What I taught today: gene regulation and signaling

Today was more context and a bit of a caution for my developmental biology course. I warned them that we’d be primarily talking about animals and plants (and mostly animals at that), but that actually, all of the general processes we’re describing are found in bacteria and other single-celled organisms — that in a lot of ways, microbiology is actually another developmental biology course. Yes, I went there: developmental biologists tend to be imperialists who see all the other sciences as mere subsets of the one true science. Of course, you could also take that as developmental biology being a synthetic discipline that steals bits and pieces from everywhere…

So the primary lessons today were reviews of stuff these students should have gotten in cell and molecular biology, with bits of biochemistry and microbiology thrown in. We talked about genes getting switched on and off, and the example I used was the classic: the lac operon in E. coli. What? You don’t know about it? It’s a beautiful system, in which the bacterium switches on the genes needed for digesting the sugar lactose only when the sugar is available in the environment. I showed this nice little 3 minute video:

Switching genes on and off? That’s development! It gets a little more intricate in multicellular animals, but all of the fundamental logic is right there in E. coli: activators and repressors, positive and negative feedback, the boolean logic of gene regulation. I also mentioned that when we’re reading Carroll’s Endless Forms Most Beautiful, he’s going to make a big deal out of exactly this kind of regulation, but I want them to remember that it’s not unique to butterflies or fruit flies or frogs, it’s a common theme in all kinds of diverse cells.

We then talked about cell signaling. How does a cell know which genes are supposed to be off and on? It interacts with its environment (as in the lac operon) or its neighbors to make decisions about activity. To illustrate that, we went through quorum sensing and biofilms — again, cell signaling is not unique to animal development, it was all worked out in principle in single-celled organisms. I gave them a little foreshadowing and mentioned that we’d be discussing Sonic Hedgehog and Notch and Delta later in the course, classic examples of signaling in multicellular systems, but in bacteria we have things like hapR and AHL signaling.

Finally, I raised the issue of a phenomenon we’ll be talking about on Wednesday: patterning. Why aren’t your arms growing from your hips, why don’t you have fingers on your feet instead of toes, why are your eyes paired and on the front of your head? Because there is positional information in the embryo that can be read by cells and tissues and lead to development of appropriate structures in their proper places. But once more, this is not unique to multicellular animals. A paramecium, for instance, is not a generic blob, but has a definite shape and orientation; it has organelles in predictable places, and is covered with a nearly crystalline lattice of cilia with specific axes of orientation. I showed them choanoflagellates and pointed out that these protists, representing a multicellular precursor, had a specific shape and a collar organ in a specific functional location: how do they know how to do that?

That’s the question we’ll be asking next. I warned them too that I won’t be lecturing at them on Wednesday, so they’d better have their morning coffee. I’m expecting them to read a review paper on positional information in embryos (pdf), and I’m going to make them explain it all to me for a change.

Slides for this talk (pdf)

For Wednesday:

Kerszberg M, Wolpert L (2007) Specifying Positional Information in the Embryo: Looking Beyond Morphogens. Cell 130(2):205–209.

You can’t buy good teaching

This little talk from Lawrence Krauss is one I agreed with right up to the last little conclusion, which is a complete non sequitur.

That first part is excellent: good education does involve getting students to ask questions and think deeply, rather than being able to recite answers back at us; I also think it’s true that a good science educator has to be comfortable in the field and be competent in the topic. And that means investing more in teacher training. It also involves paying them more to attract better teachers, because sometimes what happens is that a person with a family or special needs will find they can’t meet all their obligations on a teacher’s salary.

So far, so good. Here’s the concluding paragraph that I find disagreeable, however. It’s the one where he proposes different pay scales for science and math teachers rather than those other teachers.

I don’t think that science and math are more important than writing; I believe in communication. It’s incredibly important. I write. But for better or worse, in the free market, if you have a training in science, in general, you can go out and not become a teacher and earn more money than you would if you were a teacher. So I think we have to consider paying in order to recruit better teachers who have a training in science and mathematics, the possibility of differential pay scales to accommodate the free market. I know many teachers unions would be vastly opposed to that. But I think we at least have to consider that possibility if we want to recruit the people with the skills into the schools to be able to connect with the students.

My problem here is that after praising the value of asking good questions, critical thinking, general competence, and all that jazz, suddenly we switch gears to talking about competition in the free market. That is something completely different with no relationship to the values previously stated.

Teachers of English, theater, history, philosophy, art, music, etc. can also be inspiring, inquiring critical thinkers who lead students to deeper understanding, who get students to ask insightful questions. In that context, it’s silly to single out science and math teachers as somehow special — in my personal history, science and math teachers have been more likely to fall back on rote and massive data dumps than teachers in other fields, and also, at the college level at most universities, teaching skills are less valued in the sciences than in other more liberal artsy disciplines; the number one job skill for scientists is getting grant money. It’s very much a free market thing.

But that’s the other side of the coin, too. Why would anyone think free market competition for higher salaries would attract more people with better teaching skills? An economic battle between educational institutions and for-profit industry is going to have one foregone conclusion: the schools will lose. Demanding stable funding so the schools can hire people at a reasonable living wage is one thing, but trying to draw scientists from industry (where teaching is not a major factor in advancement) into the schools with financial inducements is not going to work, and is going to prioritize the wrong set of values.

Way back when I was on the job market, I had the choice of better paying jobs in tech fields, vs. the Research I rat race, vs. the low paying liberal arts track. I was tempted by bigger money, but what won me over was finding places where good teaching was actually respected and rewarded. That’s how you get good teachers: treat them like their skills are respected and important, give them opportunities to improve and learn, and let them explore new ideas. That’s why I’m in this business; it’s certainly not because of the pay scale (although if it were low enough it would drive me away), but because it lets me do what I love doing.

New bloggers for Science!

As is my custom, my upper level courses have an expectation that students will do this blogging thing. They’re just now getting set up so there isn’t a lot of content yet, but here’s the current list of student web pages. Cruise on by and talk to them!

Jenna Cavelle wants to correct ‘Chinatown’

If you’ve heard any history of the California desert at all, you’ve likely heard of the Owens Valley Water War.

Here’s the canonical version of that War: The Owens Valley is watered by runoff from the immense snowfall from the Sierra Nevada to its west, much of which runs into the Owens River when it melts. The Owens Valley is an endorrheic basin: it has no outflow. The Owens River never reaches the ocean. Instead, it flows into Owens Lake, in the valley’s lowest point at its south end.

Late in the 19th Century a thriving network of agricultural communities was developing due to the river’s water, growing a vibrant local economy along with their crops. Enter the Los Angeles Department of Water and Power, led by engineer William Mulholland. DWP quietly bought up water rights throughout the Owens Valley in a series of deceptive land deals, then built a 223-mile aqueduct to bring Owens River water to Los Angeles. The aqueduct was finished in 1913 — 100 years ago this November — and farms started going out of business in the decade after. Owens Valley farmers dynamited parts of the aqueduct in 1924, but the rebellion was short-lived. Owens Lake, which had been a rich habitat for waterfowl, dried up and is now the single largest point source of particulate matter pollution in the U.S.

As canonical histories go, it’s pretty accurate. Or at least more accurate than the version a lot of people have in their heads due to the film Chinatown, which was based on the Owens Valley story. But it’s a woefully incomplete history nonetheless. The history of the Owens Valley didn’t start in the late 19th Century. Before the first European settlers arrived there were people living in the Owens Valley for thousands of years. The Owens Valley Paiute took advantage of the relatively well-watered landscape by gathering seeds, hunting the Valley’s abundant game, and — though this hardly ever gets mentioned in any of the formal histories — diverting the water of the Owens River and its tributaries to irrigate their crops.

Journalist Jenna Cavelle wants to correct the canonical history to include the Owens Valley Paiute, who are still very much alive and shaping the valley:

This film documents the history of Paiute Native Americans who constructed 60 miles of intricate irrigation systems in Owens Valley for millennia long before LA secured its largest source of water through modern engineering a century ago. After the Indian War of 1863, surviving Paiute returned to the Valley from the Eastern Sierra and White Mountains to find their ancient waterworks taken over by white settlers. Today, over 150-years later, the Paiute continue to fight to save their waterworks, which are remnant in the Owens Valley landscape, along with water rights the city of LA never granted. PAYA (“water” in Paiute) stands to recover both Paiute history and water rights by increasing awareness through the powerful medium of documentary film.

She’s working to put together a set of resources, centering around a documentary film, before the last remaining Paiute elders who have some tenuous personal knowledge of their ancestors’ irrigation systems aren’t around to document anymore.  Here’s Cavelle’s Kickstarter trailer:

She’s halfway to her goal with half her fundraising period left. This project combines history, the California desert environment, and social justice, so you won’t be surprised that I really want to see it happen. I’m scratching together a few bucks to throw Cavelle’s way: maybe you’ll want to as well.

Should we resurrect the Neandertals?

I was reading an interview with George Church, who was discussing that very same question, and somehow I had to rethink some things.

There was the question of technical feasibility, and Church thinks it’s going to be entirely possible in the near future.

The first thing you have to do is to sequence the Neanderthal genome, and that has actually been done. The next step would be to chop this genome up into, say, 10,000 chunks and then synthesize these. Finally, you would introduce these chunks into a human stem cell. If we do that often enough, then we would generate a stem cell line that would get closer and closer to the corresponding sequence of the Neanderthal. We developed the semi-automated procedure required to do that in my lab. Finally, we assemble all the chunks in a human stem cell, which would enable you to finally create a Neanderthal clone.

I agree entirely: no problem. It would be very hard and expensive to do right now, but not impossible. Biotechnology is advancing at such a rapid rate, though, that in 5 years it will be difficult but within the range of what a few well-funded labs could do, in ten years it will look like a straightforward, simple exercise, and in 20 years high school kids will be doing it in their garage.

The technology is not the issue, and it isn’t even a particularly interesting technological problem. The issue is one of ethics. Church takes a reasonable tack on that one: he punts.

I tend to decide on what is desirable based on societal consensus. My role is to determine what’s technologically feasible. All I can do is reduce the risk and increase the benefits.

Fair enough. We will face clear social dictates as the tech becomes more and more readily doable, and that’s ultimately going to determine whether the experiment is done or not.

But I started to think about reasons for and against, and I must confess something terrible: my first thought was that it shouldn’t be done, and to come up with arguments against it. I know, that’s weird…my mad scientist gland must be on the fritz. But my primary concern was that this is science that could create a human being, a human being with significant genetic differences from other human beings, and that should be accompanied by heavy responsibilities — a lifetime of responsibilities. It’s easy to look at it as an exercise in gene-juggling, but this is an experiment you don’t get to dump into the biological waste receptacle when the molecular biology is all done — it has an outcome that is conscious and communicating, damn it. It’s an experiment that at its end makes someone in the lab a parent, with all the obligations associated with that. And that’s a tremendous burden. There’s the cost, the time, the emotional investment…not stuff we usually take into account in the lab.

So I tried to think about what we’d have to do to morally justify Neandertal cloning. As Church also mentions, we couldn’t just do one, we’d have to create a cohort so that these people wouldn’t be alone. The budget would have to include a substantial trust fund for each — you can’t just create a person and then kick them out into the street to fend for themselves.There would have to be adults dedicated to providing for the emotional needs of these children…

Wait a minute. That’s where my brain froze up for a moment. If a scientist is expected to feel that kind of moral responsibility for his children, what about other people? We live in a culture where teenagers carry out a similar experiment every day, with no thought at all except personal need and gratification, and are then compelled to carry the experiment to term and produce a baby they are ill-equipped to care for, because their parents insist that that is what good Christians must do. Single mothers are treated like scum, and on average have the lowest income of any group — they are expected to raise children in poverty. We let children starve to death in this country all the time. Even when they’re fed, we feel no obligation to provide them with a good education — we’re in the process of dismantling the public school system and letting future generations fester in ignorance. There is a societal consensus right now, and it’s nowhere near as demanding as I expected!

And with that, my mad scientist gland was unshackled and grew two sizes larger. We can do the experiment! We should just go ahead and do the molecular biology, produce human stem cells with Neandertal sequences inserted (ooh, even partial sequences — that would be exciting!) and get them implanted and born, do a few preliminary experiments on their behavior, and then wrap them up in a blanket, put ’em in a basket, and have a grad student drop them off at the nearest orphanage. Especially if it’s a Catholic orphanage. Easy! There don’t seem to be any societal constraints against doing that with Homo sapiens sapiens infants, which we supposedly value most highly, so there shouldn’t be any ethical concerns at all in doing it with the mutant lab-born spawn of a test tube and a sequencer.

My mistake was in holding scientists to a higher ethical standard. If all we’ve got to do is match societal norms, we’re suddenly open to doing all kinds of ghastly horrible things to children.

Of course, this grand plan would be short-circuited if society did start expressing higher concerns for children and demanded better of parents. I’m thinking as a developmental biologist, I should start voting Republican, simply to keep the raw material of our work sufficiently devalued and cheap.

The radical King

Perhaps it is a good idea today to remember what Martin Luther King was really about, rather than the sanitized conciliatory sweet little Negro memorialized in this holiday.

America began perverting Dr. Martin Luther King Jr.’s message in the spring of 1963. Truthfully, you could put the date just about anywhere along the earlier timeline of his brief public life, too. But I mark it at the Birmingham movement’s climax, right about when Northern whites needed a more distant, less personally threatening change-maker to juxtapose with the black rabble rousers clambering into their own backyards. That’s when Time politely dubbed him the "Negroes’ inspirational leader," as Gene Roberts and Hank Klibanoff point out in their excellent book Race Beat.

Up until then, King had been eyed as a hasty radical out to push Southern communities past their breaking point — which was a far more accurate understanding of the man’s mission. His "Letter from a Birmingham Jail" is in fact a blunt rejection of letting the establishment set the terms of social change. "The purpose of our direct-action program is to create a situation so crisis-packed that it will inevitably open the door to negotiation," he wrote, later adding, "We know through painful experience that freedom is never voluntarily given by the oppressor; it must be demanded by the oppressed."

North Dakota, chickenshit capitol of the world (plus a bonus poll!)

Professors Molly Secor-Turner and Brandy Randall of North Dakota State University were recently awarded a $1.2 million federal grant. Good news, right? The state should be happy, the university should be happy.

NDSU is turning it down and returning the money.

WHY? Because this is a grant to provide comprehensive sex education to teenagers in the Fargo area, in collaboration with Planned Parenthood. The state legislature, stacked as it is with regressive conservative jerkwads, freaked out and went scrambling to find a legal way to forbid it. And the president of the university, Dean Bresciani, is going along with it.

“Whether technically or not, in my evaluation, it’s not respecting the intent of our Legislature,” he said. “And that’s close enough to me. We’re not looking for loopholes to work around our Legislature; we work in respect of our Legislature.”

Bresciani said the recent discovery prompted him to freeze the funding. If the money can’t be redirected appropriately, he said, it will be returned to the federal government.

“What we’ve found is a very specific codicil of the law that makes it clear that it cannot be with Planned Parenthood,” he told Hennen. “And unless we can work around that, and again I’m not holding out hope on that, we’ll have to go to the direction of returning the resources.”

I have some words for you, Bresciani: your mission, as the president of a major university, is to improve the knowledge of the citizens of your region. Your faculty know that. Your students are going to your school for that purpose. When your legislature is actively working to undermine the mission of a university, it should be your job to oppose them. I know, they hold the purse strings; but that’s why you get paid the big bucks, because you have the difficult job of negotiating with idiots to serve a higher purpose. If you’re just going to cave in and do their bidding, well, the legislature could save even more money by simply hiring a dullard who would say “yes” to everything they ordered. Or did they already do that?

Oh, wait. Maybe that’s too many words, too long, too difficult. How about one word?

Chickenshit.

That’s a chickenshit move by a chickenshit administrator serving a chickenshit legislature.

Better?

What’s also rotten, as the paper makes clear, is that the North Dakota legislature is dishonestly strong-arming the university. There is no specific law that says the university cannot receive this federal grant. Here’s the stretch they made:

In 2011, North Dakota lawmakers approved a law effective as of July 2012 that requires K-12 schools in the state to ensure any sexual health curriculum “includes instruction pertaining to the risks associated with adolescent sexual activity and the social, psychological, and physical health gains to be realized by abstaining from sexual activity before and outside marriage.”

However, the NDSU professors awarded this grant previously told The Forum that law wouldn’t apply to their program because it was to be taught outside of the schools and only to those teens who voluntarily agreed to participate with parental consent.

Not only is that a chickenshit law, it doesn’t apply. And man, but North Dakota really wants to keep their young people ignorant.

Oh, look. The paper has a poll to go with the article.

Do you agree with the NDSU president’s decision to freeze funds for a sex ed program in partnership with Planned Parenthood?

Yes 37.7%

No 54.1%

Don’t know 8.3%