Editorial Insights from a Blind Cavefish

Mexican Tetra as Blind Cave FishYou’ll be wanting to look at this screenshot. The ICR article that we’re looking at (“Blind Cavefish Shed Light on Creation,” by Brian Thomas) looks like that as I write this, but it will almost certainly have changed before you see it.

It has always been clear that the ICR has some form of editing process – the relative paucity of typos, the long publication delay, and the fact that for them to do otherwise would be unprofessional being the more obvious clues – but I’ve long been interested in learning about it. This article has been misposted in an annotated draft form, and provides clues I never thought I’d see. My sincere thanks, then, to whoever made the mistake, and I hope nobody gets annoyed with you for it.

Let’s work through it:

Blurb: How do seeing fish make the remarkable transformation to blind cavefish, and should that process really be called “evolution”?

This line – which will be repeated in a modified form as the first sentence of the article proper – will almost certainly be the text given when it appears in the RSS feed and other places like the main page.

The subject of the research, so that everyone is on the same page, is the evolution of blind Mexican tetra, a species of fish with both eyeless and sighted forms. The “classical” hypothesis that would be put forward in this situation is that when tetra encountered dark caves their eyes were detrimental to the point of uselessness, and therefore eye-related mutations would freely accumlate in their descendants to the point where they would disappear entirely. But this would take a while, so the researchers were investigating whether there were any other aspects to the system that would speed it up.

They found, through a series of experiments that I wont detail, that in the conditions of the caves where the fish live the protein HSP90 is depleted. The result of this is that considerable pre-existing (“cryptic”) variation in the size of eyes is revealed in the tetra raised in these conditions, the upshot of which is that the early stages of mutation accumulation can be outright bypassed. The paper abstract says:

This variation [...] can be selected for, ultimately yielding a reduced-eye phenotype even in the presence of full HSP90 activity.

(See Ed Yong’s blog post for a better explanation than you’re going to get here.) This is being sold in both the Whitehead Institute and the Marine Biological Laboratory (MBL) press releases as an “alternative mechanism for evolutionary change,” which might be a poor choice of words though it is undeniably an important discovery. Thomas’ complaint is along these lines, in that he doesn’t think it even counts as evolution at all. We’ll get to that a little later, but we’ve got a few more lines to go before we even make it to the article.

Image: Mexican blind tetra. Susan has had trouble finding these. Can we use the same images as Whitehead Inst? http://wi.mit.edu/news/archive/2013/rapi

Wiki image: http://en.wikipedia.org/wiki/File:Mexica

Presumably these are suggestions for the header image they used. The (uncredited) picture they settled on is present in the MBL release (which does give the source), and the wikimedia image is the not-so-great photo I’ve used myself above. “Susan” here is almost certainly Susan Windsor, who does many of the ICR’s nice images and graphics.

There are a couple more lines here which restate the breadcrumbs and title etc, and then we get to the first paragraph of the article:

How do seeing fish make the switch to blind cavefish, and should that process really be called “evolution?” This transformation fascinates biologists—picture the scene—a normal-looking fish lays normal-looking eggs, but its hatchlings look like something from science fiction. Thin, pale-pink skin covers not just their bodies but their shrunken eye sockets as well.

There are no annotations here, but I must say that this is a little muddled. It’s also inaccurate: fully sighted fish do not give birth to blind fish as if some switch had been pulled, but to fish with a variety of different eye sizes which natural selection can operate on.

MIT biology professor Susan Lindquist [CS1] led a project group [CS2] in testing the role of a protein called “HSP90”—no, it’s not a workout video—in developing Mexican tetra (also known as blind cavefish) embryos.1[CS3]  [CS4]

This second paragraph has a bunch of notes. There are two types of annotation references used over the article: the more numerous [CS#] and the rarer [MS#]. I’m going to refer to the people that made them as CS and MS respectively, as they are definitely different people (they conflict later in the article) and probably represent initials or titles. CS’s first item is:

[CS1]Brian, she is not the last author listed in the credits. Just want to confirm she was the lead?

Lindquist is not the lead author here – the first author is Nicolas Rohner and the last is Clifford J. Tabin, both from Harvard – but she does lead the Whitehead Institute laboratory that the Whitehead Institute press release is highlighting in the press release that Thomas is using. Lindquist’s research was of crucial importance, and Thomas is not incorrect in what he says, but she is neither the last nor the lead author of a paper that has more to it than simply her work.

 [CS2]Trying to find a different use of wording other than “team of researchers” so we can use that later…

What this implies is that CS has replaced the perfectly accurate “team of researchers” to the “project group” seen in this version so as to avoid using it twice, although there is no actual second use of the phrase. If I were Thomas I’d appeal, as “project group” is not a good alternative by any means. What this example tells us is that this is not merely a first draft that has been annotated, but that some editing has already been done by people other than Thomas.

 [CS3]Need to document the first mention of study—can you confirm this is the right footnote?

Presumably this is asking for a confirmation that this is the first footnote, or somesuch. The footnote itself, in this draft, reads:

1. Rohner, N. et al., 2013. Cryptic Variation in Morphological Evolution: HSP90 as a Capacitor for Loss of Eyes in Cavefish. Science. 342 (6164): 1372-1375. [http://www.sciencemag.org/content/342/6

Normally the ICR does not provide hyperlinks to web versions of papers. I suspect, based on this, that they are often provided by Thomas but edited out because they lead, as in this case, to a paywall. Here’s another link to the abstract, but unfortunately I can’t find a public pdf link so you can properly stick it to the Man (email me if you want it).

The final note for this paragraph says:

 [CS4]Results from these other studies are not mentioned later, so can we remove this statement?

It looks like “this statement” has in fact been removed, showing that CS is not the last person to have edited this version.

A final comment on this paragraph: what’s with the “no, it’s not a workout video” parenthetical? That sounds like one of my attempts at humour, not anything we usually see from Thomas (though I don’t know anything about workout videos). This suggests that there is significant editing yet to come. If and when the corrected version appears this will be something to note.

Moving on:

Publishing in the journal Science, the team found that environmental cues somehow communicate to HSP90 in developing fish and that the protein does indeed control genetic variation for tetra eye function and eye socket size.1

I usually leave out the citation indexes in these articles, but considering [CS3] above I’m leaving them in today. There’s not much to say about this paragraph – there are no annotations, and we already covered this stuff – but saying that “environmental cues somehow communicate to HSP90″ is probably an inaccurate understanding of the processes at play.

The researchers ran two experiments. In one, they raised tetra with a chemical in the water that suppresses HSP90 activity. In another, they raised tetra in water with low-conductivity, mimicking that of cave water[MS5] . Both tests induced essentially the same variations—a wide range in eye dimensions, even from parents with normal, average-sized eyes. Therefore, it looks like the developing fish detect water conductivity, which inhibits HSP90, while still in their eggs.1 This appears to be one of the interrelated internal mechanisms that helps generate blind cavefish traits.

The way Thomas is looking at this is as if God programmed the fish with instructions on what to do if they encountered a cave. Instead, the nature of the cave water happens to break the function of a protein which allows some cryptic variation to be expressed, some of which happens to be a useful first step in the road to eyelessness. The rest, of course, is eliminated by natural selection.

Here’s our first MS comment:

 [MS5]Did they raise them in the dark?

They do not seem to have done so – it’s not the darkness that is causing the appearance of the variation.

The study authors wrote of their results, “This strongly suggests an involvement of HSP90 in cavefish evolution and provides an actual case in nature for Waddington’s classic theory of the role of canalization in evolution.” They stated that “changes in HSP90 function can lead to changes in phenotype.”1

Waddington showed that when subjected to certain conditions, like heat or chemicals, fruit flies would develop strangely as if they had been mutated. The paper says:

Waddington proposed that developmental processes are quite robust and produce the same phenotype regardless of minor genotypic variation, a phenomenon he termed “canalization” (3). In such conditions, cryptic variation can accumulate and can be maintained without consequence. He further proposed that under certain environmental conditions, this property could be lost (“decanalization”), resulting in expression of the cryptic variation on which selection could act (4).

It goes on to say:

More recently, Lindquist demonstrated that HSP90 (heat shock protein 90) provides a molecular mechanism for buffering genetic variation and releasing it in response to environmental stress (510). The HSP90 chaperone assists in the folding of proteins that are metastable signal transducers, such as kinases, transcription factors, and ubiquitin ligases. HSP90 is normally present at much higher concentrations than needed to maintain these proteins, allowing it to act as a buffer, protecting organisms from phenotypic consequences that would otherwise be caused by genetic variants of these proteins. Because protein folding is so sensitive to environmental stress, changes in the environment can exhaust the chaperone buffer, unmasking vulnerable polymorphisms. And because multiple variants can be unmasked at the same time, this system provides a mechanism to create complex traits in a single step (11).

There’s where Lindquist’s (past) research comes in, and the true mechanism of the environmental signalling that Thomas thought was so mysterious (the protein just gets overworked).

Moving on to the next paragraph:

However, using the term “evolution” might prove as slippery as a cavefish. Textbook descriptions of evolution detail endless morphing between creature kinds through natural selection of mutants. But the sightless Mexican tetra exhibits development of helpful, cave-specific traits—not from harmful mutations but through genetic variability buffered by HSP90. For example, they acquire [CS6] heightened, non-visual, sensory capabilities like those that detect motion, chemicals, and conductivity—and their lack of sight aids these capabilities[MS7] [CS8] . Plus, multiple subpopulations of the same fish kind have generated exactly the same cave-specific features in different caves at different times, and sighted and blind varieties have even interbred.2

There’s a lot here. First, is this evolution?

Thomas has apparently got some very poor textbooks. Natural selection is but one mechanism for evolutionary change – there are others, such as genetic drift. From one way of looking at it, this “decanalization” is another mechanism of evolution, from another it has a role in evolution as the line Thomas quoted earlier says. I’m not sure how it should be best referred to, but this is a fruitless exercise in semantics nonetheless.

 [CS6]We’ve used “develop” or “development” a lot—can this be a substitute?

There are indeed a number of uses of those words in the article, and with good reason: it seems to be the best choice. CS has replaced one with “acquire,” but there’s plenty more work to do.

 [MS7]Perhaps add an explanation of how the fish’s brain redirects its focus from seeing to smelling and feeling.

MS wants to know how the fish gained these enchanced abilities, but Thomas doesn’t seem to have an explanation or even a reference to the fact that they do. The afore-linked wikipedia article on the fish, in a section entitled “Blind cave tetras and creationism,” gives a citation on this latter issue to a book called The Diversity of Fishes, but that still doesn’t mean that there is any link between the process studied and the acquisition of those characteristics.

 [CS8]I think this paragraph is already complex enough—don’t think it needs further explanation.

Here’s that disagreement I mentioned, along with proof that CS is writing after MS.

The second reference, tacked on at the end of the paragraph to back up the claim that there has been paralell evolution in the fish, is:

2. See references in: Thomas, B. Evolution Made Cavefish Go Blind? Creation Science Update. Posted on icr.org February 7, 2012, accessed December 27, 2013. [http://www.icr.org/article/evolution-ma

The references in that article are solely to a paper and its press release, which Thomas apparently did not want to cite directly for some reason. The article itself is essentially a long winded way of saying “isn’t the loss of eyes devolution, not evolution?” I said at the time that this was like arguing:

  • Cars are supposed to be able to turn right
  • This is an example of a car turning left
  • Therefore, cars do not exist

After this the annotations become more scarce, and we get into Thomas’ point:

Since the changes in these fish probably do not occur by natural selection of mutants, does  attributing them to “evolution” help explain the real, underlying biology? Mutations do not cause all changes in living things, so lumping both mutational and non-mutational causes together under one category (evolution) can be misleading. Instead, these observations align with design and built-in adaptability, not slow and gradual evolution.

He’s playing with definitions a lot here: evolution has been equated to the “natural selection of mutants,” so anything else can’t be evolution and must therefore be design. Easy, isn’t it?

The above quote also refers to canalization, an idea that Conrad Waddington—a 20th Century British geneticist, embryologist, paleontologist, and Marxist philosopher—published in 1942. The Science authors summarized his ideas, writing, “Waddington proposed that developmental processes are quite robust and produce the same phenotype [physical trait] regardless of minor genotypic [genetic] variation, a phenomenon he termed ‘canalization.’ In such conditions, cryptic [hidden for generations] variation can accumulate and can be maintained without consequence.”1

As you should remember, I’ve already quoted that passage. But there was more to it – to refresh, here is the last sentence of that paragraph:

He further proposed that under certain environmental conditions, this property could be lost (“decanalization”), resulting in expression of the cryptic variation on which selection could act.

There’s where evolution can act, and one of the experiments in this study – one of the ones that Lindquist didn’t do – showed that this works in the situation being studied:

To test whether the cryptic variation in eye size uncovered by HSP90 inhibition can be genetically assimilated, we treated a population of embryonic surface fish with Radicicol. We then selected for smaller eye size by intercrossing fish from this treated brood whose eye size was smaller than any of the untreated fish raised in parallel. The resultant F2 fish, raised in the absence of the drug, all had eyes and orbit sizes at the lower end of the range of sizes observed in the parental fish and included many individuals with eyes and orbits smaller than any seen in the untreated surface fish and comparable with the smallest of the treated fish (Fig. 3, A and B). Thus, the individuals that develop the smallest eyes in the presence of HSP90 inhibition contain alleles that can contribute to inheritance of small eye size in the absence of treatment.

But Thomas says:

In other words, Waddington recognized that creatures can overcome certain changes in their genetic makeup or environment when they generate the same useful trait variations. [MS9]

I’ve broken this paragraph in two. MS, in the last annotation for the article, says:

 [MS9]This is confusing.

I agree: it makes no sense. This may have something to do with how Thomas is determined to exclude reference to the decanalization previously mentioned, forcing him to contort his explanation.

The second part of the paragraph says:

But he may not have realized that an expert programmer must have been at the helm, writing genetic code so robust and forward-thinking that it essentially anticipates both internal and environmental challenges and steers an organism’s development around the obstacles.

There is actually a programming-related concept relevant to this issue: the jocular refrain “that’s not a bug, it’s a feature.” Mistakes in programs are “bugs,” but on occasion they are in some small way useful. In this case, as I have already mentioned, when environmental stress over-taxes the HSP90 protein it inadvertently betrays the underlying genetic variation of the fish. This happens to be a good thing for evolution, but not necessarily the fish itself – the variation is not nessisarily beneficial. The Whitehead Institute press release says:

Lindquist’s work found that the normally robust cellular reservoir of HSP90 becomes depleted during periods of physiological stress. The loss of HSP90 activity allowed phenotypic changes to emerge quite rapidly. Although some emergent traits found in her lab were not adaptive, some clearly were.

They’re mostly interested in the good stuff, but don’t let that make you forget that there is more. Thomas wants you to think that this is a divinely created mechanism to aid in non-evolutionary adaptation to new environments, but it’s certainly not a very nice one.

Here’s Thomas’ final paragraph:

Although researchers wave the flag of evolution over all this, cavefish biology rests on expert design, including a “delicate balance of protein folding,” according to a press release from the Whitehead Institute for Biomedical Research.3 By showing that specific biochemical mechanisms like variable amounts of HSP90 generate trait variations inside developing fish, these Science results fall right in line with the idea that a great Creator crafted high-tech genetic programming.

Very buggy programming, perhaps, but that’s the best you can say. For completeness, reference 3 is given as:

3. Fearer, M. Rapid Evolution of Novel Forms: Environmental Change Triggers Inborn Capacity for Adaptation. Whitehead Institute for Biomedical Research. Posted on wi.mit.edu December 12, 2013, accessed December 23, 2013. [http://wi.mit.edu/news/archive/2013/rap

I hope it wasn’t too confusing going between the actual content of the article and its editing, but it would have been quite difficult to do one without the other. I was very interested to see this work in progress – right now it’s still up, but it wont be for long. Somebody is due for a shock in the morning.

Ed #1, 08/01/14: I managed to misspell “insights” in the title as “inisights,” somehow – this is what editors are for. :D

Ed #2, 09/01/14: So they’ve fixed it now, obviously (new screenshot – also, it’s seems I screwed up linking the first one). The first two paragraphs are changed in small ways and a number of paragraphs near the end have been moved to a footnote or removed entirely. There are no substantive changes, however, so I wont go over it again.

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4 thoughts on “Editorial Insights from a Blind Cavefish

  1. Nice catch there. Interesting stuff. I think it is safe to say that that these fish that are well adapted to cave life have more than a few genetic modifications. There are many genetic modifications and many of those would be new characteristics not just degeneration of old characteristics. There has to be a number of other physiological adaptions other than loss of eyesight. Although the most obvious change (well I guess loss of pigmentation is the most obvious) these are not the most dramatic changes from a genome perspective.

  2. Noticed an interesting comment by Thomas: “But the sightless Mexican tetra exhibits development of helpful, cave-specific traits—not from harmful mutations but through genetic variability buffered by HSP90.” Why would he suggest any mutation would be “harmful”? Any time a mutation helps an organism adapt to its environment, even through the loss of a structure or function, it’s helpful, not harmful.

  3. Glen: Thomas must combine the word “mutation” with “harmful” always, it’s their religion.

    So far as we know, the underlying genetic variations are normal copying errors, although they did not produce phenotypic variation until Hsp90 was stressed. But Thomas is dishonestly trying to make it appear as if the underlying genetic variations were programmed by God himself, “a great Creator crafted high-tech genetic programming.” It is, again, random mutation, even if its effects are temporarily hidden, and it is surprisingly low-tech, and it is not programming.


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