A quote from Ed Abbey, who died 24 years ago today

The geologic approach is certainly primary and fundamental, underlying the attitude and outlook that best support all others, including the insights of poetry and the wisdom of religion. Just as the earth itself forms the indispensable ground for the only kind of life we know, providing the sole sustenance of our minds and bodies, so does empirical truth constitute the foundation of higher truths. (If there is such a thing as higher truth.)

It seems to me that Keats was wrong when he asked, rhetorically, “Do not all charms fly … at the mere touch of cold philosophy?” The word “philosophy” standing, in his day, for what we now call “physical science.” But Keats was wrong, I say, because there is more charm in one “mere” fact, confirmed by test and observation, linked to other facts through coherent theory into a rational system, than in a whole brainful of fancy and fantasy. I see more poetry in a chunk of quartzite than in a make-believe wood nymph, more beauty in the revelations of a verifiable intellectual construction than in whole misty empires of obsolete mythology.

The moral I labor toward is that a landscape as splendid as that of the Colorado Plateau can best be understood and given human significance by poets who have their feet planted in concrete — concrete data — and by scientists whose heads and hearts have not lost the capacity for wonder. Any good poet, in our age at least, must begin with the scientific view of the world; and any scientist worth listening to must be something of a poet, must possess the ability to communicate to the rest of us his sense of love and wonder at what his work discovers.

What I taught today: molecular biology of bat wings

Hard to believe, I know, but this class actually hangs together and has a plan. A while back, we talked about the whole cis vs. trans debate, and on Monday we went through another prolonged exercise in epistatic analysis in which the students wondered why we don’t just do genetic engineering and sequence analysis to figure out how things work, so today we reviewed a primary research paper by Chris Cretekos (pdf) that teased apart the role of one regulatory element to one gene, Prx1, in modifying the length of limbs. It’s a cool paper, you should read it. It’s kind of hard to replicate the teaching experience in a blog post, though, because what I did most of the hour was ask questions and coax the students into explaining methods and figures and charts.

I’m afraid that what you’re going to have to do is apply for admission to UMM, register for classes, and take one of my upper level courses. I always have students read papers direct from the scientific literature, and then I torture them with questions until they extract meaning from them. It’s fun!

Although…it would also be cool to have a scientific-paper reading and analysis session at a conference, now wouldn’t it? Especially if it could be done over beer.

What I taught today: farewell to flies (for a while)

A good portion of what I’ve been teaching so far uses Drosophila as a model system — it’s the baseline for modern molecular genetics. Unfortunately, it’s also a really weird animal: highly derived, specialized for rapid, robust development, and as we’ve learned more about it, it seems it has been layering on more and more levels of control of patterning. The ancestral system of establishing the body plan was far simpler, and evolution has worked in its clumsy, chance-driven way to pile up and repurpose molecular patterning mechanisms to reinforce the reliability of development. So I promised the students that this would be the last day I talk about insects for a while…we’ll switch to vertebrates so they can get a better picture of a simpler, primitive system. What we’ll see is many familiar genes from flies, used in some different (but related!) ways in vertebrates.

But today I continued the theme of epistatic interactions from last week. Previously, we’d talked about gap genes — genes that were expressed in a handful of broad stripes in the early embryo, and which were regulated in part by the even broader gradient of bicoid expression. The next level of the hierarchy are the pair rule genes, which are expressed in alternating stripes — 7 pairs of stripes for 14 segments.

First point: notice that we are seeing a hierarchy, a descending pattern of regulatory control, and that the outcome of the hierarchy is increasing complexity. One gene, bicoid sets up a gradient that allows cells to sense position by reading the concentration of the gene; the next step leverages that gradient to create multiple broad domains; and the pair rule genes read concentrations of gap genes and uses the boundaries between them to set up even more, smaller and more precise domains of stripes that establish the animal’s segments.

This is epigenesis made obvious. The 14 stripes of the pair rule genes are not present in the oocyte; they emerge via patterns of interactions between cells and genes. The information present in the embryo, as measured by the precise and reproducible arrays of cells expressing specific genes, increases over time.

So part of the story is hierarchy, where a complex pattern at one stage is dependent on its antecedents. But another part of the story is peer interaction. Cells are inheriting potentials that are established by a cascading sequence of regulatory events, but in addition, genes at the same approximate level of the hierarchy are repressing and activating each other. We can tease those interactions apart by fairly straightforward experiments in which we knock out individual pair rule genes and ask what the effect of the loss has on other pair rule genes. I led the students through a series of epistatic experiments which started out fairly easy. Knock out a pair rule gene that is expressed in odd numbered parasegments, for instance, and it’s complement, the pair rule gene expressed in even parasegments, expands its expression pattern to fill all segments. Sometimes.

Some of the experiments reveal simple relationships: hairy suppresses runt, and runt suppresses hairy. That makes sense. They have mutually exclusive domains, so it’s no surprise that they exclude each other. But then we looked at other pair rule genes which are expressed in patterns slightly out of phase from the hairy/runt pair, and there the relationships start getting complex. Genes like fushi tarazu are downstream from all the others, and their effects are straightforward (their loss doesn’t disrupt the other pair rule genes), but genes like even-skipped have much messier relationships, and the class was stumped to explain the results we get with that deletion.

So I asked them to come up with other experiments to tease apart these interactions. I was somewhat amused: when I think along those lines, I come up with more genetic crosses and analyses of expression patterns — I think about regulatory logic and inferring rules from modifications of the pattern. Students nowadays…they’re so much more direct. They want to go straight to the molecular biology, taking apart the genes, identifying control elements, building reporter constructs to see gene-by-gene effects. I felt so old-fashioned. But we also had to talk about the difficulty of those kinds of experiments, and that often the genetic approach is better for building a general hypothesis that can be fruitfully tested with the molecular approach.

Then we stopped — we’ll come back to flies later, and start looking at some specific subsets of developmental programs. Next, though, we’re going to take a big step backward and look at early events in vertebrates and progress through that phylum until we see how they build segments. I’m hoping the students will see the similarities and differences.

Slides for this talk (pdf)

Sadly, it’s International Women’s Day

It’s that day when we’re supposed to celebrate the accomplishment’s of women. I say “sadly,” because unfortunately there are way too many people out there who would rather sneer at and diminish women’s status in the world.

Case in point: on twitter, I ran across this lovely tweet from one of those repugnant slymepitters.

On #IWD remembered the nearly 0 wimmin – Nobels in science, highbrow art, chess GMs, great standups, but 100s of pop-culture hos #ftbullies

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Yes. Let’s remember those women.

Let’s remember Lise Meitner, Hilde Mangold, Chien-Shiung Wu, Rosalind Franklin, and Jocelyn Bell — who were all well-qualified (men won the prizes for work equivalent to what they did, instead) to win a Nobel but didn’t get one.

Rather than 0 women, perhaps we should remember Marie Curie and Maria Goeppert Mayer, who won Nobels in physics; Irène Joliot-Curie, Dorothy Crowfoot Hodgkin, and Ada E. Yonath in chemistry; Barbara McClintock, Carol W. Greider, Christiane Nüsslein-Volhard, Elizabeth H. Blackburn, Françoise Barré-Sinoussi, Gertrude B. Elion, Gerty Cori, Linda B. Buck, Rita Levi-Montalcini, and Rosalyn Yalow, in physiology or medicine. Clearly women are not intrinsically incapable of scientific work at the highest levels. Of those whose work I’m familiar with in detail, I have to tell you that McClintock blows me away with the stunning brilliance of her abstract reasoning — I know of no other male scientist whose work is at all comparable (that of course is a matter of taste!)

The relatively lower frequency of women recieving Nobels is not something any man should take pride in; what it really indicates is that we’ve been shortchanging half the human population, depriving them of opportunities to excel. Wait — we’ve been doing worse than shortchanging women; we’ve been depriving all of humanity of the potential in those minds. This pattern of discrimination against women has hurt us all.

Let’s not forget also all the people, men and women alike, deprived of opportunities because of their race or class — deprived by the kind of endemic bigotry that would, for instance, denigrate an entire group of people as “pop-culture hos”. And it’s not just science — it was good of our petty MRA to remind us that we’ve also lost their contributions to art and theater and games.

That’s what I think of everytime some bigot crows about the absence of some group of people from some field of endeavor — it’s a reminder of all that we’ve lost to selfish stupidity.

My university in the news!

Now if only it were good news. It seems we’re the victim of bureaucratic excess.

College administrators have found an interesting new way to strike it rich: quitting their jobs. Upon leaving his role as executive vice president of NYU for a job with Citigroup in 2006, Jacob J. Lew (the current Secretary of the Treasury) took a $685,000 bonus from the university. Harold S. Koplewicz, an executive at the NYU Medical Center, got a $1.2 million severance after choosing to leave voluntarily. Given that NYU’s tuition and fees are among the highest in the nation, we’re curious how students who took out hundreds of thousands of dollars in loans feel about their money going towards generous benefits and severance packages for administrators.

At least NYU is a private institution, so tax dollars are not spent to cover its inflated costs. As the New York Times notes, public universities are just as guilty of letting a bloated and inefficient administration drive up tuition costs. The University of Minnesota employs 19,000 administrative officials employees, and administrative personnel account for 24 percent of its total payroll, compared with only 20 percent in 2001. At Purdue, the number of administrative employees grew by 54 percent in the last decade.

Overall, the number of administrators hired by colleges and universities increased 50 percent faster than the number of instructors hired between 2001 and 2011, according to the U.S. Department of Education.

We’ve felt the pain down here in the trenches, too. Our core biology curriculum was disrupted a bit by the reluctance of our administration to hire replacement faculty — they saved a few pennies by bringing in temporary faculty as replacements and deferring filling tenure track lines. The replacements were good people, but when you’ve got students coming up through a curriculum pipeline, you really want stability and continuity at the base.

The good news, though, is that the blockages have been uncorked and we’re finally expanding our biology faculty from 8 to 9 — a big boost at a small college.

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.

Atlanta News, Weather, Traffic, and Sports | FOX 5

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.