A surprising Nobel

I would never have guessed this one. The Nobel Prize in Medicine has gone to Robert G. Edwards for his pioneering work in in vitro fertilization. It surprises me because it’s almost ancient history — he is being rewarded for work done over 30 years ago. It’s also very applied research — this was not work that greatly advanced our understanding of basic phenomena in biology, because IVF was already being done in animals. This was just the extension of a technique to one peculiar species, ours.

I don’t begrudge him the award, though, because the other special property of his research was that it was extremely controversial. These were procedures that simply burned through scores (or hundreds, if you count the ones with such little viability that they weren’t implanted) of human zygotes in order to work out reliable protocols, and throughout faced serious ethical risks — these were procedures that had a chance of producing the worst possible result, a viable embryo that came to full term, but had serious birth defects. The public opposition to the work was tremendous, funding was tenuous, and even many in the scientific community opposed the work and ostracized Edwards and his colleague, Steptoe (who did not live to see this day, and so did not receive the award).

Nowadays, IVF is practically routine and about 4 million people were ‘test tube babies’. It’s still controversial, though, with extremist anti-abortion groups, such as the Catholic church, still fighting it, and the redundant, unused zygotes from the procedure still being a point of major contention (ever heard of ‘snowflake babies’? That’s what they’re talking about).

I’m reading a couple of messages in this award. One is simply acknowledging a hard-working scientist, but the other is a signal that we should soldier on through all of the opposition to reproductive health technologies, that science will be rewarded and the Luddites will find themselves in the dustbin of history. I can’t help but see this as, in part, the Nobel committee making an unmistakeably rude gesture at the anti-science, anti-choice fanatics of the religious right.

(For those who are unfamilar with the IVF procedure that Edwards and Steptoe developed, here’s a lovely summary diagram from the Nobel Foundation.)

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TimeTree

People are always asking me for the source of those nice t-shirts that illustrate how long we’ve diverged from a given species. I think the name must be hard to remember: they’re at evogeneao.com. Now there’s a little software widget that will be just as neat-o.

Look up TimeTree, and remember to show it to the kids. This is a page with a simple premise: type in the name of two taxa (it will accept common names, but may give you a list of scientific names to narrow the search), and then it looks them up in the public gene databases and gives you a best estimate of how long ago their last common ancestor lived.

Grasshoppers and I, for instance, shared a many-times-great grandpa 981 million years ago. My zebrafish and I are practically cousins, with our last shared ancestor living a mere 454 million years ago. Hey, tree, we’ve been apart for 1407 million years, how’s it going? Sparrow! Long time no see! 325 million years, huh?

You get the idea. It’s great for getting the big perspective. The kids will pester you all the time for dates. Especially since…it’s got an iPhone app! Get on the App Store on your smart phone or iPad and search for TimeTree — it’s totally free (except for the cost of owning such a gadget, of course).

Oh, and once you’re done entertaining the children and yourself, it’s actually a serious tool. Tap on the results and it’ll take you to all the scientific details: breakdown of mitochondrial vs. nuclear date estimates, source papers, all that sort of thing.

For details on how it works, there’s also a published paper:

Hedges SB, Dudley J, Kumar S (2006) TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 22(23):2971-2972.

Look, a cat! 92 million years.

Astroturfing the scientific databases: spamming the lobster eye

The Encyclopedia of Life is a cool tool which is a sort of wikification of taxonomy — it allows a large number of contributors to add descriptions of species with the goal of eventually documenting all 1.8 million known species in a single searchable source. Look at the page for my experimental animal, Danio rerio; lots of information in a standard format with links and references. Thumbs up!

However, there’s a problem here: the sources. To organize that much data, a large mob of contributors are needed, and that means some fairly open policies to allow contributors have been instituted, and that in turn means that there will be parasites on they system. And a reader sent me an example of a doozy.

Take a look at the page for the order Decapoda. It has an oddly random article on the reflecting superposition eyes of lobsters up top.

A lobster’s eye works on a principle of reflection rather than that of refraction…The most outstanding characteristic of the lobster eye is its surface, which is composed of numerous squares…these squares are positioned most precisely.

It’s OK — it seems to be a rough and unhelpful paraphrase of a section of Michael Land’s wonderfully informative book, Animal Eyes, and it’s correct as far as it goes — lobster eyes do have an array of mirrored light guides that are square in section. The surprise is at the end, where it names the author: Harun Yahya. That’s right, the Turkish creationist. This is taken straight from one of his creationist ravings, where he discusses some amazing detail of biology and concludes that it couldn’t possibly have evolved because he, a wealthy playboy and former mental patient and convicted criminal now representing himself as the Islamic source of creation science, could not imagine it so.

How did Harun Yahya become a source on EoL?

The page links to its source and holder of the copyright on the article: it’s the Biomimicry Institute, an entirely credible educational source, with a specific page, the Ask Nature reference, which is, again, an open source resource with multiple contributors. And yes, there’s Harun Yahya stuffing articles in there.

I did a google search on a few of the phrases in the text, and whoa — it’s everywhere. Harun Yahya’s organization has been dumping this same bit of text, and others, in various of their own websites and also in just about any legitimate source that allows them to open an account and create public content, including Ask Nature and EoL. It has also been picked up by numerous creationist sites as well, all echoing the same unwarranted conclusion: this eye works really well, therefore it couldn’t have evolved.

Try googling for information on lobster eyes. It’s a mess. There are a few credible sources that appear on the first page, like Wikipedia, but for the most part it’s a smear of creationist sites.

I know, this is a truism: don’t trust the Net of Lies, learn to vet your sources, watch out for anything on the net. But it looks to me like the Turkish creationists have been waging a successful astroturf campaign to infiltrate sources that we would normally regard as pretty good, and are thereby corrupting sources even more. It also allows them to pass casual review because their articles are very widely sourced.

I hope the editors of various scientific web sites that allow open submissions will take a look at their collections, and purge them of anything from Harun Yahya. He is not a scientific source, he has absolutely no background in the sciences, and he mangles the information to serve his ideological goals. What he’s doing here is using repetition to make his name widely known, and parasitizing on the good name of some websites to falsely elevate his reputation. There’s a hobo on the train, people, and he’s pretending he’s a railroad executive.


Just in case you are wondering about those lobster eyes, they actually are extremely interesting, using reflecting mirrors instead of refracting lenses to focus light on photoreceptors. It’s not hard to see how they would work: to focus incoming light on a photoreceptor surface, we need to bend light to a target, and refraction or reflection can do the job.

Here’s Mike Land’s summary diagram of the process (and, incidentally, Animal Eyes is an excellent survey of the diversity of biological optics):

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I don’t see how you can argue that the one on the right is evidence of creation, any more than the one on the left. Both take advantage of ordinary physical properties to focus an image on a retina.

The interesting phenomenon is the transition: the eye on the left is almost certainly the ancestral state, since some crustaceans have both kinds of eyes, and also they may have the refracting eye on the left in the early stages of development, and it then transforms into the mirrored eye…and we don’t have good evolutionary examples of the historical transition. That the eye can switch between two forms during development at least implies that no magic is necessary, though, so this may be an open question but it is not a question that requires the invention of a supernatural designer to answer.

Hawking on King

Stephen Hawking was on Larry King Friday night, and here’s a little video of the event. Through no fault of his own, Hawking isn’t exactly a dynamic stage presence — he’s a bag of bones in a wheelchair with a computer voice speaking for him — and Larry King is…well, King is a genuinely dumb interviewer whose weak-minded talents are better suited to celebrity airheads.

That isn’t the whole thing. There’s also part 2 and part 3, which includes Leonard Mlodinow (who’s good, but sucks up too much to the other panelists), and a couple of people whose intelligence is a better match to King’s: Deepak Chopra, who is so far out of his depth in a discussion of physics that he feels the need to overcompensate by babbling buzzwords, and Robert Spitzer. Spitzer? Who? He’s a Catholic apologist, and even more annoying than Chopra.

This is the gist of his argument: it’s the tiresome old first cause claim.

Father Robert J. Spitzer, president and founder of the Magis Center of Reason and Faith in Irvine, says he believes that both physics and philosophy offer proofs of the existence of God.

“No metaphysician I know of believes that nothing can give rise to something,” Spitzer, a philosophical metaphysician and a Jesuit priest, said in an interview Thursday. “Nothing can only come from nothing. If it was nothing, it didn’t bring itself out of nothing.”

He hasn’t been following along, apparently. Something does emerge out of nothing all the time, and even if you did need some specific causal event, it is neither necessary nor sensible to invoke a supernatural intelligence. Hawking’s whole point seems to be that natural causes, all that stuff physics is good at examining, seems to be sufficient for all.

I think I’ll trust a physicist over a Jesuit any day, especially when the subject is physics.

SETI built on GIGO

I’ve never been a fan of SETI, the search for extraterrestrial intelligence. It’s like playing the lottery obsessively, throwing down lots of money in hopes of a big payoff, and I don’t play the lottery, either.

I’d really like to know if Seth Shostak is innumerate enough to play the lottery, though, because his recent claim that we stand a good chance of discovering extraterrrestrial intelligence within 25 years. All right, bring it: let’s see your evidence for such a claim.

“I actually think the chances that we’ll find ET are pretty good,” said Seth Shostak, senior astronomer at the Search for Extraterrestrial Intelligence Institute in Mountain View, Calif., here at the SETIcon convention. “Young people in the audience, I think there’s a really good chance you’re going to see this happen.”

Shostak bases this estimation on the Drake Equation, a formula conceived by SETI pioneer Frank Drake to calculate the number (N) of alien civilizations with whom we might be able to communicate. That equation takes into account a variety of factors, including the rate of star formation in the galaxy, the fraction of stars that have planets, the fraction of planets that are habitable, the percent of those that actually develop life, the percent of those that develop intelligent life, the fraction of civilizations that have a technology that can broadcast their presence into space, and the length of time those signals would be broadcasted.

Reliable figures for many of those factors are not known, but some of the leaders in the field of SETI have put together their best guesses. Late great astronomer Carl Sagan, another SETI pioneer, estimated that the Drake Equation amounted to N = 1 million. Scientist and science fiction writer Isaac Asimov calculated 670,000. Drake himself estimates a more conservative 10,000.

The Drake Equation? That’s it? I hate the Drake Equation. It’s seven arbitrary parameters plugged into a simple formula, of which we have reasonable estimates of one (the rate of star formation), growing evidence of values for another (the number of planets around each star), and the other five are complete wild-ass guesses, most of them dealing with biology and culture, and we’ve got astronomers who know next to nothing of either inserting optimistic values. When biologists amend the values to something more reasonable, the likelihood of intelligent life plummets. Not that their wild-ass guesses are necessarily more accurate (although they are based on the history of life on this one planet), but it does say something that the equation can yield results that vary by six orders of magnitude, depending on who does the calculation.

It’s a useless formula. You can’t calculate anything from a formula in which almost all of the variables are complete unknowns, and it’s also meaningless in that no matter what result we acquire from empirical evidence, it can all be retrofitted to the magic formula. I really don’t understand the appeal of the Drake Equation, except that it turns our ignorance into a pseudo-sciencey string of fake math…but smart people ought to be able to recognize garbage.

I can’t really make a prediction here, unlike Shostak, who seems willing to gamble everything on promises he doesn’t have to worry about fulfilling. He could win the lottery. But I’m not going to place any bets on it.

Blaschko’s Lines

One of the subjects developmental biologists are interested in is the development of pattern. There are the obvious externally visible patterns — the stripes of a zebra, leopard spots, the ordered ranks of your teeth, etc., etc., etc. — and in fact, just about everything about most multicellular organisms is about pattern. Without it, you’d be an amorphous blob.

But there are also invisible patterns that you don’t normally see that are aspects of the process of assembly, the little seams and welds where disparate pieces of the organism are stitched together during development. The best known ones are compartment boundaries in insects. A fly’s wing, for instance, has a normally undetectable line running across the middle of it, a line that cells respect. A cell born on the front half of the wing will multiply and expand its progeny to cover a patch on the surface, but none of its offspring cells will cross over the invisible line into the back half. Similarly, cells born on the back half will never wander into the front.

We can see these invisible lines by taking advantage of mosaicism: generate a fly wing with two genetically distinct cell types, for instance by making one type express a pigment marker and the other not, and the boundaries become apparent. There are many ways we can generate mosaics, but in Drosophila we can use somatic recombination — with low frequency, chromosomes in the fly can undergo crossing over in mitosis, not just meiosis, so sometimes the swapping of chromosome segments will turn a daughter cell that should have been heterozygous for an allele into one that is homozygous, allowing a marker allele to express itself.

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(Click for larger image)

(A) The shapes of marked clones in the Drosophila wing reveal the existence of a compartment boundary. The border of each marked clone is straight where it abuts the boundary. Even when a marked clone has been genetically altered so that it grows more rapidly than the rest of the wing and is therefore very large, it respects the boundary in the same way (drawing on right). Note that the compartment boundary does not coincide with the central wing vein. (B) The pattern of expression of the engrailed gene in the wing. The compartment boundary coincides with the boundary of engrailed gene expression.

It’s like a secret code written in molecules hidden to the eye until you illuminate it in just the right way to expose it. And these lines aren’t just arbitrary, they’re significant. The wing boundary defines the expression of important molecules that define the identity of specific structures. The posterior half of the wing is the domain of expression of a molecule called engrailed, which is part of the machinery that makes the back half a back half. We can also stain a wing for just that gene product, and also expose the hidden lines.

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We can also mutate the pathway of which engrailed is part, and do interesting things to the fly wing, like turn the back half into a mirror image of the front half. So these lines actually matter for the proper development of a fly.

So you might be wondering if we have anything similar in humans…and no, we don’t have strict compartment boundaries like a fly. However, we do have normally invisible lines and stripes of subtle molecular differences running across our bodies, which are occasionally exposed by human mosaicism. These are marks called the lines of Blaschko, after the investigator who first reported a common set of patterns in patients with dermatological disorders in 1901.

Don’t rip off your shirt and start looking for the Blaschko lines — they’re almost always invisible, remember! What happens is that sometimes people with visible dermatological problems — rashes, peculiar pigmentation, swathes of moles, that sort of thing — express the problems in a stereotypically patterned way. On the back, there are V-shaped patterns; on the abdomen and chest, S-shaped swirls; and on the limbs, longitudinal streaks.

Here is the standard arrangement:

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And here are a few examples:

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Note that usually there isn’t a whole-body arrangement of tiger stripes everywhere — there may be a single band of peculiar skin that represents one part of the whole.

Where do these come from? The current hypothesis is that a patch of tissue that follows a Blaschko line represents a clone of cells derived from a single cell in the early embryo. These clones follow stereotypical expansion and migration patterns depending on their position in the embryo; this would suggest that a cell in the middle of the back of a tiny embryo, as it grows larger with the growing embryo, would tend to expand first upwards towards the head and then sweep backwards and around to the front. One way to think of it: imagine taking a piece of yellow clay and sandwiching it between two pieces of green clay into a block, and then pushing and stretching the clay block to make a human figurine. The yellow would make a band somewhere in the middle, all right, but it wouldn’t be a simple rectilinear slice anymore — it would express a more complex border that reflected the overall flow of the medium.

What makes the lines visible in some people? The likeliest example is mosaicism, a difference between two adjacent cells in the early embryo that then appears as a genetic difference in the expanded tissues. There are a couple of ways human beings can be mosaic.

The most common example is X-chromosome inactivation in women. Women have two X-chromosomes, but men only have one; to maintain parity in the regulation of expression of X-linked genes, women completely shut down one X. Which one is shut down is entirely random. That means, of course, that all women are mosaic, with different X-chromosomes shut down in different cells. This normally makes no difference, since equivalent alleles are present on each, but occasionally an X-linked skin disorder can manifest itself in a splotchy pattern. Another familiar example is the calico fur color in female cats, caused by the random expression of a pigment gene on the feline X chromosome.

A more spectacular example is tetragametic chimerism. This rare event is the result of the fusion of two non-identical twins at an early stage of development, producing an embryo that is a kind of salt-and-pepper mix of two individuals. After the fusion, the embryo develops normally as a single individual, but genetic or molecular tests can detect the patches of different genotypes. (No scientific tests can tell whether the individual has two souls, however.)

Another way differences can arise is by somatic mutation. Mutations occur all the time, not just in the germ line; we’re all a mixture of cells with slightly different mitotic histories and some of them contain novel mutations, usually not of a malign sort, or you wouldn’t be reading this right now. But what can happen is that you acquire a mutation in one cell that may predispose its clone of progeny to form moles, or acquire a skin disease, or even tilt it towards going cancerous. It’s a fine thing to undergo genetic screening to find that you may not carry certain alleles associated with cancer, but you aren’t entirely off the hook: you may have patches of tissue in your body that are perfectly normal and functional except that they carry an enabling mutation that occurred when you were an embryo.

One final likely mechanism is epigenetic. Throughout development, genes are switched on and off by epigenetic modification of the DNA. This process can vary: epigenetic silencing doesn’t have to be 0 or 100% absolute, but can differ in degree from cell to cell. It can also vary by chromosome — you’re all diploid, and epigenetic modification may affect one chromosome of a pair to a different degree than the other. Since epigenetic modifications are inherited by the progeny of a cell, that means these differences can be propagated into a clonal patch…that on the skin, will likely follow the lines of Blaschko.

Don’t fret over these lines; they aren’t a disease or a problem or even, in most cases, at all visible. The cool thing about them is that there is a hidden map of your secret history as an individual embedded in silent patterns in your skin — you were not defined as a single, simple, discrete genetic entity at fertilization, but are the product of complicated, subtle changes and errors and shufflings and sortings of cells. We’re all beautiful pointillist masterpieces.

Kiss space goodbye

Charlie Stross examines the economics and physics of colonizing other planets, and he isn’t at all optimistic. Forget going to planets around other stars — the distances are absurdly excessive. But also forget about colonizing planets in our solar system: not only is it ridiculously expensive just to put a human being on another planet, it isn’t even an attractive proposition.

When we look at the rest of the solar system, the picture is even bleaker. Mars is … well, the phrase “tourist resort” springs to mind, and is promptly filed in the same corner as “Gobi desert”. As Bruce Sterling has puts it: “I’ll believe in people settling Mars at about the same time I see people settling the Gobi Desert. The Gobi Desert is about a thousand times as hospitable as Mars and five hundred times cheaper and easier to reach. Nobody ever writes “Gobi Desert Opera” because, well, it’s just kind of plonkingly obvious that there’s no good reason to go there and live. It’s ugly, it’s inhospitable and there’s no way to make it pay. Mars is just the same, really. We just romanticize it because it’s so hard to reach.” In other words, going there to explore is fine and dandy — our robots are all over it already. But as a desirable residential neighbourhood it has some shortcomings, starting with the slight lack of breathable air and the sub-Antarctic nighttime temperatures and the Mach 0.5 dust storms, and working down from there.

Sterling is being optimistic there — no way is it only 500 times more expensive to go to Mars rather than the Gobi.

I love to read space opera, but face it, it’s about as realistic as your goofiest high fantasy novel with elves and gnomes and magic swords. It’s not going to happen, ever, but it is still fun to dream.