Tuesday, August 03, 2004

Bizarro perspectives on education

Over on Skeptical Notion, Morat discusses this incredible article about Tom Ridge:

Homeland Security Secretary Tom Ridge is considering stepping down after the November election, telling colleagues he is worn out from the massive reorganization of government and needs to earn money in the private sector to put his teenage children through college, officials said.
[...]
Ridge owns an $873,000 home in Bethesda, Md., with his wife, Michele, which they bought last year with a $784,800 mortgage, according to property and banking records. Ridge's most recent financial disclosure reports, filed in early 2003, showed that he owned between $122,000 and $787,000 in stocks and funds, including modest ownership in The Walt Disney Co., General Electric, Nike, Oracle Corp. and Microsoft Corp.

That hits home with me in a couple of ways.

15-20 some years ago, my wife and I stupidly planned and had three kids—not only is it too many, but we had them 3-4 years apart. That means they are going to overlap in college, and there may well be a couple of years where we're trying to simultaneously support two collegians at once. Since I was clearly an idiot, I was also embarking on a career that promised to never pay more than a small fraction of Tom Ridge's paltry earnings while he was directing Homeland Security (he makes $175K/year, a sum that I will never, ever even approach). I'm afraid I'm going to have to tell my second son that we're going to have to hold him back in high school for a few years, and my daughter...well, sorry, we're going to have to send her back. Either that, or just keep her uneducated and ignorant. Since she is a girl, that may well be acceptable to our Republican Overlords, who would probably laugh at her dream of med school.

The other place it hurts me is that I'm kinda dependent on the well-being of our educational system—if only scions of the extremely wealthy can afford the university, either small colleges like mine will wither and die, or tuition will climb to even more exorbitant levels and I'll end up teaching tiny classes of spoiled snots who will laugh at my shabby clothes and sneer at my scent of boiled cabbage. Not to mention that I have this idealistic delusion that democracies function best with an informed and educated electorate.

I'm with Morat on this one: this ought to be a campaign issue. If you make less than $175,000/year, the Republicans think you're too poor to send your kids to college. Right now, universities feel proud of themselves if they can restrict tuition increases to single digit percentage increases per year—and that's part of the 'booming prosperity' the current administration has given us.

Bio-stupid

Salon has an interesting account of a biotech conference that touches on the same issues as those Rice Wars editorials: appropriate regulation of biotechnology.

In early June, representatives of the biotech industry met in San Francisco in a "biotech summit" organized by the Biotechnology Industry Organization. The BIO conference attracted hundreds of protesters, hundreds of police and one Salon writer on biotech issues who was better positioned than most to appreciate both sides of the debate.

There are some important and legitimate topics of discussion here—I don't think a native American tribe can claim exclusive ownership of a species that has part of its range on their land, but I also don't think BigPharma has any rights of ownership, either—but you can't build a productive debate on a foundation of ignorance and superstition.

Creationist e-mail: Gary Luce thinks biology promotes Haeckel

I've been sending my standard e-mail policy response to the creationists who dun me with their misconceptions, and what do you know, one actually agreed to let me address his complaints publicly. It's on the high end of the literacy scale (I'd feel a bit guilty to be picking on an illiterate, after all), but about on par with most creationist mail on the comprehension scale, so it's easy stuff. Here's the first letter from Dr Gary Luce.

Paul, I read your entry on the nmsr website and took the trouble to run down your email address. I am a Ph.D. physical organic chemist employed at Eastman Chemical Company, and in the interest of honesty, have to tell you that I am a Creationist and tend to follow that mode of thinking. Now please do not dismiss me as a crank on that basis. I do not have peer reviewed publications as bona fides, but I do have a number of U.S. patents and have designed and supervised the startup of 4 new chemical plants for my employer. I obtained my Ph.D. under B. L. Shapiro and Ken Harding who graduated from Carnegie Mellon and were postdoctural students under the great (some say greatest) organic chemist R. B. Woodward at Harvard University. So my bona fides are in fact....bonda fide. I had a good education.

A good education in chemistry. I had two years of training in chemistry as an undergraduate, which is far more chemistry than most chemists have of biology, but I wouldn't think of going down to Eastman and telling them how to improve their chemical processes. It's funny how everyone thinks they have the background to dismiss evolutionary biology.

 

I was very interested in what you wrote on the nmsr website concerning Haechel's embryos. Your writing on the website does in fact contain true statements that Haeckel's theory was discounted in the 19th century and, yes, evolutionary theory is not based on Haeckel's work. If it stopped there, all would be well.

I guess the surprise to me is that Haeckel's material is still taught as fact in public schools. When I took Embryology as an undergraduate at Texas A&M University in the fall of 1973, my professor made great note of his work. I still have my class notes and textbook, "Foundations of Embryology", Bradley M. Patten, McGraw-Hill Publishers, 1958. Now that is an old reference, but the fact is, my two sons who have taken honors level biology classes in high school have been taught the same thing in two different states (Texas and Tennessee). It seems to me, that the evolution-creation debate suffers from a considerable amount of memory of convenience. In other words, the science education system continues to promote outdated and disproven concepts such as Haeckel's, and then when confronted, bring up the discreditation story. Creationists lob a few shells over the wall attacking such discredited theories and then snicker. How are we ever going to get past this when so much is at stake? As an educator, I would encourage you to challenge the education system to root out the facts and not just continue to regurgitate the same old tired theories. Our future, the lives of our students and the souls of men are depending on it.

They use 25 year old textbooks at Texas A&M?

Note the erroneous elision and broken logic. 1) admission that biology discounts Haeckel's concepts, 2) complain that biology still uses Haeckel's 'material', 3) accuse biology of dishonesty for continuing to promote Haeckel's concepts. Dr Luce doesn't comprehend what he is talking about, and is using a tiny amount of information to draw a false conclusion. To use a chemical analogy, it's as if I remembered just enough chemistry to know that the phlogiston theory was discredited, but then learned that my kids were being taught about rust and burning in high school chemistry. Why, those dastardly chemists! That's just phlogiston, all gussied up in a fancy new word, "oxidation". How dare those professionals lie to us! How clever I am to know something those fancy-pants Ph.D.s thought they could fool me with!

Haeckelian recapitulation is in the same boat with phlogiston. It's a discarded theory that is not taught anymore, except as an instructive episode in the history of science. But that doesn't mean that embryos don't go through a broad stage where they resemble one another as they assemble key elements of the body plan; just as it doesn't mean that things stopped burning when phlogiston was evicted from the body of science.

And no, it doesn't mean that every time a teacher shows a picture of a chick and a human embryo that they have resurrected the corpse of Haeckel. It means they are teaching them good biology.

Here's his second e-mail, in response to my request that I address it publicly.

I'm sure you do get some "unusual" mail and, yes, I would agree to a public reply with my name associated with it. And here is why. I am not just trying to pick a fight, or "prove" someone else wrong or myself to be in the right. I am a deeply committed scientist as well as a believer. I don't agree with some of the tactics of the intelligent design and creationist movement. I think there is an element of self-righteousness associated with it that is unnecessary and destructive to useful debate. I think the same thing exists on the side of proponents of evolution. And the more I have read and studied over the years, the more I have felt misled by the system that provided my education. And that is what prompted my email to you. I think we all need to back up a couple of steps and listen to the other side a little more.

As a trained scientist, Dr Luce should know that scientists back up and change their ideas all the time—in response to evidence. Evidence. That's the key thing. And the creationist side has consistently failed to present any. What he calls "self-righteousness" is actually exasperation at all these people who demand that we abandon the evidence to conform to their superstitions.

Note also the interesting construction, "misled by the system that provided my education". Along with the usual careful list of their credentials, this is a phrase that must be required by the creationist mind-set, I've seen it so often. I have never yet seen one say, "misled by my religion."

As a Christian, I have long had difficulty with the young earth scenario. Yet at the same time, if the Lord God is really who he says he is in the scriptures, then the old earth becomes a problem as well.

Why, yes. And if Hello Kitty is the apotheosis of perfect organic design, then the oral cavity is an abomination and we commit heresy every time we speak. Everything becomes a problem when you start admitting absurdities as a premise. That doesn't mean we throw out the realities of the world we see around us, it should mean that we reject the premise.

Dinosaurs are obviously very real. In fact, I live only about 25 miles from the new site at Gray, TN where highway construction has uncovered a very rich "pit like" discovery of rhinoceros, horse, cat, and other intact fossils similar to the LaBrea tar pits. I have myself walked the dinosaur trail at Glen Rose, TX. I must admit I don't agree with the conclusions of the park staff with regard to that find, but that is the nature of our field. There are in fact different options.

How unscientific of Dr Luce. No, all proposals are not equal; they are more than "different options." Some are reasonable, promising, and supported by the evidence. Some are not. As scientists, we give greater weight to good ideas than we do to baseless speculation or antique superstitions.

And yet when I think back to when I was in junior high. I remember a book my parents gave me for Christmas that talked about the classic theory of a wet, hot swampy earth, coal formation and fossil preservation. Even then I simply could not rationalize what I understood about decay, scavenger behavior and bacterial decomposition. As a 15 year old kid I could look at the information and form my own conclusion, "that is just not possible."

Why, yes, creationism becomes tenable if we approach it with the uninformed mind of a teenager, reject anything that seems counterintuitive, and base our intuition entirely on our extremely limited personal experience. Is this supposed to be a legitimate example of support for creationism, or an account of creationist shortcomings?

That 15 year old kid's understanding about decay was simply wrong. I'd tell him now that he ought to look up the magic word "taphonomy" and read up on it.

And of course I could go on and on, and will in fact if that should prove useful to our discussion. But the bottom line is this. The classic problems of biochemistry, cosmology, physics and paleontology have become less clear, not more clear with time and increasing advances in our technology development for study of them. Old problems like Haeckel's embryos should have been dealt with forcefully and clearly long ago. As scientists and educators, we owe it to the generations that follow us to see to it that truth is as rigorously maintained in our debate as it is in our collection and interpretation of data. Again Paul, if the claims of the scriptures are true, and I believe that they indeed are, then there is far more at stake than at first appears. The result will not be temporal, but eternal.

Another tired creationist canard I hear over and over again, that science is making evolutionary interpretations increasingly untenable. This is not true. I just got back from a major scientific meeting where people were discussing the latest, hottest stuff in developmental biology, and there was more talk about evolution there now than there was twenty years ago; what we're seeing is an amazing synergy between evolutionary biology and other disciplines, with each informing the understanding of the other. Claiming otherwise is like hearing some crank argue that we've lost clarity in our understanding of chemistry, because once upon a time there were only four elements, and now there's around 112, and those danged godless nuclear chemists keep trying to add more.

Haeckel's embryos have been dealt with forcefully and clearly repeatedly. Von Baer argued forcefully against the interpretation of recapitulation thirty years before Haeckel, Gould dealt with it at length in the 1970s, and I and every developmental biologist I know teaches that it is plainly wrong. The only people who have "memory of convenience" on this matter are creationists. And rigorous maintenance of the 'truth' (not a term we use much in science) demands that we treat creationism as old garbage.

Both of Dr Luce's letters end with another common creationist trope, the threat. They are more politely phrased in this case than the more common, "You're going to burn in hell," but it's still the same old thing. No, Dr Luce, I do not accept your absurd, unfounded belief that some invisible hobgoblin is going to do mean things to me once I'm dead, all because I try to teach the most honest interpretations of the material world around us. I do not even consider it. It is not part of the equation when I am trying to weigh the accuracy of truth-claims in the real world, although clearly it is part of yours.

Monday, August 02, 2004

Rice wars

The editorial page of yesterday's Star-Tribune was full of articles on a 'controversy', the sequencing of the wild rice genome. I read them all through twice, and I still don't see what the problem is…other than that usual bug-a-boo of foolish religion. Here's the short summary of the wild rice battle:

Hard feelings over the University of Minnesota's wild rice research had been simmering for a half-century when Mark Yudof took the lid off the stewpot in 1998. A law-school dean who had recently become university president, Yudof paid a goodwill visit to White Earth tribal council members and -- perhaps forgetting the trial lawyers' injunction against asking questions before you know the answer—he inquired how the university might serve the Ojibwe people. Their reply, in essence: Halt your new research into the genetic code of wild rice, our most important spiritual resource. Since then, as the research proceeded, the university has given assurances that it has no plans to genetically modify the rice, and that merely mapping its DNA poses no threat to the reservation's wild stocks. These have not satisfied the challengers at White Earth, who see the gene-mapping itself as an intrusion on something sacred—and as an opening to inevitable exploitation from quarters far beyond the university.

If you're like me, you're saying, "umm, what?" right now. For religious reasons, the Ojibwe are asking us to preserve their ignorance and to be ignorant ourselves. It's a microcosm of the history of the conflict between religion and science—with superstition mixing up a stewpot of ridiculous slop, science lifting the lid and looking inside, and the religious getting all frantic and huffy about it—but you usually don't see it so baldly stated.

Frankly, it's a stupid conflict. If science were charging into the temple with prybars and pickaxes and threatening to smash up a few things while excavating the truth, I could see the problem. But…it's a grain of rice. Nobody's tearing up the traditional rice fields of the Ojibwe (well, actually, farmers and industrialists are, but not scientists, who are generally more interested in preserving clean and healthy rivers). Researchers are growing rice in the lab and sequencing its genome—it doesn't take food out of the mouths of native Americans, nor does it dictate that they aren't allowed to treat manoomin, as they call the rice, as a sacred whatchamajigger.

Among the editorials is a short history of wild rice use in agriculture, with this apology:

In the Ojibwe culture, wild rice is central to the origin stories of the Ojibwe and to traditional rituals, feasts and ceremonies. Wild rice is the sacred gift from the Creator. The Ojibwe know this to be true. They need not question.

Alternatively, the culture of Western science is based on questioning. Those who enter fields of science, medicine and engineering are educated, trained, evaluated and rewarded on their ability to successfully pursue the unanswered question. Nothing is accepted without the proverbial "defense" and replication of methods that are published for all to challenge.

OK, some of the Ojibwe want to close their minds and not question a traditional belief. I think that's fine. No one should go up to one of these people and start reciting the nucleotide sequence at 'em. Similarly, some of us like to question things. As long as they aren't defacing tribal property or carrying out some equally objectionable infringement of their rights, others should be free to do as they please.

Another article gives the Anishinabe perspective.

To Western science, the mere thought that something spiritual might impede scientific research is absurd, unnecessary and only would serve as an unnecessary obstacle to inevitable progress. To Anishinabe people, the sacred relationship with the manoomin is central and cannot be ignored in any discussion on the natural gift as it has been given.

The guy read my mind. "Spirit" is mere fuss and vapor. Using that as an excuse has no weight at all with me, especially since there is nothing about me looking at a grain of rice that prevents someone else from treating a grain of rice as sacred.

There may be other reasons why the Anishinabe are raising this issue, though.

There is more than ample evidence that government understood this special standing manoomin had in the lives of the Anishinabe. The treaties certainly speak to this understanding.

The University of Minnesota School of Agriculture has been involved in research affecting wild rice for the past 50 years. Yet pitifully little was done to assure that the Anishinabe people would have any significant involvement in research with such a direct impact on their lives.

Nevertheless, the University of Minnesota School of Agriculture, as part of a land grant school, has ethically and morally defaulted on the larger university and its commitment to be good partners with the public citizens of Minnesota.

Could it be that the Anishinabe communities, in an ill-considered act of institutional racism, were purposefully excluded from the process?

Now we are faced with corporations wishing to patent what they consider intellectual property rights as well as the emerging medicinal properties inherent in the manoomin. Some call it profit-driven concerns; others call it greed.

Ah, profit. And greed. There is gain to be had from scientific knowledge; and the Ojibwe want a cut, maybe. There is a legitimate issue here, and one that I would be much more sympathetic to than the mystical hokum most of the editorials are babbling about. Who owns a genome? By what right is a pharmaceutical company or agribusiness allowed to profit from information acquired by publicly funded research on an organism that, if owned at all in any way, belongs to a community?

The most annoying article, I thought, was one written by two UM professors, Hassel and Spangler. It irritated me right from the title: "Science isn't the only way to truth".

Should wild rice be considered as a crop to be domesticated for purposes of economic development, or as a sacred gift from the Creator? Is research on the wild rice genome a sacred obligation of our research universities or a continuation of five-plus centuries of colonizing? Is the role of humankind to subjugate nature with dominion and control, or to more humbly live in harmony with "all that is"?

What about "none of the above"? Or even "all of the above"? They've just puked up a bunch of false dichotomies, which really aren't relevant to the issue at hand. And it just gets worse, bringing up the usual moonbat relativism that tries to pretend we should regard all points of view as equally deserving of respect, and does so by serving up a false, phony image of science.

The wild rice issue challenges the academy to bring more critical attention to our own preconceived beliefs and foundations. Is science our only source of genuine knowledge, or might indigenous knowledge offer valuable understandings? Can "scientific" knowledge rightly be considered objective, or does objectivity remain an aspiration beyond our reach? Does science produce reality itself, or merely a map of reality that we find useful?

Too often, science is portrayed as reality, as objective, and a final (or superior) arbiter of truth without bothering to surface and examine the underlying philosophical tenets that frame (and therefore limit) our practice of science everyday.

As the philosopher of science Gonzalo Munevar noted, "What appears to be the most solid of data may be based on theoretical assumptions, and the difficulties of those assumptions can only be uncovered by looking at the world from a different point of view. ... To keep science strong, then, we must allow the pursuit of unusual ideas. This means that even non-Western cultures may have important contributions to make in some areas of science ... and that we not use the success of science in the West to put down non-Western cultures."

I'm sorry, but I will place fairy tales about the Gitchi-manidoo way, way down in the list of reasonable 'truths', and in particular I will dismiss as undeserving of respect any cultural tradition that demands that believers (and unbelievers as well!) must simply accept it without question. Religions that insist on secrets and mysteries seem to me to be self-serving excuses to conceal their own lies. I'm willing to listen to other voices, but not to voices whose first commandment is, "don't listen to any one but me."

Testing Meme Propagation In Blogspace: Add Your Blog!

This posting is a community experiment that tests how a meme, represented by this blog posting, spreads across blogspace, physical space and time. It will help to show how ideas travel across blogs in space and time and how blogs are connected. It may also help to show which blogs are most influential in the propagation of memes. The dataset from this experiment will be public, and can be located via Google (or Technorati) by doing a search for the GUID for this meme (below).

The original posting for this experiment is located at: Minding the Planet (Permalink: http://novaspivack.typepad.com/nova_spivacks_weblog/2004/08/a_sonar_ping_of.html) --- results and commentary will appear there in the future.

Please join the test by adding your blog (see instructions, below) and inviting your friends to participate -- the more the better. The data from this test will be public and open; others may use it to visualize and study the connectedness of blogspace and the propagation of memes across blogs.

The GUID for this experiment is: as098398298250swg9e98929872525389t9987898tq98wteqtgaq62010920352598gawst (this GUID enables anyone to easily search Google (or Technorati) for all blogs that participate in this experiment). Anyone is free to analyze the data of this experiment. Please publicize your analysis of the data, and/or any comments by adding comments onto the original post (see URL above). (Note: it would be interesting to see a geographic map or a temporal animation, as well as a social network map of the propagation of this meme.)

INSTRUCTIONS

To add your blog to this experiment, copy this entire posting to your blog, and then answer the questions below, substituting your own information, below, where appropriate. Other than answering the questions below, please do not alter the information, layout or format of this post in order to preserve the integrity of the data in this experiment (this will make it easier for searchers and automated bots to find and analyze the results later).

REQUIRED FIELDS (Note: Replace the answers below with your own answers)

(1) I found this experiment at URL: http://uti.dinggraphics.com/archives/000307.html

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(3) I posted this experiment at URL: http://pharyngula.org/

(4) I posted this on date (day, month, year): 02/08/04

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SDB 2004: The Discovery Institute's disciple

I spent a long evening at the SDB meetings with Paul Nelson of the Discovery Institute, who was presenting a poster on "Problems with characterizing the protostome-deuterostome ancestor." It's difficult to write about, because Nelson is actually a pleasant, personable fellow, but…

(Yeah, you know it was coming, an immense, insurmountable, horrendous "but".)

…but the poster was just plain bad.

The first gigantic problem is that there was absolutely no data on the poster. I hope everyone who has read my summaries of the SDB meetings would be getting the strong idea that every talk was data-centered. People are making observations and doing experiments and presenting the results, and in the process giving their interpretations, placing it in the context of other people's work, etc. Strolling through the posters is a technicolor experience, with huge photos of in situs and blots and gels and details of embryonic anatomy all around. This particular meeting wasn't big on theory and modeling, but I talked to a few old pals who were doing that sort of thing, and it was all math and charts and simulations.

Nelson's poster was all words and speculation. There was no substance there, no details to grapple with. It was awkward to discuss, because there really was no handle to grasp. My usual strategy when going through a poster with the author is to find the interesting detail that is relevant to my particular research interests, ask questions about it, and let the discussion spiral from there to the author's context. I just couldn't do that here.

What was it about? Well, the gist of it, as near as I can tell (and I would hope Nelson will chime in with comments to correct anything) was the usual creationist argument from personal incredulity. The center of the poster was a drawing, a simple oval. We were supposed to imagine that this was the egg of the hypothetical pre-Cambrian common ancestor of both protostomes and deuterostomes. Next, we were supposed to imagine what the adult of this organism would look like. Then Nelson had a few photos of an adult fly, nematode, and sea squirt. Finally, we were supposed to imagine that modification of the development of modern organisms was impossible, that the modification of the development of the protostome/deuterostome ancestor was similarly impossible, and therefore, evolution was impossible.

That's it.

No data. No experiments. No predictions. Just a request to build up a model of evolution and development in our imaginations. I'm sure it works for creationists, and being liberated from demands for evidence makes it easy to compound one's biases and come up with the answer Nelson wants, but in this mob of good practical naturalists who expect at least a nod towards some data, it fell flat. I'm afraid that when I was free to just imagine the adult protostome/deuterostome ancestor that would arise from his evocative, all-powerful Oval of Infinite Potential, I had no problem scribbling up a cartoon of a crude triploblastic worm, and saw no obstacle to incremental specialization of it's component parts in development and evolution.

Now you could argue that that's just compounding my atheistical, materialistic biases, and is as meaningless as Nelson's assumption of a conclusion. I would make two arguments against that, though. One of the purposes of a scientific presentation is to share the evidence and logic that leads to a particular conclusion in such a way that there isn't much room for argument, and that argument is at least directed towards constructive, alternative hypotheses. An open thought experiment that encourages unfettered guesswork is not science. For another, I wasn't alone in the conversation. Another passing scientist joined in, and she was also baffled by the point of the poster, and saw real power in evolutionary explanations. And, it turns out, she is an evangelical Christian, a regular and active church-goer (yes, such things exist with significant frequency in science; religious sensibilities are not automatically antithetical to good scientific thinking, no matter how desperately the Discovery Institute tries to dichotomize and polarize.) She wasn't rejecting the work out of the prejudice of an atheist, but out of our shared commitment to good scientific thinking.

I do have to commend Nelson for having the guts to expose the hollow vacuum at the heart of anti-evolutionary thinking to the critical eyes of a swarm of practicing scientists, but there is another troubling problem here. This presentation is going to go on a list at the Discovery Institute of Intelligent Design forays into mainstream scientific venues. You know it's going to be presented to some school board or court someday, with the disingenuous claim that "See? We really are doing real science, really!" It isn't. It's non-science. It's bad science. One thing we have to make clear is that placing something under the banner of the Society for Developmental Biology and getting it published in the offical program of an international meeting does not automatically make it scientific—especially since the conference presentations were not peer-reviewed for admissibility, and anyone willing to pay the conference fees could put up a poster for anything they want. And even the imprimatur of the magic words "peer-review" should never be assumed to be a guarantor of quality.

I wouldn't propose changing the open nature of conferences, and would actually encourage more creationists and other wild-eyed weirdos to try and attend scientific meetings. The purpose of these meetings is to throw out new ideas and get input from the scientific community on what to do next, and the real measure of success is not the presentation, but what follows from it.

Nothing will follow from Nelson's presentation. There won't be any research done as a consequence of his poster—there's none that can be done. He may be a nice guy, but niceness doesn't count in science. And the absence of substance is what has to be emphasized to school boards and courtrooms where this kind of work will get cited.

SDB 2004: Stem Cells

The last session I attended at the meeting we the Tuesday morning stem cell symposium. Now that stem cells have been coopted as a political football, everyone has their own idea about the nature of the stem cell debate, and their own expectations about what activists in the field would be talking about. Most people would be wrong. There was absolutely no discussion about adult vs. embryonic stem cells: that's been long settled in the scientific community, and there is near-universal agreement that we ought to be researching both. No, the question here wasn't about whether we should do stem cell research, but what we have learned from the current work, and where to go next.

John Gurdon was first, on "nuclear reprogramming by Xenopus oocytes", although his talk covered more ground than was implied by the title. (I've got to say that John Gurdon is just a wonderful fellow to listen to: he's got that rich British accent, and he's slender and dapper and topped with those 'long flowing locks'...it's like getting a lecture from an elder David Bowie.) Reprogramming is an important issue. It has become increasingly clear that the egg nucleus isn't just a blank slate, a pile of DNA stripped of the restrictive modifications of the adult differentiated cell. It has it's own special pattern of modifications.

The functioning genome is more than just its sequence of DNA. The DNA is looped and folded in specific ways by the arrangement of proteins that ensheath it, and carries a suite of specific transcription factors that enable and disable transcription of different genes. In addition, one property that Gurdon discussed is methylation: methyl groups are covalently attached to stretches of the DNA backbone that silence those regions. The pattern of methylation is different in different cell types, including the oocyte, and there are also sex-specific methylations.

The reason we need to continue to study embryonic stem cells is that they already possess the appropriate pattern of extra-genetic modifications for a totipotent cell, and we currently have no idea how to impose that pattern on a nucleus. We don't even know what that pattern is. I think that someday we'll have the information or the recipe to switch the naked genome to a totipotent state, but we'll only get that by working with embryonic cells that already have that desired state; I can imagine a future in which we don't need embryonic stem cells at all, but the current political situation is, ironically, blocking progress towards that condition.

Gurdon gave a specific example. In frogs, we know that the egg cytoplasm has some reprogramming activity. If you extract the nucleus from a fully differentiated adult cell type, such as from an intestinal cell, and inject it into an enucleated egg, you will sometimes get a seemingly normal adult frog. We've been doing this for almost 50 years, but the efficiency hasn't improved much: it works about 15% of the time. One trick is to do serial transfers. Transplant the intestinal nucleus to an egg, let it incubate for a while, transfer it to another, then another, and the extended exposure to the egg cytoplasm boosts efficiency to 22%. Furthermore, one common result is that the developing embryo is abnormal, but may have patches of tissue that look healthy; extracting a nucleus from the healthy bits of your ugly embryo and resetting it by transplanting to another oocyte brings you up to a 30% success rate.

What is the mechanism of nuclear reprogramming? It's obvious that the egg is doing something to the DNA to prepare it for development. One system Gurdon is working with is a method of inducing the reprogramming in a large number of nuclei, or even better, plasmids, by injecting numerous quantities into the germinal vesicle of the frog egg. He can squirt 100 nuclei into the egg, which is not going to produce something that can develop to adulthood, but all he wants to see is how the egg biochemically modifies the injected DNA in the first few steps. He is assaying one particular gene, OCT4, a mammalian transcription factor that is not expressed in somatic cells, but is a reliable marker for stem cells. The promoter region of OCT4 is heavily methylated in cells of the thymus, which blocks its expression there. Upon transfer to the oocyte, those sites are demethylated by some activity there, and OCT4 is expressed. He can see exactly the same thing by putting a minimal promoter for OCT4 on a plasmid, and that also gets demethylated. One advantage there is that he can tweak the DNA and identify the bits that signal the occyte to demethylate, and he has identified several sites in the DNA that must be present for demethylation to occur.

The bottom line is that he has identified a strong, selective demethylating activity in frog oocytes, and that selective promoter demethylation is a necessary step in reprogramming somatic cell nuclei.

---

Another speaker, R. Jaenisch, hit on the same theme of nuclear cloning, stem cells, and reprogramming of the genome. The central problem of cloning of any kind, exemplified by Dolly the sheep, is that embryonic genes must be activated and somatic genes must be deactivated, and the current procedures all involve the hope that something in the oocyte will do that job for us.

Jaenisch is doing a kind of hopeless cloning—he's using cells that he knows aren't going to result in a healthy adult, or that are extremely difficult to reprogram, because, like Gurdon, he is interested in the process, not just the end result. For instance, he is cloning mice from lymphoid cells. Cells of the immune system rearrange their DNA during differentiation, stripping out chunks of immunologically significant sequence that they aren't going to use, which means a successful clone would be immuno-compromised...but that rearrangement is an unambiguous marker that one is working with what was a differentiated cell, and that one isn't working with a clone fortuitously derived from a somatic stem cell. He has also been working with nuclei from neurons, which are post-mitotic and about as differentiated as you can get, if one could put differentiation on a scale.

Most of his clones die after implantation. There is a decline in potency with increasing age of the donor—and the state of differentiation matters. The frequency of survival to adulthood in clones derived from B or T cells, or neurons, is less than 0.001%, which is why working with mice is an advantage for this kind of research.

Jaenisch has found that there are many genes like OCT4, and all of them need to be reactivated for success, but OCT4 is an instructive place to start. He has made a genetically modified mouse carrying an inducible OCT4—that is, a copy of the gene that he can switch on at will, at any time in development, including adulthood. Remember, OCT4 is always off in somatic tissues; turning it on in an adult mouse does horrible things. It triggers rapid proliferation of epithelial cells while suppressing fibroblast cells, producing multiple, massive, invasive cancers and death in less than a week. (One side effect of stem cell research that isn't mentioned enough is that it's good for more than just cloning. This reprogramming of cells into a proliferative, multipotent state is also a cellular property at the heart of cancer; knowing how to reprogram cell states is a step on the road to a cure.) The next step in his work is to use his inducible OCT4 cells to see if they can be used to improve the efficiency of cloning.

He's optimistic. There are no barriers in principle to therapeutic cloning, there are only technical problems.

Sunday, August 01, 2004

Another perspective on scientific meetings

What do you know...Piled Higher and Deeper is blogging a scientific conference this week.

SDB 2004: Anchorman!

Well. The scheduled Monday afternoon symposium was on microRNA, and I'm sure it was spectacular and fascinating and informative, but my brain was a little toasty, and I'd been neglecting my poor dutiful son, who was chauffeuring me back and forth from the meeting and our hotel through ghastly Calgary traffic, so I played hooky for an afternoon.

Actually, we decided to engage in some serious professional development for Connlann, who is one of the assistant managers at the theater here in Morris. The Morris Theater is a nice, old-fashioned single-screen theater, very traditional, and quite comfortable and homey. The nearest theater to our hotel was something called Famous Players.

It's a 16-screen megaplex. It doesn't have a refreshment stand, it had a few acres of floor space ringed by fast-food emporia—you could pick up a greasemeat sandwich at Burger King to bring into the movie with you. It was also extravagantly decorated in an Egyptian theme, with immense cobras and pharoah's death masks looming overhead. The arcade was a beeping, banging roar and hordes of teenagers were milling about. This was one intimidating place.

So, as an exercise, we came up with a short list of reasons why the humungous Calgary multiplex wasn't anywhere near as nice as our theater back home.

10. Admission: $4 vs. $12. The exchange rate isn't that good.
9. 16 screens? I only have two eyes.
8. Sit in one movie, hear the soundtrack to 16.
7. 16 times as many gum-chewing, giggling, popcorn-tossing teenagers!
6. The theater is easily mistaken for an airport terminal, and the security is even tighter.
5. Why go to Canada if all they're going to show is the same ol' American/Hollywood dreck?
4. All that glitz, and the arcade still didn't have "Dance Dance Revolution."
3. 1300 miles is an awfully long drive to catch a movie.
2. Sticky theater floors…with poutine!
1. A giant cockroach crawling over the facade isn't particularly inviting.
   
   (Scarabaeidae, Blattellidae…who the heck cares when it's 10 meters long?)

We saw Anchorman. It's an incredibly stupid movie, but somehow it was just stupid enough to make us laugh. The spectacle of badly-dressed bands of egotistical nerds battling over trivia did leave me feeling like I was still back at the conference, though. At least we've replaced TelePrompters with PowerPoint. (uhh, wait...isn't that a step backwards?)

Connlann also got to try some real Indian food at a place with the cheesy name of the Taj Mahal on MacLeod Trail, but it really was excellent, with phenomenal service. Here he is getting his first thal.

If Myers will not voyage to Arcturus…

…then Arcturus must voyage to Myers. Chez Pharyngula had a visit this weekend from Jay Manifold (and, despite sounding like a great name for a transdimensional warp drive physicist in a science fiction novel, "Jay Manifold" is not a pseudonym, I learned) of A Voyage to Arcturus. He's on a road trip, cruising through our sparsely populated region of the upper midwest, popping in to meet a few webloggers as he goes. It made for a pleasant and intellectually stimulating evening here, at least, and we'll have to try it again.

It's a great idea. Morris, Minnesota isn't exactly a hot tourist destination, so it's not as if we're overwhelmed with visitors. Anyone reading this who feels an urge to visit the prairie, feel free to drop by. As an added inducement, I'll mention that Jay and I got Free Beer at the local pub. Free Beer! It's like paradise!^* (I now expect John Wilkins to magically appear on my doorstep.)

One very weird thing; after leaving here, Jay was heading north towards Fargo to visit the author of Fresh Bilge, who has also commented on the event. My son Connlann happened to have left Saturday to spend the weekend with a young lady friend and her parents at a lake cabin up that way…and wouldn't you know it, Fresh Bilge, Jay, Connlann, Katie, and her parents were all converging in oddly serendipitous synchronicity. As the guy says,

The whole damn Midwest is one enormous small town.

Fresh Bilge was all wet on one thing, though. I don't think Jay and I talked about politics or Kerry at all—it was all science and books and culture. I can't swear that I didn't occasionally mutter anti-Bush slogans under my breath, because, you know, that's what we fervent Democrats do in a kind of low-level physiological reflex function, but it certainly wasn't the topic of conversation.

^*OK, it's not like there's always free beer…the bartender gave us free beer to apologize for a long delay in getting us our food. But hey, two bloggers shooting the breeze? It's not as if we even noticed the delay.

Pharyngula

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