Evolutionary biologist Larry Moran tries calculating with big numbers re evolution

Ragnar, FYI, its called 'blockquotes' Googling it will be easier because if I try to explain it here, the blockquotes activates and it wont appear in the explanation and if I type out the characters separately, they wont appear either. So google it and follow the instructions. Hope that helps.

How do you do that box thing that you’re apparently supposed to put sited work in???

Steve

Looks to me like Behe's estimate was statistically confirmed here: http://www.malariajournal.com/content/9/1/217 A few orders of magnitude don't matter with very large numbers. -Q Querius

Darwinists learn not to gamble with Dr. Behe: How Many Ways Are There to Win at Sandwalk? - Michael Behe - August 15, 2014 Excerpt: At University of Toronto professor Laurence Moran's blog Sandwalk, named for Darwin's famous "thinking path," I've followed a discussion of the evolution of de novo chloroquine resistance by malaria (which I wrote about here). The exchange has touched on a few issues that seem to confuse people easily. One is how we should view the probability of winning something. In questioning my malaria numbers, a commenter remarked that it's misleading to focus retrospectively on a single event, such as winning a familiar game of cards, to calculate the odds of that exact arrangement of cards and declare it to be the likelihood of winning at the game. After all, there may be very many other ways to win, too. In order to correctly calculate the odds, he explained, one would have to take into account all of the ways to win, not just a single hand. I agree completely. Fortunately, in the huge number of malaria cells exposed to chloroquine, all the proverbial hands have already been dealt many times over, so we can confidently calculate the odds from the statistics. Here's an analogy. Suppose we observe a hall where around a thousand people are each dealt ten cards -- but not our normal playing cards. Instead there's a variety of strange symbols on the cards, in different colors and sizes, which we assume are distributed randomly to the players. We don't know the game they are playing or any of the rules, but we see that nobody in the group wins. That group shuffles out of the hall and a fresh group of a thousand people takes its place, is dealt ten cards, and again no one wins. This goes on until the 43rd group, where one person jumps up smiling and is declared to be a winner. Another 61 groups follow before there is another winner. After watching for a long time we record that on average the size of each crowd is a thousand people, and somebody wins once every 50 crowds. So what are the odds of winning that game? Of course it's 1 in 50,000 -- the statistical average number of people it takes to get a winner. Since we don't know the rules, there may be just one way to win the game, or many different ways. There may be one rare card that is needed, or multiple different specific combinations of cards. When we eventually learn more about the game we might be able to figure out the rules and understand why the odds are what they are. But that doesn't matter for this. The odds of winning themselves won't change outside of our statistical uncertainty. They'll remain approximately 1 in 50,000. We can deduce another pertinent lesson. There may be card combinations other than what have so far been dealt that win the game. But if there are, the probability of their occurrence is less than or equal to that of other ways to win that have already happened. The reason of course is that card combinations with significantly higher probabilities would already have been dealt in the large number of hands. The lesson, then, is that once we have good statistics, the probability of winning is fixed. It already implicitly includes any and all of the ways there are to win. So, too, with chloroquine resistance in Plasmodium falciparum. The best current statistical estimate of the frequency of de novo resistance is Nicholas White's value of 1 in 1020 parasites. That number is now essentially fixed -- no pathway to resistance will be found that is substantially more probable than that. Although with more data the value may be refined up or down by even as much as one or two orders of magnitude (to between 1 in 1018-1022), it's not going very far on a log scale. Not nearly far enough to lift the shadow from Darwinism. What's more, we can also conclude that the mutations that have already been found are the most effective available of any combination of mutations whose joint probability is greater than 1 in 1020, since more effective alternatives would already have occurred and been selected if they were available. That's a point of great public health consequence. Before investigating what it takes at the molecular level to confer chloroquine resistance, we might have conjectured that there was one exceedingly rare, necessary mutation, or a combination of several mutations, or a dozen different paths each with several required mutations. We would nonetheless expect that when we did uncover the pathway, we would be able to reconcile the likelihood of each of its steps with the statistical evidence. Although it was pretty easy to predict from the sequence evidence even as early as ten years ago, that is what Summers et al.'s recent work allows us to do now with great confidence. The fact that several point mutations are required before low chloroquine-pumping activity is observed for PfCRT, coupled with the known mutation rate, easily gets us very close on a log scale to Nicholas White's statistic, 1 in 1020. There is no particular reason to grasp for other explanations. Nor would it do any good. There is a lot of chatter at Sandwalk deriding the idea of "simultaneous" mutations (which was not intended in my book The Edge of Evolution in the sense it is being taken there, and which at this point I would gladly replace with other words simply to avoid the distraction). Yet it matters not a whit for the prospects of Darwinian theory whether the pathway consists of two required mutations that are individually lethal to a cell and must occur strictly simultaneously (that is, in the exact same replication cycle), or whether it consists of several mutations each with moderately negative selection coefficients, or consists of, say, five required mutations that are individually neutral and segregating at some appreciable frequency in the population, or some other scenario or combination thereof. The bottom line for all of them is that the acquisition of chloroquine resistance is an event of statistical probability 1 in 1020.,,, http://www.evolutionnews.org/2014/08/how_many_ways_a088981.html bornagain77

Hey all, Check this out: The paper was published in 2010 and titled “Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty.” http://www.malariajournal.com/content/9/1/217 -Q Querius

Thank God that the malaria parasite isn't actually trying to evolve chloroquine resistance. An obvious, though curiously favorable to humans, design flaw. Mung

It’s from the 3/22 1975 Awake! magazine published by Jehovah’s Witnesses. The article is called: “How Much Chance in ‘Chance’?” I’ll post the whole thing if you guys want

1975. Wasn't that the year that JW's predicted would be the end of the world? Or was that 1914? Or 1894? Or... Mung

gpuccio, Glad to know you were on vacation! Good for you! :) Also good to read you're working on the procedures post. I look forward with increasing anticipation to reading that post, but at the same time don't want to see you hastening your writing, because it covers a most important subject, and I sense that it will cause a powerful wave in this blog and even beyond it, and it will provoke very animated follow-up commentaries and a wide range of reactions from different readers. Your post could very well be a game changer in the ongoing debate. Mile grazie! Dionisio

Dionisio: Glad to be here again, and to find you! :) I was away for a while (vacation!). By the way, I am still working on the procedures post. Fascinating! gpuccio

Swine Flu, Viruses, and the Edge of Evolution - Casey Luskin - 2009 Excerpt: “Indeed, the work on malaria and AIDS demonstrates that after all possible unintelligent processes in the cell–both ones we’ve discovered so far and ones we haven’t–at best extremely limited benefit, since no such process was able to do much of anything. It’s critical to notice that no artificial limitations were placed on the kinds of mutations or processes the microorganisms could undergo in nature. Nothing–neither point mutation, deletion, insertion, gene duplication, transposition, genome duplication, self-organization nor any other process yet undiscovered–was of much use.” Michael Behe, The Edge of Evolution, pg. 162 http://www.evolutionnews.org/2009/05/swine_flu_viruses_and_the_edge020071.html bornagain77

Mark: Just a few further comments. My point is that, to attain completely new sequences, as it is the case for new protein domains and superfamilies, which show no homology to older existing ones, conjugation, exon shuffling, sexual reproduction, you name it, offer no advantage in respect of simple point mutations. The probabilistic barriers remain the same, whatever mechanism you may invoke. And, whatever the time you allow, and the population numbers, and the possible recombination mechanisms, you will never be able to explain the hundreds of ultra-conserved aminoacids in ATP synthase, or in thousands of other proteins, when even a two aminoacid variation is something of a problem. As you well know, the probabilistic barriers increase exponentially with the increase of the number of specific aminoacids that are requested to implement the biochemical function. Hundreds of specific aminoacids, like in ATP synthase, are a probabilistic barrier even for some optimistic multiverse! gpuccio

Mark Frank- sexual reproduction is the bane of universal common descent. At least with asexual reproduction it is fairly certain that any mutation the parent has will get passed down to its offspring. That isn't so with sexual reproduction. Sexual reproduction tens to keep the norm and weed out any deviates. Sexual reproduction is where universal common descent died.

Sexuality has brought joy to the world, to the world of the wild beasts, and to the world of flowers, but it has brought an end to evolution. In the lineages of living beings, whenever absent-minded Venus has taken the upper hand, forms have forgotten to make progress. It is only the husbandman that has improved strains, and he has done so by bullying, enslaving, and segregating. All these methods, of course, have made for sad, alienated animals, but they have not resulted in new species. Left to themselves, domesticated breeds would either die out or revert to the wild state—scarcely a commendable model for nature’s progress. (snip a few paragraphs on peppered moths) Natural Selection, which indeed occurs in nature (as Bishop Wilberforce, too, was perfectly aware), mainly has the effect of maintaining equilibrium and stability. It eliminates all those that dare depart from the type—the eccentrics and the adventurers and the marginal sort. It is ever adjusting populations, but it does so in each case by bringing them back to the norm. We read in the textbooks that, when environmental conditions change, the selection process may produce a shift in a population’s mean values, by a process known as adaptation. If the climate turns very cold, the cold-adapted beings are favored relative to others.; if it becomes windy, the wind blows away those that are most exposed; if an illness breaks out, those in questionable health will be lost. But all these artful guiles serve their purpose only until the clouds blow away. The species, in fact, is an organic entity, a typical form, which may deviate only to return to the furrow of its destiny; it may wander from the band only to find its proper place by returning to the gang. Everything that disassembles, upsets proportions or becomes distorted in any way is sooner or later brought back to the type. There has been a tendency to confuse fleeting adjustments with grand destinies, minor shrewdness with signs of the times. It is true that species may lose something on the way—the mole its eyes, say, and the succulent plant its leaves, never to recover them again. But here we are dealing with unhappy, mutilated species, at the margins of their area of distribution—the extreme and the specialized. These are species with no future; they are not pioneers, but prisoners in nature’s penitentiary.- Giuseppe Sermonti- geneticist

Joe

Gpuccio 1) What is the point of this estimate? If your objective is to compare the number of individuals of sexually reproducing species with asexually reproducing species then it is rather stunning to only consider vertebrates! But any way that is not the question. I don’t doubt there are many more asexually reproducing organisms than there are sexually reproducing.  The question is how big an evolutionary advantage does it give a species to be sexually producing in terms of producing viable variety.  I have no idea how you estimate that.

2) Sexual reproduction can help in mixing existing alleles in a population. However, recombination of whole sequences is perfectly possible even in bacteria, by translocations and other mechanisms. SPN is not the only mechanism available, even in prokaryotes

 I had forgotten about conjugation. Have you an estimate of how frequent and effective that process is compared to recombination?  In any case the fact remains that conjugation and recombination before provide ways of mixing and transferring whole strings and substrings of viable DNA. The probability calculation for this seems almost impossible to me but it certainly isn’t the same as for independent point mutations. If, as I suspect, the only route to chloroquine resistance is via these two independent mutations then the conjugation alternative is not available whereas both conjugation and recombination are available for other types of evolution.

And anyway, I cannot see how sexual reproduction should help in generating completely new complex functional sequences: about two thirds of those basic protein domains arose in LUCA, prokaryotes and single celled eukaryotes, without relevant contribution from sexual reproduction.

Fair enough. I suspect conjugation may well play a role here. Of course they had vastly more time to happen in vast populations

3) The important point is that, in the few cases where an intermediary state is known, it is not selectable. In almost all cases no intermediary state is known, and that is not a good thing for the neo darwinian model. Not a good thing at all, whatever darwinists may say.

Do you have a list of those evolutionary episodes where the intermediary state is known? On second thoughts don’t bother … I really don’t have time to study them.

4) I love your “ifs”.

Glad to provide some amusement.  Mark Frank

bornagain77- you mean "leading the evidence to where materialists want it to go" ;) - and that Lewontin quote never gets old Joe

"Face it, it isn’t science.", But Joe, not following the evidence where it leads HAS TO BE SCIENCE for the materialist, the alternative is simply unthinkable for him!!!,,, "It is not that the methods and institutions of science somehow compel us to accept a material explanation of the phenomenal world, but, on the contrary, that we are forced by our a priori adherence to material causes to create an apparatus of investigation and a set of concepts that produce material explanations, no matter how counter-intuitive, no matter how mystifying to the uninitiated. Moreover, that materialism is absolute, for we cannot allow a Divine Foot in the door. - Lewontin http://www.drjbloom.com/Public%20files/Lewontin_Review.htm or to put materialism another way: Think Inside The Box - picture http://si.wsj.net/public/resources/images/RV-AK835_INNOVA_G_20130614181900.jpg bornagain77

It's fun to observe how some of you guys complement each other by commenting on different aspects of the same subject, from different perspectives. A real example of teamwork. If this were football, your team would have won the world cup easily ;-) However, on some occasions you all remind me the Amazonian piranhas, because as soon as an oblivious animal steps into these waters, y'all quickly come out and devour it with a barrage of solid arguments! Well done, folks! ;-) Dionisio

Mark Frank- Your position can't account for sexual reproduction so that would be a problem. Geez if it can't even account for the requirement of two-four specific mutations, how do you it could account for something more complex? Heck unguided evolution can't even get beyond the given starting point of prokaryotes. It can't even be modeled. Face it, it isn't science. Joe

gpuccio Glad to see you're back here! :) I was -and most probably many others were- missing your insightful commentaries. Dionisio

Mark: 1) With malaria we are talking of about 10^18 plasmodia for one million human infestations. For higher species reproducing sexually (in particular, vertebrates), I have found the following estimates (total population on our planet): Fish at least 10^13 Land Amphibians 10^12 to 10^13 Land Reptiles 10^12 to 10^13 Land Birds 10^10 to 10^11 Land Mammals 10^11 to 10^12 I don't know how accurate they are, but it seems obvious that, even if we sum all vertebrates, we are still a few orders of magnitude short versus the mere number of malaria parasites. 2) Sexual reproduction can help in mixing existing alleles in a population. However, recombination of whole sequences is perfectly possible even in bacteria, by translocations and other mechanisms. SPN is not the only mechanism available, even in prokaryotes. And anyway, I cannot see how sexual reproduction should help in generating completely new complex functional sequences: about two thirds of those basic protein domains arose in LUCA, prokaryotes and single celled eukaryotes, without relevant contribution from sexual reproduction. 3) The important point is that, in the few cases where an intermediary state is known, it is not selectable. In almost all cases no intermediary state is known, and that is not a good thing for the neo darwinian model. Not a good thing at all, whatever darwinists may say. 4) I love your "ifs". :) gpuccio

#17 Gpuccio

Asexual reproduction is vastly balanced by the huge population number.

Show me the calculations that prove this (just an order of magnitude will do)

Moreover, you have to show how sexual reproduction can help in generating new functional protein sequences.

Is it not well accepted both theoretically and empirically that sexual reproduction greatly increases the rate of variation and evolution? I have never bothered to understand this in detail but surely sexual reproduction allows recombination which means that whole sequences of viable DNA are mixed in new combinations.  This completely changes the probability model from simple mutations.

I love your “no selection for intermediary state” thing. Does it evoke old discussions we had? Could you please show where “selection for intermediary state” happened in natural history, say to generate ATP synthase, or any other new complex functional protein?

There is a difference between not knowing what the intermediary state is (and therefore not knowing whether it is selected for) and knowing what it is and therefore knowing it is not selected for. 

And why the “limited number of solutions”? That solution is just the simplest one. Couldn’t the neodarwinian algorithm generate a new complex protein cascade with the function of metabolizing or inactivating chloroquine, for example? After all, the model is supposed to have done those things all the time, throughout natural history!

Perhaps I should have said - only one solution as far as we know. Perhaps there is another possible solution which is even more difficult to evolve. The point is not whether it is simple or not - but how easy it is to evolve.  A more complicated solution might well be easier to evolve if it was the result of intermediary stages that also brought selective advantage. Mark Frank

Darwinists are fond of denying ID as "science" by asserting that there is no metric by which a biological feature can be ascertained as the product of ID. The problem they never seem to understand is that if there is no metric for determining ID necessary in the production of a feature, there can be no metric for determining non-ID nature (chance & law determined mechanisms) sufficient. Every time a Darwinist denies that ID has a metric to support it's claim, they are admitting their is no metric supporting Darwinism. You'd think any reasonable person would recognize that the commitment to Darwinism (materialist explanations of evolution) are obviously ideological and not warranted by any known logic or evidence. Darwinian evolution is assumed, and it is assumed in the face of the overwhelming appearance of design in biology. William J Murray

Mark Frank: So you are saying that this is an exception rather than a general finding? It is really one of the few cases we can observe to occur therefore it would be difficult to convincingly accept it is an exception. Further, as the theory of evolution maintains, microbes became man. Therefore, if we have to exclude asexual reproduction we simply move the goalposts but miss half of the target. How did a microbe with asexual reproduction evolve into a multicellular organism? How did asexual reproducers evolve to sexual reproduction? In addition, this is not the first case of demonstrating the need for a specific mutations needed to go from one function of a protein to another variation. See: http://www.evolutionnews.org/2014/06/more_strong_exp087061.html where essentially we see that even with supposed neutral mutations, those that are needed despite being neutral, are quite specific in their identity. The bottom line is that the evidence is heavily stacked (and stacking) against randomness (that material evolution requires and is founded upon – not a feature of, but its foundational structure) being sufficient to account for novel functional proteins arising (from existing proteins). Even more so how difficult/improbable is it for life to arise from no order in the very first place? For multicellularity to arise from unicellularity? These findings cannot hide behind asexual reproduction, intermediatory stages, and the rest because the point is that this evidence shows that often, intermediate stages are not likely (due to deleterious nature of mutations) and when they are (e.g. neutral evolution) they are often very specific requirements thus multiple specificities to accumulate require vastly improbable odds. Again, I emphasise, this is just thinking about 1 protein. Now think about the spliceosome, and its ~150+ protein construction and ask yourself how would the odds look for those proteins to arise from chance, be able to interact with the other proteins that arose by chance, and retain catalytic activity towards the overall goal. To believe that such a structural machine, essential for complex mammalian life, could come about by chance with such vast interactions and activities and precision in splicing is beyond common sense and has no chance whatsoever of standing up to mathematical probabilities. Dr JDD

Mark: Asexual reproduction is vastly balanced by the huge population number. Moreover, you have to show how sexual reproduction can help in generating new functional protein sequences. I love your "no selection for intermediary state" thing. Does it evoke old discussions we had? :) Could you please show where "selection for intermediary state" happened in natural history, say to generate ATP synthase, or any other new complex functional protein? And why the "limited number of solutions"? That solution is just the simplest one. Couldn't the neodarwinian algorithm generate a new complex protein cascade with the function of metabolizing or inactivating chloroquine, for example? After all, the model is supposed to have done those things all the time, throughout natural history! gpuccio

aqeels @ 14, the nail head got hammered by you! It is not, nor has it ever been, primarily about the evidence, it has always been primarily about the atheistic metaphysics. “For scientific materialists the materialism comes first; the science comes thereafter. We might more accurately term them “materialists employing science.” And if materialism is true, then some materialistic theory of evolution has to be true simply as a matter of logical deduction, regardless of the evidence.,,, Darwinism is based on an a priori commitment to materialism, not on a philosophically neutral assessment of the evidence. Separate the philosophy from the science, and the proud tower collapses.” Phillip Johnson - The Unraveling of Scientific Materialism, First Things, 77 (Nov. 1997), pp. 22 – 25. http://www.firstthings.com/article/2008/09/002-the-unraveling-of-scientific-materialism-26 Verse and music: Proverbs 1:7 The fear of the LORD is the beginning of knowledge. Stubborn fools despise wisdom and discipline. Steven Curtis Chapman – Lord of the Dance (Live) http://www.youtube.com/watch?v=hDXbvMcMbU0 bornagain77

#8 Gpuccio But surely there are other characteristics of chloroquine resistance that are extremely unfavourable for Darwinian reproduction. Asexual reproduction, no selection for intermediary stage, limited number (in fact only one) solution to the problem (from the plasmid's PoV that is). Mark Frank

Gpuccio @8 - your point is well made (as usual). "So what" translates to "Yes we know it can be highly unlikely but these are mere details that science will work out in due course. That evolution happened in an unguided way as espoused by Darwin is not under debate here so thanks for your calculations but I will choose to ignore them!" aqeels

to back this claim from post 2 up,,,

Moreover it is interesting to note, since the debate between Moran and Behe is centered on mathematics, that there is the little problem that mathematics cannot even be rationally grounded in the materialistic/Darwinian worldview in the first place. Not a minor problem for Darwinists!

,,,to back that claim up,,, I cite Wallace, the co-discover of natural selection, Gödel, the discoverer of incompleteness, and Berlinski, the first class pain in the Darwinian backside :)

New Thoughts on Evolution (1910) Views of Professor Alfred Russel Wallace, O.M., F.R.S. "Nothing in evolution can account for the soul of man. The difference between man and the other animals is unbridgeable. Mathematics is alone sufficient to prove in man the possession of a faculty unexistent in other creatures. Then you have music and the artistic faculty. No, the soul was a separate creation." Alfred Russel Wallace - An interview by Harold Begbie printed on page four of The Daily Chronicle (London) issues of 3 November and 4 November 1910. http://people.wku.edu/charles.smith/wallace/S746.htm "Either mathematics is too big for the human mind or the human mind is more than a machine" - Kurt Godel Kurt Godel - Incompleteness Theorem and Human Intuition - video http://www.metacafe.com/watch/8515973/ An Interview with David Berlinski - Jonathan Witt Berlinski: There is no argument against religion that is not also an argument against mathematics. Mathematicians are capable of grasping a world of objects that lies beyond space and time …. Interviewer:… Come again(?) … Berlinski: No need to come again: I got to where I was going the first time. The number four, after all, did not come into existence at a particular time, and it is not going to go out of existence at another time. It is neither here nor there. Nonetheless we are in some sense able to grasp the number by a faculty of our minds. Mathematical intuition is utterly mysterious. So for that matter is the fact that mathematical objects such as a Lie Group or a differentiable manifold have the power to interact with elementary particles or accelerating forces. But these are precisely the claims that theologians have always made as well – that human beings are capable by an exercise of their devotional abilities to come to some understanding of the deity; and the deity, although beyond space and time, is capable of interacting with material objects. http://tofspot.blogspot.com/2013/10/found-upon-web-and-reprinted-here.html Dr. David Berlinski: Head Scratching Mathematicians - video http://www.youtube.com/watch?v=hEDYr_fgcP8 quote from preceding video: “John Von Neumann, one of the great mathematicians of the twentieth century, just laughed at Darwinian theory, he hooted at it!,,,There is a consistent group of people, among mathematicians, among physicists, among some very good speculative biologists, who simply don’t accept it (Darwin’s theory). (They) don’t even regard it as a scientific theory in any reasonable sense.” Dr. David Berlinski

Thus it is not surprising that mathematics should be found to be so utterly antagonistic to Darwinian claims. Materialism can't even begin explain our mathematical intuition in the first place! Verse and Music:

2 Peter 1:16 For we did not follow cleverly devised tales when we made known to you the power and coming of our Lord Jesus Christ, but we were eyewitnesses of His majesty. Made New - Lincoln Brewster http://myktis.com/songs/made-new/

bornagain77

Many thanks BA77 - was reading other people's summaries of the work in haste so would have been wise to read the original! So again we have an example of "evolution" that allows survival under this selection pressure but with a reduction of information/complexity and at a fitness cost. Hardly instilling confidence that you could go from microbe to man. Dr JDD

Dr JDD,,, from post 2:

Metabolic QTL Analysis Links Chloroquine Resistance in Plasmodium falciparum to Impaired Hemoglobin Catabolism - January, 2014 Abstract: Drug resistant strains of the malaria parasite, Plasmodium falciparum, have rendered chloroquine ineffective throughout much of the world. In parts of Africa and Asia, the coordinated shift from chloroquine to other drugs has resulted in the near disappearance of chloroquine-resistant (CQR) parasites from the population. Currently, there is no molecular explanation for this phenomenon. Herein, we employ metabolic quantitative trait locus mapping (mQTL) to analyze progeny from a genetic cross between chloroquine-susceptible (CQS) and CQR parasites. We identify a family of hemoglobin-derived peptides that are elevated in CQR parasites and show that peptide accumulation, drug resistance, and reduced parasite fitness are all linked in vitro to CQR alleles of the P. falciparum chloroquine resistance transporter (pfcrt). These findings suggest that CQR parasites are less fit because mutations in pfcrt interfere with hemoglobin digestion by the parasite. Moreover, our findings may provide a molecular explanation for the reemergence of CQS parasites in wild populations. Summary: Chloroquine was formerly a front line drug in the treatment of malaria. However, drug resistant strains of the malaria parasite have made this drug ineffective in many malaria endemic regions. Surprisingly, the discontinuation of chloroquine therapy has led to the reappearance of drug-sensitive parasites. In this study, we use metabolite quantitative trait locus analysis, parasite genetics, and peptidomics to demonstrate that chloroquine resistance is inherently linked to a defect in the parasite's ability to digest hemoglobin, which is an essential metabolic activity for malaria parasites. This metabolic impairment makes it harder for the drug-resistant parasites to reproduce than genetically-equivalent drug-sensitive parasites, and thus favors selection for drug-sensitive lines when parasites are in direct competition. Given these results, we attribute the re-emergence of chloroquine sensitive parasites in the wild to more efficient hemoglobin digestion. http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004085

bornagain77

Sorry phone autocorrect fail: et = wt (I.e. wild type) Dr JDD

Can anyone tell me / does anyone know: Does the double mutant equal or outperform the et parasite in the wild, in the absence of chloroquine? Just curious. Mark frank: let us say an existing gene duplicated and gave a framework for evolution to manipulate to generate novel functionality. To get to a novel function this required 20 amino acids to be mutated out of 300. That is a reasonably generous (favourable) scenario. Let us say 12 of those are neutral, 2 are advantageous and 6 are deleterious. Again, generosity assumed. Now let us forget about the time to include the 14 mutations that are positive and neutral (which would he large to get just all the correct neutral ones together anyway). Thus you are left with 3 lots of the chloroquine resistant type mutations needed (in. Addition to the 14 others). If the 10^18 is a true probability of 1 double occurring, the 3 doubles (to achieve 6 mutations) would be the product which is 10^54. This is simply not achievable with any organism on the face of the earth in all of life's history. And that is from an existing protein. We haven't even discussed abiogenesis or how the simplest organism with multiple proteins interacting with each other would be (im)possible. Dr JDD

Mark: The point is simple. The malaria parasite under the extremely strong selection of chloroquine is a model extremely favourable to the neo darwinian algorithm: huge populations, very high reproduction rate, very strong and precise selective pressure, and a rather simple advantageous variation thta can be attained (just two AA variation to confer resistance to a lethal drug). We can say that this the perfect scenario for the neo darwinian model, and a good way to measure its powers. Now, in such a favourable scenario, how does the model work? It works (in the end, chloroquine resistance arises), but it definitely requires a lot of time and huge population numbers. IOWs, it happens with some difficulty. That's all. That difficulty is exactly what is needed to infer how much more "difficult" (indeed, impossible) it would be for the same neo darwinian model to explain the emergence of a new complex protein when the necessary transition is, say, of 300 AAs, and the population number, reproduction rate and selective pressure are much less favourable to the model. For example, to evolve just one new useful protein in vertebrates or mammals. That is, and always has been, Behe's point. And the point of ID. Can you really say "so what" to that argument? gpuccio

Behe's arguments are, as always, impeccable. gpuccio

I must be missing something important. As far as I can see everyone seems to agree that the mutations required for chloroquine resistance are extremely improbable and this is born out by the rarity of such resistance in the wild. So what? Mark Frank

No living organism can survive without a gene repair mechanism that fixes genetic mutations when they appear. How did such a mechanism evolve since the organism cannot survive without it? Compute that, Moran. Mapou

How do you do that box thing that you're apparently supposed to put sited work in??? Ragnar

Calculate this Moran: the total probability of the horse coming about by chance, not in an instant but according to the blind, undirected, blind mechanisms of natural selection and random mutation is 1,000 X 10 to the 1 millionth power! For God's sakes, that number is so inconceivable it's not even funny. (Though probably the same probability is true if a horse suddenly came about by a tornado going through a warehouse with all the elements to build a horse). Here's that part of the article where I found it from: ---Actually, the chances are so dim that even avowed evolutionists acknowledge it is all but impossible to believe. Says Julian Huxley: “A little calculation demonstrates how incredibly improbable the results of natural selection can be when enough time is available.” He asks, What are the odds that a horse could be produced by chance alone? In his answer Huxley refers to “the fantastic odds against getting a number of favorable mutations in one strain through pure chance alone,” and then he adds: “A thousand to the millionth power [1,0001,000,000], when written out, becomes the figure 1 with three million noughts after it; and that would take three large volumes of about five hundred pages each, just to print! Actually this is a meaninglessly large figure, but it shows what a degree of improbability natural selection has to surmount . . . One with three million noughts after it is the measure of the unlikeliness of a horse—the odds against it happening at all. No one would bet on anything so improbable happening.” Nevertheless, Huxley turns around and incredulously says: “Yet is has happened.” How consistent does that seem to you? If anyone wishes to believe odds of that nature, that is his foolish decision. But he cannot honestly say that the burden of evidence—the odds—rests with his case.--- It's from the 3/22 1975 Awake! magazine published by Jehovah's Witnesses. The article is called: "How Much Chance in 'Chance'?" I'll post the whole thing if you guys want Ragnar

It is interesting to note that Chloroquine Resistance, as hard as it is for Darwinian processes to account for, (whether in the 1 in 10^14 calculation or in the 1 in 10^20 observation), it is not even a gain in functional complexity for the malaria parasite in the first place but is a loss of functional complexity for the parasite.

Metabolic QTL Analysis Links Chloroquine Resistance in Plasmodium falciparum to Impaired Hemoglobin Catabolism - January, 2014 Summary: Chloroquine was formerly a front line drug in the treatment of malaria. However, drug resistant strains of the malaria parasite have made this drug ineffective in many malaria endemic regions. Surprisingly, the discontinuation of chloroquine therapy has led to the reappearance of drug-sensitive parasites. In this study, we use metabolite quantitative trait locus analysis, parasite genetics, and peptidomics to demonstrate that chloroquine resistance is inherently linked to a defect in the parasite's ability to digest hemoglobin, which is an essential metabolic activity for malaria parasites. This metabolic impairment makes it harder for the drug-resistant parasites to reproduce than genetically-equivalent drug-sensitive parasites, and thus favors selection for drug-sensitive lines when parasites are in direct competition. Given these results, we attribute the re-emergence of chloroquine sensitive parasites in the wild to more efficient hemoglobin digestion. http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004085

Thus the resistance, as crushing as it is, number-wise, for Darwinists to explain the origin of, is doubly crushing for Darwinists, since the adaptation, as hard as it was for Darwinian processes to acquire, was still 'downhill' evolution anyway and adds nothing as to explaining microbes to man evolution is remotely possible in a Darwinian scenario! Another place where these big numbers play out is, as Dr. Behe points out, in the comparative reproduction rates:

Waiting Longer for Two Mutations - Michael J. Behe Excerpt: Citing malaria literature sources (White 2004) I had noted that the de novo appearance of chloroquine resistance in Plasmodium falciparum was an event of probability of 1 in 10^20. I then wrote that 'for humans to achieve a mutation like this by chance, we would have to wait 100 million times 10 million years' (1 quadrillion years)(Behe 2007) (because that is the extrapolated time that it would take to produce 10^20 humans). Durrett and Schmidt (2008, p. 1507) retort that my number ‘is 5 million times larger than the calculation we have just given’ using their model (which nonetheless "using their model" gives a prohibitively long waiting time of 216 million years). Their criticism compares apples to oranges. My figure of 10^20 is an empirical statistic from the literature; it is not, as their calculation is, a theoretical estimate from a population genetics model.,,, http://www.discovery.org/a/9461

As well, these comparative reproduction rates play out like this, if evolution were actually the truth about how all life came to be on Earth then the only 'life' that would be around would be extremely small organisms with the highest replication rate, and with the most mutational firepower, since only they would be the fittest to survive in the dog eat dog world where blind pitiless evolution rules and only the 'fittest' are allowed to survive. The logic of this is nicely summed up here:

Richard Dawkins interview with a 'Darwinian' physician goes off track - video Excerpt: "I am amazed, Richard, that what we call metazoans, multi-celled organisms, have actually been able to evolve, and the reason [for amazement] is that bacteria and viruses replicate so quickly -- a few hours sometimes, they can reproduce themselves -- that they can evolve very, very quickly. And we're stuck with twenty years at least between generations. How is it that we resist infection when they can evolve so quickly to find ways around our defenses?" http://www.evolutionnews.org/2012/07/video_to_dawkin062031.html

i.e. Since successful reproduction is all that really matters on a neo-Darwinian view of things, how can anything but successful reproduction be realistically 'selected' for? Any other function besides reproduction, such as sight, hearing, thinking, etc.., would be highly superfluous to the primary criteria of successfully reproducing, and should, on a Darwinian view, be discarded as so much excess baggage since it would, sooner or later, slow down successful reproduction. Moreover it is interesting to note, since the debate between Moran and Behe is centered on mathematics, that there is the little problem that mathematics cannot even be rationally grounded in the materialistic/Darwinian worldview in the first place. Not a minor problem for Darwinists! bornagain77

Repeat after me: "Evolution doesn't need any steekin' numbers. Evolution doesn't need any steekin' probabilities. We are comforted by the fact that universal common descent via evolution by descent with modification has occurred. Whether or not we ever fill in the numerous blanks is besides the point." Yeah baby... Joe