Does the Darwinian theory require modification or replacement?

I don't want to misinterpret you, but are you of the opinion that some mutations are directed?

Are you referring to random mutation as "proven" in re "directed mutations" or it is proven, end of story?

Then you will have a tough time understanding why you are wrong. The way in which Shapiro uses sleight of hand to replace "fitness" with "potential biological utility" should be a big hint. Like I have stated elsewhere, Shapiro is using salesmanship to sell his ideas. It takes knowledge of the data and field to understand this.To use an analogy, would you cite a Mercedes salesperson as an expert on why Mercedes are the best cars? Would you reject any criticisms made by auto mechanics about a specific problems with Mercedes models, even though you have no expertise in auto mechanics? Would you tell us that the auto mechanic's criticisms are off base because you have opinions from an authority on Mercedes cars, namely the Mercedes salesperson?

Fair enough.Now, do you understand why calling something the "null hypothesis" does not call the hypothesis into doubt?That hypothesis testing does not, never was meant to, "prove" a hypothesis but is a tool to eliminate false ones?That in designing an experiment to test for "directed" mutations it is useful to assign "random mutations are the cause of genotypic variation" as the null hypothesis to which you compare the data?Do you comprehend any of this at all?

Given that you've chosen to ignore nearly my entire post, I will restate my objections.Here is your original claim. When I pointed out that Cairns backpedalled his "challenge" as fast as he could, you resorted to backpedalling too. What, praytell, was Cairns' "challenge" to random mutation if not directed mutation?When you first mentioned Zheng, you said: When it was pointed out that you misunderstood "null hypothesis", you repeatedly stated: Do you, or do you not understand, that if the null hypothesis is NOT DISPROVEN the null hypothesis is considered, for all intents and purposes, PROVEN?Zheng is a mathematician. In the paper I presume you read, Mathematical Issues Arising From the Directed Mutation Controversy, Zheng set out to untangle the math used by Cairns. Zheng is offering ALTERNATIVE explanations to directed mutation. NOT supporting directed mutation.Here's the bottom line.
You misunderstood Zheng as supporting directed mutation. He didn't.
You picked a REALLY bad paper by Cairns to support your claim of directed mutation. Even Cairns doesn't support directed mutation these days (after getting his ass handed to him by other labs).Can you cite any papers that support directed mutation?

Here is one we have been discussing in this post.Journal of Bacteriology, June 2000, p. 2993-3001, Vol. 182, No. 11
0021-9193/00/$04.00+0
Copyright 2000, American Society for Microbiology. All rights reserved.MINIREVIEW
A Biochemical Mechanism for Nonrandom Mutations and Evolution
Barbara E. Wright*Division of Biological Sciences, The University of Montana, Missoula, MontanaINTRODUCTION
Top
Introduction
Conclusion
ReferencesAs this minireview is concerned with the importance of the environment in directing evolution, it is appropriate to remember that Lamarck was the first to clearly articulate a consistent theory of gradual evolution from the simplest of species to the most complex, culminating in the origin of mankind (71). He published his remarkable and courageous theory in 1809, the year of Darwin's birth. Unfortunately, Lamarck's major contributions have been overshadowed by his views on the inheritance of acquired characters. In fact, Darwin shared some of these same views, and even Weismann (106), the father of neo-Darwinism, decided late in his career that directed variation must be invoked to understand some phenomena, as random variation and selection alone are not a sufficient explanation (71). This minireview will describe mechanisms of mutation that are not random and can accelerate the process of evolution in specific directions. The existence of such mechanisms has been predicted by mathematicians (6) who argue that, if every mutation were really random and had to be tested against the environment for selection or rejection, there would not have been enough time to evolve the extremely complex biochemical networks and regulatory mechanisms found in organisms today. Dobzhansky (21) expressed similar views by stating "The most serious objection to the modern theory of evolution is that since mutations occur by `chance' and are undirected, it is difficult to see how mutation and selection can

Yes I do now understand it. I admit at first I thougt calling it a "null hypothesis" was saying the hypothesis was not proven.
I understand the term null hypothesis does not falsify the hypothesis.However I have form postings on this board gotten the impression that random mutations was a proven hypothesis, and was fact.Shapiro in his papers and his e-mail answer to me stated that the random mutation hypothesis was not a fact.What is your position. Is random mutation a fact? or is it a hypothesis that may in the future possibly be falsified?

Thats a pretty serious accusation against Shapiro. Are you saying he is a phony, promoting his theory for some type of professional or financial gain?Isn't it more likely ,that he is convinced based upon his research ,
that he is correct?

I'm of the opinion that some mutations that occur in bacteria are directed or non-random in the sense that Wright describes in her paper. But I'm not at all sure that you and I agree on what non-random or directed means. I also don't see any way the mechanisms Wright and Shapiro discuss would work in higher animals. I note that in your email exchange, Shapiro is careful to say that the non-random mutations occur in some cases.As I understand it, non-random/directed simply means that either the mutation rate or the portion of the genome that that sustains the mutation may be affected by an environmental stimulus (e.g. starvation).I don't think there is evidence that of mechanism where a stimulus generates the perfect fix so that natural selection is out of the picture. But the directed mechanisms might decrease the amount of time needed to hit a beneficial mechanism and reduce the genetic damage inflicted by mutations over a completely random approach.I think the mechanisms discussed in Wright's paper are real, but of course I haven't had a formal class in biology since high school.Edited by NoNukes, : replace effected with affected

Shapiro did not say anything like that. He said that there is evidence for some non-random mutations.Do you understand Shapiro to state that random mutations do not occur and that natural selection is not an important or relevant part of the evolutionary theory?You talk about random vs non-random as if it were one or the other. I don't believe Shapiro or any other non-kook biologist shares that opinion.

Yes, we know how you interpret Shapiro.Why didn't Shapiro answer your question with a "Yes"? Instead, he gave you a quite carefully worded response that was completely consistent with what he says in his paper. What do you think the word "potential" means in his response? What did "certain changes" mean?

I don't think Shapiro is a phony. But he is promoting his theory for professional gain. Nothing wrong with that. I'd accuse him of doing some "puffing".

Yes, random mutation is the major vector of genotypic variation. This is fact.Where you may be confusing things is that biologists, like Dr. Wright, have identified some possible mechanisms that cause an organism to "derepress" (lessen the mechanisms that repress or fix mutations) thus allowing hypermutation to occur.There may even be derepression mechanisms that have been selected and preserved through evolution that target specific suites of genes (metabolism or respiration) that get activated by environmental conditions (in times of food shortage or atmosphere change). And there may be others yet unidentified influencing other capabilities.But the point is that the individual mutations themselves are random. There just happens to be whole lot of them going on in a very short period of time.These derepression mechanisms (if they actually exist) may have been preserved by natural selection because they often hit on novel sets of (random) mutations that allow adaption to the new environmental conditions in shorter order then the natural rate of mutation could achieve.The language used within these papers is intended for the scientifically astute and (all too) often use word choices (like "directed") that are open to misunderstanding. Dr. Wright's use of the word is, I contend, used to convey the idea that the environment "directs" (affects) the mechanisms that speed up or slow down the mutation repression mechanisms.She did not intend to imply that any individual mutation was directly intended as known or planned before hand.Edited by AZPaul3, : No reason given.

Sorry to have cut that first response short. Other lives sometimes interfere.Now let's take this whole shebang and put it into some perspective.Cairns and company were talking the same kind of "directed" mutation Wright was using. His experiments sought to show some "derepress" mechanisms in bacteria. Meaning a mechanism that would shut down the normal processes used to fix the randomly generated mutations in the DNA. He was not looking for some intelligent hand directing specific mutations with foreknowledge of a specified outcome. He was just looking for the mechanisms that would allow copious mutations to remain thus increasing the chances that some beneficial random mutations would come along.As noted, other labs, duplicating his work, found some anomalies and posited other reasons for the data.In comes Zheng and takes the more philosophical approach. Cairn's, and other biologist's, data on "directed mutations" appeared to support the contention that some mechanism of "directed mutation" (again meaning allowing large numbers of random mutations to remain unfixed) existed. What Zheng showed through the use of the "null hypothesis" tool was this:If the null hypothesis of these studies were "random mutation" instead of "directed mutation" (keeping in mind the scientific 'directed' here) then the data generated by those studies did not conflict with the "random" null hypothesis either. In other words the studies showed absolutely nothing!You misunderstood Zheng's use of the null hypothesis. You misunderstood Cairn's and Wright's use of the word "directed" as applied to their studies. I suspect (though I cannot be certain since I do not know Shapiro's work) you misunderstand Shapiro and misunderstand his responses to your e-mails.Nowhere in any of this is anyone suggesting that "directed mutations" are intelligently directed with foreknowledge of a specified outcome.All are talking about "directed mutations" as a cascade of natural chemical events leading to the increased retention of randomly generated mutations within the genes. Some speculate that some of these cascades could be "targeted" to specific genes or suites of genes and only come into play when some other chemical cascades, responding in a completely natural non-intelligent way to some environmental change, kick them into action.The controversy here is not about some intelligent agent specifically causing some specific mutation with the intent of creating some specific change. It is about whether these natural chemical cascades responding to the environment really exist and whether they can affect the rate of retained random mutations in the genome.There is nothing here for any religionist or ID advocate or woo-woo believer to point to as proof of god or magic or inter-dimensional intelligence. There is only real work for real biologists and some fodder for charlatans to pick stupid peoples' pockets.

That isn't what Wright means by derepression. Derepression is simply a form of gene regulation where a gene that is constitutively repressed, usually by the binding of some transcription factor, has that repressive element removed. Derepression usually allows for a more rapid transcriptional response than the traditional program of transcriptional activation.Wright's argument is simply that when genes are specifically derepressed in response to some environmental factor, in most of her examples this is starvation for a specific metabolite, then genes relevant to the metabolism of that factor will often be derepressed and their expression strongly upregulated. Since transcriptional activity makes DNA more susceptible to mutation these newly transcriptionally active sites wil be significantly more prone to mutation than they were in the non-starved environment.She then argues that by increasing the level of mutation in a specific locus related to that metabolic pathway you will generate more mutants relevant to that pathway and therefore have a higher chance of generating beneficial mutants in that pathway.Just to add futher to what I said previously in the thread about these mechanisms not being relevant to evolution out of the microbial sphere. I seem to have previously missed Wright stating this outright in her own paper ... So she acknowledges that while multi-celled organisms show transcriptional responses to starvation there is no apparent mechanism for that to feedback to the genome as she proposes in bacteria.TTFN,WKEdited by Wounded King, : No reason given.