Reed A. Cartwright posted Entry 1426 on August 31, 2005 03:27 PM.
Trackback URL: http://www.pandasthumb.org/cgi-bin/mt/mt-tb.fcgi/1422

Michael Lynch’s critique of Behe and Snoke (2004) is now available as is a reaction by Behe and Snoke. Don’t forget to read the editor’s message about it as well.

We’re still discussing it, but here is Lynch’s abstract.

Lynch M (2005) Simple evolutionary pathways to complex proteins. Protein Science, 14:2217-2225.

Abstract: A recent paper in this journal has challenged the idea that complex adaptive features of proteins can be explained by known molecular, genetic, and evolutionary mechanisms. It is shown here that the conclusions of this prior work are an artifact of unwarranted biological assumptions, inappropriate mathematical modeling, and faulty logic. Numerous simple pathways exist by which adaptive multi-residue functions can evolve on time scales of a million years (or much less) in populations of only moderate size. Thus, the classical evolutionary trajectory of descent with modification is adequate to explain the diversification of protein functions.

Ricardo Azevedo has some view up on his blog: BS Model Gets Lynched.

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Comment #45932

Posted by Steven Thomas Smith on August 31, 2005 4:53 PM (e)

I’ve posted the exchange between Lysenko and Kolmogorov that took place Comptes Rendus before—I believe that it is apropos in this thread and I hope that you don’t mind if I repeat it here.

The crackpotism of the Lysenkoists and the crackpotism of intelligent design creationists share many characteristics. As well as the improper use of statistical and mathematical reasoning, skillful use of the press and public relations to promote their pseudoscience, angry disregard of thoughtful criticism, Lysenko and IDers give the same reason for opposing the genetic sciences:

T. D. Lyssenko wrote:

“We biologists, however, do not want to submit to blind chance … We maintain that biological regularities to not resemble mathematical laws.”

A.N. Kolmogorov used mathematical biology in a sly and brave way to counter Lysenkoism in the Soviet Union. When one of T.D. Lysenko’s followers published an article with experimental data claimed to be at odds with Mendelian genetics, A.N. Kolmogorov published a response that showed up a statistical error and complemented the author’s hard work confirming an established scientific fact with new data. This was nothing less than courageous—Lysenko used his position to imprison and murder any biologist that opposed him. Kolmogorov wished to defend scientific truth in his country and was aware of Fisher’s work on the neo-Darwinian synthesis. It was a good thing for Kolmogorov that Stalin understood the utility and international prestige that Kolmogorov brought his country.

Because of the interesting parallels between Lysenkoism and modern-day intelligent design creationism, I’ve excerpted Lysenko’s response to Kolmogorov here in full. It is worth reading to the end to see that Lysenko’s opposition to Mendelian genetics stems from the same philosophical discomfort held by intelligent design creationists: revulsion to “blind chance.” Also note Lysenko’s feigned expertise that would easily fool journalists and other nonspecialists, as well as his reliance on poorly-defined yet reasonable-sounding terms that are in fact nonsensical—what does Lysenko mean by “family”? I’ve highlighted the money quotes in bold italics, and kept the transliterated names as they appear in the original English translation.

“In Response to an Article by A. N. Kolmogoroff,” by T. D. Lyssenko, Member of the Academy

Published in Comptes Rendus (Doklady) de l’Académie des Sciences de l’URSS, 1940, Vol. XXVIII, Nº 9.

The Comptes Rendus of the Academy of Sciences of the USSR, vol. XXVVII, No. 1, 1940, carries an article by the well-known mathematician A. N. Kolmogoroff, entitled «On a New Confirmation of Mendel’s Laws». In his desire to prove the truth and invulnerability of of Mendel’s law, the author provides mathematical arguments, formulae and even curves. I do not believe I am competent to pass an opinion on these mathematical proofs and arguments. Moreover, as a biologist I am not interested in the question whether or not Mendel was a good mathematician. As to my opinion of Mendel’s statistics, I have expressed it in many occasions in the press and I claim that they have no bearing whatever in biology.

What I wish to say in my short Note here is that Kolmogoroff’s article, too, has no bearing on biological science.

While explaining Mendel’s principle of 3:1 segregation, Kolmogoroff says in his article that it makes no difference whether a single family or a group of many families, produced by different pairs of heterozygous parents of the Aa type, are taken for analysis.

Indeed, it may seem to Kolmogoroff that all the plants produced by different pairs of heterozygous parents of the Aa type are alike. But we, biologists, know that no two plants can be quite identical in their hereditary qualities. We know that in a family of the second generation of crossbred wheat, 150 out of 200 plants may be of the beardless type and 50 of the bearded one, but in another family of the same combination there may be as many as 190 beardless plants and only 10 bearded, and in a third family we may even find that all the 200 plants are of the ordinary beardless type, and so on and so forth. In other words, each family has its variety.

To Kolmogoroff this is of no interest, since his only concern is that the mean should coincide with the mathematical conclusions. But we, who are concerned with genetics and breeding work, cannot be indifferent to such phenomenon.

If, for instance, we have singled out some wheat plants for reproduction within a family including a large ratio of bearded type (50 out of 200), i.e., a family showing great variety, we may be sure that the progeny of selected plants will show great variety, too. Under such conditions selective breeding may prove hard and futile. It will be different, however, if we take seed from a family in which all the 200 specimens are more uniform. For this reason seeds from various plants of the first generation of crossbreeds should not be mixed, but should be sown separately, each family apart.

That is why we, biologists, do not take the slightest interest in mathematical calculations which confirm the useless statistical formulae of the Mendelists.

Kolmogoroff’s article is based on the results of Ermolaeva’s work. But Ermolaeva in her work has shown that the progeny of various families of crossbred peas of the same combination vary, each in a different way, whereas according to Kolmogoroff the variety manifested by the plants of different families falls within the limits of mathematically admissible error. We biologists, however, do not want to submit to blind chance, even though this chance is mathematically admissible. We maintain that biological regularities to not resemble mathematical laws. We are of the opinion that in this controversy between Kolmogoroff, Member of the Academy, and post-graduate Ermolaeva, it is Ermolaeva who is in the right, and not Kolmogoroff.

I recommend to the interested reader David Joravsky’s history The Lysenko Affair (Harvard University Press, 1970), who in Chaper 3 titled “Harmless Cranks” says of Lysenko:

Lysenko … had the benefit of education, but the peasant style of thought survived the years he spent at the Kiev Agricultural Institute. What he did learn very well—unless it was the gift of his genes—was the art of self-advertisement. In 1927, when he was only twenty-nine years old, working at an obscure experiment station is Azerbaidjan, he managed to get a boost from Pravda itself. A feature article said he had “solved the problem of fertilizing the fields without fertilizers and minerals.” … Such miracles will seem trite to anyone who is familiar with the Soviet press, but this miracle worker was quite original.

Skinny, with prominent cheeckbones and closecropped hair [later replaced with a lank forelock], … this Lysenko gives one the sensation of a toothache. God grant him health, he is a man of doleful appearance. Both stingy with a word and unremarkable in features, except that you remember his morose eye crawling along the earth with such a look as if he were at least getting ready to kill someone. He smiled only once, this barefoot scientist. …

[T]he young man’s masterful way with journalists, his skill at using newspapers to make scientific discoveries of great practical importance, this was not ephemeral. It would be a constant feature of Lysenko’s entire career, from the Pravda article of 1927 until the end of 1964, when Pravda and all the other newspapers would finally turn against him.

The reporter of 1927 confessed that he stared at Lysenko’s notebook with ignorant awe. He did not understand the “scientific laws” by which the barefoot scientist had quickly solved his problem, without trial and error. … He made a primitive error in statistical reasoning, and he paid almost no attention to the lessons learned by previous investigators of this problem. …

Lysenko then revealed another of his chief and lasting characteristics: a total, angry refusal to give any thoughtful consideration to criticism.

Comment #45934

Posted by Dan Hocson on August 31, 2005 5:06 PM (e)

Hmmm. I may be the only one in the forum without a subscription to Protein Science, but the main link above requires you to be a subscriber to access. Anyone care to provide a synopsis?

Comment #45935

Posted by Dan Hocson on August 31, 2005 5:10 PM (e)

My bad. Ricardo’s blog does provide some insight into Lynch’s critique and the BS response. Would be nice to see the original documents without violating copyright.

Comment #45937

Posted by Dave Cerutti on August 31, 2005 5:17 PM (e)

Behe and Snoke’s reply is a hoot.

1.) If Lynch assumed complete neutrality, then he’s making an unwarranted assumption. However, he went into extensive references, including those used by Behe and Snoke, to back up that part of the model. And there was a caveat which I didn’t catch–did anyone else catch it?

2.) Of course.

3.) Well, so Behe and Snoke are assuming that intermediate states always decrease function? That very well may be closer to the truth than Michael Lynch’s assumption, but they’re still assuming very broad things about the nature of mutation.

4.) But, if you first have to sacrifice function, then it’s a cost you pay up front. Or, as Bush would way, “I never said you had to give up your social security benefits, you simply forfeit them in order to possibly achieve more wealth under a privatized system.”

5.) Gee, gotta look these things up. The next part of Lynch’s sentence is “as the latter authors do not explicitly model the evolutionary process, whereas the stochastic computer simulations presented here precisely track the joint dynamics of allele frequencies.” It sounds pretty darned pendantic for Behe and Snoke to go telling Lynch about the fundamentally different models, which he stated very clearly himself. Lynch is saying that it’s hard to compare the models, because one is essentially invalid. But Behe and Snoke don’t let this opportunity to twist things slip by.

6.) Yes, IIRC Behe and Snoke used a general point mutation rate in their model and have no sleective effect operating on intermediates. This implies that the forward and reverse reaction rates are equal, which is what Lynch said. “But, officer, I didn’t speed through that school zone. I never accelerated past the 35-mph posted speed limit.”

7.) Perhaps Lynch is over-simplifying Behe and Snoke. But it depends on what they meant by “strongly selected against.”

8.) And that mutations are assumed to be deleterious is the fundamental reason that this is a non-Darwinian model, and an unrealistic one. This is the central point of Lynch’s critique, and one they seem to blithely ignore. “It’s because our model assumes this to be the case, of course. Oh, we didn’t realize he was criticizing the fundamentals of our model… well why didn’t he say so?”

9.) But it seems that it shoudl still hold for a model like theirs, even if mutations are always deleterious– 0 = 0.

10.) And they’re going for the gusto–no matter how bad their model is, they’re out to claim that Darwinian processes aren’t gonna cut it.

Comment #45964

Posted by Qualiatative on August 31, 2005 7:15 PM (e)

Behe and Snokes’s actual points (as opposed to Cerutti’s spin):

1. Experimental studies contradict Lynch’s assumption of complete neutrality as a rule; the majority of amino acid substitutions decrease protein function.
2. Lynch’s and our models are not mutually exclusive. Some evolutionary pathways might involve both deleterious and neutral mutations.
3. Lynch writes in the section “The Model” that we “imply that all amino acid changes lead to nonfunctionalization.” We imply no such thing. Although we assumed that intermediate mutations required for a new feature decreased function, we wrote, “it can be calculated that on average a given position will tolerate about six amino acid residues and still maintain function.” Our estimation of {rho} explicitly takes into account the tolerance of sites for substitution.
4. In “The Model,” Lynch writes, “As in Behe and Snoke (2004), this adaptation is assumed to be acquired at the expense of an essential function of the ancestral protein….” We made no such assumption. In our model, the final mutation might restore and enhance the original function.
5. In the Discussion, Lynch writes, “It is difficult to pinpoint the source of the difference between the results of Behe and Snoke and those contained herein….” The differences are largely due to opposing starting presumptions about whether mutations are deleterious.
6. In the Discussion, Lynch writes, “Behe and Snoke assume that the forward and backward point-mutation rates (per amino acid residue) are equal.” We do not. The mutation rate we use is the nucleotide point-mutation rate.
7. In the Discussion, Lynch writes that we assume mutations have “lethal pleiotropic effects.” We did not assume mutations to be either lethal or pleiotropic. We only assumed that they are “strongly selected against.”
8. In the Discussion, Lynch writes, “If the intermediate steps … are entirely neutral after gene duplication, as Behe and Snoke assume, then there is no compelling reason that ‘one-off’ (type-2) alleles should be absent from the population prior to duplication.” The reason for no “one-off” alleles before duplication in our model is that intermediate mutations are assumed to be deleterious in a singlecopy gene.
9. In the Discussion, Lynch writes, “Behe and Snoke failed to realize that a completely linked pair of duplicate genes has a mutational advantage equal to the mutation rate to null alleles….” Such an effect does not hold for a model like ours in which intermediate mutations are postulated to be deleterious.
10. A recent report (Gao and Innan 2004) presents evidence that the gene duplication rate is lower by several orders of magnitude than that assumed both by Lynch and by us based on the work of Lynch and Conery (2000). If so, then both his and our calculations for the population sizes needed to fix a mutation in a duplicated gene are substantial underestimates.

Comment #45967

Posted by Dave Cerutti on August 31, 2005 7:36 PM (e)

Behe and Snoke’s actual points are available on the links provided at the top of the thread. I have responded as I see appropriate, but not being a geneticist I’m not authoritative. I was hoping that other PTers might be able to better inform me.

I love how this stuff works, though: presenting to an audience? Spin your case so as to appeal to the broadest number of people possible. Arguing with a scientist? Keep the burden of proof on him, and then (if he slips up or says something wrong) pound him for all you can, or (if he makes factual points that you can’t argue with) call it all a bunch of political spin and crown him with the encomium “oh, too good! You’re a better spinmeister than I, but someday you evolutionists won’t have all the money and choke-hold on what’s allowed to pass for truth!”

Comment #45970

Posted by 'Rev Dr' Lenny Flank on August 31, 2005 7:59 PM (e)

Behe and Snokes’s actual points (as opposed to Cerutti’s spin):

How come I, uh, don’t see any actual scientific theory of ID anywhere in Behe and Snoke’s, uh, actual points … ?

Comment #45971

Posted by 'Rev Dr' Lenny Flank on August 31, 2005 8:01 PM (e)

someday you evolutionists won’t have all the money and choke-hold on what’s allowed to pass for truth!”

Waterloo !!!! Waterloo !!!! Waterloo !!!!!!

I wonder why Behe and Snoke done have any, uh, actual scientific theory of ID anywhere in their, uh, actual points ….

Comment #45979

Posted by Reed A. Cartwright on August 31, 2005 8:26 PM (e)

When people read Behe and Snoke (2005) remember Behe’s statements at DDDV about his work:

So the point is that, whenever you have an apparatus that needs three or more proteins in order to work, that’s essentially beyond the capacity of random mutation and natural selection to produce. Even when you have something that only has two proteins stuck together, that’s a very very rare event in the history of life on earth. So the tentative conclusions from this–and there are a couple of caveats that I haven’t gone into but which I’d glad to talk about if you wanted to–two tentative conclusions: that is that the formation of new protein-protein interactions would be very rare in the history of life, and the formation of two such interactions in an irreducibly complex complex is practically impossible. So what I think is going to turn out to be the case–although we will be required to do it–is that design is going to be seen to extend very deeply into the cell and perhaps beyond that as well.

(Transcribed form an audio recording.)

Does Behe really not subscribe to triumphant views of his work?

Comment #45986

Posted by Michael White on August 31, 2005 10:18 PM (e)

Another variation on this theme can be found in an advance online publication in Nature Reviews Genetics: Missense meanderings in sequence space: a biophysical view of protein evolution. One of the authors is Daniel Hartl, author of a popular textbook on population genetics. (The link gets you to the abstract and a summary of the paper - you need a subscription to get the whole thing.)

These authors take a different view of point mutations from BS and Lynch - they claim that few missense mutations have an impact on a protein’s biochemical function; instead most mutations have an impact on a protein’s stability. This is a distinction not found in the Protein Science articles, as far as I can tell.

I think this paper is an even better answer to the BS one.

Comment #45987

Posted by Cleetus the Creationist Quote Miner on August 31, 2005 10:31 PM (e)

[QUOTE]Taken as a whole, recent findings from biochemistry and evolutionary biology indicate that our understanding of protein evolution is incomplete, if not fundamentally flawed.[/QUOTE]

Michael, I seriously recommend you look over that article again. I’m no biochemicals expert, but that opening sentence really blows a hole in the propaganda this site seems bent on forcing into the minds of America’s shool kids.

When one of your own admits that evolution’s a bunch of hooey, the gig’s pretty much up, as they say…

Comment #45991

Posted by PvM on August 31, 2005 11:10 PM (e)

When one of your own admits that evolution’s a bunch of hooey, the gig’s pretty much up, as they say…

Nice quote mining but you are ofcourse missing the point a bit. Of course even if our understanding is flawed, this does not mean that evolution did not happen nor that there is much support for the creationist ID viewpoint.

from the article wrote:

# We propose a new model of protein evolution that is reminiscent of a constrained ‘random walk’ through fitness space, which is based on the fitness consequences and distribution of mutational effects on function, stability, aggregation and degradation.
# This model can account for both the micro-evolutionary events that are studied by biochemists and the long-term patterns of protein evolution that are observed by evolutionary biologists

Now that is interesting…

Comment #45993

Posted by ts (not Tim) on August 31, 2005 11:32 PM (e)

typically confused creationist wrote:

When one of your own admits that evolution’s a bunch of hooey, the gig’s pretty much up, as they say…

This is like saying that, if our understanding of star formation is incomplete, then stars don’t form.

Comment #45996

Posted by Dave Cerutti on August 31, 2005 11:44 PM (e)

Umm, you guys did realize from the name on my post that I was joking, right? Or shall I pull another admonitus and impersonate a creationist of some bizarre strain for many days before letting the cat out of the bag?

Comment #45998

Posted by ts (not Tim) on September 1, 2005 12:04 AM (e)

Umm, you guys did realize from the name on my post that I was joking, right?

Short of admitting it, parodies of creationist quote miners are not reliably distinguishable from the real thing, when we have folks like Sal Cordova referring to an “honest quote mine” maintained by IDists.

Comment #46003

Posted by Dave Cerutti on September 1, 2005 1:45 AM (e)

Oh, well, in that case I suppose it’s finally time to let the cat out of the bag.

I’m actually the one who posts as Sal Cordova.

The IP addresses show up differently because I only post as him when I’m in a certain building on campus, which I’m in frequently enough. He was a character I invented a long time ago, and trolling Dembski’s blog pretending to be a sycophant of that man has been more than hilarious, at least from my perspective. Of course I had to keep up the ruse, by insulting Sal now and then when I came to PT or Dembski’s blog as myself. But, it’s been fun. There may be periodic reappearances of Sal, but just know that he’s not in fact a real person.

Comment #46005

Posted by ts (not Tim) on September 1, 2005 3:18 AM (e)

I’m seeing it now … Dave Cerutti … D C … Designed Creationists … ah, my own Antony Flew moment.

Comment #46010

Posted by 'Rev Dr' Lenny Flank on September 1, 2005 4:08 AM (e)

When one of your own admits that evolution’s a bunch of hooey, the gig’s pretty much up, as they say…

“Intelligent design itself has no content”.

Is that a gig I see?

Comment #46016

Posted by SEF on September 1, 2005 4:30 AM (e)

1. Experimental studies contradict Lynch’s assumption of complete neutrality as a rule; the majority of amino acid substitutions decrease protein function.

That assertion of decreasing function would be to ignore: that any optimisation has already taken place at all via evolution; that proteins can have more than one function which might be affected in different ways (eg acquiring a new useful one which offsets a slight reduction in effectiveness at an old one); that the environment can change to affect the relative fitness (eg some codings work better at higher temperature through being more stable against denaturing while others work more rapidly at a cooler temperature, or acid/alkali environment, or mineral-rich/poor environment etc).

Comment #46021

Posted by Ian Musgrave on September 1, 2005 6:52 AM (e)

In Comment #45964

Qualiatative wrote:

1. Experimental studies contradict Lynch’s assumption of complete neutrality as a rule; the majority of amino acid substitutions decrease protein function.

This simply isn’t true. Lynch quotes several experimental studies (eg Guo et al. (2004)) that show that the majority (~70%) of substitutions are neutral, even the papers quoted by Behe & Snoke in their original paper show that the majority of substiutions are neutral (see Theory is as Theory does for a detailed discussion of this (you have to scroll down a bit)).

The rest of Behe & snokes points are like this one, either flat out wrong, or completely missing the point

Comment #46028

Posted by Russell on September 1, 2005 7:54 AM (e)

Bottom line: Behe & Snoke are committed to their religious preconceptions, and are not going to ever concede anything. Do I “know” this, in the same way I know, say, vertebrates share a common ancestry? No. I “know” it in the same sense I know that Dubya will never concede that his Iraq adventure was miscalculated, and the same sense that I “knew” Clinton was lying about Monica.

Any of these pieces of “knowledge” I would be perfectly comfortable taking to the bank, but to try, through logical discourse, to get the principals to concede, would be tilting at windmills. All you can do is force them to retreat to ever more bizarre evasions. Sometimes that’s worth it; sometimes it’s not.

Comment #46091

Posted by steve on September 1, 2005 12:51 PM (e)

Comment #46003

Posted by Dave Cerutti on September 1, 2005 01:45 AM (e) (s)

Oh, well, in that case I suppose it’s finally time to let the cat out of the bag.

I’m actually the one who posts as Sal Cordova.

Yeah, right, and I’m Intelligent Design Theorist Timmy.

Comment #46094

Posted by Steve Reuland on September 1, 2005 1:11 PM (e)

Ian Musgrave wrote:

This simply isn’t true. Lynch quotes several experimental studies (eg Guo et al. (2004)) that show that the majority (~70%) of substitutions are neutral, even the papers quoted by Behe & Snoke in their original paper show that the majority of substiutions are neutral (see Theory is as Theory does for a detailed discussion of this (you have to scroll down a bit)).

Actually, the Guo paper (and others) show this proportion of substitutions maintain some function, not that they’re necessarily neutral. This is what B&S are dickering over. Lynch took pains to point out evidence showing that even substitutions that lower activity are tolerated and can be fixed. There is no reason to believe that just because an enzyme’s activity goes down by 20% that selection is going to weed it out. (For most enzymes, this would be selectively neutral, or nearly so.)

Comment #46109

Posted by Dave Cerutti on September 1, 2005 5:17 PM (e)

[quote]Yeah, right, and I’m Intelligent Design Theorist Timmy.[/quote]

Intelligent Design Theorist Timmy, it’s time to really shake things up around the ID world.

Comment #46123

Posted by Intelligent Design Theorist Timmy on September 1, 2005 9:18 PM (e)

For the time being, I have nothing to contribute. Michael Behe decisively refuted evolution. So did William Dembski. And David Heddle. And Charlie Wagner. And Ken Ham. And Kent Hovind. And myself. We have proven the same thing at least seven times conclusively. But there is a little delay in the recognition by the authorities-that-be. So now all there is to do is sit around and wait for the paradime change. Sometime soon it will happen. Beginning at Harvard and CalTech, and the other Ivies, and continuing through the lowly state colleges, and across the world, biology departments everywhere will cancel most of their erroneous research, empty their libraries of millions of disproven papers, and finally, replace most of their staff with experts in the new paradime. Freed from the clueless old evolution paradigm which has smothered biology for 140 years, biology will enjoy a huge rebirth, and finally be able to make some progress.

Comment #46131

Posted by Henry J on September 1, 2005 10:56 PM (e)

You accidentally spelled “paradigm” correctly in one place.

Henry

Comment #46132

Posted by Intelligent Design Theorist Timmy on September 1, 2005 11:13 PM (e)

Can you evolutionists do anything other than Ab Homonym?

Comment #46134

Posted by Reed A. Cartwright on September 1, 2005 11:25 PM (e)

I have become bored of you people playing pretend creationists. Please cut it out for the rest of this thread.