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Author Topic:   Explaining the pro-Evolution position
Dr Adequate
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Posts: 16097
Joined: 07-20-2006


(4)
Message 53 of 393 (792400)
10-08-2016 9:19 PM
Reply to: Message 10 by Kleinman
10-07-2016 1:51 PM


Why does combination therapy work for the treatment of HIV?

See here.

Anything else I can help you with, Alan?


This message is a reply to:
 Message 10 by Kleinman, posted 10-07-2016 1:51 PM Kleinman has responded

Replies to this message:
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Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 84 of 393 (792453)
10-09-2016 11:30 PM
Reply to: Message 76 by Kleinman
10-09-2016 10:04 PM


Re: This seems like a good place...
Let's say that in order for your family to survive, your family must win two lotteries. And the probability of winning the first lottery is 1 in a million and the probability of winning the second lottery is 1 in a million. For you to win both lotteries, that probability will be 1 in a million times 1 in a million, 1 in a trillion, a very low probability. But let's say you are lucky enough to win one of the lotteries and now you are very wealthy and because of all your wealth, you can raise a very large family. And now all your descendants start buying tickets to the second lottery. As soon as you have enough descendants, you will have a reasonable probability that your family will win both lotteries.

If you wish to say that evolution does not require all beneficial mutations to appear simultaneously, but that rather they can be accumulated by natural selection over many generations, then you could say so.

Indeed, you don't really need to say that: we are familiar with the theory of evolution. Perhaps, then, you could simply proceed to whatever point it is you wish to make. Thank you.


This message is a reply to:
 Message 76 by Kleinman, posted 10-09-2016 10:04 PM Kleinman has responded

Replies to this message:
 Message 97 by Kleinman, posted 10-10-2016 4:58 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 103 of 393 (792502)
10-10-2016 6:25 PM
Reply to: Message 97 by Kleinman
10-10-2016 4:58 PM


Re: The reason the theory of evolution is not true
But what happens if we use two drugs? Let's say the first drug requires mutations A, B, and C and the second drug requires mutation X, Y and Z. Even if some lucky member gets mutation A, the second drug interferes with the amplification of that member. And if some lucky member gets mutation X, the first drug interferes with the amplification of that member. It is this principle that has led to the successful treatment of HIV.

Well, in fact it is possible for diseases to evolve resistance to combination therapies. It just takes a while. Here's one of the key papers in the development of combination therapy for HIV. Note that it says:

For three-base-change mutants, the situation is different. In single replication cycles, less than 10⁻⁷ of all possible three-base mutants are generated per day (Table 6.1). Thus, it is extraordinarily unlikely that any particular three-base-change mutant will arise spontaneously. However, such mutants can be selected by sequential mutations if one- or two-base mutants replicate.

Also, one can hardly take the evolution of resistance to combination therapy as a paradigm for evolution in general. In nature, most species are not being simultaneously assailed by three different poisons carefully designed and selected to fuck them up. If someone were to feed a population of humans on arsenic, cyanide and thallium then the population would not evolve resistance (because of going extinct) but this sheds little light on whether birds evolved from dinosaurs.

Edited by Dr Adequate, : No reason given.

Edited by Dr Adequate, : No reason given.

Edited by Dr Adequate, : No reason given.


This message is a reply to:
 Message 97 by Kleinman, posted 10-10-2016 4:58 PM Kleinman has responded

Replies to this message:
 Message 105 by Kleinman, posted 10-10-2016 6:35 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


(1)
Message 104 of 393 (792503)
10-10-2016 6:26 PM
Reply to: Message 100 by Kleinman
10-10-2016 5:32 PM


Re: Kleinman's argument
PaulK, the reason there is no rational way that feathers can evolve from scales by rmns is there are too many genetic loci which must be transformed simultaneously.

That's an interesting assertion. Do you have any evidence for it?


This message is a reply to:
 Message 100 by Kleinman, posted 10-10-2016 5:32 PM Kleinman has responded

Replies to this message:
 Message 106 by Kleinman, posted 10-10-2016 6:39 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 107 of 393 (792506)
10-10-2016 6:44 PM
Reply to: Message 98 by Kleinman
10-10-2016 5:09 PM


Re: It's already peer reviewed
http://www.ncbi.nlm.nih.gov/pubmed/27501057

I note that your own paper says: "Recently, it has been seen that combination therapy for the treatment of malaria has failed to prevent the emergence of drug-resistant variants."

Similarly, here's a paper on the evolution of resistance to combination therapy in HIV patients.

So if you propose that there was some set of natural conditions, without planning and forethought, that somehow prevented dinosaurs from evolving into birds over millions of years --- with greater efficiency that we, with intelligence, forethought, and understanding of the underlying microbiology, can prevent the evolution of drug resistance in pathogens over mere decades ... well, that's not a proposition that anyone's going to swallow without a great deal of evidence for it; it seems intrinsically unlikely.


This message is a reply to:
 Message 98 by Kleinman, posted 10-10-2016 5:09 PM Kleinman has responded

Replies to this message:
 Message 110 by Kleinman, posted 10-10-2016 6:55 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 108 of 393 (792507)
10-10-2016 6:46 PM
Reply to: Message 106 by Kleinman
10-10-2016 6:39 PM


Re: Kleinman's argument
But to judge by the abstracts of those papers there is nothing in them which relates to the number of loci which must mutate simultaneously to convert a dinosaur into a bird. We would all concede that simultaneous adaptive mutation of loci is unlikely; the question is, can you prove that such a thing would be necessary to dinosaur-bird evolution?

Edited by Dr Adequate, : No reason given.


This message is a reply to:
 Message 106 by Kleinman, posted 10-10-2016 6:39 PM Kleinman has not yet responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 109 of 393 (792508)
10-10-2016 6:55 PM
Reply to: Message 105 by Kleinman
10-10-2016 6:35 PM


Re: The reason the theory of evolution is not true
Doc, I never said that HIV has no possibility of evolving to 3 drug therapy. It just that the probability of someone winning three lotteries is very low, much, much lower than to two lotteries.

But as you correctly point out in message 76, the evolution of three things doesn't have to be like winning three lotteries; it can be like one person winning a lottery, and then one of his descendants winning a lottery, and then one of his descendants winning a lottery.

And selection pressures are just that, something that kills or impairs the replication of some or all members of a population. Do you think that rmns to starvation and thermal stress work differently then to targeted toxins to enzymes?

I think that nature isn't actually designed to thwart evolution, and so is likely to be even less successful at doing so than things which are.

To return to dinosaurs and birds, I suppose you could look at it that way and say that there were some dinosaurs that were killed or impeded in replicating for want of being able to fly. That's hardly a reason why they should not have evolved flight, is it?

Edited by Dr Adequate, : No reason given.


This message is a reply to:
 Message 105 by Kleinman, posted 10-10-2016 6:35 PM Kleinman has responded

Replies to this message:
 Message 113 by Kleinman, posted 10-10-2016 7:20 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 111 of 393 (792510)
10-10-2016 6:59 PM
Reply to: Message 110 by Kleinman
10-10-2016 6:55 PM


Re: It's already peer reviewed
And there is a straightforward explanation why that happens. Malaria can achieve populations of a trillion or more in an infected individual. When you have populations that large, the probabilities will become realistic that you will get members of that population with double beneficial mutations.

Is there some reason why the evolution of resistance in this case can't involve two or more sequential mutations?

What prevents reptiles (or dinosaurs if you wish) evolving into birds is the multiplication rule of probabilities.

Well, the multiplication rule of probabilities would apply if, as you say, the mutations required for the evolution of birds had to happen simultaneously (or if some large number of them did). But do you have any evidence that this is the case?


This message is a reply to:
 Message 110 by Kleinman, posted 10-10-2016 6:55 PM Kleinman has responded

Replies to this message:
 Message 115 by Kleinman, posted 10-10-2016 7:42 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 112 of 393 (792511)
10-10-2016 7:19 PM


It seems to me that you have only half an argument. On the one hand, you have seen the force of what Darwin said 150 years ago, that natura non facit saltus --- nature does not take leaps. So far we are in agreement. We can also agree why this is the case: because a simultaneous coordinated set of beneficial mutations is extraordinarily unlikely on statistical grounds. So far, so good.

But then you add the proposition that the evolution of birds must have required such a leap. And this premise appears simply to have been plucked out of thin air.


  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


(1)
Message 114 of 393 (792513)
10-10-2016 7:27 PM
Reply to: Message 113 by Kleinman
10-10-2016 7:20 PM


Re: The reason the theory of evolution is not true
That's correct, that's the way MRSA came about. When Staph evolved resistance to penicillin, methicillin was used, when methicillin failed, the next drug was used... The use of single targeted selection pressures sequentially is the way to evolve multidrug-resistant microbes.

But as we can see from the example of HIV and malaria, applying targeted selection pressures simultaneously also leads to the evolution of resistance.

I don't know what you mean by "designed".

I mean simply that the combination therapies were designed, by us, to mess with the pathogens and indeed in particular to make it harder for them to evolve resistance. (And yet they still manage it!) Nature was, surely, not designed with the aim of thwarting evolution. No part of it is the result of a vast endeavor by teams of brilliant scientists determined to prevent dinosaurs from evolving flight.

If dinosaurs wanted to fly, they will need the alleles that would enable them to do this. And there are too many genetic loci needed to be transformed for scales to become feathers by rmns.

There are too many for them all to be transformed simultaneously, we can agree on that. If you wish to maintain that there are too many for them to have changed sequentially, over the course of millions of years, then please show your working.


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 Message 113 by Kleinman, posted 10-10-2016 7:20 PM Kleinman has responded

Replies to this message:
 Message 117 by Kleinman, posted 10-10-2016 7:56 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 119 of 393 (792518)
10-10-2016 8:16 PM
Reply to: Message 115 by Kleinman
10-10-2016 7:42 PM


Re: It's already peer reviewed
Amplification requires improved fitness to reproduce. However, if the selection pressures don't drive the population to extinction, it is possible that a particular lineage which doesn't amplify but is still able to reproduce for enough generations will do enough replication trials that the necessary beneficial mutation can still occur. This is why the residual population of HIV in a well treated patient is still a danger. The vast majority of times 3 drug therapy works for HIV but the residual viral population requires monitoring for this possibility.

Is that a no?

No, the multiplication rule applies whether the mutations occur sequentially or simultaneously. Amplification alters the value of the probabilities but the probabilities are still computed multiplicatively.

I presumed that by "the multiplication rule" you meant that P(A & B) = P(A) * P(B) if the events are independent. Hence for example we can use this rule to calculate the probability of me throwing six on two dice. If instead I keep rolling one die until I get a six, and then keep rolling a second die until I get a six, that's a whole different question, and the probability of me getting two sixes is in fact 1. I arrived at that result without using the multiplication rule, and indeed without using multiplication.

No, what I am saying is that the creation of new alleles by rmns only works efficiently when a single gene is targeted by a single selection pressure. And that process is governed by the multiplication rule of probabilities. As soon as selection pressures target more than a single genetic locus, the process is slowed even more so because of the more complex evolutionary trajectory where the probability of each step is governed by the multiplication rule.

Well, it seems to me that you also said something about birds, and I wondered if you had any evidence for it.

Edited by Dr Adequate, : No reason given.


This message is a reply to:
 Message 115 by Kleinman, posted 10-10-2016 7:42 PM Kleinman has responded

Replies to this message:
 Message 121 by Kleinman, posted 10-10-2016 9:07 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


(2)
Message 120 of 393 (792519)
10-10-2016 8:29 PM
Reply to: Message 117 by Kleinman
10-10-2016 7:56 PM


Re: The reason the theory of evolution is not true
Do you think that starvation selection pressures can not occur simultaneously with thermal stress in nature. What do you think would happen to a population that was subjected to starvation selection pressure alone vs starvation selection pressure with thermal stress? What about diseases occurring during starvation and thermal stress, what about predation and starvation?...

Yes, many pressures are always acting on a population. Which, of course, weakens your point. A strain of bacteria evolving resistance to just one antibiotic does so in the teeth of a thousand selection pressures. Adding the antibiotic makes it a thousand and one.

And still they evolve.

What I can show you is the empirical evidence of how mutation and selection works and the underlying physics and mathematical principles which govern this phenomenon.

Well, I was already aware of that stuff. What I am unaware of is any reason why this gives us a compelling argument against the evolution of birds.

If you believe that dinosaurs can transform scales into feathers by rmns, let us know what the sequential selection pressures were and the targeted genetic loci which would do this.

I don't have a description of the sequence of mutations which produced birds, which I why I have never claimed that I did and then gone on to adduce this as a proof of the evolution of birds.

You, however, seemed to be claiming that you had a proof that no such pathway exists. If you don't, then this thread is about done.


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Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


(1)
Message 122 of 393 (792521)
10-10-2016 9:47 PM
Reply to: Message 121 by Kleinman
10-10-2016 9:07 PM


Birds and HIV
Yes, but it is not a simple no. It can take thousands of generations for something like you described to happen. Evolution will have to occur at a rate of much greater than a thousand generations per beneficial mutation if scales are going to be transformed into feathers.

Show your working?

Yes. But the probability problem you must solve is the probability of a beneficial mutation occurring in a given number of replications.

So, we'd need to know the number of beneficial mutations, the number of generations, and also, and this would be the really awkward bit, we'd need enough data to avoid the Sharpshooter Fallacy: what we need to know is not the probability of evolving the exact birds we have, but the probability that w'd be having this sort of conversation.

What I have evidence of is real, measurable and repeatable examples of random mutation and natural selection.

But very little about birds.

What I can tell you with mathematical certainty is that as you target more genes with selection pressures, the evolutionary process becomes too slow to support the theory of evolution.

Well, if you have mathematical certainty, you must have some actual math. Perhaps you could demonstrate it using dinosaurs and birds as an example.

I debated this issue with Edward Max, supervising medical doctor of the FDA who writes essays saying that rmns can account for all the complexity of life. I critiqued one of his essays and told him that if he believed that reptiles could transform scales into feathers by rmns, it would have to be one gene at a time because that was the only way that rmns works efficiently. Max didn't understand my argument and responded by sending me a link to a paper where the researchers studied the genomes of reptiles and the genomes of birds and asked which genes would have to be transformed to turn a scale into a feather. They identified at least eight different genes which would have to be transformed. My response was, "Very interesting, how can you transform eight genes at a time subject to selection when HIV, the fastest evolving replicator known can not evolve efficiently to 3 selection pressures targeting only 2 genes?"

To which the answer would be, "one locus at a time, over a long period".

Let's have a look again at how fast HIV adapts to combination therapy, shall we?

Reverse transcription inhibitor (RTI) mutations increased 0.5 mutations per y (STD = 0.8 mutations per y), while major protease inhibitor (PI) resistance mutations increased at a rate of 0.2 mutations per y (STD = 0.8 mutations per y) and minor PI resistance mutations increased at a rate of 0.3 mutations per y (STD = 0.7 mutations per y).

That's fast. It doesn't tell us much about dinosaurs, though, since on the one hand HIV has a higher mutation rate and population, and on the other hand the HIV is evolving to selection pressures specially designed and selected to be hard to adapt to. Still, this at least makes it look plausible that dinosaurs could evolve much more slowly than that and still produce feathers etc, since they do have an awfully long time to do it in.

Edited by Dr Adequate, : No reason given.


This message is a reply to:
 Message 121 by Kleinman, posted 10-10-2016 9:07 PM Kleinman has responded

Replies to this message:
 Message 125 by Kleinman, posted 10-10-2016 10:27 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


(1)
Message 129 of 393 (792528)
10-10-2016 11:24 PM
Reply to: Message 125 by Kleinman
10-10-2016 10:27 PM


Re: Birds and HIV
Study the Lenski experiment where he subjects a population of e coli to starvation selection pressure. His populations take over a thousand generations for each beneficial mutation to improve fitness against this selection pressure. His populations are not being subjected to thousands of selection pressures at the same time.

Well, they are, as I pointed out; it's just that most of these are conservative. As would of course be the case with dinosaurs.

But to even start applying this to dinosaurs we'd need to know how many beneficial mutations get your from dinosaurs to birds and how long it took.

It's not all that awkward, we have empirical examples that we can measure.

But examples of something else. In order to do the working in the dinosaur-to-bird case, we'd need to know these things about dinosaurs and birds. How many beneficial mutations? How many generations? What mutation rate? What is the strength of the selection pressures? Which operated concurrently and which consecutively? How many other evolutionary pathways would have struck us as equally remarkable?

It doesn't matter what the replicator is, rmns works the same for all replicators.

Right, but in order to do the math we need the actual data.

By analogy, the formula area = width × height works the same for all rectangles, but in order to apply it to any particular rectangle we would need to know the particular width and height.

If we were to assume that birds evolved as fast as HIV does, then you, Kleinman, wouldn't have a leg to stand on. But we know that they don't. So in order for us to figure out how much water your argument holds, it's kind of important to have some actual data about birds.

Perhaps you want to try and argue that recombination makes a difference?

Well, everything that's different about the two cases makes a difference. Though I seem to remember that HIV is diploid and undergoes recombination.

Interesting, do you want to tell us what those targeted selection pressures were and how nature applied those targeted selection pressures sequentially?

Once again --- I don't go about telling people that I've found such an evolutionary pathway.

You, on the other hand, claim to have a proof that there is no such pathway. That's for you to demonstrate.

(What on earth you mean by "targeted" in this context I cannot begin to imagine, perhaps you could explain?)

High mutation rates and huge populations and only two genetic loci targeted. People still live for decades when combination therapy is used. And that's without driving the population to extinction. On the other hand, single drug therapy gives resistant variants in a week. There's a mathematical lesson to be learned here. Populations subject to multiple simultaneous selection pressures that are not driven to extinction don't evolve efficiently to the selection pressures, they drift.

And yet as I have pointed out, everything is subject to multiple simultaneous selection pressures, yet and many things do in fact evolve efficiently. This empirical observation beats your "mathematical lesson" (which does not appear to involve any mathematics).

Edited by Dr Adequate, : No reason given.

Edited by Dr Adequate, : No reason given.

Edited by Dr Adequate, : No reason given.


This message is a reply to:
 Message 125 by Kleinman, posted 10-10-2016 10:27 PM Kleinman has responded

Replies to this message:
 Message 158 by Kleinman, posted 10-11-2016 6:09 PM Dr Adequate has responded

  
Dr Adequate
Member
Posts: 16097
Joined: 07-20-2006


Message 130 of 393 (792529)
10-10-2016 11:30 PM
Reply to: Message 127 by Kleinman
10-10-2016 10:55 PM


Re: It's already peer reviewed
Effective treatment of HIV still leaves populations at least in the hundreds of thousands. Isn't that enough for rmns to work to evolve resistance?

Yes.

Millions of years? Did you hear about the guy who went to the natural history museum? While on tour, the tour guide said, "This dinosaur skeleton is one million and six years old"! And the guy says to the tour guide, "What, how do you know that this dinosaur skeleton is one million and SIX years old"??? And the tour guide said, "I came to work here six years ago and the dinosaur skeleton was a million years old then"!

If you could manage to prove that the Earth isn't old, that would be a much more effective answer to evolution than anything you've shown us so far. You would need to start a new thread so as not to annoy the moderators.


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