: knock out F, for instance, and ask what happens to the expression patterns of A, B, C, D, E, G, and H. Or upregulate D, and ask what all those other genes do. If you like logic puzzles, you’ll love epistatic studies, because that’s what they are: grand complicated logic puzzles with multiple cascading effects and usually only partial knowledge about what each component does. You’ll either have great fun with it all, or cultivate great headaches.

So most of the class hour was spent going through examples of these puzzles. The gap genes, for instance, are expressed in broad stripes in the embryo, and we can try to decipher the rules that establish the boundaries by taking out components. If hunchback is deleted, what do the giant, krüppel, and knirps stripes look like? Take out krüppel, what happens to knirps? So I led them through this series of experiments, asking them to come up with general rules regulating the expression of each stripe, and then using those rules to predict what would happen if we did a different experiment. I think they mostly got it.

But of course the discussion today was mostly about the gap genes, which are the second tier of genetic interactions (analogous to my third figure above). Next I introduced the pair rule genes, the third tier, rather like my fourth diagram. These are genes that are expressed in alternating stripes corresponding to parasegments in the fly…so we’ve gone from a few broad stripes to many narrow stripes. Each of those stripes, too, is independently regulated, with distinct control regions for each.

The real nightmare begins in the next class, when we start taking apart the many ways all of the pair rule genes interact with each other, and how their position is established partly by regulation by the gap genes and partly by mutual sorting out with combinations of activating and repressing interactions. It’s going to be loads of fun!

Today’s slides.

A little blogging exercise for my students

In my development class, students have been blogging away for the last few weeks, and I asked them to send me links to ones they wouldn’t mind seeing advertised. I’ve told them that an important part of effectively blogging is to link and comment, so they’re supposed to write something this week that adds to one of these posts and links to it on their own blog, and they’re also supposed to leave a comment on their fellow students’ work.

I warned them too that I’d highlight these publicly and urge my readers to look and say a few things: so go ahead and comment, criticize, praise, whatever — I told them that the good will come with the bad.

I suspect I’ll have to explain to them how to kill spam and remove irrelevant or outrageous comments in the next class…

As usual, it’s not the message, it’s the mere existence of atheists

American Atheists have put up a new set of billboards, with a “go godless” campaign theme.

new-atheist-billboard-split-story-top

What’s interesting, though, is the media response:

Atheists ratchet up rhetoric, use billboards to attack Republican politicians

Hang on there…”Go godless instead” is ratcheting up the rhetoric? It seems like a rather mild suggestion to me — presenting an extremist religious position and then offering an alternative is an entirely reasonable approach.

As for attacking Republican politicians…has CNN noticed that the religious right has staked itself out in the Republican party? If Democrats were saying things as stupid as the Republicans, I’m sure Dave Silverman would be ripping on them just as aggressively. And if the Republicans were not basing bad policy on religious dogma, there wouldn’t be much concern about them and they wouldn’t be appearing on those billboards.

Maybe if they sink a lot of the budget into special effects…

There is no accounting for taste or credulity. Universal Pictures is planning to make Eben Alexander’s book into a movie. You remember Alexander; the Proof of Heaven guy, the surgeon who ‘died’ on the operating table and claimed to have visited heaven?

It might be interesting to see the effort. The whole tone of Alexander’s fantasy is one of vagueness, ineffableness, incomprehending awe — he talks about seeing indescribable beings like birds or angels that he can’t do justice to in words, for instance…I don’t think crisp CGI is exactly going to work in his favor.

What I taught today: the great cis vs trans debate

My students get a full exposure to the Sean Carroll perspective in his book, Endless Forms Most Beautiful, and I’m generally pro-evo devo throughout my course. I do try to make them aware of the bigger picture, though, so today we had an in-class discussion/’debate’ (nothing so formal as a debate, and it was more a tool to make them think about the arguments than to actually resolve a question). Fortunately, there’s one really easy exercise we can do in developmental biology, because some big names in the field have already clearly laid out their positions in a couple of relatively succinct papers, so I had a shortcut to bring the students up to speed on the issues. I split the class on Monday, having half read a paper by Hoekstra and Coyne on “The locus of evolution: evo devo and the genetics of adaptation” (pdf), which argues for the importance of trans-acting mutations in evolution, and another by Wray on “The evolutionary significance of cis-regulatory mutations” (pdf), which argues for the importance of developmental changes through changes in cis regulatory regions.

I drew this little cartoon on the board to illustrate the situation: that changes in the coding regions of genes produce mutations that can have broader effects throughout the cell (trans: they can affect other genes not on the same chromosome), while changes in regulatory DNA will have discrete effects on just the gene on the same strand of DNA they are (cis).

cistrans

Then I asked them put together an argument as a group advocating for the significance to evolution of their ‘side’, cis or trans, which they then delivered to their opponent, with opportunities for rebuttal and counter-rebuttal.

Ah, pitting the students against one another…always the fun part of teaching.

There was good friendly discussion. Both sides had to dig into their respective papers to find the arguments, and then restate them to make their point, both of which are good exercises. The battle waged to and fro, and then our hour was up and I asked them to vote for who ‘won’, in the subjective sense of making a good argument and persuasively advancing their position. The results:

Which position do you think makes the best case for the significance of their phenomenon in evolution?

Team trans: 1
Team cis: 0
Both positions are important: 8

Minnesota mildness for the win!

I did think one student comment was perceptive and exposed the whole argument for a sham. If they were to go off to graduate school in developmental biology, they wouldn’t be picking Team trans or Team cis: they’d be pursuing a phenotype or a pattern of interest, and then analyzing how it worked and came to be, and they’d simply accept the evidence, cis or trans or both, however it turned out. Follow the data, always.

Now that’s a healthy attitude.

I can defend both Lawrence Krauss and philosophy!

Philosophers are still grumbling about Lawrence Krauss, who openly dissed philosophy (word to the philosophers reading this: he recanted, so you can put down the thumbscrews and hot irons for now). This is one of those areas where I’m very much a middle-of-the-road person: I am not a philosopher, at least I’m definitely not as committed to the discipline as someone like Massimo Pigliucci, but I do think philosophy is an essential part of our intellectual toolkit — you can only dismiss it if you haven’t thought much about it, i.e., aren’t using philosophy at all.

So I’m pretty much in agreement with this post about the complementarity of philosophy and science. In fact, I’ll emphatically agree with this bit:

Scientists and mathematicians are really doing philosophy. It’s just that they’ve specialised in a particular branch, and they’re employing the carefully honed tools of their specific shard just for that particular job. So specialised, and so established is that toolkit, that they don’t consider them philosophers any more.

I’ll also agree with the flip side, where he defines philosophy:

Philosophy’s method is bounded only by the finite capacities of human thought. To the extent that something can be reckoned, philosophy can get there. As such, philosophy will never stop asking “why”.

But then I start to quibble (oh, no! I must be infected with philosophy!).

So what this is really saying is that science is a bounded domain of philosophy, while philosophy is unlimited, which sounds like philosophy has the better deal. But I’d argue otherwise: what’s missing in philosophy is that anvil of reality — that something to push against that allows us to test our conclusions against something other than internal consistency. It means philosophy is excellent at solving imaginary problems (which may be essential for understanding more mundane concerns), while science is excellent at solving the narrower domain of real problems. Science has something philosophy lacks: a solid foundation in empiricism. That’s a strength, not a weakness.

I think that’s where philosophers begin to annoy us, when they try to pass judgment using inappropriate referents — which is also how scientists like Krauss can annoy philosophers. And philosophers are so good at rationalizing disagreement away while carping on others. For instance…

Because scientists have a rather poor track record when it comes to doing philosophy.

Sam Harris’s attempt to provide a scientific basis for morality springs to mind, where he poo poos metaethics only to tread squarely in a metaethical dilemma. Or Richard Dawkins and his dismissal of religion as a false belief system, meanwhile dismissing the rather significant psychological and cultural functional roles it has played throughout human history, and may still play today.

Or Krauss, who without a hint of irony, suggests that good philosophers are really just bad scientists, when in fact he’s a good scientist doing philosophy badly. His definition of “nothing” comes not from within science, but is a grope in the dark for a definition that conforms with his particular theoretical predilections. That’s not how one defines things in polite (philosophical) circles, as David Albert pointed out.

After stating that scientists are philosophers and that science is a branch of philosophy, we’re now told that scientists do philosophy poorly. So is he saying that scientists must do science poorly? I know who’s not going to get invited to my next cotillion, that’s for sure.

Rather, scientists do their brand of philosophy very, very well — philosophers seem to be playing a two-faced game here of wanting to claim science as one of their own when they like what it accomplishes, but washing their hands of it when they don’t like it. Nuh-uh, people, you want to call us philosophers, you have to live with the stinking chemicals and the high energy discharges and the reeking cadavers now too.

His examples aren’t persuasive. I’ll skip over Harris, I’m not particularly fond of his efforts to explain morality, but the Dawkins complaint is weird. He does not disregard the immense psychological and cultural roles of religion: in fact, those are reasons why he and I both detest religion, because we’re aware of all the harm it does and has done. That we think the physical and psychological harm is enough that we should change it is not a sign that we’re doing bad philosophy at all; it’s a sign that we scientifical philosophers consider reality and empiricism to be extremely important factors in our thinking…apparently to a greater degree than many non-scientifical philosophers.

As for Krauss, I thought the Albert review was awful — typical unbounded philosophy with no anchor to the truth. Krauss’s definition of “nothing” was not just a grope in the dark. It was a definition built on empirical and theoretical knowledge of what “nothing” is like. Krauss is describing the nothing we have, Albert is describing the nothing he thinks we ought to have. Krauss is being the scientist, Albert is being the philosopher, and the conflict is driven because the philosopher is unable to recognize the prerequisites to doing science well.

I think that appreciating the boundaries of both disciplines as well as their strengths is important for getting along. Krauss may not have appreciated what philosophy has to offer, but a substantial reason for the friction is the smugness of philosophers who disrespect the functional constraints required for doing good science. Scientists don’t get to be “bounded only by the finite capacities of human thought”. We also have to honor the physical nature of reality.

In my head I have the capacity to flap my arms and fly. In the real working world…not so much.

I know this feeling

Maybe you know the feeling, too. You’ve got a career that you work at every day for years, that you take seriously and try to improve constantly, and you’re periodically dragged off to meetings where administrators and bureaucrats tell you what you should be doing — and the information is useless because they’ve never even tried to do it, preferring instead to kibitz professionally. So I felt that familiar sinking pit of despair as I read this article about the current political strategies for ‘fixing’ education. All that saved me from spitting on the screen was the author’s reply.

I’m thinking about the current health care debate. And I am wondering if I will be asked to sit on a national committee charged with the task of creating a core curriculum of medical procedures to be used in hospital emergency rooms.

I realize that most people would think I am unqualified to sit on such a committee because I am not a doctor, I have never worked in an emergency room, and I have never treated a single patient. So what? Today I have listened to people who are not teachers, have never worked in a classroom, and have never taught a single student tell me how to teach.

What I taught today: maternal effect genes

You know I teach the 8am courses every term, right? Every semester for years I get my oddball classes that weren’t present in the curriculum 13 years ago (when I started here) stuffed into the cracks of the schedule. I’m slowly getting to be a little pushier and am gradually making my way into wakier hours with other classes, but so far, developmental biology is still in the darkness. Fortunately, this talk was so jam-packed with excitement and action that they couldn’t possibly sleep through it! Right?

Just a word about the presentation slides: I’m a firm believer that less is more. My goal is not to display my lecture notes, or lists of bullet point slides that make my points for me, but to show complex and interesting illustrations that I talk about and explain — whoa, I know, how radical. I’ve sat through too many talks that flash 60-80 slides at me in an hour, and it’s too much. Take your time, people! That said, I used 18 slides in a 65 minute lecture today, which I felt was a little excessive — I aspire to someday do a lecture with half that number. But I am weak and need the crutch now.

Also, I returned exams today. People asked if I’d post their answers. No way in hell! These are exams and have the privilege of privacy. I will say that in general the students answered well. The goal of that kind of exam isn’t to confront students with a question that has a specific answer, but with a problem that they should explore, defend, or criticise.

So the subject today was maternal effect genes in Drosophila, specifically the prepatterning information that specifies the anterior-posterior and dorsal-ventral axes. Yes! I can tell you’re all excited!

So I gave them the precursor observations to the actual molecular biology, all this lovely modeling of gradients and information domains that was rich with Turing elegance, and then I dashed their optimism with the cold water of reality: molecular biology has shown that instead of beautifully designed systems, we’ve got bits and pieces cobbled together in a functional kludge. Any pretty patterns we do see are the product of brute force coding.

So they got the overall picture of A/P patterning in flies: a gradient of the Bicoid protein, high in front and low in back, is read by cells to determine their location — its the GPS signal of the early fly. The Nanos protein, also found in a gradient but from back to front, is a hack: it’s only purpose is to clear away a leaky remnant of another gene, Hunchback, which isn’t supposed to be expressed yet (although Nanos may be the diminished rump of a more elaborate ancestral posterior patterning scheme). And the Torso related genes are specifically involved in ‘capping’ the front and back ends of the fly.

The main point of interest about the terminal genes like Torso is their mechanism: we sometimes talk about maternal genes as like a paint-by-number system in which Mom lays out the lines for different areas of differentiation in Baby, and then the embryo fills in the details. The terminal genes are like a perfect example of that: in the follicle, cells literally paint the vitelline membrane of the fly with different informational molecules during the construction of the egg, and then as the embryo develops, these molecules trickle across the perivitelline space (a gap between the outer membrane and embryo proper) to bind receptors and trigger regional differentiation.

It’s also a nice segue into the dorsal/ventral patterning genes, because flies do something similar there: proteins imbedded in discrete regions of the vitelline membrane diffuse to Toll receptors, where they selective activate the Dorsal protein by freeing it from the Cactus inhibitor. We go from a paint-by-number kit to a restored gradient from back to belly side of localization of free Dorsal protein to the cell nucleus. By the way, in case they were getting bored with flies, Dorsal is homologous to NF-κB in us vertebrates, using the same nuclear exclusion/inclusion mechanism, and NF-κB is a hot molecule in biomedicine and cancer research right now.

That was my hour. I closed by threatening them with talk of zygotic genes, specifically the gap genes, next week.

Also, Wednesday we’re going to try something a little different. We’ve finished chapter 5 of Carroll’s book Endless Forms Most Beautiful so they should be ready to weigh the importance of various mechanisms, so I split the class in two and told half of them to read Wray’s article on the importance of cis-regulatory mutations in evolution, and Hoekstra and Coyne’s article that argues for a more balanced emphasis. I’d love to have a fight break out in the room.