A Long Story of nonsense: antibiotic resistance, the Lenski experiment and more

[Nesslig20]

Yes, it is long story short (LSS) again. If you are new, I have talked about him and the videos he makes for the Discovery Institute before. More recently here, and on the main thread here. For almost a year now, me and Ration alMind have collaborated together with Jackson Wheat to make response videos to this guy. We are still planning to finish the last rebuttal video to the topic of whale evolution, but lately we have been working on other things.

Recently, I got a notification that LSS uploaded a new video.



Apparently, this video was uploaded on the youtube channel of the discovery institute a few weeks before, but I don't pay any attention to that channel. As you can see, LSS here is talking about antibiotic resistance. In LSS's first video that he made for the Discovery Institute, which was about homology, he did mention at the end that he was going to do videos about other arguments for evolution, including antibiotic resistance. In the response video on Jackson Wheat's channel, we expressed our expectations as such:

Oh, goodie, I can already hear him repeating the exact same flawed arguments...antibiotic resistance isn't new information, it's variation or loss of information. Resistance is also associated with a cost in fitness.

And indeed, LSS here makes these EXACT same arguments that we anticipated. How predictable. And there is a whole lot more wrong with this video. The only positive thing I can say is that it didn't go as far as making the "They are still bacteria, they didn't turn into humans/elephants/whales [or any other complex multi-celled organism]". Talk about a low bar. I notified Jackson Wheat about this, but he made it clear that he is no longer making any response videos to LSS after we wrap up the ones on whale evolution. It's not really worth to continue on like this in video format. Best to focus more on promoting educational stuff and less on debunking nonsense. But hey, I finished with my home work. Feeling a bit bored and in the mood to write something again on the League of Reason forum. So why not tackle this video here instead.

1. Antibiotic Resistance
1.1 The 'orthogenesis' straw man

Antibiotics are a wonderful medicine when dealing with bacterial infections, but unfortunately they're sometimes misused. When antibiotics are misused it can lead to them suddenly not working anymore. And if you ask folks like Richard Dawkins and Bill Nye the science guy, the answer is that this is incontrovertible proof of evolution right before our very eyes. It's an evolutionary arms race they say, as our weapons of medical warfare get stronger and more sophisticated, so too the bugs we're fighting are getting stronger, they're evolving better defenses, making them immune to the best we can throw at them. The power of natural selection and random mutation laughs at our incompetent medical prowess, bacterial evolution and antibiotic resistance is one of the all-time greatest hits regarding evidence for evolution. [...] But is this a demonstration of the creative power of Darwinian evolution or is there something else going on? Let's take a look more closely.

After watching the video to this point, I could already see what he was doing. Notice where he says "better" and "stronger", ambiguous buzzwords that convey the notion of 'superiority'. These 'bugs' are 'progressing' to be 'better'. He is painting evolution as a process where (as Kent Hovind likes to say) everything is getting bigger, better, stronger, and smarter. MISCONCEPTION: Evolution results in progress; organisms are always getting better through evolution. To be fair though, there are instances were proponents of evolution use this type of language as well, a historical left over of the 'scala naturae' concept. Evolution, as was also realized (although not consistently adhered to) by Darwin, is not a 'progressive' process where organisms have a tendency to evolve towards some teleological goal. This concept is called orthogenesis. Natural selection is not a force that does this, as selective pressures change on the population, so do the criteria for what variant counts as "more fit". What is "better" is relative. It dependents on the context of the environment and the niche of the population occupies. Not one species or variant is the 'best' in a general nor absolute sense. Don't think in terms of ladders. Think about trees instead.

By painting this orthogenic picture of antibiotic resistance, and also inserting the idea of the "all mighty creative power" of evolution, LSS is artificially raising the impressiveness of antibiotic resistance is to the viewers, so that he later can refute this impression, and proclaim victory after he set the straw man on fire. As it turns out, these bugs aren't actually "better" or "stronger" [in every conceivable way] after all!! And they gained nothing NEW!! So much for the creative power of evolution!! Of course, that is what he is does.

1.2 Yes...it is evolution...ant not trivially so.

it's true that antibiotics do sometimes stop working and antibiotic resistance is a form of evolution, narrowly speaking.

Not "narrowly speaking". Is the rise and increase in occurance of antibiotic resistance among pathogenetic bacteria (and some other organisms as well) explained through processes that are corner stones of evolutionary theory, e.g. natural selection? Yes! When pressed on this, most creationists and ID-proponents would agree, sometimes after a bit of growling and squirming. Although, they will inevitably dismiss it as trivial. But understanding how antibiotic resistance comes to be and spreads is definitely NOT trivial. It is literally a matter of life or death, which is exactly why a lot of attention is payed to antibiotic resistance by evolutionary biologists.

1.3 Resistance was already there before...what's your point?

Let's get to know these bacteria killers we affectionately call antibiotics. How do they keep us alive where do they come from what's their favorite kind of ice cream? There's a lot of ways for antibiotics to defeat bacteria. Some explode it, some gum up the works, some starve the little bugs out, others prevent them from multiplying and so on, but there's essentially only one or two ways that bacteria can become resistant to antibiotics. The first and most common way bacteria gain resistance is that it's always been there. Antibiotic resistant bacteria actually pre-exist the invention of modern antibiotics. There's an interesting story of some arctic explorers from back in the 1800s turns out they froze to that before the discovery and use of antibiotics some morbid scientists found them recently and took samples of their gut bacteria and found that they already had resistance to some of our most powerful modern antibiotics, just like some people are naturally short and immune to limbo bars some bacteria naturally have a pre-existing resistance to antibiotics not because they've gained this ability after an encounter with the antibiotic, but it's just always been the case. That said bacteria do have a neat special ability that short people don't have. They love to share not just cooking recipes and financial advice but super personal things like their very own DNA they'll swap loops of DNA called plasmids in a process called horizontal gene transfer or HGT, like third graders with Pokemon cards. They have no idea how they got them or even what they do, but they'll trade them back and forth and occasionally they'll share these resistance genes. Nothing new has been made or evolved though bacteria already had the ability to trade plasmids and the genes for resistance already existed before antibiotics. This is hardly an arms race, and it's not a demonstration of Darwinian creative power, since there's no new mutations and no new genes that have been made.

Yes, very often, the mutations responsible for the resistant phenotype occurred before the selective pressure (prominent use of antibiotics). So what? We don't expect the beneficial mutation to occur exclusively RIGHT at the moment (or after) when this would be beneficial. Natural selection is not a driving force that causes the "needed" mutations to arise!! Selection acts on existing variation that was already established, and any variation that may later appear in the population via mutation, recombination, migration, horizontal gene transfer, etc. MISCONCEPTION: Natural selection gives organisms what they need.

This is not a clever rebuke on evolution as he might have thought. LSS is (once again) proving he has little understanding of this subject. The fact that antibiotic resistant bacteria can (and often do) exist prior to being exposed to antibiotics is one line of evidence that supports the hypothesis that mutations are largely random (or non-directed), i.e. the relative rate of a particular mutation is not influenced by whether the organisms inhabits an environment that would make the mutation beneficial, harmful or neutral. Though there may be exceptions. As mutations are generally random, the ones that causes bacteria to be resistant to antibiotics could happen just as easily before or after when the antibiotics are first used. So it is likely that some pre-existing resistant mutants managed to linger in small numbers just prior to the use of antibiotics. This is where natural selection comes in, as these resistant bacteria now have a reproductive advantage of the others. Resistance becomes more common in the population to the point when they become actually noticeable and a nuisance.

Also, LSS is implying that, since these existed before, these resistant varients have always existed. They aren't the result of mutations. However, these are likely too the result of mutations. As LSS says next, such resistant mutations would likely have a disadvantage with regard to the "vanilla bugs", but if that were the case, how did they last so long before antibiotics gave them the upper hand? It is likely that antibiotic resistance appeared by mutation and dissapeared by selection repeadidly, before the use of antibiotics. (Although some antibiotics occur naturally, so that's one way that antibiotic resistance could persist by selection. That's not the case with synthetic antibiotics).

1.4 Evolution expelled, NO trade-offs allowed?

Not only that but these extra resistance genes are frequently a net negative on fitness. Bacteria with extra useless genes tend to be less fit than regular old vanilla bugs. Imagine you're in a foot race you usually don't need a duffel bag filled with camping supplies a pickaxe spare bowling balls and a weed whacker during your typical foot race if you do great otherwise it's a huge waste of energy lugging all that stuff around and it makes you less competitive. Bacteria with extra genetic load tend to be less fit than regular old vanilla bugs.

What about mutations though? This is the second less common, but more interesting way that bacteria develop resistance to antibiotics. How does it work? Scientists are aware of pre-existing resistance so to exclude it as a possibility in experiments they can start with a single normal non-resistant bacteria and let that multiply over and over again and eventually the bacteria population can still develop resistance on its own. Here's how. When copying their DNA organisms are pretty accurate and mutations are relatively rare but given enough time errors do sneak in like typos or auto correct. When you're texting someone sometimes they're no big deal and you can get along in spite of them, but sometimes these mutations really do do something and can confer resistance or even immunity to antibiotics. Amazing, that must demonstrate the mighty power of evolution. Well hold your horses, it's sort of like someone who has no arms saying that they're immune to handcuffs, no legs you're immune to toenail fungus, no teeth congratulations you're immune to cavities, think of how much you'll save on toothpaste and floss expenses. Deaf and blind you're immune to getting annoying songs stuck in your head. Wow this poor soul might technically be immune to those things in a perverse way, but it comes at a cost he's hardly a more fit organism and these mutated bacteria are just hobbled busted up versions of the original. Darwinian evolution can get very far by breaking things. Eentually it'll run out of things to break and in reality.

When antibiotics are removed from the environment, these super bugs just sort of die out, because without the help of antibiotics keeping the stronger normal bacteria at bay they can't compete and they die out.

The fact that resistance often comes with a cost is not a gotcha against evolution. As the saying goes, there is no free lunch. Evolution does not produce perfect organisms with "super powers" without any downsides. MISCONCEPTION: Natural selection produces organisms perfectly suited to their environments. In evolution, it is often the case that a phenotype that is beneficial in one environment is accompanied by a cost, which results in a net loss of fitness in other environments where the phenotype isn't of much benefit. This is known as an "evolutionary trade-off". And the whole point of a trade-off is that the benefit gained is greater than the costs, such that there is still a NET increase in fitness. And, again, whether there is a net benefit to a phenotype remains dependent on the environment.

If you look JUST at the last sentence of the quote above, LSS seems to get this. However, he previously spend most of his time to give the impression that resistant bacteria are "less fit" in a general way. Like with his horrendous analogy of how people without any arms, legs, and eyes who have no net benefit under any reasonable circumstance. It misses the whole point that, in spite of the trade-off of resistance, there is still a net benefit. I have a better analogy. There trade-off between power and endurance, exemplified here with the marathon runner and sprinter. (Perhaps this is not an actual trade-off, but that's beside the point)

Now, borrowing the rhetoric of LSS, I can say that the sprinter isn't more fit, since he has more weight to carry around. Without the help of trivial distances keeping the stronger marathoner from performing at his best, the sprinter cannot compete. Conversely, I could also say that the marathoner isn't more fit, since he has less powerful muscles. He isn't as strong, and cannot compete with the sprinter in a 100m dash. Without long distances, the marathon runner cannot compete. See how this argument can be done both ways?? LSS says "without the help of antibiotics keeping the stronger normal bacteria at bay they can't compete and they die out", but I could just as easily flip the script and say that the normal bugs can only survive better in a lazy "upper-class" environment that contains no challenges such as antibiotics. The resistant bacteria are clearly stronger as they are able to overcome these hurdles that the "vanilla bugs" can't. Of course, both of these notions assume that "better" is objective, but the fact that you can reverse this argument by switching between different contexts shows that it is not.

Now, understanding the trade-offs in the evolution of resistance is actually important to the application of medicine, and not just regarding bacteria. Viruses such as HIV and even cancer cells evolve and to be resistance to our drug therapies. The evolvability of resistance is at the center of this research, such that better therapies can be designed that take evolution into account. We can also use evolutionary analysis to predict how new resistant strains might emerge. In addition to understanding how resistance arise via mutation, and how these spread by selection, is exactly why the evolutionary aspects of resistance is very important and not something to be trivialized. It is why proponents of evolution use it as a clear example of evolution that impacts our daily lives, not exclusive to the curiosity of academics. In fact, we even did a video explaining this.



One final thing to be noted is that....not all resistance causing mutations are a "loss of function" or "just breaks things". It's again the orthogenesis view of evolution, where everything is supposed to be progressing towards higher complexity, and the observation of evolution towards simpler forms, or the lose of parts, is taken as a point against evolution. It's not. As said before, evolution has no direction in mind. Evolution can proceed towards higher complexity or lower complexity, or both at the same time, as long as they confer a survival and reproductive benefit within the environment (or not, natural selection isn't the only mechanism).

In regards to antibiotic resistance, they can also develop via "gain-of-function" mutations in genes that encode transporters, efflux pumps, that make the export of the drug outside the cell more efficient, or in regulatory elements that permit tolerance. See examples, here and here. One particular example is where mutations to an aminoglycoside acetyltransferase enzyme, that normally breaks down aminoglycoside antibiotics (e.g. kanamycin and neomycin), is now able break the synthetic fluoroquinone antibiotics (e.g. ciprofloxacin). Not just that! The enzyme didn't lose the ability to break the previous aminoglucoside antibiotics, even though the structures of these substrates are entirely different. So these mutations lead to one enzyme capable of conferring broad-spectrum antibiotic resistance.

2. The Lenski experiment
2.1 If it wasn't as impressive as I said it was, it doesn't count.

Okay forget about antibiotics. Let's look at the experiment that darwinists always point to to show evolution right before our very eyes. The granddaddy of bacterial lab work Richard Lenski's long-term evolution experiment. In this famous experiment Lenski has simulated in the lab over the course of a few decades more than one million years of evolution with bacteria, since humans and other large organisms can take years or even decades to reproduce, it's difficult to see any change between generations happening in our lifetimes. But smaller microorganisms like the bacteria E coli can reproduce in just minutes, letting us observe tens of thousands of generations and the changes that go along with that in real time. This is what Lenski has done for the past quarter of a century or so, just let a bunch of E coli bacteria reproduce and watch what happened. Pretty soon after the experiment began he noticed that they started to grow much faster than normal. Then a while later Lenski's e coli suddenly gained a new ability to eat something new called citrate. This was an earth-shattering find in the world of evolutionary biology, scientists were swooning in the streets to hear them tell the story this was a huge new evolutionary leap, proving beyond a shadow of a doubt the power of random mutation in natural selection.

Here, he is again raising the expectations of how impressive this evolutionary event was. Holy Crap! They learned to eat something they couldn't do before! However, E. coli was able to eat citrate before, just not under aerobic conditions. Now it can. That's the novelty. Another novel aspect of this is that, while E. coli normally needs (in addition to a lack of oxygen) another substrate to metabolize citrate (co-metabolism), this E. coli strain also gained the ability to rely on citrate as the sole carbon source. That's what Lenski found and that's how he reported this finding in the literature. LSS is making the straw man that the general ability to metabolize citrate was the novelty, as if all the genes necessary to import and digest this substance were all absent before.

2.2 Loosing...and gaining...flagella

But would you believe it if i told you there was a problem with this explanation as evidence for the creative power of evolution? No? good! Because that would be untrue. There are at least three problems with this explanation, what exactly happened to cause the e coli to grow so much faster, well they broke their flagella. What is that and why would it make them grow faster? The flagella is a little outboard motor of the bacteria it helps them move around and do their thing, but Lenski's bugs were in flasks that were swished around constantly, allowing them to get nutrients without ever having to move. They were spoon-fed lazy bugs. This usually vital part was not currently needed, so it was a waste of energy and they got rid of it. It's like selling the wheels off your car when you're at a stoplight you'll save a lot of gas that way sure but you haven't really made a better car and it'll sort of be a problem the next time you need to go anywhere.

They weren't exactly "spoon-fed" since there only usable source of carbon, glucose, was in limited supply. This was the challenge that the researchers put them through. To see whether and how the bacteria would evolve to adapt to better grow and reproduce in this new environment. Furthermore, the original strain was already non-motile. And flagella aren't exactly vital parts, there are plenty of bacteria that move by other means, or they do not actively move at all.

What happened here was that one particular mutation of a regulatory gave the bacteria a significant advantage in this environment. One of the proposed reasons why is that this mutation led to the reduced expression of flagella-encoding operons. But, something LSS doesn't mention is that the same regulatory mutation could also be responsible for increased rate in the transcriptional machinery, thereby raising the maximal growth rate.

Parallel changes in gene expression after 20,000 generations of evolution in Escherichia coli​

Tim F. Cooper,* Daniel E. Rozen,† and Richard E. Lenski

Mechanistic Basis for the Effect of the spoT Mutation on Fitness. ​

Because ppGpp influences the expression of many genes including those also controlled by cAMP-CRP (32), it is impossible to elucidate the precise physiological basis for the advantage of the spoT mutation. However, at least two possibilities can be suggested. First, the array data show that the spoT mutation lowers expression of the flagella-encoding flg operons (Table (Table1).1). The ancestral strain used in the evolution experiment was non-motile, the selective environment lacked physical structure, and the production of flagella is known to be costly (34). Hence, reducing the expression of these genes could be beneficial (35). Second, a reduction in the concentration of ppGpp, shown to result from mutations in the regulatory region of spoT (32, 36), might increase the rate of transcription from tRNA and rRNA promoters (37). This increased transcription raises the maximal growth rate (38), presumably via an increased speed of translation during growth in minimal medium (39). Although tRNA and rRNA genes are not present on the arrays that we used, we can examine the expression of genes with products that are associated with them such as ribosomal proteins and aminoacyl tRNA synthetases. Consistent with this possible advantage, the spoT mutation increased the expression of 62 of 94 stable RNA-associated genes when it was moved into the ancestral genome. This proportion is significantly more than half (P = 0.0027, one-tailed binomial test).

Previous work on yeast showed that replicate populations underwent parallel changes in gene expression during 250 generations of evolution (16). We extend this result to another system by demonstrating that expression in independently evolved populations of E. coli changed in parallel during 20,000 generations. We then also used these data to gain insight into the genetic basis of adaptation by focusing on the parallel changes, which often indicate important targets of selection. Analysis of these changes led to the discovery of a mutation in the spoT gene. This mutation had large phenotypic effects, conferring a very substantial competitive advantage and having widespread pleiotropic effects on the expression of many genes controlled by ppGpp.

So it seems that the bacteria were adjusting their gene regulation to relocate energy from things that were redundant to others that were more important in their environment. So Lenski's experiment wasn't just "loosing" things, nor just down-regulating redundant genes, but also up-regulating genes that promote growth.

But LSS was right saying that this loss (or rather a reduction in expression) was most likely one way the bacteria reserved their energy. But hey, perhaps LSS would still hammer down the point that "Darwinian evolution can get far by loosing things." Alright.... The thing that in Lenski's e. coli didn't loose the flagella genes themselves, they were down regulated, the genetic "switch" was turned off. So, it can be turned back on again, right? But what if didn't just turn it off at first, what if we destroyed the switch all together and put bacteria in an environment where flagella would be highly beneficial, and the cost of producing doesn't outweigh their benefit? So the only way to get the flagella back is by evolving a switch that replaces the old one that controls these genes. Well, that's exactly what was observed in this study, and within just 96 hours!! There is even a neat little video on this.

Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system​

A central process in evolution is the recruitment of genes to regulatory networks. We engineered immotile strains of the bacterium Pseudomonas fluorescens that lack flagella due to deletion of the regulatory gene fleQ. Under strong selection for motility, these bacteria consistently regained flagella within 96 hours via a two-step evolutionary pathway. Step 1 mutations increase intracellular levels of phosphorylated NtrC, a distant homolog of FleQ, which begins to commandeer control of the fleQ regulon at the cost of disrupting nitrogen uptake and assimilation. Step 2 is a switch-of-function mutation that redirects NtrC away from nitrogen uptake and toward its novel function as a flagellar regulator. Our results demonstrate that natural selection can rapidly rewire regulatory networks in very few, repeatable mutational steps.

So, switches can be turned off, or lost and be turned back on or replaced. Clearly, evolution is not just breaking or loosing things.

2.3 A broken switch, or a duplication "override"?

Well, what about the citrate thing. It's got to be obviously true that being able to eat a brand new substance is a good thing for these little fellas, like if we could eat dirt or something imagine the possibilities. Well to make a long story short, all of the complex genetic pathways and proteins needed to transport and metabolize citrate were there all along. Not only that, but e coli also already had a sophisticated mechanism to turn this ability on and off depending on its environment so that they could prioritize their optimum food source, glucose, and not waste energy. All that happened was that the sophisticated control mechanism, the switch broke. This bacteria lost the ability to turn off an ability that they already had. Now it was stuck, always on wasting energy to try and transport and metabolize citrate, even when it wasn't necessary. It's sort of like this alarm clock, it has the ability to make this lovely noise it's a nice ability but it can be turned on and off but what if the alarm clock was broken so that it made that noise forever and could never be turned off much better right right how could this not be a win. Sometimes it's good for your alarm clock to make noise but it's very good to be able to turn it off too. e coli could already do a thing and they were broken so that they did that thing constantly. Whether they needed it or not.

LSS's description of a "broken switch" on the mutations that was involved in the Cit+ phenotype is just plain wrong to say the least. The particular gene in question that allows E. coli to utilize citrate is the citT gene, that encodes for a transporter protein that lets citrate (as well as other substances) to pass through the cell membrane. Now, normally, the citT gene is not expressed when oxygen is present because it is controlled by a promoter that is silenced under aerobic conditions. The Cit+ e.coli possesses novel regulatory module, which includes a citT gene under control of another co-opted promoter, which is not silenced in the presence of oxygen, thus allowing this strain to express the transporter protein and use citrate from the environment.

What happened was that a tandem duplication occurred that put a copy of the citT gene under the control of a copy of the rnk promoter.

Which means that the original "switch" is still there, intact, it wasn't broken. There is a new regulatory module. What is really strange about this is that LSS does allude to this duplication, not with words, but with the tiny letters he put on screen under the animations which said "a gene duplication overrode the citrate importer control region". Which still ambiguous about what actually happened, saying nothing about the novel regulatory model. Also, it a very different description than "the switch broke". This doublespeak (intentional or not) doesn't sit well with me.

2.4 Who is the one equivocating here?

Maybe you call that evolution, but Darwinian evolution demands innumerable new genes new proteins new body plans new organs and complex characters that we see in nature. This is not that. It's equivocation, using language so ambiguously that it misleads. For example, Aristotle was greek. Greek is a delicious kind of food. Aristotle must have been delicious. Evolution has so many definitions that it's sometimes difficult to pin down what is meant by it. One could mean a shift in pre-existing populations, like darwin's finches, or peppered moths, or breeding or cultivation like dogs or plants, but these are miles apart from extrapolating random mutation and natural selection can build new organs or body plans. Or universal common ancestry, Zucchini are related to tuna fish.

Which is even further apart from the wild claim that it all happens strictly through materialistic processes.

Darwinists equivocate when evidence is presented to prove one definition of evolution where there is evidence and everybody agrees. And then another definition is quietly swapped in based on wild extrapolations to hoodwink people who aren't paying close enough attention. To extrapolate from antibiotic resistance, to the larger kinds of changes evolution would need to make new animals ,it's kind of like saying last week this cow could jump one foot high. This week she can jump two feet high. Doubling at that rate in just 30 more weeks you'll be able to jump clear over the moon. It's a bad extrapolation. There's a hard limit to how high cows can jump and there's a hard limit to the time and populations available to evolution and to the number of features bacteria can break before running out of things to break. Darwin didn't write a book called how pre-existing organisms break themselves, he purported to explain how novel species came about from a single common ancestor. And at least as far as this is concerned, it was a failure.

Jeez...This section is full of BS....

Who said that antibiotic resistance, or Lenski's experiment was evidence of common descent? I mean, there might be someone someone that did cite these as evidence of common descent? But I haven't seen any who say so. As previously explained, the evolution of antibiotic resistance is often used by proponents because it is relevant to human health, one clear reason WHY understanding evolution matters in everyday life.

Lenski's experiment gave us great insight into how evolution works in extreme genetic detail. One of the big controversies within evolution is whether evolutionary trends are "deterministic" or "contingent". Natural selection is deterministic, but mutation is very stochastic, so the question is whether natural selection is efficient enough such that evolutionary trends are highly predictable, or whether mutations make it very unpredictable. Borrowing Gould's thought experiment, if you could replay the history of life, would it turn out the same? In Lenski's experiment, they started with 12 genetically identical population evolving in parallel under the same environment. So if the same or similar adaptations observed occur in all or most populations predictably, then evolution seemed to be very deterministic. And that is also what they have observed, as all populations experienced similar changes. However, the cit+ phenotype in particular is very interesting, since it only occurred in one population. Because they froze samples of all population at every stage, they could look back at what happened and they found that the evolution of the cit+ phenotype was preceded by a "potentiation" phase were mutation(s) occurred that were not beneficial by themselves, but they were still needed in order to establish the genetic background that made it possible for other mutations to "actualize" the cit+ trait, followed by further "refinement".

Thereby showing that, at least sometimes, evolution doesn't operate by natural selection sequentially on every single mutation at every step. Some changes are contingent on chance events. That's one of many reasons why Lenski's experiment gained so much attention.

LSS is making the straw man that these are meant to show common descent, and since they don't...it was a failure. But for their ACTUAL purposes, they didn't fail at all. LSS accuses scientists darwinists of equivocating different definitions of evolution such that when they demonstrate evolution by one definition, they switch the definition around to use it as proof of something else. However, the only ones I see equivocating evolution with other things are ID-proponents/creationists, as they often lump everything they disagree with the "box" of evolution. Big bang cosmology, stellar nucleosynthesis, planetary accretion, deep time, abiogenesis, uniformaterianism, radiometric dating, plate tectonics, common descent, etc....sometimes even geocentrism and geosphericity.

Here, LSS is conflating "evolution" with "the theory of evolution", the model that explains why evolution proceeds via the mechanisms, i.e. selection, drift, mutation, etc, as well as explaining biodiversity from common ancestry. LSS also uses the term "darwinists" a lot as the equivalent of "evolutionary biologist" or "proponent of evolution". However, "darwinism"....being evolution exclusively driven by Darwinian mechanisms (natural/sexual selection + mutation) has been effectively dead for a long time. Even the "neo-darwinism", the integration of Darwinism with Mendelian inheritance, is also preceded as we now know of non-darwinian mechanisms for evolution as well as non-mendalian inheritance. This has been explained to LSS before. So there aren't a lot of "darwinists" anymore, and I disagree with the few who tend to ignore the non-darwinian mechanisms, like Dawkins and Coyne.

But what irritated me the most is when LSS conflated evolution, with methodological naturalism, and that with philosophical naturalism (see the line in the middle above). For this, I need to establish some terms first.

PHILOSOPHICAL naturalism is the claim that nothing exists outside the natural world. This pertains to ontology, the philosophy of existence.
METHODOLOGICAL naturalism is the assumption that says we only acquire reliable knowledge from what can be empirically tested and investigated. Meaning, we only consider "natural" causes as viable explanations for observed phenomena. The "supernatural" is not considered precisely because it is beyond empirical investigation. To make this clear, this NOT asserting that the supernatural doesn't exists. It just says that, even if it does, we don't have any method by which we can know anything about it. Methodological naturalism only pertains to epistemology, the philosophy of knowledge.

Science, in all fields, make the assumption of methodological naturalism. It's the basis of scientific inquiry. Science wouldn't be science without it. When scientists empirically investigate the cause behind a phenomenon via falsifiable testing, they must make the assumption that the cause is natural, i.e. they assume the cause CAN be empirically investigated. It could be the case that the true cause is indeed supernatural, but these cannot be investigated empirically. Scientists who consider supernatural explanations that are not testable are at a dead end. Because of the distinction, scientists (including evolutionary biologists) are not necessarily making the claim of philosophical naturalism. So, LSS is completely wrong when he implied that (one definition of) "evolution" is the claim that things happen only by materialistic means. The scientists that use methodological naturalists as a tool of inquiry can still have personal beliefs about the supernatural and many of them do.

But I wouldn't be surprised if LSS rejects that methodological naturalism is part of what makes science, science. After all, he is now making videos for the Discover Institute who published the wedge document wherein they reject "scientific materialism" (again, confusing philosophical with methodological naturalism) in favor of "a more broadly theistic understanding of nature". They pretend this is defending "sound" science, but it is exactly the opposite. It's undermining that which makes science work. See the video made by c0nc0rdance for more.

2.5 Ending with the "new information" canard

Darwin can't get very far by squandering pre-existing genetic information. Darwin's mechanism creates variation largely by throwing genetic information overboard, and selecting for damaged or broken genes, blissfully unaware that it's marooning itself on an island of genetic fragility, making organisms ironically less able to adapt in the future, thus hindering larger scale changes from accumulating. There's an old joke that perfectly summarizes what's going on. Wow you're so rich what's your secret to becoming a millionaire oh it's easy first start with a billion dollars and then light a bunch of it on fire. Bacterial evolution is lauded as a premier example of darwinism in action, as dawkins puts it before our very eyes, and actually it is. It doesn't demonstrate darwinism's creative power, though instead it's a perfect demonstration of darwinism's impotence.

I have already shown previously that antibiotic resistance also proceeds via gain in function mutations, that Lenski' experiment included the up-regulation of genes, as well as the formation of a novel regulatory module. I also have shown one instance were a regulatory switch was co-opted to replace one that was removed. Examples such as these aren't few and far between. One of my favorite is the antarctic ice fish, which acquired an an anti freeze protein that evolved via a repeated duplication of an old protease gene called trypsinogen that is expressed in the pancreas. And the evolutionary origins of the hemoglobin is a classic example, one that was even mentioned in one of my textbooks.

These are just a few examples of how gene duplication can lead to functional novelties, and there are many more instances of this identified in the scientific literature. But there are also examples for the evolution of de novo genes, which we included in a previous response video to LSS.

However, what constitute as "new information" is ambiguous. When you give examples such as the above, you can readily expect them to cry foul. These are not "new information" they are just modifications of information that was already there before. Nothing truly NEW was created. These complaints are pretty telling. It implies that they demand to see evolution create something, a gene or a regulatory pathway even something as complex as the eye, to appear out of nothing. Which is ironic since that is not the position of evolution. Evolutionary biologists do not claim that anything was created out of nothing, that's the position of ID/creationism. So this demand of "new information" being created ex nihilo might stem from psychological projection.

Lenski also responded to such objections.

The claim that “no new genetic information evolved” is based on the fact that the bacteria gained this new ability by rearranging existing structural and regulatory genetic elements. But that’s like saying a new book—say, Darwin’s Origin of Species when it first appeared in 1859—contains no new information, because the text has the same old letters and words that are found in other books.

In an evolutionary context, a genome encodes not just proteins and patterns of expression, but information about the environments where an organism’s ancestors have lived and how to survive and reproduce in those environments by having useful proteins, expressing them under appropriate conditions (but not others), and so on. So when natural selection—that is, differential survival and reproduction—favors bacteria whose genomes have mutations that enable them to grow on citrate, those mutations most certainly provide new and useful information to the bacteria.

That’s how evolution works—it’s not as though new genes and functions somehow appear out of thin air. As the bacterial geneticist and Nobel laureate François Jacob wrote (Science, 1977): “[N]atural selection does not work as an engineer works. It works like a tinkerer—a tinkerer who does not know exactly what he is going to produce but uses whatever he finds around him, whether it be pieces of string, fragments of wood, or old cardboards; in short, it works like a tinkerer who uses everything at his disposal to produce some kind of workable object.”

To say there’s no new genetic information when a new function has evolved (or even when an existing function has improved) is a red herring that is promulgated by the opponents of evolutionary science.

FIN

 

[Nesslig20]

Again...Who is equivocating here?

I have now a conversation with LSS under the youtube comment of the antibiotic video on his channel. You can go there if you want, there isn't a lot of comments so it will be easy find find the comments. So far, he isn't very impressive, but I have invited him to come over here on the forum since it will be easier to discuss it here, rather than in a YT comment section.

However, I noticed something that struck a nerve in me. The point LSS keeps hammering down is that he is just directly responding to the arguments being made by the popular and authoritative (e.g. Richard Dawkins and Bill Nye) who are using equivocation to use antibiotic resistance as evidence for all the large scale evolution, common descent, etc.

As of yet, he hasn't provided a quote that shows someone making the argument

Antibiotic resistance - ergo - universal common ancestry

Or something similar. And even if he did, that wouldn't reduce true significance of antibiotic resistance in evolution. And then there's still all the clap trap about antibiotic resistance only "breaking genes, throwing them over board, marooning itself on an island of genetic fragility", for which I have provided several examples of gain-in-function mutations, and I also showed that his description of "the switch broke" regarding the Lenski experiment is completely wrong, among other things.

But then, I noticed this interaction between LSS and Crispr CAS9




Did you also noticed what happened here? Remember that LSS is complaining about evolutionists using the term "evolution" to equivocate different things? As if they are saying "Evolution is proven (see antibiotic resistance) therefore evolution is true (common descent, etc)". Here LSS is accusing CRISPR of equivocating two different things: A mutation yielding a binding motif with mutations needed to produce a novel functional protein, e.g. a transcription factor that binds to said motif.

But here is the dirty little secret... CRISPR did NOT commit this equivocation!!

As you can see here, CRISPR was responding to this claim made by LSS

Your reasoning here is incorrect because gain of function mutations tend to require multiple simultaneous changes to work

And as CRISPR pointed out, this claim is wrong, gain of function mutation can quite easily occur with even a single mutation. And he gives DNA binding motifs as an example. Clearly, LSS was wrong to make this claim.

LSS does admit that DNA binding motifs can be gained by a single mutation, but rather than admitting his mistake, he tries to downplay it by calling it a matter of "semantics" and "triviality. And then he does what is called moving the goal post. The binding motifs already showed he was wrong, but he "moved the goal" from that to transcription factor proteins. By accusing CRISPR of equivocating when he used binding motifs as an example, LSS is pretending the argument was always about novel proteins such as transcription factors. But it clearly wasn't.

This utter failure is just one more reason for me to be highly skeptical of LSS when he accuses evolution proponents of equivocating. Perhaps this is the same story as with CRISPR. LSS sees someone provide a clear example of evolution, e.g. antibiotic resistance. But LSS moves the goal post and then accuses them of equivocation. Of course, LSS can provide the quotes to show he is right with his accusations regarding these people, but in this case...regarding CRISPR...LSS is plainly wrong.

Lastly, I actually went out of my way to look up some paper on the evolution of transcription factor protein, since LSS is apparently very interested in those. I found an interesting paper that showed using ancestral protein reconstruction to show the mutations that were responsible for the evolution of novel TFs binding specificyt. How many mutations were required provide binding specificity to a new DNA motif? Three!



Here is the paper. And here is a review paper that goes over several other examples of protein specificity evolution (not just Transcription factors).

 

[Nesslig20]

Keeping a record of the the back-and-forth between Long Story Short and Crispr CAS9 & Me
....for safekeeping

In one thread
I addressed this video on the league of reason forum: A long story of nonsense: antibiotics, the Lenski experiment and more

LSS: @Nesslig 20 Thanks Nesslig, I hadn't seen your other comment. I found the write up. Thanks for the time you put into responding, I know it’s quite the effort to do something like that.

Overall, I’m not particularly moved by your arguments, it seems they miss the mark. Your straw man claims fall flat because I’m quoting evolutionists and arguing against what they claim. Just because I’m not addressing your particular view doesn’t make it a straw man.

If Dawkins and other popularizers were more honest with what they mean by “evolution before our very eyes” people would be far less impressed by their arguments. Bacteria don’t do anything to prove the claims made by some in your camp. Now your other points toward the end of your write up like the antifreeze fish are a different topic, beyond the scope of what was discussed in the video.

@Long Story Short

Thanks Nesslig, I hadn't seen your other comment. I found the write up. Thanks for the time you put into responding, I know it’s quite the effort to do something like that.Overall, I’m not particularly moved by your arguments, it seems they miss the mark. Your straw man claims fall flat because I’m quoting evolutionists and arguing against what they claim.​

I don't think you understand what a straw man means. It means someone is misrepresenting your arguments. Exactly where have I done so? Simply citing the fact that you "quote evolutionists" doesn't show that I misrepresented any of your arguments. Also, I did not see any quote from the "evolutionists". I did see that you cited some work of Dawkins and Bill Nye....as in....a chapter from each of their books. That's not exactly a quote. What lines am I supposed to look at here that you are referencing?

Just because I’m not addressing your particular view doesn’t make it a straw man.​

Right, the fact that you are misrepresenting evolution as a whole is what makes it a straw man. That's why I spend most of the time correcting you by explaining what evolution ACTUALLY entails.

If Dawkins and other popularizers were more honest with what they mean by “evolution before our very eyes” people would be far less impressed by their arguments.​

This is the point I have directly addressed in section [2.1] and in particular [2.4]. To me it is often very clear what the "evolutionists" mean when they say evolution. When IDcreationists say "evolution" it can anything from big bang to abiogenesis to dogs giving birth to cats. In fact, YOU have equated "evolution" with methodological naturalism, and that with philosophical naturalism. The likely the reason why you think we aren't honest with what they mean by "evolution" is because you are very confused about this topic, as you have repeatedly demonstrated.

Bacteria don’t do anything to prove the claims made by some in your camp.​

The claims? What claims exactly? By some? Who? Don't weasel, be specific. I have made it clear that I do not agree with all "evolutionists" everywhere ever, including Dawkins. If you showed that person X used antibiotic resistance to argue for common ancestry, then I would agree that this person made a bad argument. But that clearly not the only point you want to make here. You claim that antibiotic resistance is at best a "trivial" example of evolution. It isn't, as I have explained repeatedly. Antibiotic resistance poses a significant problem, and understanding how this problem arises (which is due to evolution) is important. Wouldn't you agree [not a rhetorical question]?

Now your other points toward the end of your write up like the antifreeze fish are a different topic, beyond the scope of what was discussed in the video.​

At the end you were talking about "new information" and I explained that many mutations of antibiotic resistance were in fact gain of function mutations. These were MORE examples of evolution that cannot be described as "loss of information". Although, as I have pointed out, what is exactly meant by "new information" is ambiguous. If you want to further argue the specifics, you can readily join the League of Reason forum whenever you want. It is a better format to discuss this.

LSS: @Long Story Short I'm answering arguments that are being made by popular and authoritative in the field (that of arms races, the things we see in lab environments are the same as what produced everything else we see, this is evidence of large scale evolution, equivocation etc.). These are arguments actually made, maybe you don't make them, but I wan't attempting to answer you. This is no straw man. Antibiotic resistance can be a significant problem in the medical field, but it is no evidence of the kind it is purported to be.

1st: The kind of things for which it is purported to be evidence of that I have seen are the ones that I laid out in my response...e.g. it's relevancy in medicine. So far, you haven't given even an example of where anyone (let alone Dawkins or Bill Nye) have made the argument of "Antibiotic resistance ergo common descent" or something similar. Again, citing chapters isn't exactly providing a quote. I could read the whole chapters I try to guess which lines you are referring to, but that would likely cause to me to misrepresent you and then you complaining about it. So be specific with your complaint.

2nd: It is a straw man if you present a bad argument from one person (while they are popular, Dawkins nor Bill Nye are not exactly authoritative, at least not anymore regarding Dawkins) as if it represented the whole field. If you argument is that some evolution proponents have made some bad arguments, then of course there are. I know of actual scientists who made some pretty bizarre claims like octopus eggs are from space, or caterpillars are hybrids between velvet worms and insects, or the humans are pig-chimp hybrids. Of course these are not representatives of the consensus. But showing that some evolutionary scientists make bad arguments, and explaining that this doesn't represent the field, is clearly not the point you are trying to convey here. You're argued that resistance is at best a trivial example of evolution, and that the s-called evolutionists (in general) are using it to equivocate with other things like common descent.

3rd: In addition to this, you have made claims that were either irrelevant or clearly wrong. Like, you pointing out that sometimes resistance was already present before? So what? We don't expect the mutations to only occur right after bacteria encounter the antibiotics. Or that trade-offs is somehow an argument against evolution. Or that the trade-offs observed in resistance is equivalent to someone who is quadriplegic, blind, and toothless...completely missing the point that, despite the trade-off, there is still a NET benefit which is why antibiotic resistance continue to persist, unlike blind, toothless quadriplegic people. You also claimed that resistance doesn't evolve via new mutations that add information, but just breaking things or sharing pieces of already existing DNA via HGT. This will eventually lead to a dead end where no more genes can be "thrown overboard". No, we have observed proteins gained a new function(s) by mutations that are involved in bacteria resistance, and more. Or when you misrepresented the Cit+ mutations seen in the Lenski experiment as "breaking the switch", but at the same time you put a small text of "a duplication override" on the screen, which is a type of doublespeak that didn't sit well with me. Of course, the switch wasn't broken, there was instead a novel regulatory module of which you made no mention of...oh I wonder why. And lastly, when you (hypocritically) equivocated evolution, with philosophical naturalism with methodological naturalism.

[also seen you other comment] Again...we can all discuss this better on the league of reason forum, rather than the YT comment section. The offer is still open.



In the second thread

Crispr CAS9: @Long Story Short If pre-existing antibiotic resistance genes aren't the product of mutation and they make their carriers less fit, they would not persist in the population. So pick which way you want to be wrong. Also, not all observed novel protective mutations are loss of function mutations. So you're wrong about both things.

LSS: @Crispr CAS9 Thanks for the thoughtful comment, antibiotic resistance is sometimes due to mutations, you're right about that, I said as much in the video. However, these tend to be degradative mutations, see the Harvard Mega Plate experiment as a great example. Extra unused genetic load, especially on an organism as small as bacteria, is indeed a drag on fitness. I never claimed that all beneficial mutations are loss of function, would you like to discuss any particular mutation?

Crispr CAS9: @Long Story Short You state in your video (@1:48) that 'there are 'essentially only one or two ways' for antibiotic resistance to occur in bacterial populations. The first being (@1:53) that 'it's always been there' and the second being (@4:00) that they develop de novo mutations in non-resistant populations. My comment had two parts, the first targeted to the first option, the second to the second. Your reply apparently treats both parts of my comment as responding to the second option only.

Consider your first option: It is evident that you accept some of the 'pre-existing' variants found in bacterial populations to represent gain-of-function differences in comparison to the non-resistant type from your analogy to the foot race (@3:30). You claim that these are uncommon because the costs associated with carrying unnecessary genes is functionally detrimental in bacteria, which is reasonably true. However, this is actually a defeater of your position. If you claim that the mutations have 'always been there', then these gain-of-function variants can't result in any deleterious effect in normal bacterial populations because selection is so efficient in bacteria. So it is impossible for it to be true that these variants are detrimental AND have always been there in the absence of de novo mutations. That is, the only way that every population of bacteria can be expected to carry a particular class of gain-of-function variant of the sort in your footrace analogy is if such variants occur constantly in all populations regardless of the presence or absence of antibiotics. So while the capacity to survive antibiotics has always been there, this capacity would be represented by a novel de novo occurrence in each population.

You did strongly imply that all beneficial mutations are loss-of-function. I'm unsure how else to interpret your analogy @4:50, and indeed this implication is required for your ultimate conclusion (@11:24). To say that evolution can't work because it is variants are 'mostly' deleterious is patently absurd, you only need a tiny fraction to be beneficial for it to work. Since you evidently agree that such a fraction exists, however tiny it might be, the conclusion must be that mutations can produce gain-of-function variants which can be selected for.

LSS: @Crispr CAS9 Thanks for clarifying. It isn't impossible that pre-existing resistance can be beneficial or detrimental depending on the environment, this is what we in fact find in nature. Low levels of resistant populations relative to non-resistant populations. That is, until antibiotics are introduced, then the resistant populations take over as most dominant. If resistance were a cost free benefit for bacteria we should expect them to outcompete across every environment. I think we agree there, perhaps I'm misunderstanding your point though?

I think your more important point is about what proportion of mutations are adaptive due to loss of function or gain of function (ie: breaking things or inventing new things). Your reasoning here is incorrect because gain of function mutations tend to require multiple simultaneous changes to work (and as a result far more time), whereas loss of function mutations are stumbled across much more quickly. Look into Behe's work on the malaria data for more details (Darwin Devolves and the Edge of Evolution). To badly paraphrase him: the quick fix that breaks a gene will be selected for first, by the time a more complex and beneficial mutation could come on the scene it isn't needed any longer because the selective pressure was already alleviated. This mechanism ironically makes organisms more tightly suited to whatever their current environment is and less able to adapt in the future. See "Getting There First: An Evolutionary Rate Advantage of Adaptive Loss-of-Function mutations"

Crispr CAS9: @Long Story Short

"It isn't impossible that pre-existing resistance can be beneficial or detrimental depending on the environment" ​

It is impossible that both versions would have survived that many generations in population sizes that large in the absence of continuous production by de novo mutation.

"Low levels of resistant populations relative to non-resistant populations." ​

In the absence of an antibiotic, the genes in question are either deleterious, beneficial, or neutral. Given the amount of time in question, if they aren't being continuously produced by de novo mutation, a single allele would have reached fixation in all three cases. Thus, this statement alone necessitates the continuous de novo generation of gain-of-function mutations.

"That is, until antibiotics are introduced, then the resistant populations take over as most dominant." ​

Which requires them to already be there, which is only possible with continuous de novo production in the absence of the antibiotic because otherwise on allele would have already gone to fixation.

"If resistance were a cost free benefit for bacteria we should expect them to outcompete across every environment." ​

Yes, most selectively advantageous allele in a population will go to fixation. Which is why both alleles wouldn't be maintained in the population without continuous de novo production. I feel like I'm repeating myself, but hopefully the point is getting through.

"Your reasoning here is incorrect because gain of function mutations tend to require multiple simultaneous changes to work" ​

This is a claim you've made, that doesn't appear to be supported by current data. Alteration of regulation can occur with a single mutation, and in fact every random stretch of DNA of reasonable length will contain dozens of sequences one mutation away from a consensus binding motif. Thus, single base mutations can, and do, alter genetic regulation in a variety of ways able to canalize expression patterns. These are necessarily gain-of-function mutations.

"Look into Behe's work on the malaria data for more details" ​

I'm already familiar, and Behe's work on malaria is off by 4-6 orders of magnitude. He is also wrong about the nature of the mutation in question.

@Crispr CAS9 "

"Your reasoning here is incorrect because gain of function mutations tend to require multiple simultaneous changes to work" This is a claim you've made, that doesn't appear to be supported by current data. "Look into Behe's work on the malaria data for more details" I'm already familiar, and Behe's work on malaria is off by 4-6 orders of magnitude. He is also wrong about the nature of the mutation in question."​

We did (on Jackson's channel) a response video on exactly these points. Behe's assertion that "they had to occur at the same time" is not supported by the data. These mutations can occur one after another, and some single mutations even increased resistance without the need of being combined with a second mutation. It seems LSS is just very reluctant to listen from criticism and actually learn from them. I am also writing a response to this video here on the League of Reason forum. Should be finished soon.

LSS: @Crispr CAS9 Thanks for the reply Crispr, There is selective pressure to keep the resistance genes within a population. The selection would be taking place in other reservoirs and not in our gut where an antibiotic resistance bacterium could cause a lot of damage. New mutations can confer resistance (see the mega plate experiment for a cool example), but these tend to not be the "arms race" kind but more of the degradative kind that makes them genetically more fragile.

Your second remark amounts to semantics. Binding motifs where a protein binds to a given stretch of DNA/RNA, are usually 8-22 nucleotides in length. This is orders of magnitude shorter than the length of DNA sequence and complexity necessary for the protein (transcription factor) that binds to that motif. That’s an insurmountable problem. It’s great if random mutation might be more likely to yield a binding motif, but equivocating that with de novo creation of a novel functional protein by the same process is a leap.

Behe & Snoke's work wasn't off by orders of magnitude, see the back and forth with Durrett & Schmidt and see who got the best of the exchange. Durrett & Schmidt themselves admit they got it wrong. When correcting for their errors their numbers agree nicely with the empirical data.

@Nesslig 20 I believe I responded to your comments on the other video already Nesslig. It's simply not true, I provided the links to the discussion between Behe and Durrett & Schmidt and they even admitted they got it wrong. I've yet to hear any reply back from you or Jackson on that matter.

@Long Story Short We already covered the in the video Still Misunderstanding Transitional Fossils Pt. 2 Were we showed your gross misunderstandings of the topic, like thinking that the Durret and Schmidt were attempting to tackle the Behe and Snoke paper, it wasn't. We go over the points made by both parties (Durrett/Schmidt and Behe) in their responses, including the part where D&S admitted an error. D&S calculated that Behe was overestimating the waiting time by a factor of 5 million, but they acknowledged a correction that reduced this error by a factor of 30... ..meaning Behe was still off by a factor of 150.000!! They certainly didn't admit that they "got it wrong" as in they conceded the argument in general. The only thing they got wrong was in calculating HOW MUCH Behe was wrong. Behe wasn't off by a factor 5 million, but by a factor of 150.000. Not as wrong as they initially calculated, but still very wrong. This is not exactly something to be celebrating over LSS.

"Behe & Snoke's work wasn't off by orders of magnitude, see the back and forth with Durrett & Schmidt and see who got the best of the exchange. Durrett & Schmidt themselves admit they got it wrong. When correcting for their errors their numbers agree nicely with the empirical data."​

LSS...again...to make this hopefully clear to you....the onlly error they admitted meant that Behe was wrong by a factor of 150.000 (instead of 5 million). So Behe is STILL off by orders of magnitude. You are either being very dishonest by deliberately misrepresenting the admission of error to mean "they admitted that Behe was right" or you are grossly ill informed about this subject. I prefer the later.

LSS: @Nesslig 20 Ok good, you acknowledge Durrett & Schmidt made a mistake that put them off by 30-fold. The number of individuals with the first mutation is not a mistake by Behe, it is an element of the publicly available data on malaria. He does not assume one individual with the first mutation as you incorrectly assert. There are known waiting times for development of resistance to antimalarial drugs. This is not part of a model, but empirical observation.

Regarding whether or not the first mutation neutral is a bald assumption on the part of Durrett and Schmidt, they say as much in their reply. They leave it to biologists to debate whether or not it is deleterious or neutral, but their model assumes neutrality. If it is deleterious (as Behe claimed, and the data seems to indicate) then their calculations were off by a factor of 10^4. For more on where you are mistaken there see Behe's interactions with Jerry Coyne https://www.discovery.org/a/back-and-forth-with-jerry-coyne-part-2/ (note wherever that article says "1020" is a rendering error, it should say 10^20). That should deal with, in principle at least, the claims from the more recent 2016 paper as well.

FYI, Behe'e 2007 book the Durrett & Schmidt's paper was referencing was based off Behe & Snoke's 2004 work.

@Long Story Short

//Ok good, you acknowledge Durrett & Schmidt made a mistake that put them off by 30-fold.// ​

We (Jackson et al) have already acknowledged that in the video several months ago. Remember, this figure is about the degree of error on Behe's part. D&S first calculated Behe was off by 5 million fold. Taking the 30-fold correction into account, Behe is off by 150.000. So Behe went from being wrong by 6 orders of magnitude to 5 orders of magnitude. ....Oh my, what a relief for Behe!! <cough>... DO YOU acknowledge this?

//The number of individuals with the first mutation is not a mistake by Behe, it is an element of the publicly available data on malaria. He does not assume one individual with the first mutation as you incorrectly assert. There are known waiting times for development of resistance to antimalarial drugs. This is not part of a model, but empirical observation.// ​

This was also addressed in our video. Behe argued against D&S's model by saying that after the first mutation occurred, when you are waiting for a mutation to complete the 10/10 binding from the 9/10 binding site, there is a higher chance that a mutation would cause it to be 8/10, thereby reducing the odds that the binding site will be completed. However, this objection would ONLY count if you have only one individual with the first mutation. I know that Behe doesn't explicitly assume that there is only one individual, but his objection would ONLY be relevant if there is one individual. When you have a population of individuals with the first mutation, then any mutation that makes 9/10 into 8/10 wouldn't have an effect on the waiting time since you still have plenty of other individuals with the 9/10 binding site remaining. It wouldn't change anything, as D&S already explained. Behe just outright refuses to get this and is complaining about "not having made the assumption of 1 individual" but that is completely missing the point as was explained. This doesn't hinge on the data on malaria, as you mistakenly think it is. That is immaterial when it comes to particular dispute, as it only concerns the math of the models. Again, showing that you don't understand this subject very well.

//Regarding whether or not the first mutation neutral is a bald assumption on the part of Durrett and Schmidt, they say as much in their reply. They leave it to biologists to debate whether or not it is deleterious or neutral, but their model assumes neutrality.//​

So you acknowledge that they weren't talking about two beneficial mutations, as you mistakenly first claimed in your video? Also this is not all what they said: "If the first mutation is mildly deleterious (a fitness loss of order equation M4), then the waiting time is increased by a factor of 2 or 3. If the loss of fitness were 0.1, then the mean waiting time would be 1/(20Nu1u2). We leave it to biologists to debate whether the first PfCRT mutation is that strongly deleterious." I.e. they did not just provide one model that assumes neutrality and leave it at that. They provided several models where the mutation is neutral, slightly deleterious and strongly deleterious. Since they are only concerned in providing the mathematical framework, the question of whether the mutation is actually neutral or not is something they could decide. This is something called intellectual honesty.

//If it is deleterious (as Behe claimed, and the data seems to indicate) then their calculations were off by a factor of 10^4.// ​

Also addressed in the video. This is actually an assumption that Behe made, which is that the mutation is "seriously deleterious" and he (just like you here) did not provide the data for this. Michael Lynch also addressed Behe's assumption that most aa substitutions are detrimental is not supported by pointing out that proteins and their functions are actually fairly robust to a broad spectrum of aa substitutions. We also mentioned that Behe has on other occasions cited a paper that shows ONE of the mutations involved is by itself deleterious. However, it also shows that other multiple mutations are neutral. And finally we showed a paper that demonstrated that each of the mutations involved could confer increased antibiotic resistance. So Behe assumption that the first mutation must be or is likely to be deleterious is not supported by the data.

//So the one deleterious mutation could have been the last one that finally conferred resistance. or more on where you are mistaken there see Behe's interactions with Jerry Coyne. That should deal with, in principle at least, the claims from the more recent 2016 paper as well.// ​

This is from 2007....how could this possibly deal with the 2016 paper?

//FYI, Behe'e 2007 book the Durrett & Schmidt's paper was referencing was based off Behe & Snoke's 2004 work.// ​

....ok...and?? It is still the case that D&S's actual target was the book, specifically the part about drug resistance in Plasmodium. Also, the model presented in Behe and Snoke concerned the evolution of a protein evolving a new function after duplication, and that the new function could only be expressed after a series of initially neutral point mutations, occurring sequentially....not simultaneously. Which is different from the scenario discussed in regards to the drug resistance thing where Behe assumed the mutations were not neutral and occurred at the same time. The fact that you are trying so hard to avoid correcting yourself.....even on a very trivial matter....is quite astounding to say the least.

Crispr CAS9: @Long Story Short "There is selective pressure to keep the resistance genes within a population."
What is the selective pressure for antibiotic resistance in environments without any antibiotics?

"but more of the degradative kind that makes them genetically more fragile."
Claim without support.

"This is orders of magnitude shorter than the length of DNA sequence and complexity necessary for the protein (transcription factor) that binds to that motif. That’s an insurmountable problem."
It isn't a problem at all. One mutation allows binding where there wasn't any before, thus different functionality.

"It’s great if random mutation might be more likely to yield a binding motif, but equivocating that with de novo creation of a novel functional protein by the same process is a leap."
I'm not. I'm saying that a new binding site responsible for modulating expression resulting in antibiotic resistance is a gain of function without a loss of anything.

"Behe & Snoke's work wasn't off by orders of magnitude"
Yes, it is.

"see the back and forth with Durrett & Schmidt and see who got the best of the exchange."
I have, have you?

"Durrett & Schmidt themselves admit they got it wrong."
By one order of magnitude. You'll note that my comment gave a range. Behe is still wrong by five orders. Five is in the range of 4-6. Notice how that works? Yes, Behe is wrong. Badly, embarrassingly, and completely wrong.

@Crispr CAS9

//"It’s great if random mutation might be more likely to yield a binding motif, but equivocating that with de novo creation of a novel functional protein by the same process is a leap." I'm not. I'm saying that a new binding site responsible for modulating expression resulting in antibiotic resistance is a gain of function without a loss of anything.// ​

I also noted you being accused of equivocating, even when you clearly did not, in a post on the League of Reason forum, below the thread "A long Story of nonsense: antibiotic resistance, the Lenski experiment and more". LSS is repeatedly saying that he addressing the claims of the "evolutionists" who are equivocating different definitions of evolution in order to use antibiotic resistance as proof for large scale evolution, common descent, etc. But seeing how he falsely accused you of equivocating so easily, that only makes him and his accusations look more dubious.

LSS: @Nesslig 20 Yes it's from 2007 but people are still making the same mistakes regarding Behe's work, read it instead of dismissing it. The 2016 paper is very nice, very well done. The authors, however, don’t seem to think that CQ resistance was a step-by-step process. They write:

“Notably, for both CQ and md-CQ modeling, mutational sequences 0→1→3→4and 0→3→4 yielded realization probabilities up to ~10^5-fold greater than those for the 0→1→2→3→4 scenario... This suggests the possibility that rare bursts of multiple mutations facilitated the emergence of CQR-conferring pfcrt alleles.”

I'm not sure how it helps your case or hurts Behe's. It seems you've got a fundamental misunderstanding of the argument Behe is making.

@Long Story Short As I have asked your before multiple times, if you want to discuss more thoroughly come over to the league of reason forum. That's is a much better venue for having these discussions. Do you accept the invitation?

Another thing that I have to repeat, as it was an actual question. About the 30-fold correction. We (Jackson et al) have already acknowledged that in the video several months ago. Remember, this figure is about the degree of error on Behe's part. D&S first calculated Behe was off by 5 million fold. Taking the 30-fold correction into account, Behe is off by 150.000. So Behe went from being wrong by 6 orders of magnitude to 5 orders of magnitude. ....Oh my, what a relief for Behe!! <cough>... That's why you aren't doing yourself any favor in repeating the 30-fold correction as if it meant that Behe "got the best of the exchange". DO YOU acknowledge this? [not a rhetorical question]

Furthermore, I did not dismiss this 2007 blog. I asked how this could this possibly deal with the 2016 paper? This is a problem I frequently run into when analyzing your arguments. They are often too vague such that I have to do all the guess work get a coherent point. What exactly does Behe say in that 2007 post that addresses what exactly from the 2016? Not only do I have to argue against you, I apparently have to construct your points to even argue against.

Lastly, as you have said yourself and you agree with him, Behe asserts that the intermediate mutation is likely highly deleterious. This means that the mutations for resistance had to occur simultaneously. That was the biggest difference in the models between Behe and D&S. What the 2016 paper shows is that, there are four mutations that conferred resistance, and there are multiple scenarios of mutational pathways along the adaptive landscape where at every single step, there is an increase in fitness. Hence, the intermediate mutations aren't necessarily deleterious, contrary to the assumption that Behe made in his calculation.

About your quote, they modeled different mutational pathway scenarios and calculated the probabilities and compare them to each other to determine which scenario is the most probable one. They modeled scenarios where mutations were acquired step wise 0-1-2-3-4 and other scenarios where multiple mutations were acquired in some steps. Scenarios that included one step of 2 mutations (0-1-2-4; 0-1-3-4; 0-2-3-4), scenario with two steps of 2 mutations (0-2-4) and scenarios that includes one step of 3 mutations (0-3-4; 0-1-4). They found that scenarios with one multi-mutational step (2 or 3 mutations) were more likely to occur than a sequential series of separate 4 mutations. Furthermore, they made it clear in the discussion that by applying this model they hypothesize that the mutations occurred near- simultaneous emergence of these mutations. That's different from Behe who would say that they ALL mutations must occur within a single individual, exactly at the same time since any intermediate is probably deleterious.