Her defense looks pretty sound to me. But I’m just a layperson. Perhaps I missed something.
I skimmed it, and found it to be a longwinded response to unlinked and unreferenced “critics,” focused largely on details or how an online tool works. To be “pretty sound,” to me, it would need to link to the critiques, explain what those critiques asserted, then discuss whether and how those critiques are wrong or are unclear. This piece mostly aims to nuance Behe’s overall claim and to defend that.
Re the APOB story, it’s a really interesting story and we don’t know how it ends. At this point it seems clear that the APOB variants were strongly positively selected in polar bears. Gauger and others are completely correct in noting that this implies nothing about whether the variants represent gains of function, or losses of function, or changes in function. Any of those could explain why the mutations were fixed in that lineage. The debate, then, is about whether the current evidence points in any particular direction on that compass. And that debate will not be settled, or even advanced, by talking about what PolyPhen-2 does. (In fact, I agree with Richard Lenski about what PolyPhen-2 can and can’t do. And lookie there, I just linked to a critic who is almost certainly one of the experts Gauger is answering.)
But the more interesting discussion should be about what we know about APOB, so far, from studies in mice and humans. Nathan Lents summarizes this, and shows how Behe presented a rebuttal to the original critique. I don’t think Gauger rescues Behe’s argument at all. And she doesn’t even address (unless I missed it) the serious concerns about how Behe presented findings from the Cell paper. Leaving all of that aside, there is this fact about our current knowledge: we don’t know the functional ramifications of the mutations in the polar bear APOB. Behe argues that we have pretty good reason to postulate that they are “damaging.” His case is substantially weakened by the data that Lents references, but his argument has not been disproven. Contrary to Gauger’s apparent claim, a basic test of the hypothesis would not require darting polar bears or making new animal models. It could be simpler than that.
There really is no need for Gauger to link to the sources. The question is how to interpret the Liu paper. She makes clear that it is referring to damages to genes, not to phenotypes.
I disagree. Gauger’s well-reasoned argument is that the evidence of PolyPhen-2 does point in a particular direction: that APOB has indeed probably sustained damaging mutations.
Yes, you don’t mind linking to Lenski’s article. But you don’t link to Behe’s reply:
Since you like skimming, I quoted Behe at length here, but the moderator thought there might be copyright problems and edited it out. Behe provided an extended rebuttal as to why it’s likely the mutations in APOB were damaging. But I doubt you’ll take the time to read it.
As to Lents, he assumes that the mutations must be listed as probably damaging in both lists before it should be considered probably damaging. However, as both Gauger and others have stated, that is not how it should be interpreted. Rather, if a mutation is listed as probably damaging in either list, then it is probably damaging.
Two posts have been deleted. Discussion not bickering, please.
Bilbo, the full name for the tool is “Polymorphism Phenotyping version 2”. It seems similar inventing a “hammer version 2” and someone saying “no, the purpose of the tool is not hammering”.
The responses of Gauger and Behe to these critiques have made their hypothesis/suggestion look worse. Once you learn about what PolyPhen-2 does, it’s easy to see that it can’t stand alone as a test for “damage” to a gene. It was one place, one way, to look at how the mutations might have affected the protein. We have other data that makes it seem a lot less likely (to me) that the mutations in APOB reduce or eliminate its function. Behe is right that the phenotype of the heterozygous nulls shows that reducing APOB dosage/function can be protective in a high-fat diet situation. But the fact that human mutations so frequently lead to metabolic disease is a problem for the “damage-as-adaptation” hypothesis, and the clustering of the mutations in regions of interest for lipid transport is suggestive of changes (not just losses) in function.
Again: we don’t know the functional relevance of the APOB mutations, but we won’t nail them down using PolyPhen-2. I think Behe is wrong on this one, but his suggestion is plausible and testable.
The problem I have with all of this is that all of these arguments by the writers at evolution news… why aren’t they publishing in scientific journals? That seems to be the case for all anti-science writers that are out there where they are entirely able to critique all kinds of scientific publications because they know better than the people who did x, y or z study. Yet at the same time they never participate in the studies themselves, nor provide substantial experimental evidence for their hypothesis- just cherry pick scientific literature to make it say whatever one wants it to.
From their website:
“PolyPhen-2 (Polymorphism Phenotyping v2) is a software tool which predicts possible impact of amino acid substitutions on the structure and function of human proteins using straightforward physical and evolutionary comparative considerations.”
In other words, the tool is not trying to predict impact on phenotype. It is trying to predict impact on “structure and function of human proteins.” And it concludes that some of the amino acid substitutions in APOB in polar bears would probably be damaging on the structure and function of that protein.
The issue is that a tool like polyphen can only tell you whether a change is likely to disrupt the existing function of a protein; it can’t tell you whether the disruption leads to a slightly different function.
I’ll just quote one paragraph of Behe’s reply to Lenski and hope the moderators don’t delete it:
“Just to be extra clear about the relevance of the mouse results to the interpretation of the polar bear genome, let me state my reasoning explicitly. Given the experimental results with mice, it is most parsimonious to think APOB is broken or blunted in polar bears. For mice, having only half as much APOB activity protects them from a high fat diet. For polar bears, having mutated APOB genes protects them from a high fat diet. If those polar bear mutations decreased the activity of APOB by half or more, then we might expect a similar protective effect as was seen in the mouse. Given that computer analysis also estimated the APOB mutations in the polar bear as likely to be damaging, it is most reasonable to think the activity of the protein has been blunted by the mutations.”
What’s interesting is that mutations in APOB can lead to either hypercholesterolemia or hypocholesterolemia. One of the purposes of LDL is to ward off bacterial infections. I suspect that the hypo version would be more tolerable in colder regions, where bacteria have more difficulty breeding. If my hunch is correct, we could see how the mutations would still be damaging, but more adaptive for mammals living in polar regions.
Hmmm…I think the charge of “cherry picking” is unfair. Behe is basing his argument on an exhaustive review of lab experiments that resulted in adaptive changes.
Meanwhile, since there is no direct evidence of a designer, ID proponents are forced to use inference for unseen designers, similar to SETI. Of course, scientists often use inference to unseen things. At the moment, dark matter and dark energy are two good examples.
It claims to tell you whether the mutation is likely to be damaging or not to a protein. Whether that results in a different function is something everyone, critics and proponents of ID, agrees needs to be studied further.
What gives anyone the impression that ‘the moderators’ would delete it?
I don’t know how else to say it, but that statement is dead wrong.
This is true. One of the easiest ways to predict a phenotypic change is to first look at the underlying biochemistry. But that does not change the fact that the tool is, in fact, designed to predict phenotypic change. If you doubt it, check with the people that wrote the software for “Polymorphism Phenotyping - Version 2”.
As @glipsnort has stated, the program will only predict if a mutation is likely to produce phenotypic change. It is unable to distinguish between a “positive” or “negative” change at the biochemical level (despite the nomenclature). Therefore, it is being misused as evidence for Behe’s “First Rule”.
The persecution complex is strong with this one.
Again this is not some kind of experimental work (albeit useful) but rather a summary of what other people have done on the topic. But such evolutionary experiments don’t exactly mimic what we see in nature with the integration of genetic material from other organisms occurring quite frequently in bacteria and also in eukaryotes (i.e. with ERV insertions and subsequent exaptation).
Except with SETI we are looking for signals that are like what human beings would do. And then the conclusion would be intelligent life like human beings made this signal. That has nothing to do with what a deity would do and any SETI signal cannot be extrapolated to the existence of any deity.
Except that we have mathematics to describe dark matter and dark energy. There can be specific calculations and measurements of these, which again, is nothing like ‘detecting a supernatural being who just so happens to be the God of the Bible as understood by Christians.’
There’s no persecution complex. We deleted a quote that was too long earlier in this thread because of copyright infringement concerns. The excerpt above is much shorter and fine.
I did have a student write in their analysis of the Kitzmiller v. Dover trial that the ID leaders dropped out because they were receiving death threats and thus an indication that someone was trying to suppress true knowledge. They never got back to me when I asked for sources.