James Tour and his 60-day challenge

[lee_merrill]

@Art

Lee, you should not take intermittent participation on my part as “withdrawal”.

Alright, just please leave a note if you have to be away for an extended period, and I will set my timeout interval accordingly. And thanks for resuming discussion!

@Art

Once you come up with something that is more than referring to essays that we already know are either irrelevant or ineffective, I will comment. You haven’t to date.

But I don’t recall posting excerpts or referring to essays in my previous comments to you, I do recall going through your essay and presenting my points in reply.

@Art

It’s also perfectly OK to start at this point and ask questions about the aspects of this discussion you clearly do not understand.

Alright again, the forum here doesn’t seem to have a good search function, so I’ll just take a fresh run at this.

Now first of all, I think this post depicts more accurately what Axe did than this essay on Panda’s Thumb. Axe wasn’t trying to measure part of the base of the wild-type enzyme, he was trying to evaluate the whole peak of the partially-disabled enzyme, as you depict in the former post. So I’ll address the former post, not the latter article.

Secondly, I don’t see why Axe needed to come up with a conversion factor from the peak in your Figure 3 to the peak in Figure 1. I don’t see what that would accomplish, to get an estimate of the percentage of functional variants generated from the wild-type enzyme, to have this along with the estimate for the disabled enzyme variants. Axe’s aim was to estimate “the Prevalence of Protein Sequences Adopting Functional Enzyme Folds” in general, so having two samples instead of one wouldn’t seem to be helpful or necessary.

Then you write that “Anyone who has plated transformed E. coli on ampicillin or other beta-lactams knows that this isn’t a very quantitative method, and certainly not suited to quantitatively distinguishing enzyme variants with differing activities.” Yet here I read: “Volume Accuracy: Ensuring the precise volume of the sample is critical for certain quantitative analyses.” Which implies you have to be very careful, but it can be done. Similarly here: “The standard plate count is a reliable method for enumerating bacteria and fungi.” They continue: “Accuracy in quantitation is determined by accurate pipette use and adequate agitation of dilution tubes.” Implying quantification can be done accurately.

Then you state: “More to the point of the JMB paper, Axe’s BioComplexity paper shows that, in cases where enzyme activity may be very low, this assay cannot reliably distinguish between low and zero enzyme activity. This is very important – I believe the conditions used by Axe in the 2004 JMB paper cannot distinguish between mutants with low but significant activities and those with no activity. In other words, the accuracy of Axe’s estimates in the 2004 paper cannot be known, and he may be wrong by tens and tens of orders of magnitude or more.”

So I went through this paper, and couldn’t find any statement along the lines of “where enzyme activity may be very low, this assay cannot reliably distinguish between low and zero enzyme activity.” Could you quote the relevant section?

[lee_merrill]

@Faizal_Ali

@lee_merrill

And my reply has been that this shows getting halfway back to where they had claimed to be.

This is where I remind you that you have yet to cite any OoL researcher claiming to have solved homochirality. They seem to exist only in your fervid imagination.

I did find and post a link, but this forum’s search function is not very effective. So here is an excerpt from Wikipedia about this: “Some of these models propose three distinct steps: a mirror-symmetry breaking mechanism to create a minute enantiomeric imbalance (enantiomeric excess or ee) from a racemic mixture, subsequent chiral amplification to achieve a larger ee or full homochirality (i.e., ee=100%), and finally chiral transmission/propagation to transfer chirality from one set of molecules to another.^[9][10] “

And here are the references:

Ozturk, S. Furkan; Sasselov, Dimitar D. (2025-08-26). “Life’s homochirality: Across a prebiotic network”. Proceedings of the National Academy of Sciences. 122 (34) e2505126122. doi:10.1073/pnas.2505126122. PMC 12403148. PMID 40828029.

Ozturk, S. Furkan; Sasselov, Dimitar D.; Sutherland, John D. (2023-08-14). “The central dogma of biological homochirality: How does chiral information propagate in a prebiotic network?”. The Journal of Chemical Physics. 159 (6). doi:10.1063/5.0156527. ISSN 0021-9606. PMC 7615580. PMID 37551802.

So it seems your imagination is what is active here?

@Faizal_Ali

@lee_merrill

If Axe claims his results only apply for this mutated form of a protein, then yes, he should not claim this applies to proteins in general.

I’m sorry, what? But if he claims that his results for one mutated form of this one protein applies to every form of every protein (which he in fact does), that’s OK?

Does that really make sense to you?

Well, the reviewers evidently thought it did! And we should also throw out these papers? (referenced here in Uncommon Descent)

”As I noted in my previous post, Axe’s 2004 JMB paper is not an isolated result. I cited a number of papers which attained similar results with respect to the rarity of functional domains within sequence space. In one study, published in Naturein 2001 by Keefe & Szostak, it was documented that more than a million million random sequences were required in order to stumble upon a functioning ATP-binding protein, a protein substantially smaller than the transmembrane protein specified by the gene, T-urf13, discussed by Hunt. In addition, I noted, a similar result was obtained by Taylor et al. in their 2001 PNAS paper. This paper examined the AroQ-type chorismate mutase, and arrived at a similarly low prevalence (giving a value of 1 in 10^24 for the 93 amino acid enzyme, but, when adjusted to reflect a residue of the same length as the 150-amino-acid section analysed from Beta-lactamase, yields a result of 1 in 10^53). Yet another paper by Sauer and Reidhaar-Olson (1990) reported on “the high level of degeneracy in the information that specifies a particular protein fold,” which it gives as 1 in 10^63.”

@Faizal_Ali

@lee_merrill

But the authors in the paper you pointed to said more work needs to be done for the other nucleotides, implying their results did not apply more generally.

Exactly.

Hilariously, I suspect you don’t realize you just admitted that I have been right all along.

Eh? If their results did not apply more generally, yes, that was my point, you can’t claim the homochirality problem has been solved, as you seemed to be claiming.

@Faizal_Ali

Anyway, here is just one example, from just a short while ago, out of many, many others I could have chosen

Art Hunt is back! And I am resuming my conversation with him. This does not show that Axe was refuted, the discussion continues.

@Faizal_Ali

@lee_merrill

So how does Swamidass’ point not address the question, and so on? So again, please point to a post I did which is just a “bunch of words” that don’t address what someone said?

The very comment I am responding to know will suffice as an example. Or almost anything you have ever written on this board.

I assume you meant “now” instead of “know”? But you don’t address how Swamidass’ post does not address the question, nor do I see how asking for “how and where?” does not respond to what you said.

[lee_merrill]

@RonSewell

@lee_merrill

To some degree, so in order to keep abreast of the field, you have to read papers, and listen to presentations at conferences, and consult with colleagues. That’s taking things on authority.

Reading experimental and observational data is not the same a taking things on authority.

But just reading data is not enough, there’s no point in just reading, if you don’t check the calculations from the data. And you still have to take on authority that they gathered and reported the data properly.

[lee_merrill]

@Mercer

@lee_merrill

That was my initial claim, my reason for not reading the rest of the paper, which depended on this.

Your claim is false. You told another two lies that are falsified by that paper. And “rest of the paper” is really dishonest when you didn’t go beyond the first sentence of the Introduction.

How did the paper falsify my claim though? They would have had to renounce this sentence in their introduction.

@Mercer

@lee_merrill

But again, you accept nothing on authority?

I do, but I don’t pretend to understand those things at the same depth as experts do. I would never conclude that an entire scientific field is wrong based on the claims of a handful of people outside that field.

I don’t claim to have the same depth of understanding as experts in a field I haven’t studied, either. But Tour’s claims, and Ed Peltzer’s support, seem more credible if the experts can’t answer their challenges. Lee Cronin debated James Tour! And Jack Szostak responded to one of Tour’s complaints, too. So it’s not like they are dismissing or completely ignoring him. You, however, are doing just that. That gives me reason to believe you have no good answers, either, and increases my confidence in what they say.

@Mercer

@lee_merrill

“complex molecules go to pieces”

Which is bogus. For the third time, what happens to the polymerase?

My claim was that complex molecules go to pieces in hydrothermal vents, which would include polymerase. Certainly polymerase could be preserved under carefully controlled conditions, and temperatures less than you’re likely to find in vents.

@Mercer

@lee_merrill

Your counter example still proves my point.

How so?

As I said, DNA disassembles with rising temperatures.

@Mercer

What happened to your claim that ATP isn’t involved in RNA synthesis?

I wasn’t claiming that, I was saying incorporation of ATP like a nucleotide is not the way in which the cell typically uses ATP.

@Mercer

@lee_merrill

But I will ask this, what substantial OOL progress has been made in 18 years? And I’m not asking for papers, I’m asking for progress.

Progress is demonstrated in the papers you are obviously incapable of reading.

And the papers that are incapable of being quoted? I did examine one paper, which turned out to be based on an implausible claim.

@Mercer

@lee_merrill

Such as membrane construction.

OOL research is not an engineering problem. Only ignorant engineers pretend that’s the case.

Fine, membrane generation, is that better? Membranes have to assemble somehow, and this has not be explained, for membranes like living cells have.

@Mercer

@lee_merrill

Tour says they still only use one lipid.

Then one or more of the following must be true:

1. Tour was lying,
2. Tour was lying when he claimed to have read the OOL papers, and/or
3. You were lying when you claimed that Tour had read them.

Then please point to a description of a protocell that has more than one lipid. I’m sure Tour would be interested in hearing about this, too.

@Mercer

In addition, because membranes aren’t limited to lipids, it’s a stupid criticism even if it was correct.

Encyclopedia Britannica says this: “Cell membranes are composed primarily of fatty-acid-based lipids and proteins.” Then they discuss the proteins: “One type, called the extrinsic proteins, is loosely attached by ionic bonds or calcium bridges to the electrically charged phosphoryl surface of the bilayer. They can also attach to the second type of protein, called the intrinsic proteins. The intrinsic proteins, as their name implies, are firmly embedded within the phospholipid bilayer.”

So the lipid bilayer is primary, which what I assume Tour meant.

@Mercer

Now, if only someone in this very thread had cited and linked to a full-text version of a lipid-centric OOL paper that shows Tour’s claim to be false! Can you guess which one, Lee?

I do remember Rumraket pointing to an OOL paper that discussed protocells, and ATP diffusing inside of them, and being used. This latter point I still dispute, but in any case, Tour’s point still stands, the described protocells don’t have anything like real cell membranes. With thousands, more than 40,000 lipids! And ion pumps and channels. And don’t forget the proteins mentioned in Encyclopedia Britannica! And so on.

@Mercer

@lee_merrill

Put a molecule of DNA in a hydrothermal vent, and I think more will happen, it will arguably, go to pieces.

How do the critters that live there possibly survive, then?

They’re quite remarkable, I agree! They’re called extremophiles for a reason. I don’t claim to know how they manage, I did a quick search, which mentioned extremozymes, I expect research is ongoing. But you didn’t answer my challenge: put a molecule of DNA in a hydrothermal vent, and I think more will happen, it will arguably, go to pieces. And I don’t see how examining denaturation temperatures and what they are proportional to somehow gives evidence that large molecules in isolation can stay together in hydrothermal vents.

@Mercer

@lee_merrill

@Mercer

Does the DNA polymerase get denatured?

I think more would happen, it wouldn’t hold together in a hydrothermal vent, it would go to pieces, per Ed Peltzer.

I don’t. What range of temperatures are present in vents, and what’s the stability of the polymerase? No opinions are involved, just measurements.

I certainly haven’t made measurements myself! But per Wikipedia, temperatures in such vents range from “60 °C (140 °F)^[6] up to as high as 464 °C (867 °F).^[7][8] “ I would expect that temperatures in the higher range, say 300-464 degrees C, would disassemble most any large molecule, including DNA polymerase.

@Mercer

@lee_merrill

This is what you need to refute, and even your counterexample shows DNA disassembling due to raising the temperature.

“Disassembling” is a lie and you know it.

Pulling one molecule into two parts would seem to be disassembling it.

@Mercer

@lee_merrill

@Mercer

You just made my point by disregarding the OOL papers.

So papers are now evidence?

The primary literature contains evidence by definition. Not all scientific papers are primary. Is this a difficult concept for you?

But you didn’t say “primary”. You said “OOL papers”, and I agree, they are all potential sources of evidence.

@Mercer

@lee_merrill

But what OOL papers have I disregarded? I do try and address points people make here, especially if they point to a paper..

That’s a lie.

Again I ask, what OOL papers have I disregarded?

@Mercer

@lee_merrill

To some degree, so in order to keep abreast of the field, you have to read papers, and listen to presentations at conferences, and consult with colleagues.

Correct.

@lee_merrill

That’s taking things on authority.

It’s anything but, because for real scientists doing real science, all three involve presenting evidence.

Sure, but you must still take much of what they say, on authority. When you read papers, do you insist on reproducing their results before you believe them? Do you do the same with presentations at conferences? Do you suspend judgement on what your colleagues have said until you prove for yourself that what they say is true?

@Mercer

@lee_merrill

But certainly scientists also do their own experiments

The results of which they present in papers, at conferences, and in consultation with colleagues.

Sure.

@Mercer

@lee_merrill

All right, I got off track.

That’s not how ethical people acknowledge false statements they’re called out for making.

I kowtow! I grovel! I roll in the dust…

@Mercer

@lee_merrill

If Axe claims his results only apply for this mutated form of a protein, then yes, he should not claim this applies to proteins in general.

Good, then we agree that the paper has zero relevance to proteins in general.

But Axe doesn’t claim that, he claims a general result, and the reviewers didn’t tell him to withdraw that part of his conclusion.

@Mercer

Have you even read the 2004 paper you love so much? Axe isn’t claiming that his results start with a mutated form of a protein, he tells the reader that flat out.

Yes, he does.

@Mercer

But this, as the vast majority of all facts presented here, flies over your head, while you remain far too arrogant to admit it.

No, I admit what I don’t know, or when I am mistaken. When I do conclude I understand something, then I’m willing to speak up. Unlike when you claim you understand how Ed Peltzer is wrong, but you won’t tell us why.

[Mercer (John Mercer)]

@lee_merrill

How did the paper falsify my claim though?

The claim you regurgitated from Tour.

@lee_merrill

As I said, DNA disassembles with rising temperatures.

Stop lying. Denaturation is a functional property of DNA. It is not disassembly. I suspect that even you know that.

@lee_merrill

I wasn’t claiming that, I was saying incorporation of ATP like a nucleotide is not the way in which the cell typically uses ATP.

That’s some goalpost move. Is RNA synthesis not a typical use of ATP? I’m pretty sure that you never used “typical” before; did you finally look it up?

@lee_merrill

And the papers that are incapable of being quoted? I did examine one paper, which turned out to be based on an implausible claim.

According to you, someone with zero expertise.

@lee_merrill

Fine, membrane generation, is that better? Membranes have to assemble somehow, and this has not be explained, for membranes like living cells have.

Wasn’t that the point of the paper you didn’t read?

@lee_merrill

@Mercer

@lee_merrill

Tour says they still only use one lipid.

Then one or more of the following must be true:

1. Tour was lying,
2. Tour was lying when he claimed to have read the OOL papers, and/or
3. You were lying when you claimed that Tour had read them.

Then please point to a description of a protocell that has more than one lipid.

I already did.

@lee_merrill

I’m sure Tour would be interested in hearing about this, too.

I’m sure the opposite is true.

@lee_merrill

@Mercer

In addition, because membranes aren’t limited to lipids, it’s a stupid criticism even if it was correct.

Encyclopedia Britannica says this: “Cell membranes are composed primarily of fatty-acid-based lipids and proteins.”

Yes, they aren’t limited to lipids. Did you miss the “and proteins” at the end, too?

@lee_merrill

So the lipid bilayer is primary, which what I assume Tour meant.

I don’t, but then I’m a biochemist.

@lee_merrill

@Mercer

Now, if only someone in this very thread had cited and linked to a full-text version of a lipid-centric OOL paper that shows Tour’s claim to be false! Can you guess which one, Lee?

I do remember Rumraket pointing to an OOL paper…

Unbelievable.

@lee_merrill

I don’t claim to know how they manage…

You claimed they can’t, remember?

@lee_merrill

But you didn’t answer my challenge:

Liar:

@Mercer

DNA denaturation temperature is directly proportional to _______ concentration. Simple fact, but you’re not curious enough to look for it.

@lee_merrill

But you didn’t say “primary”. You said “OOL papers”, and I agree, they are all potential sources of evidence.

I did. The secondary literature is not–it tells you where to find the evidence. Is this too complex for you?

@lee_merrill

@Mercer

@lee_merrill

But what OOL papers have I disregarded? I do try and address points people make here, especially if they point to a paper..

That’s a lie.

Again I ask, what OOL papers have I disregarded?

The one I’m reminding you of above.

@lee_merrill

@Mercer

@lee_merrill

That’s taking things on authority.

It’s anything but, because for real scientists doing real science, all three involve presenting evidence.

Sure, but you must still take much of what they say, on authority.

Absolutely not.

@lee_merrill

When you read papers, do you insist on reproducing their results before you believe them?

Depends. But describing methods is not about authority.

@lee_merrill

@Mercer

@lee_merrill

If Axe claims his results only apply for this mutated form of a protein, then yes, he should not claim this applies to proteins in general.

Good, then we agree that the paper has zero relevance to proteins in general.

But Axe doesn’t claim that, he claims a general result, and the reviewers didn’t tell him to withdraw that part of his conclusion.

Another violation of the Ninth Commandment. You have no idea whether they did or not. You have no idea if Axe sneaked in changes in the proof.

You just lie, again and again.

@lee_merrill

@Mercer

But this, as the vast majority of all facts presented here, flies over your head, while you remain far too arrogant to admit it.

No, I admit what I don’t know, or when I am mistaken.

No, you definitely rarely do either.

@lee_merrill

When I do conclude I understand something, then I’m willing to speak up.

That’s the problem.

@lee_merrill

Unlike when you claim you understand how Ed Peltzer is wrong, but you won’t tell us why.

Another lie. I wrote that I don’t care what he has to say. I care about the evidence.

Dude, stop lying.

[RonSewell (RonS)]

@lee_merrill

But just reading data is not enough, there’s no point in just reading, if you don’t check the calculations from the data. And you still have to take on authority that they gathered and reported the data properly.

Secondary peer review is by definition, not taking a paper on authority.

[Mercer (John Mercer)]

@lee_merrill

I certainly haven’t made measurements myself! But per Wikipedia, temperatures in such vents range from “60 °C (140 °F)[6] up to as high as 464 °C (867 °F).[7][8] “ I would expect that temperatures in the higher range, say 300-464 degrees C, would disassemble most any large molecule, including DNA polymerase.

You’re predictably moving the goalposts. You didn’t qualify your earlier claim.

Now provide the knowledge supporting your expectation. Be sure to account for pressure in your explanation.