Doug Axe supposed protein functions are rare and isolated in sequence space.
That is a scientific hypothesis.
No, that’s merely an extrapolation and a supposition that didn’t even account for mountains of extant data at the time he made it.
If Axe viewed it as a hypothesis, Axe would have bothered to test its empirical predictions more than once in the last 17 years, or at least proposed experiments that would test it.
He also would have corrected others in the ID movement who routinely state his unwarranted supposition as simple fact, even today.
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It was a hypothesis most us think is inconsistent with the data, and I’m only stating it imprecisely here. There is nothing inherently religious about the hypothesis.
The issue in this case is how he tested the hypothesis and his analysis of that test.
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It was an extrapolation Axe already knew was inconsistent with his very own data:
Using a sensitive biological screen, we find that a strikingly high proportion of these mutants (23%) retain enzymatic activity in vivo. Further substitution at the 13th core position shows that a similar proportion of completely random hydrophobic cores supports enzyme function. Of the active mutants produced, several have no wild-type core residues. These results imply that hydrophobicity is nearly a sufficient criterion for the construction of a functional core and, in conjunction with previous studies, that refinement of a crudely functional core entails more stringent sequence constraints than does the initial attainment of crude core function. Since attainment of crude function is the critical initial step in evolutionary innovation, the relatively scant requirements contributed by the hydrophobic core would greatly reduce the initial hurdle on the evolutionary pathway to novel enzymes.
https://www.pnas.org/content/93/11/5590
He didn’t even cite anything following this statement:
One of two approaches is typically used in these studies. The first, which could be termed the forward approach, involves producing a large collection of sequences with no specified resemblance to known functional sequences and searching either for function or for properties generally associated with functional proteins. If the relevant sort of properties can be found among more or less random sequences, this provides a direct demonstration of their prevalence.
At the time Axe published this in 2004, there had already been many hundreds of catalytic antibody papers published since 1987 that showed precisely that.
How you are stating it is irrelevant; it’s simply not a hypothesis TO THEM. They have advanced zero scientific hypotheses to test or even to suggest that others test.
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Why do you think these papers are relevant to Axe’s work?
Because Axe himself said that this type of search was relevant in the bit that I quoted!
“If the relevant sort of properties can be found among more or less random sequences, this provides a direct demonstration of their prevalence.”
So there were hundreds of papers with such direct demonstrations that Axe ignored.
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I agree if you can show these papers were good comparisons with Axe’s work. Other objections I have seen were comparing apples and oranges.
As I have already done so in great detail right here with Axe’s colleague, Ann Gauger, your smug challenge is vacuous. It’s also about whether it fits his criteria, not that it’s comparable to his work, which is minimal–a mediocre graduate student could have done everything in the paper in only 2-4 weeks. He claims to have assessed function without bothering to assay the continuous function of enzyme activity.
In what way do catalytic antibodies not constitute finding the “relevant sort of properties” “among more or less random sequences”?
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This is your argument claiming Axe should have included the research around catalytic antibodies.
His experiment was with e coli bacteria and that the sequence producing beta lactamase effective enough to resist a given concentration of penicillin was rare in sequence space or 10^77 probability of finding it with a random search. The sequence existed in bacteria. The question is what is the origin of this sequence. How does the study of catalytic antibodies help with this question? What is the origin of the system that produces catalytic antibodies?
@Art is the most familiar with this experiment maybe he could weigh in. He used a different argument approach which stated that Axe’s results were in an expected range.
So why aren’t you answering my question?
There’s one problem with his paper. He didn’t test activity. Why do you think he didn’t bother?
No, that was an extrapolation, not data.
Does real-life evolution need “enough to resist a given concentration of penicillin” or much less activity than that?
False. Axe cheated by starting with a temperature-sensitive mutant enzyme to skew the results. Why did he do that?
The mutant enzyme sequence came from mutagenesis and selection. Axe didn’t use the wild-type enzyme. Why not?
Axe explained how very clearly.
The system that produces the catalytic part is "more or less random sequences.” Since Axe wrote that, why did he ignore all of those papers?
No, Art said basically the same thing that I am saying. The problem is that you don’t understand any of the three of us.
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I would be shocked if they were comparisons to Axe’s work. They are almost certainly nowhere near as shoddy and incompetently performed as Axe’s experiment was.
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Because that was required to explain all the errors Axe made.
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10^-10 → 10^-63 (or thereabout): this is the range of estimates of the density of functional sequences in sequence space that can be found in the scientific literature. The caveats given in Section 2 notwithstanding, Axe’s work does not extend or narrow the range. To give the reader a sense of the higher end (10^-10) of this range, it helps to keep in mind that 1000 liters of a typical pond will likely contain some 10^12 bacterial cells of various sorts. If each cell gives rise to just one new protein-coding region or variant (by any of a number of processes) in the course of several thousands of generations, then the probability of occurrence of a function that occurs once in every 10^10 random sequences is going to be pretty nearly 1. In other words, 1 in 10^-10 is a pretty large number when it comes to “probabilities” in the biosphere.
Real life need to have real new enzymes form and get fixed in populations to have evolution be the cause of what we are observing. How does even the low end of the range that @Art discusses accomplish this? What specifically is the mechanism that generates a new enzyme?
I think we can say it’s not an interesting or useful hypothesis, because the answer was already known. Poor methodology doesn’t make it any better.
I also question if this is even an ID hypothesis. Even if true it only means that function may be rare. This gives no positive evidence for design; it only recalls similar failed probability arguments. There is also no means to falsify this claim of design, so doesn’t even qualify as a hypothesis.
My list of testable ID hypotheses remains at 2.
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Then, since Axe derived his extrapolation from a single mutant enzyme created in the lab to be unstable and never fixed in any population, not a real-life enzyme, you must agree with me that his 2004 paper is worthless.
Once we establish your consistency on that matter, we can move on.
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This is an interesting point of debate. He was trying to find the edge where natural selection could start. If the experiment started with the wild type (and it’s catalytic capability) as the requirement wouldn’t the probability of finding that sequence be more challenging?
It’s also never stated as an ID hypothesis by anyone in the ID movement. There clearly is zero interest in testing it.
Agreed. I find it disturbing that @swamidass would cite it as an ID hypothesis.
I can think of plenty. The problem is that the ID movement pathologically avoids clearly stating and testing hypotheses. This can be seen with irreducible complexity and @pnelson’s strange claims that his concepts constitute actual hypotheses.
No, it’s a point of fact, a fact that according to you, disqualifies the experiment from any consideration whatsoever. I disqualify it because there was no testing of enzyme activity, which would have been easy to do. Its absence is extremely suspicious.
No, he very clearly was not trying to do anything of the sort.
Please keep in mind that I have literally decades of experience in studying how mutations change protein function, even to the point of intelligently designing mutations that will alter function in desired ways.
I have no idea what this word salad means, sorry.
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These are, of course, rhetorical questions, since you have been provided their answers many, many times, and there is no way you could be so stupid as to not understand or remember the answers by now.
Ah, but you forget: Axe does not claim to have determined the likelihood of that particular sequence arising. He claims to have determined the percentage of all sequences in sequence space that are functional in any manner.
So it seems you are beginning to understand why his experiment is a failure.
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