Respectful Insolence

Creationists muscling in on my territory

i-0f2bd71cb060209b3a5ad68e39430ab2-060720_eyegraphic_hsmall_1p.widec.jpgAlright, now they’ve gone too far.

I thought I’d seen every specious and fallacious argument and example that creationists could throw out there to annoy scientists and be gobbled up by the credulous, but I was wrong. They’re muscling in on my turf now! No, they’re not making fallacious arguments about how chemotherapy resistance says nothing about evolution. Been there, done that, and I doubt I’d bother if I were to see yet another such post. No, they’re not twist the fact that cancer is often due to mutations in oncogenes and tumor suppressors regulating cell growth and differentiation as “evidence” that all mutations are harmful. Again, been there, done that. Seeing more of the same would provoke a big yawn.

No, Tom Magnuson and Australian creationist Stephen Jones are taking a fascinating new paper that shows how angiogenesis (the growth of new blood vessels) is regulated in the cornea and trying to hold it up as evidence against evolution and for “intelligent design.” This is the very same paper that Bora mentioned last week.

The focus of my laboratory happens to be tumor angiogenesis. My NIH funding is to study angiogenesis. I’ve worked on tumor angiogenesis since 1997. I can’t stand idly by while creationists hold up such a fascinating finding in angiogenesis research and misrepresent it as evidence against evolution. I”m guessing that you all know what that means.

Yes, friends, it’s time to apply some Respectful Insolence™ and school me a couple of creationists!

But first, I should give a brief primer on what angiogenesis is. In short, angiogenesis is the growth of new blood vessels from preexisting blood vessels. It is a normal physiological process that occurs during wound healing, the changes in the lining of the uterous during the menstrual cycle, embryonic and fetal development, and inflammation. Tumors hijack this process in order to feed their need for oxygen and nutrients. They have to; the diffusion of nutrients and oxygen is limited to only around 1 mm in aqueous solution. Without angiogenesis, tumors can only grow to a diameter of less than 2 mm.

i-565c2a3a068622664f4a3f83eba4304e-Angiogenesis.jpg

Tumors induce angiogenesis by a variety of strategies, but most commonly they secrete large amounts of factors, usually small proteins, that stimulate the endothelial cells (cells that line blood vessels) to invade the basement membrane upon which they sit, migrate towards the stimulus, form tubes, and finally form functional blood vessels. The most common and studied of these factors belong to the vascular endothelial growth factor (VEGF) family. Usually, tumor vessels tend to be tortuous and “leaky,” and indeed the original name for VEGF was vascular permeability factor, because of its ability to increase the leakiness of blood vessels.

My interest in this field developed when Judah Folkman discovered endogenous and powerful peptides that can block angiogenesis, in particular angiostatin and endostatin. You may recall the hype in the popular press from around 1998, when Folkman reported being able to produce remarkable degrees of shrinkage in tumors in mice using these compounds, even to the point of shrinking them to a tiny ball of cells that would not grow, a state he referred to as “tumor dormancy.” These cells could be stimulatd to form tumors again, but the concept (and the dream) was to use antiangiogenic therapy to turn cancer into a chronic disease, manageable by repeated doses of these agents. Obviously, the dream is yet to be realized, because, as is the case with many breakthroughs in cancer therapy, translating these mouse results to humans was not as straightforward. As Folkman would say, “If you’re a mouse and you’ve got cancer, we can cure you.” Even so, the results of this research have produced anti-VEGF antibodies, such as Avastin, and several clinical studies have shown a significant improval of survival in advanced cancers when Avastin is added to chemotherapy, and the addition of antiangiogenic therapy can improve the efficacy of radiation therapy as well.

i-6c6972aabf1d8638e0bda14fa04b0573-tum.gifCancer is not the only disease, however, in which there is too much angiogenesis or disordered angiogenesis. The study of angiogenesis is particularly relevant to the eye. Diabetic retinopathy, for instance, is thought to be due to disordered angiogenesis, and the latest treatment for macular degeneration is based on Avastin. Angiogenesis is also relevant to the cornea, but in a negative way. The cornea is one of the few parts of the body that is kept avascular. (Cartilage is another.) It’s not too hard to figure out that blood vessels growing into the cornea would be a disaster for visual acuity, and the reason that the cornea is so crystal clear is precisely because there are no blood vessels within it. Diseases such as trachoma and herpetic karatitis can result in the vascularization of the cornea and outright blindness. Indeed, in extreme cases, in the early days of extended wear contact lenses, corneal vascularization could result from the hypoxia caused by the relatively poor gas exchange these lenses had. (Hypoxia is the major physiologic trigger to induce angiogenesis.)

The mechanism by which the cornea remained avascular, however, has remained largely a mystery–until now. We’ve known for a long time that its avascularity has something to do with the corneal epithelial cells (the cells covering the cornea), because de-epithelialization of the cornea can result in unwanted angiogenesis, as inflammation begins and the cornea heals. As the paper states:

Because of its lack of vascularity, the cornea has served as the principal in vivo model system for studying vasculogenic processes, specifically corneal hemangiogenesis (CHA) and more recently lymphangiogenesis. However, the mechanisms underlying maintenance of corneal avascularity remain poorly understood. Several angiogenic growth factors, especially of the VEGF family, have been implicated in mediating corneal angiogenesis. As a potential counterbalance, several antiangiogenic factors including thrombospondins 1 and 2, endostatin, pigment epithelium-derived factor, and tissue inhibitor of metalloproteinases have been identified in the cornea. In addition, soluble VEGF receptor 1 (VEGFR1) (interacting with VEGF-A) is thought to be involved in corneal avascularity. However, to date, no single factor has been identified as being critically responsible for maintaining corneal avascularity.

So, what did the investigators find and how did these creationists twist it to “demonstrate” that the cornea was “designed”? First let’s describe the researcher’s findings (from the best summary I could find a news report, so as not to subject you to more scientific jargon, such as in the above passage):

In most other tissues of the body, blood vessel growth or angiogenesis occurs in response to a need for increased blood flow to heal an injured or infected area. The immune system sends in growth factors such as vascular endothelial growth factor (VEGF) to bind with a protein receptor called VEGFR-2 on blood vessels to trigger vessel growth. Three forms of VEGF–A, C, and D–bind with this receptor. Two of them, C and D also bind with VEGFR-3, which is usually found on cells lining lymphatic vessels, to stimulate the growth of lymphatic vessels.

Dana’s team began to suspect the involvement of VEGFR-3 in stopping blood growth in corneas when they noticed unexpectedly that large amounts of the protein seemed to exist naturally on healthy corneal epithelium, a previously unknown location for the receptor. Dana and his team were already aware from clinical experience that the epithelium most likely played a role in suppressing blood vessel growth on the cornea, having witnessed blood vessels develop on corneas stripped of their epithelial layers.

They began to theorize that the large amounts of VEGFR-3, in this new, non-vascular location, might be attracting and sucking up all the C and D VEGF growth factors, thereby blocking them from binding with VEGFR-2. And, because this binding took place in a non-vascular setting, the growth factors were neutralized.

To test their theory, the team conducted a series of experiments.

Using corneal tissue from mice, the team did the following.

They conducted chemical analyses that demonstrated that VEFGR-3 and the gene that expressed it were indeed present on the corneal epithelium. Next, in two separate experiments, they compared corneas with and without epithelial layers that were injured. They found that only the corneas without epithelial layers developed blood vessels, implicating the role of the epithelium in suppressing blood vessel growth To further prove their theory, they added a VEGFR-3 substitute to corneas stripped of their epithelial layers and found that vessel growth continued to be suppressed, replacing the normal anti-angiogenic role of the epithelium. Finally they exposed intact corneas to an agent that blocked VEGFR-3 and found that blood vessels began to grow, formally demonstrating that the corneal epithelium is key to suppression of blood vessels and that the key mechanism is expression of VEGFR-3.

“The results from this series of tests, confirmed our belief that the presence of VEGFR-3 is the major factor in preventing blood vessel formation in the cornea,” says Dana, who says that the discovery will have a far reaching impact on the development of new therapies for eye and other diseases.

“Drugs designed to manipulate the levels of this protein could heal corneas that have undergone severe trauma or help shrink tumors fed by rapidly growing abnormal blood vessels,” he says. “In fact, the next step in our work is exactly this.”

This is some pretty elegant work that provides convincing evidence that the VEGFR-3 “sink” prevents corneal angiogenesis. Not only does this study elucidate what appears to be the major mechanism by which the cornea maintains its avascularity but it it also suggests possible therapies for diseases that cause corneal vascularization and blindness. I could quibble with the reporter using the word “theorize” instead of “hypothesize,” but overall the above passage is a pretty succinct summary of what the researchers did.

So how did Jones try to represent this as “evidence” for “design” and against Darwin? By a little quote mining coupled with a strawman. First the quote-mining:

[The PNAS paper says that "Transparency of the cornea, the window of the eye, is a prerequisite for vision" (my emphasis):

"Transparency of the cornea, the window of the eye, is a prerequisite for vision. Angiogenesis into the normally avascular cornea is incompatible with good vision and, therefore, the cornea is one of the few tissues in the human body where avascularity is actively maintained. Here, we provide evidence for a critical mechanism contributing to corneal avascularity. VEGF receptor, normally present on lymphatic and proliferating blood vascular endothelium, is strongly constitutively expressed by corneal epithelium and is mechanistically responsible for suppressing inflammatory corneal angiogenesis." (Cursiefen, C., et al., "Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision," PNAS USA, July 18, 2006)

If they mean that literally, and what we were told in my biology degree classes is that scientific journal papers these days go through extensive checking, editing and rewriting, which can take many months, so I assume that they do mean that literally. That is, the cornea would have to be free of blood vessels from the beginning...

Jones took the above quote from the abstract alone, which is meant to be a very brief summary of the article and ran with one sentence as "evidence" that avascularity of the cornea is a "rerequisite" for all vision from the beginning. Not only is he stretching that sentence beyond what the authors could possibly mean, but his faith in the editorial process of scientific papers is touching. He also uses that single sentence to construct a straw man. If he had bothered to read the paper itself, it would have been clear that the authors clearly meant no such broad statement, as can be seen here:

The posterior structures of the eye, such as the choroid, are among the most heavily vascularized tissues. Yet ocular vascularity abruptly comes to an end at the cornea, the normally avascular and transparent ''window'' of the eye, which also serves as its main optical surface (Fig. 6, which is published as supporting information on the PNAS web site). Indeed, corneal clarity is critical for vision and is actively maintained in all animal species that require high visual acuity. Conversely, blood vessel growth into the cornea is incompatible with good vision and is associated with the leading causes of corneal blindness both worldwide (trachoma) and in industrialized nations (herpetic keratitis).

Note the qualification: The clarity of the cornea is critical "in all animal species that require high visual acuity." The authors say nothing whatsoever about the eye requiring an avascular cornea "from the beginning," just that such clarity is necessary in certain species. That it is necessary in (apparently all eyes) "from the beginning" is Jones' strained interpretation from a single sentence in the abstract! But he's not through. Jones blunders on to cite Dawkins:

...and so could not progress through a Darwinian "6 per cent is better than 5, 7 per cent better than 6, and so on up the gradual, continuous series"

This is the Dawkins passage to which he is referring:

"In a primitive world where some creatures had no eyes at all and others had lensless eyes, the ones with lensless eyes would have all sorts of advantages. And there is a continuous series of Xs, such that each tiny improvement in sharpness of image, from swimming blur to perfect human vision, plausibly increases the organism's chances of surviving. The book [Hitching F., "The Neck of the Giraffe," Pan: London, 1982, p.103)] goes on to quote Stephen Jay Gould, the noted Harvard palaeontologist, as saying: `We avoid the excellent question, What good is 5 percent of an eye? by arguing that the possessor of such an incipient structure did not use it for sight.’ [Gould S.J., “Ever Since Darwin,” Penguin: London, 1978, p.107) An ancient animal with 5 per cent of an eye might indeed have used it for something other than sight, but it seems to me at least as likely that it used it for 5 per cent vision. And actually I don’t think it is an excellent question. Vision that is 5 per cent as good as yours or mine is very much worth having in comparison with no vision at all. So is 1 per cent vision better than total blindness. And 6 per cent is better than 5, 7 per cent better than 6, and so on up the gradual, continuous series.” (Dawkins R., “The Blind Watchmaker,” Norton: New York, 1986, p.81)

Note that it is Jones’ assumption based on a single sentence, not anything in the findings in the PNAS paper, that corneal vascularization couldn’t conceivably go through a similar set of steps in development, but towards fewer and fewer corneal blood vessels. Nothing in this study suggests that an early light detector or eye couldn’t have evolved so that at each successive stage, there were slightly fewer blood vessels in the early cornea, with slightly better visual acuity, producing a slight advantage in survival and reproduction, ultimately leading to this beautiful, amazing avascular cornea, much as in Dawkin’s explanation above could explain how the eye itself could evolve from successive small steps.

Does this mean that’s how the cornea evolved? Of course not. It’s simply one conceivable (and probably the most likely) mechanism by which the cornea might have evolved by natural selection, just as Dawkins’ example is a mechanism by which the eye might have evolved by natural selection. It’s an example to show that the example of the complex structure of the eye is not a “mortal” blow against evolution. Far from it. Nor did Darwin “shudder and feel cold when he considered the eye,” as Magnuson put it. In fact, Darwin himself postulated a mechanism by which a complex structure like the eye might have evolved in small steps.

Jones’ argument is no more than old creationist canards about the development of the eye “disproving evolution” tarted up using a sexy new experimental finding about the vascularization of the cornea. It is, at its core, an argument from incredulity, a “God of the gaps” cop-out. Just because Jones can’t envision how an avascular cornea could possibly evolve by successive tiny alterations doesn’t mean that there isn’t a plausible mechanism in evolution by which it could have. The use of this example is lame, even by “intelligent design” creationist standards.

I wonder what the authors of the study would say if they knew their work was being misrepresented as “evidence” for “design.”

Comments

  1. #1 beth
    July 25, 2006

    Thanks for a very interesting article–of course you are right.

    As someone who just had abdominal surgery to remove what truns out to be a benign tumor, I hope your research helps bring about new treatments other than surgery–which seems to be a barbaric and rather crude “treatment”.

    Progress in medicine aren’t helped by the creationists and IDers who villify scientific thinking and scientists as immoral materialists.

  2. #2 beth
    July 25, 2006

    Correction, should read:

    “Progress isn’t helped by the creationists and IDers who villify scientific thinking and scientists as immoral materialists.”

  3. #3 pough
    July 25, 2006

    I wonder what the authors of the study would say if they knew their work was being misrepresented as “evidence” for “design.”

    If only they had such a thing as an Internet – with email – you could let them know!

  4. #4 Deacon Barry
    July 25, 2006

    Vascularisation of the cornea is called a pterygium.
    It’s great to see a post with a picture of an eye – more please! Though I think your picture shows a pretty severe retinal detachment.
    Are there no depths to which christians will not stoop, to push forward their creationist agenda? Is this a new tactic, to go through every scientific paper, looking for those fragments of sentences that can be taken out of context to suggest that goddidit?

    Ophthalmology rocks!

  5. #5 Bronze Dog
    July 25, 2006

    Hi-ho, hi-ho! It’s off to quote mine we go!

  6. #6 Deacon Barry
    July 25, 2006

    Creationist capers, in biology papers
    Hi ho, hi ho hi ho…

  7. #7 Sid Schwab
    July 25, 2006

    another Oracian post of excellence. Wasted, no doubt, on those who need most to read it. But elegant and highly worthwhile,

    One of my training-mates did a fellowship with Folkman, so I’ve had a sort of heads-up on angiogenesis for a long time. Interesting to see it get highjacked in such a way. It’s that sort of juxtaposition of actual science and ex-recto ideation that bamboozles so many people.

  8. #8 MartinM
    July 25, 2006

    Is this a new tactic, to go through every scientific paper, looking for those fragments of sentences that can be taken out of context to suggest that goddidit?

    No. They’ve been doing that for ages.

  9. #9 Dr. Steve
    July 25, 2006

    I believe a pterygium is a proliferation of the conjunctiva overlying the sclera.

  10. #10 beajerry
    July 25, 2006

    One great thing about this information age is that quote mining is easier to expose.

    Just think, 15 years ago someone could quote mine a scientific paper and it would be fairly difficult to expose that, not to mention it would also take a long time to do so.

    The BooYaa! is now almost instantaneous.

  11. #11 trrll
    July 25, 2006

    Here is a simple experiment that anybody can do to demonstrate the utter stupidity of the creationist argument. Go outside during the day. Close your eyes. Now have a friend pass his hand in front of your eyes. Can you tell when his hand is in front of your eyes? Congratulations! You have vision–through your eyelids, which happen to be a vascularized tissue. Not much visual acuity, to be sure, but vision, nonetheless.

    What use is low acuity vision? Telling day from night (useful if a dangerous predator hunts at one time or the other; also useful for regularizing biological rhythms). Telling direction from the sun or the moon. Telling up from down (useful if you are a fish). Detecting large obstacles in your path. And all of those are functions that would be improved if there was just a little bit less vasculature in the tissues between your retina and the outside world.

  12. #12 juliamd
    July 25, 2006

    Wow, Judah Folkman – he gave a keynote address at PriMed last year – what an amazing speaker and soooo smart. Angiogenesis really seems to be the way to go in terms of growth factors and inhibitors. Keep plugging and good luck on grants!!

  13. #13 Scenedesmeriffic
    July 25, 2006

    Very good point, tril!

  14. #14 Chris
    July 25, 2006

    Something that puzzles me about the original research:

    They conducted chemical analyses that demonstrated that VEFGR-3 and the gene that expressed it were indeed present on the corneal epithelium.

    Aren’t the corneal epithelial cells normal nucleated cells that contain the complete diploid genotype of the organism? What does it mean to say that “the gene that expressed” VEFGR-3 was “indeed present”?

    The only guess I can come up with is that this is a very poorly expressed way of saying that they found _mRNA_ coding for VEFGR-3, indicating that the VEFGR-3 gene was being actively transcribed in corneal epithelial cells. (Since this is from a news report, not the actual paper, I’m inclined to suspect the news reporter of the inaccurate description.) But I can’t think of any way that it would be surprising to find that the gene was _present_ in any nucleated cell.

    Anyway, it’s completely plausible (to me, at least) that the early eye was covered with _skin_ and the skin gradually became more specialized until it became a corneal epithelium.

    This would, of course, have been long before the origin of the vertebrates, which are descended from a common ancestor that already posessed reasonably good eyes. Not to say they weren’t further improved on and re-adapted for operation in air, but the creationist caricature of an eyeless monkey, squirrel or mouse trying to “develop” the eye is clearly wrong. Eyes are much older than that.

    Even an eye with skin over it is better than no eye at all – anyone who’s ever shone a flashlight through their hand or been outside on a sunny day with their eyes closed knows that some light will get through a moderate thickness of skin or muscle. And even without the capacity to form an image, you can tell when something just moved to cast a shadow on you.

  15. #15 Graculus
    July 25, 2006

    The BooYaa! is now almost instantaneous.

    Unless the quote is mined from a pre-’net paper that some helpful soul hasn’t yet transcribed. Not everything is online… yet.

  16. #16 EoR
    July 26, 2006

    A creationist in EoR’s backyard. And he thought they only festered in the US. Oh, the shame of it all…

  17. #17 Ronald Brak
    July 26, 2006

    I’ll just mention that unless he says life was created by ancestor spirits in the Dreamtime, he’s not an Australian Creationist, he’s just a Johnny come lately Middle-Eastern creationist.

  18. #18 Duplex
    September 11, 2007

    You know it’s great the generalizations I see from some of the comments and about “Christians.” No one can say evolution isn’t a natural mechanism given to us in order to survive a changing world by God, I know you all may not believe and there have and probably always will be Christians with major agenda’s and miss guided ideals but to rule what we believe completely out when science cannot state clearly why we’re here other than to say; oh big bang…, M-Theory…, evolution…, and just plain guessing is pretty stupid to say the absolute least. Quite honestly why can’t their be a divine plan and creator? For every action there is an equal and opposite reaction, why can science not equate that out when coming up with a theory for the universe forming why does it always have to be something like the big bang… I ask, why did it happen? So with that in mind Christianity is just as right as science and just like science it has it’s short bus section of crazy’s and loons. If you quote our loonies why not quote some of the more difficult arguments and bring those down…? Probably to much of a “yawn”?

    I thought it was stupid the way you act better than “Creationists/Christians” with that comment btw, quite juvenile.

  19. #19 Duplex
    September 11, 2007

    You know it’s great the generalizations I see from some of the comments and about “Christians.” No one can say evolution isn’t a natural mechanism given to us in order to survive a changing world by God, I know you all may not believe and there have and probably always will be Christians with major agenda’s and miss guided ideals but to rule what we believe completely out when science cannot state clearly why we’re here other than to say; oh big bang…, M-Theory…, evolution…, and just plain guessing is pretty stupid to say the absolute least. Quite honestly why can’t their be a divine plan and creator? For every action there is an equal and opposite reaction, why can science not equate that out when coming up with a theory for the universe forming why does it always have to be something like the big bang… I ask, why did it happen? So with that in mind Christianity is just as right as science and just like science it has it’s short bus section of crazy’s and loons. If you quote our loonies why not quote some of the more difficult arguments and bring those down…? Probably to much of a “yawn”?

    I thought it was stupid the way you act better than “Creationists/Christians” with that comment btw, quite juvenile.

  20. #20 Duplex
    September 11, 2007

    Site errored sorry double comment…