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.

Templeton prayer study meets expectations

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I have no idea how this stuff gets published. I’ve been sent a new paper that tests the effect of prayer, and I was appalled: it’s got such deep methodological problems that nothing can be concluded from it, but that doesn’t stop the authors, who argue that they’re seeing that Proximal Intercessory Prayer improves vision and hearing in people in Mozambique.Proximal Intercessory Prayer (PIP) is their very own term for what they do, to distinguish it from distant prayer. What is it, you may ask? Here is their protocol.

Western and Mozambican Iris and Global Awakening [two evangelical/missionary organizations that cooperated with the research] leaders and affiliates who administered PIP all used a similar protocol. They typically spent 1-15 minutes (sometimes an hour or more, circumstances permitting) administering PIP. They placed their hands on the recipient’s head and some- times embraced the person in a hug, keeping their eyes open to observe results. In soft tones, they petitioned God to heal, invited the Holy Spirit’s anointing, and commanded healing and the departure of any evil spirits in Jesus’ name. Those who prayed then asked recipients whether they were healed. If recipients responded negatively or stated that the healing was partial, PIP was continued. If they answered in the affirmative, informal tests were conducted, such as asking recipients to repeat words or sounds (e.g. hand claps) intoned from behind or to count fingers from roughly 30 cm away. If recipients were unable or partially able to perform tasks, PIP was continued for as long as circumstances permitted.

Vision and hearing tests were carried out before and after the procedure using eye charts and an audiometer. Subjects were recruited from a self-selected population of rural Africans who were attending a charismatic/evangelical revival…that is, people who knew they would be rewarded with acclaim if they publicly demonstrated dramatic improvements in their health under the influence of a priest. This experiment did not use single-blind trials — in fact, the subjects were hammered repeatedly with the protocol until they reported that it worked for them, subjectively.

It also wasn’t double-blind. Not only were the experimenters fully aware of what treatment the subjects received, but they knew that every single subject they tested had reported a positive effect. This study was wide open to experimental bias, and given that two of the authors of the study were not medically trained at all, but were instead members of schools of theology, and that all of the work was funded by the Templeton Foundation, we can guess what answer they wanted.

Most damning of all, there were no controls.

I repeat, no controls anywhere in the experiment.

No controls, experiment not done double-blind or even single-blind, a small number (24) of subjects self-selected from a suggestible population predisposed to demonstrate an effect…this study is total crap. All it would take to get their results is a tendency for people coming in for magical healing to exaggerate their afflictions, and minimize them after a few minutes of personal attention, and presto, PIP works. And that seems like an extremely likely situation to me.

Now there could be a real physiological effect: compelling attentiveness, physical stimulation, and just generally waking people up could generate an increase in blood flow to the head, which would lead to better sensory performance — I know I wake up bleary-eyed and wooly-headed until I’ve snapped myself awake with a little cold water and some physical activity, so we also know that sensory performance varies over time. But can we determine that from this work? No! No controls! This is completely worthless work.

What’s particularly galling is that the investigators go on to suggest that maybe the suffering people in the undeveloped world could benefit from PIP.

Although it would be unwise to overgeneralize from these preliminary findings for a small number of PIP practitioners and subjects collected in far-from-ideal field conditions, future study seems warranted to assess whether PIP may be a useful adjunct to standard medical care for certain patients with auditory and/or visual impairments, especially in contexts where access to conventional treatment is limited. The implications are potentially vast given World Health Organization estimates that 278 million people, 80% of whom live in developing countries, have moderate to profound hearing loss in both ears, and 314 million people are visually impaired, 87% of whom live in developing countries, and only a tiny fraction of these populations currently receive any treatment.

No, I think those hundreds of millions of people deserve something a little more substantial than a witch-doctor dribbling oil on their heads and chanting to their Jesus juju. And no, nothing in this work can warrant further investigation.

By the way, you may wonder why they had to go to rural Mozambique to find subjects. There is no shortage of crazy preachers and gullible believers willing to be healed by magic in the US. They reveal the answer to that in an aside.

Conducting similar studies under controlled clinical conditions in North America would be desirable, yet neither Iris nor Global Awakening claims comparable results in industrialized countries (arguing that “anointing” and “faith” are lower where medical therapies are available)—see Supplemental Digital Content for our unsuccessful attempts to collect data in the US.

Ah, the incredible shrinking god — he just doesn’t work where conditions are amenable to more thorough examination. I am not surprised.

I’m also not surprised that this garbage was funded by the Templeton Foundation. It could only have been supported by an organization that places scientific rigor a distant second to making excuses for faith.

Brown CG, Mory SC, Williams R, McClymond MJ (2010) Study of the Therapeutic Effects of Proximal
Intercessory Prayer (STEPP) on Auditory and
Visual Impairments in Rural Mozambique. Southern Medical Journal, 4 August 2010.

Engineering lungs

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This past weekend, I attended my 35th high school reunion. It’s a strange phenomenon to be meeting people you haven’t seen since you were 18, and further weirdness ensues when we discover that most of them are already grandparents. There have been a lot of life changes in 35 years. Saddest of all, though, is the ritual listing of the deceased…and I learned that one of my former classmates died in her late 40s of emphysema, a progressive and irreversible lung disease that leads to the near complete loss of lung function. The only cure right now is a lung transplant, and patients who’ve been suffering with emphysema for long typically have so many other problems that they’re poor candidates for surgery, not to mention that the waiting list for organs is long, and a transplant means a life-long commitment to anti-rejection drug treatments.

There will come a day, though, when new lungs can be built and replacement surgeries more common. That day is definitely not yet here, though, but there are promising signs on the horizon. One such sign is recent work in tissue engineering to grow lungs in a dish.

We can grow functional rat lungs in a tissue culture chamber now, which show some limited ability to support respiration when transplanted back into another rat. Here’s an overview of the procedure; I’ll go through it step by step.

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Schema for lung tissue engineering. (A) Native adult rat lung is cannulated in the pulmonary artery and trachea for infusion of decellularization solutions. (B) Acellular lung matrix is devoid of cells after 2 to 3 hours of treatment. (C) Acellular matrix is mounted inside a biomimetic bioreactor that allows seeding of vascular endothelium into the pulmonary artery and pulmonary epithelium into the trachea. (D) After 4 to 8 days of culture, the engineered lung is removed from the bioreactor and is suitable for implantation into (E) the syngeneic rat recipient.

The first step is to collect a donor rat lung. The organ is cut out of a living rat, who will quickly become a dead rat; this part of the procedure probably can’t be scaled up to human transplantations, for obvious reasons. However, lungs from dead people or perhaps even lungs from appropriately sized animals will be adequate.

This donor lung is then stripped of all of its living cells. This is done by perfusing it with a detergent solution. Membranes dissolve and rupture in the presence of detergent, so all of the cells in the lung are basically destroyed, their contents, including cytoplasm, nucleus and DNA, and membranes and organelles are washed away.

What’s left then? Connective tissue and extracellular proteins. All that’s left is a frothy, fragile matrix of fibers like collagen and elastin, and imbedded signaling proteins that will be useful in supporting the growth of new cells. It leaves behind a kind of porous, pale ghost lung, a collection of microscopic struts that just needs to be draped with new cells.

This is the key step. Lungs are complicated, delicate membranous structures, and it would be hard to regrow it entirely from scratch. Starting with an acellular scaffold, though, a kind of skeleton of a lung that sketches out the arrangement of alveoli and blood vessels gives the tissue engineering a head start. It really is amazing how much of the organization of the lung is still left when all of the cells are removed: the photos below show the air spaces left behind (on the left) and the major blood vessels (on the right). There are no cells here! This is just an outline of the structure left by the still extant connective tissue!

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What’s promising about this so far is that almost all of the antigenic components of the lung are removed; if this lacework of proteins were transplanted into another animal, it probably wouldn’t provoke an immune response. Of course, it also wouldn’t work as a lung, because there are no gas exchange surfaces present, and everything is leaky. It’s only a skeleton of a lung, remember…so let’s fix that.

The next step is to suspend the lung framework in a chamber, with tubes attached to the airways and to the blood vessels. Living, isolated lung epithelial cells are then introduced into the airways, and lung endothelial cells (the cells that line blood vessels) are introduced into the pulmonary arteries and veins. These cells stick to the scaffolds and grow. They actually grow better in the lung matrix than they do in a petri dish, probably because of the presence of growth factor proteins lurking in the acellular scaffold.

The new cells use the matrix as a guide and repopulate and rebuild the cellular structure of the lung. During this whole process, the tissue culture medium is pumped through the arteries to mimic the effects of blood pressure, and air is pumped into the airways. It works beautifully. New columnar epithelial cells grow to line alveoli, and endothelial cells line the blood vessels appropriately, and the cells produce the right secreted proteins, like surfactants that reduce surface tension and are important for allow lungs to inflate. It takes about a week for the new lung tissues to form, and they are robust, producing sheets of cells that can tolerate the same pressures as intact, normal lungs.

Now for the real test. The regrown lungs were transplanted into living rats for 45 minutes to two hours. They worked! Everything stitched together nicely, and the engineered tissues pinked up nicely as blood flowed into them. Blood was visibly oxygenated as it passed through the new lung, and measurements of the partial pressure of oxygen and carbon dioxide in the blood showed that the former went up and the latter went down, exactly as it is supposed to do.

This is all very promising, but the transplantation times were very short, and you might be wondering why. These lungs aren’t perfect. There was bleeding from the blood vessels into the airways, and also some blood clotting — for this to work, the barrier membranes have to be essentially perfect, and they aren’t, yet. The poor rats’ lungs would have spluttered and fallen apart with prolonged use, and the blood clots would have led to thrombosis eventually.

Another problem, and one that has to be solved eventually if this is ever to work for human transplantations, is the source of the cellular components. The connective tissue stuff is only weakly antigenic, so isn’t going to provoke a strong immune response, but repopulating it with foreign cells brings the rejection problem roaring right back. What we need next for long term success is to find a source of lung adult stem cells, or a way to induce pluripotent stem cells to make the cell types needed.

That’s right, we need more human stem cell research. If you need a new lung, and we’re going to have to reengineer one for you in a dish, we’ll need a population of autologous cells — cells from you — to reseed an acellular matrix taken from a cadaver or a pig with lung tissue that won’t trigger an immune response.

This is a long way from being useful for humans, with two big problems still facing us, refinement of the tissue-engineering technique to produce more reliable and complete membranes, and the all-important stem cell research to allow us to create sources of immunologically-compatible cells, but the cool thing is that the questions that need to be answered are in crystal-clear focus, and there are strategies to get us the answers. Time and money and a less restrictive regulatory environment for stem cell work is all that is needed.

Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, Gavrilov K, Yi T, Zhuang ZW, Breuer C, Herzog E, Niklason LE (2010) Tissue-engineered lungs for in vivo implantation. Science 329(5991):538-41.

Excellent interview with Craig Venter

Spiegel has a wonderful interview with Venter. The more I hear from Venter, the more I like him; he’s very much a no-BS sort of fellow. He’s the guy who really drove the human genome project to completion, and he’s entirely open about explaining that its medical significance was grossly overstated.

SPIEGEL: So the significance of the genome isn’t so great after all?

Venter: Not at all. I can tell you from my own experience. I put my own genome on the Internet. People had the notion this was the scariest thing out there. But what happened? Nothing.

There really was a lot of hysteria in the early days about how the insurance companies would abuse the information in the genome, and there was also the GATTACA dystopia. None of it has, and I daresay none of it will, come to pass.

Venter: That’s what you say. And what else have I learned from my genome? Very little. We couldn’t even be certain from my genome what my eye color was. Isn’t that sad? Everyone was looking for miracle ‘yes/no’ answers in the genome. “Yes, you’ll have cancer.” Or “No, you won’t have cancer.” But that’s just not the way it is.

SPIEGEL: So the Human Genome Project has had very little medical benefits so far?

Venter: Close to zero to put it precisely.

SPIEGEL: Did it at least provide us with some new knowledge?

Venter: It certainly has. Eleven years ago, we didn’t even know how many genes humans have. Many estimated that number at 100,000, and some went as high as 300,000. We made a lot of enemies when we claimed that there appeared to be considerably fewer — probably closer to the neighborhood of 40,000! And then we found out that there are only half as many. I was just in Stockholm for the 200th anniversary of the Karolinska Institute. The first presentation was about the many achievements the decoding of the genome has brought. Then I spoke and said that this century will be remembered for how little, and not how much, happened in this field.

Hmmm…I seem to recall that Venter’s company was one that was trying to patent an inflated number of genes, which contradicts what he’s claiming here. But otherwise, yes, the HGP isn’t yet a source of useful medical information, but it’s a trove of scientific information; I’d also add that the technology race put a lot of useful techniques in our hands.

Venter: Exactly. Why did people think there were so many human genes? It’s because they thought there was going to be one gene for each human trait. And if you want to cure greed, you change the greed gene, right? Or the envy gene, which is probably far more dangerous. But it turns out that we’re pretty complex. If you want to find out why someone gets Alzheimer’s or cancer, then it is not enough to look at one gene. To do so, we have to have the whole picture. It’s like saying you want to explore Valencia and the only thing you can see is this table. You see a little rust, but that tells you nothing about Valencia other than that the air is maybe salty. That’s where we are with the genome. We know nothing.

Exactly! Traits are products of overlapping networks of genes. Venter also explains that a lot of the effects of genes are developmental, so you can’t expect to be able to take a pill to correct something that went wrong in the assembly process in the embryo.

Here’s my favorite exchange from the interview.

Venter: Yes, and I find them frightening. I can read your genome, you know? Nobody’s been able to do that in history before. But that is not about God-like powers, it’s about scientific power. The real problem is that the understanding of science in our society is so shallow. In the future, if we want to have enough water, enough food and enough energy without totally destroying our planet, then we will have to be dependent on good science.

SPIEGEL: Some scientist don’t rule out a belief in God. Francis Collins, for example …

Venter: … That’s his issue to reconcile, not mine. For me, it’s either faith or science – you can’t have both.

SPIEGEL: So you don’t consider Collins to be a true scientist?

Venter: Let’s just say he’s a government administrator.

Oh, snap.