Some Critical Notes on Kleinman's Math

[Dennis Feenstra]

It seems Alan Kleinman is still convinced his math works out. However;

a)
na1 = n*P(Beneficial a1)u
na12 = n*P(Beneficial a1)u*P(Beneficial a2)u
na123 = n*P(Beneficial a1)u*P(Beneficial a2)u*P(Beneficial a3)u

It takes a clean-slate generation upon which mutations can arise. None of the individuals born here (/n/) actually contribute to any gene flow. It calculates what portion of a generation (/na1/, /na2/) will independently receive one specific or two specific mutations at ''birth''. It does NOT calculate fitness and how the fitness of /a1/ and /a2/ affects the spread throughout the population.

The more mutations you want to find in a single individual, the more probabilities you have to multiply, obviously lowering the amount which will have a particular combination of mutations. /na12/ is therefore a much smaller part of /n/. If /na/ = 0, just increase your single generation size (since u and P are static).

b)
P(X) = (1-(1-P(Beneficial a1)u)^n*ng)
P(A1)P(A2) = (1-(1-P(Beneficial a1)u)^n)(1-(1-P(Beneficial a2)u)^na1)
P(A1) P(A2) P(A3) = (1-(1-P(Beneficial a1)u)^n)(1-(1-P(Beneficial a2)u)^na1)(1-(1-P(Beneficial a3)u)^na12)

First off, notice something? The first equation of b) calculates for *ng (amount of generations/replications). It is entirely absent from the bottom two equations which Kleinman actually uses.

The bottom two equations simply calculate the probability for a single individual in this clean-slate generation /n/ to receive beneficial mutation A1, while also calculating subsequent beneficial mutations to arise within the /na1/ and /na2/ sections of /n/.

That's all it is. There is no natural selection, no genetic drift, no fitness impact. Nothing.

[Panthera Tigris Altaica]

He knows this. He has for a very long time been trying to hide the fact that his equations do not prove what he says they prove by simply refusing to show his calculations. This is why he will never post his calculations.

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 7:40:04 AM UTC-7, Dennis Feenstra wrote:
> It seems Alan Kleinman is still convinced his math works out. However;
>
> a)
> na1 = n*P(Beneficial a1)u
> na12 = n*P(Beneficial a1)u*P(Beneficial a2)u
> na123 = n*P(Beneficial a1)u*P(Beneficial a2)u*P(Beneficial a3)u
>
> It takes a clean-slate generation upon which mutations can arise. None of the individuals born here (/n/) actually contribute to any gene flow. It calculates what portion of a generation (/na1/, /na2/) will independently receive one specific or two specific mutations at ''birth''. It does NOT calculate fitness and how the fitness of /a1/ and /a2/ affects the spread throughout the population.

Weren't you going to tell us how reptiles grow feathers? So now you are going to try to use gene flow to explain how rmns creates new alleles? What determines the absolute fitness to reproduce of a variant is its ability to replicate in a given environment.

>
> The more mutations you want to find in a single individual, the more probabilities you have to multiply, obviously lowering the amount which will have a particular combination of mutations. /na12/ is therefore a much smaller part of /n/. If /na/ = 0, just increase your single generation size (since u and P are static).

That sounds about right but written in a very confusing manner. Since the replication is the trial, the probability of two or more particular mutations occurring in an individual is dependent on the number of replications of its progenitor.

>
> b)
> P(X) = (1-(1-P(Beneficial a1)u)^n*ng)
> P(A1)P(A2) = (1-(1-P(Beneficial a1)u)^n)(1-(1-P(Beneficial a2)u)^na1)
> P(A1) P(A2) P(A3) = (1-(1-P(Beneficial a1)u)^n)(1-(1-P(Beneficial a2)u)^na1)(1-(1-P(Beneficial a3)u)^na12)
>
> First off, notice something? The first equation of b) calculates for *ng (amount of generations/replications). It is entirely absent from the bottom two equations which Kleinman actually uses.

Let's see if we can help you with your confusion. n*ng is simply the total number of replications of the particular variant. That number of replications must be for the variant that would benefit from that particular mutation. Those replications can occur in a single generation or accumulate over multiple generations but it is the total number of replications of that variant which determines the probability of that beneficial mutation occurring. So let's give you a simple example of how you would apply this calculation in a real case, the use of combination therapy for treatment of hiv. Three drug therapy requires that three simultaneous beneficial mutations occur. If the mutation rate is e-5, it will require about e15 replications (trials) for that triple beneficial mutation to occur. So let's assume that in a well-treated patient, you still have e5 viruses replicating every generation. In about e10 generations, you will have a reasonable probability of that triple beneficial mutation occurring. This is why 3 drug therapy is adequate for giving durable treatment for hiv and 4 drugs are not needed.

>
> The bottom two equations simply calculate the probability for a single individual in this clean-slate generation /n/ to receive beneficial mutation A1, while also calculating subsequent beneficial mutations to arise within the /na1/ and /na2/ sections of /n/.

You are confused, each probability equation represents and evolutionary step. And each step requires amplification of the previous beneficial mutation before there is a reasonable probability of the next beneficial mutation occurring. It is the beneficial mutation/amplification of beneficial mutation cycle. That's how rmns works.

>
> That's all it is. There is no natural selection, no genetic drift, no fitness impact. Nothing.

Nothing which you have the capability of understanding. Natural selection for improving fitness is measured by the absolute fitness to reproduce of the particular variant. If you try to use relative fitness, you are computing survival of the fittest which does not give an improvement in fitness.
.
So when are you going to tell us how reptiles grow feathers. Is it gene flow?

[Dennis Feenstra]

Kleinman,
Lots of useless counter arguments.

1. Your a) set of calculations does not calculate evolution. Period. It calculates a single time-independent clean-slate generation, where a portion will be Na1, a portion will be Na2 and a portion will be Na12. That's it. Nothing more. None of these individuals interbreed over generations.

2. Your b) set simply calculates the probability you're pulling a single individual from an imaginary jar with the right characteristics.

This b) set of calculations is useless. You don't need to know the probability for you to draw a single individual with a certain set of characteristics.

The very fact you're using Na1, Na2 and Na12 in b) is already an admission the mutant individuals exist in the population /n/ in the first place.

Image clarifying my argument: https://i.imgur.com/A7vYsVp.jpg

[Dennis Feenstra]

Let me try to explain this again, Alan. Read very carefully.

1. If you have population N,
2. and calculate what portion of N will be NA1, NA2 and NA12,
3. by using the error rate during replication and the probability that such an error is beneficial in a particular way,
4. you haven't used any natural selection.
This is simply a clean-slate generation whose members undergo a single replication at the same time (parents are removed from the pool).

x% of N is NA1
x% of N is NA2
x% of N is NA12 (both mutations)
x% of N is N (Other)
This is probability distribution of a single round of mutation in all members.

Your second set of equations (which I referred to as b)) is about putting all of N's output into a jar and calculate the probability you'll pull out member [x] with either mutation or both.

Your second set of equations is therefore useless. Why do you need to know the probability of you pulling out the right individual?

Your b) set of equations already includes NA1, NA2 and NA12 in the equation. This is an admission that for N you will have NA1, NA2 and NA12 subpopulations,
independent of the fact there is a particular low probability you'll pull a specific indidivual out of the jar.


Stop harping about feathers from reptile scales. That's not the argument.

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 8:20:03 AM UTC-7, Dennis Feenstra wrote:
> Kleinman,
> Lots of useless counter arguments.

Dennis, I understand you are having difficulty understanding my arguments. Here's another approach to understanding the mathematics of rmns. Draw the Venn diagram of the problem and it might become clearer for you. The entire space consists of the entire population. Let the total population be N. Let Na1 be the number of members with mutation a1. Let Na12 be the number of members with mutations a1 and a2 and so on. So, for example, let the mutation rate be e-9. If N = e9, the number of members in the subset with mutation Na1 will be 1. You should know how to do that calculation, if you don't, I'll show you. Now the subset of Na1 with mutation a2 will be essentially 0. Now let N = e18. Then Na1 will = e9 and Na12 will equal 1. Draw the Venn diagrams and see if that makes sense to you.

>
> 1. Your a) set of calculations does not calculate evolution. Period. It calculates a single time-independent clean-slate generation, where a portion will be Na1, a portion will be Na2 and a portion will be Na12. That's it. Nothing more. None of these individuals interbreed over generations.

The calculations I've presented give the mathematics of an evolutionary trajectory and the probabilities for each evolutionary step on the evolutionary trajectory. And those probabilities are dependent on the absolute reproductive fitness of each variant at each step of the evolutionary trajectory. The probabilities of each evolutionary step are not dependent on the relative fitness of the variants. In fact, for a given variant on a given trajectory, it doesn't matter what other variants are doing on their evolutionary trajectories (other than they may be competitors for the resources of the environment).

>
> 2. Your b) set simply calculates the probability you're pulling a single individual from an imaginary jar with the right characteristics.

And that's exactly how rmns works. But it is not drawing from a jar that is the random trial, it is the number of replications of the particular variant which determines that probability.

>
> This b) set of calculations is useless. You don't need to know the probability for you to draw a single individual with a certain set of characteristics.
>
> The very fact you're using Na1, Na2 and Na12 in b) is already an admission the mutant individuals exist in the population /n/ in the first place.

The probability of Na12 occurring will be virtually zero in the case I describe above when N=e9 and the mutation rate is e-9. And if you use a third selection pressure and third subset, Na123 will require a population size (number of replications) to be e27 for just 1 occurrence of that variant.

>
> Image clarifying my argument: https://i.imgur.com/A7vYsVp.jpg

If you read my paper on multiple simultaneous selection pressures, you will see the same drawing. You almost understand how rmns works. Keep at it and you will understand why combination therapy works for the treatment of hiv.

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 8:40:03 AM UTC-7, Dennis Feenstra wrote:
> Let me try to explain this again, Alan. Read very carefully.
>
> 1. If you have population N,
> 2. and calculate what portion of N will be NA1, NA2 and NA12,
> 3. by using the error rate during replication and the probability that such an error is beneficial in a particular way,
> 4. you haven't used any natural selection.
> This is simply a clean-slate generation whose members undergo a single replication at the same time (parents are removed from the pool).

If you mean by "clean-slate" that no variants exist with any of the particular mutations, ok. And you are stuck with the notion that natural selection is only measured by relative fitness to reproduce. Relative fitness to reproduce is the appropriate measure of natural selection when modeling survival of the fittest but it is not the correct measure when modeling improvement in fitness. In this case, natural selection must be measured by absolute fitness to reproduce and that is the calculation you are struggling to understand here.

>
> x% of N is NA1
> x% of N is NA2
> x% of N is NA12 (both mutations)
> x% of N is N (Other)
> This is probability distribution of a single round of mutation in all members.

Bad use of terminology. These are not probability distributions. rmns governed by the binomial probability distribution but what you are talking about is subsets of a sample space based on the binomial probability distribution. The sample space for this problem is based on the sum total of all replications whether they occur in a single generation or multiple generations.

>
> Your second set of equations (which I referred to as b)) is about putting all of N's output into a jar and calculate the probability you'll pull out member [x] with either mutation or both.
>
> Your second set of equations is therefore useless. Why do you need to know the probability of you pulling out the right individual?

Read the Weinreich paper "Darwinian evolution can follow only very few mutational paths to fitter proteins". Mutation a2 must occur on a member that already has mutation a1 to improve fitness.

>
> Your b) set of equations already includes NA1, NA2 and NA12 in the equation. This is an admission that for N you will have NA1, NA2 and NA12 subpopulations,
> independent of the fact there is a particular low probability you'll pull a specific indidivual out of the jar.

Read the Weinreich paper and you may get a better understanding of this point. It requires specific mutations to improve fitness, not any mutation.

>
>
> Stop harping about feathers from reptile scales. That's not the argument.

It is if you claim that reptiles grow feathers by rmns.

[Dennis Feenstra]

Op dinsdag 3 april 2018 18:00:05 UTC+2 schreef Alan Kleinman MD PhD:

"The probability of Na12 occurring will be virtually zero in the case I describe above when N=e9 and the mutation rate is e-9. And if you use a third selection pressure and third subset, Na123 will require a population size (number of replications) to be e27 for just 1 occurrence of that variant."

I would like to ignore your second set of equations and instead focus on:

Na1 = n*P(Beneficial a1)u
Na2 = n*P(Beneficial a2)u
Na12 = n*P(Beneficial a1)u*P(Beneficial a2)u

It can't be a probability of zero if NA1, NA2 and NA12 are 0 > using this equation. As you pointed out, this requires increasingly larger size of N.

However, this set of three equations only calculates the result after, for example, replicating N and removing the parents from the pool.

NA12 does NOT arise this way in evolution and natural selection. It further invalidates even this first set of equations. How it should work:

Na1 = n*P(Beneficial a1)u
[or]
Na2 = n*P(Beneficial a2)u

Na# *ng > N *ng,
N == Na# after x amount of generations

Na# * P(Beneficial a#)u
If Na# == Na1, then P == P(a2)

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 9:40:03 AM UTC-7, Dennis Feenstra wrote:
> Op dinsdag 3 april 2018 18:00:05 UTC+2 schreef Alan Kleinman MD PhD:
> "The probability of Na12 occurring will be virtually zero in the case I describe above when N=e9 and the mutation rate is e-9. And if you use a third selection pressure and third subset, Na123 will require a population size (number of replications) to be e27 for just 1 occurrence of that variant."
>
> I would like to ignore your second set of equations and instead focus on:
>
> Na1 = n*P(Beneficial a1)u

This is the expected (mean) number of mutations a1 for a population n and a mutation rate u.
> Na2 = n*P(Beneficial a2)u
This is the expected (mean) number of mutations a2 for a population n and a mutation rate u.

> Na12 = n*P(Beneficial a1)u*P(Beneficial a2)u

This is the expected (mean) number of mutations a2 for a population Na1 and a mutation rate u.
These are not probabilities.

>
> It can't be a probability of zero if NA1, NA2 and NA12 are 0 > using this equation. As you pointed out, this requires increasingly larger size of N.

Try plugging numbers into the probability equations. Let u = e-9, and N = e9, the probability of mutation a2 occurring on a member that already has mutation a1 is of the order e-9. True, that is not a zero probability but it is virtually zero. This is why in the Kishony experiment, the colonies are large enough to be seen without magnification before the next beneficial mutation occurs and the new variant can grow in the next higher drug concentration region.

>
> However, this set of three equations only calculates the result after, for example, replicating N and removing the parents from the pool.

I did this mathematics before Kishony ran his experiment but his colonies are clearly demonstrating this mathematics. And if Kishony were to run his experiment with two drugs, the colonies will have to be exponentially larger for his experiment to work. For example, with one drug, e9 replications give a beneficial mutation. For two drugs, the colony will have to be about e18 for a double beneficial mutation to occur. Even with one drug, if the step increase in drug concentration requires 2 beneficial mutations to grow in that region will require a colony size of ablut e18 for a reasonable probability of that event double beneficial mutation occurring.

>
> NA12 does NOT arise this way in evolution and natural selection. It further invalidates even this first set of equations. How it should work:

It does if improvement in fitness requires a particular mutation to occur on a variant that would benefit from that mutation.

>
> Na1 = n*P(Beneficial a1)u
> [or]
> Na2 = n*P(Beneficial a2)u

Mutation a2 must occur on a subset of the population which already has mutation a1 in order to improve fitness. You must use Na1 in the second equation, not n.

>
> Na# *ng > N *ng,
> N == Na# after x amount of generations
>
> Na# * P(Beneficial a#)u
> If Na# == Na1, then P == P(a2)

Evolutionary trajectories operate on lineages, not the entire population. You can have multiple different variants from a population where each variant is taking their own particular evolutionary trajectory to improved fitness. The probabilities for each evolutionary step are dependent on the number of replications for each particular variant. You can not use the total population size to compute these probabilities or the expected number of a particular mutation. Read the Weinreich paper I referred to. And it is this paper which forms the foundation for the Kishony experiment.

[Dennis Feenstra]

"These are not probabilities."
The probabilities are irrelevant if a population N will have subsets of populations.
If an error rate and probability (beneficial) produces a population with 0> for NA1, NA2 and NA12, you already got your answer.

Suppose 20.000 (N) replicate themselves and the parent dies. We have 20.000 new members. Due to mutation rate X and Probability (Beneficial) Y, an X amount will be NA1, an X amount will be NA2 and an X amount will be NA12. This is inevitable.

Your second set of equations, which I ignored is about the probability you'd pull a specific organism from a specific subset from the jar (containing N). That's all it is.

"Mutation a2 must occur on a subset of the population which already has mutation a1 in order to improve fitness. You must use Na1 in the second equation, not n."

Not at all. If N is made out of subsets (N, Na1, Na2), where over generations Na1 becomes fixed due to its fitness, I can treat
N*P(Beneficial a#)u as Na1*P(Beneficial a2)u because N == Na1

[Dennis Feenstra]

"Evolutionary trajectories operate on lineages, not the entire population. You can have multiple different variants from a population where each variant is taking their own particular evolutionary trajectory to improved fitness. "

Unless certain variations produce fitness that result in fixation of a particular variation in a population. A trait of a subpopulation becomes dominant, and thus is the new N for the calculation.

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 10:25:03 AM UTC-7, Dennis Feenstra wrote:
> "These are not probabilities."
> The probabilities are irrelevant if a population N will have subsets of populations.
> If an error rate and probability (beneficial) produces a population with 0> for NA1, NA2 and NA12, you already got your answer.

Of course, these equations give the probabilities of a particular mutation occurring. And if the population of the particular variant is large enough, you will have a reasonable probability of that next beneficial mutant being in the population. The different subsets are simply different variants and the intersections of the subsets are joint probabilities computed with the multiplication rule.

>
> Suppose 20.000 (N) replicate themselves and the parent dies. We have 20.000 new members. Due to mutation rate X and Probability (Beneficial) Y, an X amount will be NA1, an X amount will be NA2 and an X amount will be NA12. This is inevitable.

You confusing probabilities and expected number. The probability of a particular mutation occurring is computed using the "at least one" rule. The expected number of members with that mutation is computed using the mean value of the binomial distribution. If N = 20,000 and u = e-9 then the expected number of members with mutation a1, Na1 << 1 and the probability of mutation a2 occurring on some member that already has mutation a1 will be extremely small since Na1 is even 1.

>
> Your second set of equations, which I ignored is about the probability you'd pull a specific organism from a specific subset from the jar (containing N). That's all it is.

No, each equation is the probability of a particular mutation occurring on some variant (subset) of the population. And unless the number of members in that subset is large, the probability of that mutation occurring will be small. And the magnitude of large depends on the mutation rate.

>
>
> "Mutation a2 must occur on a subset of the population which already has mutation a1 in order to improve fitness. You must use Na1 in the second equation, not n."
>
> Not at all. If N is made out of subsets (N, Na1, Na2), where over generations Na1 becomes fixed due to its fitness, I can treat
> N*P(Beneficial a#)u as Na1*P(Beneficial a2)u because N == Na1

That is not correct and the empirical evidence shows why. If mutation a2 occurs on some member which does not have mutation a1, it will not give an improvement in fitness. Read the Weinreich paper I referred you to in order to understand why. The sequence of mutations for a lineage have to give improved fitness at each evolutionary step in order for that evolutionary trajectory to have a reasonable probability of occurring. The Kishony experiment demonstrates this and the Kishony experiment is based on the Weinreich study.

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 10:25:03 AM UTC-7, Dennis Feenstra wrote:

> "Evolutionary trajectories operate on lineages, not the entire population. You can have multiple different variants from a population where each variant is taking their own particular evolutionary trajectory to improved fitness. "
>
> Unless certain variations produce fitness that result in fixation of a particular variation in a population. A trait of a subpopulation becomes dominant, and thus is the new N for the calculation.

You are now confusing the mathematics of survival of the fittest with the mathematics of improving fitness. Fixation is neither necessary nor sufficient for an improvement in the fitness of a lineage. Which variants are being fixed in the Kishony experiment? Which variant have gone extinct as the more fit variant is fixed? Ans: None but rmns still operates efficiently in this experiment.

[Ernest Major]

Long ago I pointed out that his model ignored standing variation in a
population. If the population is large enough that there's an
appreciable chance that a singly resistant mutation will occur it's
large enough that there's an appreciable chance that resistant
individuals are already present in the population.

That's on top of his assertion that the effects of lethal hard selection
are applicable in the cases of non-lethal selection or soft selection.

--
alias Ernest Major

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 12:25:04 PM UTC-7, Ernest Major wrote:
> On 03/04/2018 16:17, Dennis Feenstra wrote:
> > Kleinman,
> > Lots of useless counter arguments.
> >
> > 1. Your a) set of calculations does not calculate evolution. Period. It calculates a single time-independent clean-slate generation, where a portion will be Na1, a portion will be Na2 and a portion will be Na12. That's it. Nothing more. None of these individuals interbreed over generations.
> >
> > 2. Your b) set simply calculates the probability you're pulling a single individual from an imaginary jar with the right characteristics.
> >
> > This b) set of calculations is useless. You don't need to know the probability for you to draw a single individual with a certain set of characteristics.
> >
> > The very fact you're using Na1, Na2 and Na12 in b) is already an admission the mutant individuals exist in the population /n/ in the first place.
> >
> > Image clarifying my argument: https://i.imgur.com/A7vYsVp.jpg
> >
>
> Long ago I pointed out that his model ignored standing variation in a
> population. If the population is large enough that there's an
> appreciable chance that a singly resistant mutation will occur it's
> large enough that there's an appreciable chance that resistant
> individuals are already present in the population.

And those singly resistant variants are only a small number of members for the next evolutionary step. Each evolutionary step requires amplification in order to give a reasonable probability of next beneficial mutation occurring. So those singly resistant variants, if they don't amplify, the evolutionary trajectory stops at that step.

>
> That's on top of his assertion that the effects of lethal hard selection
> are applicable in the cases of non-lethal selection or soft selection.

You just don't get it. The intensity of selection does not affect the evolutionary trajectory. The greater the intensity of selection, the fewer the variants survive to have any chance of evolving to that selection pressure. In addition, if the intensity of selection is large and requires more than a single mutation to improve fitness, then the probability of evolving to that condition drops off exponentially. This is why in the Kishony experiment, the increases in the concentration of the antibiotic must be limited so that a single beneficial mutation will improve the fitness of that variant to grow in that region.
>
> --
> alias Ernest Major

[Vincent Maycock]

On Tue, 3 Apr 2018 12:39:42 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>On Tuesday, April 3, 2018 at 12:25:04 PM UTC-7, Ernest Major wrote:
>> On 03/04/2018 16:17, Dennis Feenstra wrote:
>> > Kleinman,
>> > Lots of useless counter arguments.
>> >
>> > 1. Your a) set of calculations does not calculate evolution. Period. It calculates a single time-independent clean-slate generation, where a portion will be Na1, a portion will be Na2 and a portion will be Na12. That's it. Nothing more. None of these individuals interbreed over generations.
>> >
>> > 2. Your b) set simply calculates the probability you're pulling a single individual from an imaginary jar with the right characteristics.
>> >
>> > This b) set of calculations is useless. You don't need to know the probability for you to draw a single individual with a certain set of characteristics.
>> >
>> > The very fact you're using Na1, Na2 and Na12 in b) is already an admission the mutant individuals exist in the population /n/ in the first place.
>> >
>> > Image clarifying my argument: https://i.imgur.com/A7vYsVp.jpg
>> >
>>
>> Long ago I pointed out that his model ignored standing variation in a
>> population. If the population is large enough that there's an
>> appreciable chance that a singly resistant mutation will occur it's
>> large enough that there's an appreciable chance that resistant
>> individuals are already present in the population.
>And those singly resistant variants are only a small number of members for the next evolutionary step. Each evolutionary step requires amplification in order to give a reasonable probability of next beneficial mutation occurring. So those singly resistant variants, if they don't amplify, the evolutionary trajectory stops at that step.
>>
>> That's on top of his assertion that the effects of lethal hard selection
>> are applicable in the cases of non-lethal selection or soft selection.
>You just don't get it. The intensity of selection does not affect the evolutionary trajectory. The greater the intensity of selection, the fewer the variants survive

And how is that not "affecting the trajectory"?

[Panthera Tigris Altaica]

In other words, his math doesn't work. I thought as much.

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 1:50:03 PM UTC-7, Vincent Maycock wrote:
> On Tue, 3 Apr 2018 12:39:42 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >On Tuesday, April 3, 2018 at 12:25:04 PM UTC-7, Ernest Major wrote:
> >> On 03/04/2018 16:17, Dennis Feenstra wrote:
> >> > Kleinman,
> >> > Lots of useless counter arguments.
> >> >
> >> > 1. Your a) set of calculations does not calculate evolution. Period. It calculates a single time-independent clean-slate generation, where a portion will be Na1, a portion will be Na2 and a portion will be Na12. That's it. Nothing more. None of these individuals interbreed over generations.
> >> >
> >> > 2. Your b) set simply calculates the probability you're pulling a single individual from an imaginary jar with the right characteristics.
> >> >
> >> > This b) set of calculations is useless. You don't need to know the probability for you to draw a single individual with a certain set of characteristics.
> >> >
> >> > The very fact you're using Na1, Na2 and Na12 in b) is already an admission the mutant individuals exist in the population /n/ in the first place.
> >> >
> >> > Image clarifying my argument: https://i.imgur.com/A7vYsVp.jpg
> >> >
> >>
> >> Long ago I pointed out that his model ignored standing variation in a
> >> population. If the population is large enough that there's an
> >> appreciable chance that a singly resistant mutation will occur it's
> >> large enough that there's an appreciable chance that resistant
> >> individuals are already present in the population.
> >And those singly resistant variants are only a small number of members for the next evolutionary step. Each evolutionary step requires amplification in order to give a reasonable probability of next beneficial mutation occurring. So those singly resistant variants, if they don't amplify, the evolutionary trajectory stops at that step.
> >>
> >> That's on top of his assertion that the effects of lethal hard selection
> >> are applicable in the cases of non-lethal selection or soft selection.
> >You just don't get it. The intensity of selection does not affect the evolutionary trajectory. The greater the intensity of selection, the fewer the variants survive
>
> And how is that not "affecting the trajectory"?

The trajectory remains the same, the ability of a variant to traverse the trajectory is what is affected. A simple example, consider if Kishony were to run his experiment with only two regions, a drug-free region, and a low drug concentration region. The mutations that would give resistance in the high concentration experiment don't change just because the experiment is only run with a single low concentration pressure. It is when the intensity of selection forces the variants to get more than a single mutation at a time to improve fitness which affects the probability of a variant from following the trajectory. This is why when treating a patient with an antibiotic, you want to maintain concentrations high enough to force more than single mutations that would give improved fitness. In order for Kishony to get his experiment to work, he purposely chooses concentration gradients that only require a single mutation to improve fitness.

[Wolffan]

On 03 Apr 2018, Alan Kleinman MD PhD wrote
(in article<89ea60f2-68b2-4346...@googlegroups.com>):

He’s not the one who’s confused.

And you still haven’t shown your work.

[Mark Isaak]

On 4/3/18 8:36 AM, Dennis Feenstra wrote:
> Let me try to explain this again, Alan. Read very carefully.

Your explanation is useful for most people, but if you are trying to
explain to Alan, forget it. He goes to heroic lengths to not understand.

--
Mark Isaak eciton (at) curioustaxonomy (dot) net
"Ignorance, allied with power, is the most ferocious enemy justice can
have." - James Baldwin

[Alan Kleinman MD PhD]

On Tuesday, April 3, 2018 at 10:10:03 PM UTC-7, Mark Isaak wrote:
> On 4/3/18 8:36 AM, Dennis Feenstra wrote:
> > Let me try to explain this again, Alan. Read very carefully.
>
> Your explanation is useful for most people, but if you are trying to
> explain to Alan, forget it. He goes to heroic lengths to not understand.

It's useful if you want an incorrect explanation. Dennis thinks the particular mutation can occur anywhere in a population and you will get improved fitness. The correct explanation is that the particular mutation must occur on a variant that would benefit from that mutation. That is a subset of the entire population. And as you increase the number of selection pressures, the probability of getting a beneficial mutation for each of these selection pressures in one member (the intersection of all the subsets) becomes smaller and smaller. See his figure https://imgur.com/A7vYsVp where he correctly does the Venn diagram and calculation for two selection pressures. If a third selection pressure is added, you have the correct model for the use of three drug therapy for the treatment of hiv (and for any other three selection pressure evolutionary process). rmns operates on lineages, not entire populations. You and the rest of your reptiles grow feathers crowd are just incredibly slow at getting this. And the problem of drug resistance just keeps on getting worse in the meantime, no thanks to dumb clucks like you.

[Panthera Tigris Altaica]

On Wednesday, April 4, 2018 at 1:10:03 AM UTC-4, Mark Isaak wrote:
> On 4/3/18 8:36 AM, Dennis Feenstra wrote:
> > Let me try to explain this again, Alan. Read very carefully.
>
> Your explanation is useful for most people, but if you are trying to
> explain to Alan, forget it. He goes to heroic lengths to not understand.

He understands. He understands very well that he is wrong.

[Alan Kleinman MD PhD]

Fraidy cat is a liar and a fraud.

[Panthera Tigris Altaica]

He continues to show that he understands that he is wrong. He also refuses to post his calculations. He never will.

[Alan Kleinman MD PhD]

[Panthera Tigris Altaica]

[Alan Kleinman MD PhD]

On Wednesday, April 4, 2018 at 9:10:04 AM UTC-7, Panthera Tigris Altaica wrote:
> On Wednesday, April 4, 2018 at 11:40:05 AM UTC-4, Alan Kleinman MD PhD wrote:
> > On Wednesday, April 4, 2018 at 8:20:03 AM UTC-7, Panthera Tigris Altaica wrote:
> > > On Wednesday, April 4, 2018 at 10:35:03 AM UTC-4, Alan Kleinman MD PhD wrote:
> > > > On Wednesday, April 4, 2018 at 6:55:04 AM UTC-7, Panthera Tigris Altaica wrote:
> > > > > On Wednesday, April 4, 2018 at 1:10:03 AM UTC-4, Mark Isaak wrote:
> > > > > > On 4/3/18 8:36 AM, Dennis Feenstra wrote:
> > > > > > > Let me try to explain this again, Alan. Read very carefully.
> > > > > >
> > > > > > Your explanation is useful for most people, but if you are trying to
> > > > > > explain to Alan, forget it. He goes to heroic lengths to not understand.
> > > > >
> > > > > He understands. He understands very well that he is wrong.
> > > >
> > > > Fraidy cat is a liar and a fraud.
> > >
> > > He continues to show that he understands that he is wrong. He also refuses to post his calculations. He never will.
> >
> > Fraidy cat is a liar and a fraud.
>

> Fraidy cat continues to show that he is a liar and a fraud.

[Panthera Tigris Altaica]

[Alan Kleinman MD PhD]

[Panthera Tigris Altaica]

[Alan Kleinman MD PhD]

[Panthera Tigris Altaica]

[Alan Kleinman MD PhD]

[Mark Isaak]

It goes without saying that the *real* fraidy cat is the one who edits
out the text he finds bothersome.

[Alan Kleinman MD PhD]

What really bothers me is when someone takes a graduate level course in population genetics and has no understanding of the subject. It is this lack of understanding which causes drug-resistant bacteria, herbicide-resistant weeds, pesticide-resistant and less than durable cancer treatments. Mark, you are a mathematically incompetent dumb-cluck who has no idea how to do applied mathematics. And fraidy cat is a liar and fraud because I've posted the equations and done the calculations which describe rmns multiple times, he's just too stupid to comprehend. And so are you. Go take a course in introductory probability theory and learn how to do the mathematics of rmns and stop harming people with your stupidity of reptiles growing feathers and wings and fish turning into mammals.

[Bill Rogers]

So back to the obvious question. You think biologists vastly overestimate the ability of "rmns" to cause important changes in organisms. Why would you think that they would believe that rmns could cause non-avian dinosaurs to turn into birds and yet be unable to increase the copy number of a gene for a rug export pump in a cancer cell membrane, or slightly change the configuration of a ribosomal protein to prevent tetracycline binding? You seem to think that the same people who overestimate the power of rmns suddenly underestimate it with respect to drug resistance, even though drug resistance is a canonical example of mutation and natural selection offered in pretty much every textbook on evolutionary biology. You whole claim that evolutionists are responsible for drug resistance is fantasy.

[Alan Kleinman MD PhD]

You are the perfect example. You have failed to understand the fundamental physics of a phenomenon that causes your treatment of malaria to fail. You have insisted on using the mathematics of survival of the fittest when it is the mathematics of improving fitness which you should apply to understand your problem. You have and continue to argue that competition accelerates evolution when the reference you posted says the exact opposite and the empirical evidence contradicts your claim. And you have no excuse. You understand enough about probability theory to understand the juvenile model that I've presented. Edward Tatum pointed out 60 years ago the key governing principle of rmns. You and others like you are too stubborn and arrogant to acknowledge this mathematical fact of life. It had to be rediscovered to make an effective treatment for hiv 30 years ago. How many more times will this have to be rediscovered as drug-resistance becomes a bigger and bigger problem? Fish turning into mammals, that's a bit more than vastly overestimating what rmns can do. It is a childish, stupid and harmful claim that only a mathematically incompetent nitwit could believe.

[Bill Rogers]

And yet you still cannot explain why someone would think rmns capable of "turning fish to mammals" would think rmns incapable of handling the far, far far simpler task of turning drug sensitive microbes into drug resistant ones.

Nor can you give a single example in which some biologist has argued that single drug therapy should be used because rmns could not produce drug resistant bugs.

Nor can you explain away the fact that "evolutionists" have been teaching the evolution of drug resistance as a canonical example of "rmns" for decades and that standard microbiology textbooks present the "multiplication rule of probabilities" as a rationale for combination drug therapy fr almost as many decades.

Many factors cause the emergence and spread of drug resistance: overuse of antibiotics by physicians eager to please their patients, large-scale use of antibiotics in agriculture, incomplete treatments with antibiotics, counterfeit antibiotics with much lower doses than shown on the package, availability of antibiotics without prescription in many countries.

And your model does nothing whatsoever to help. You, yourself prescribe monotherapy in circumstances in which you clinical experience, not your model, tells you it will probably work. You, yourself, have no way of estimating the probability of mutation to a resistant phenotype until it happens in practice. You talk about how Group A strep can be still be treated with penicillin monotherapy because resistance has not evolved after decades of such treatment, but you forget that at one point people thought Strep pneumoniae couldn't evolve resistance to penicillin because it had not done so yet, even after decades of penicillin monotherapy.

You go on about a "durable treatment for malaria" but all you know about anti-malarials is what you saw in a "quick Google search." And as far as I can tell, you are only familiar with a single, minor paper in the field of malaria drug resistance (and you've misunderstood that one). When I've explained to you all the factors that enter into choosing a regimen for malaria treatment your answer is "blah, blah, blah." If you want to talk about malaria therapy, go ahead and publish the specific recommendations you have for "durable treatment of malaria", based on your model; otherwise it's all just hot air.

[Alan Kleinman MD PhD]

There are millions of people who think they can beat the odds in Vegas. That should tell you something about the understanding of probability theory in our society. What makes you think that biologists are any better at understanding this topic?

>
> Nor can you give a single example in which some biologist has argued that single drug therapy should be used because rmns could not produce drug resistant bugs.

That's not the argument that biologists and physicians (who have no clinical experience) like you make. You argue that drug resistance is due to the overuse of antibiotics. So is it your claim that the reason malaria resistance occurs is because of the overuse of antimalarial agents? How did you manage to work so many years on this problem and get so little understanding?

>
> Nor can you explain away the fact that "evolutionists" have been teaching the evolution of drug resistance as a canonical example of "rmns" for decades and that standard microbiology textbooks present the "multiplication rule of probabilities" as a rationale for combination drug therapy fr almost as many decades.

Of course, selection pressures can cause directional selection when they are used inappropriately. But the simple-minded argument made by you and biologists is to stop using antibiotics to prevent the selection of resistant variants. You do that at the expense of withholding antibiotics from those who need them. Your lack of clinical experience reveals your lack of understanding of the risks associated when using this strategy of preventing drug resistance. And your lack of understanding of this problem goes beyond this. You don't understand who are the most at risk of getting resistant infections. You had an opportunity to do this in your study but you didn't do the work.

>
> Many factors cause the emergence and spread of drug resistance: overuse of antibiotics by physicians eager to please their patients, large-scale use of antibiotics in agriculture, incomplete treatments with antibiotics, counterfeit antibiotics with much lower doses than shown on the package, availability of antibiotics without prescription in many countries.

These are all secondary issues. First, you need to understand how drug resistance occurs. Then you can develop protocols that would minimize these secondary issues. You don't know how drug resistance occurs because you think it occurs by survival of the fittest. Study and understand the Kishony experiment and use that understanding to develop more durable protocols for any patient regardless of their immune status. You would have a better understanding if you had actually practiced clinical medicine. Have you actually done an H&P since you left med school? The way you talk, I think not.

>
> And your model does nothing whatsoever to help. You, yourself prescribe monotherapy in circumstances in which you clinical experience, not your model, tells you it will probably work. You, yourself, have no way of estimating the probability of mutation to a resistant phenotype until it happens in practice. You talk about how Group A strep can be still be treated with penicillin monotherapy because resistance has not evolved after decades of such treatment, but you forget that at one point people thought Strep pneumoniae couldn't evolve resistance to penicillin because it had not done so yet, even after decades of penicillin monotherapy.

And if you had ever practiced clinical medicine, you would understand why monotherapy usually works. The reason is that an otherwise healthy person, their immune system is a big factor in the success of monotherapy. But if I treat someone with immune suppression of one form or another, I'll use two or three drug therapy. But you missed the opportunity to understand this factor because when you published your paper on treatment failure, you didn't study the patients who got these resistant infections. That is sloppy incomplete work from someone who doesn't have a good idea of the problem he is dealing with, either on a theoretical basis or a clinical basis. Why don't you blame the problem of malaria resistance on over-zealous doctors giving their patients' malaria treatment just to make them happy?

>
> You go on about a "durable treatment for malaria" but all you know about anti-malarials is what you saw in a "quick Google search." And as far as I can tell, you are only familiar with a single, minor paper in the field of malaria drug resistance (and you've misunderstood that one). When I've explained to you all the factors that enter into choosing a regimen for malaria treatment your answer is "blah, blah, blah." If you want to talk about malaria therapy, go ahead and publish the specific recommendations you have for "durable treatment of malaria", based on your model; otherwise it's all just hot air.

And all you know about malaria treatment is how to write a paper on treatment failure. Too bad you don't know anything about the theory of drug-resistance and clinical medicine. You might have made some headway on this problem and actually wrote a paper on durable treatment of malaria. Keep thinking that competition accelerates evolution and models that use relative fitness will give you the correct answer and see how far you get. Not far.

[Bill Rogers]

Yes, resistance to anti-malarials is largely due to overuse of anti-malarials (as you'd know if you'd read more than a single, minor paper in the field). Chloroquine resistance first emerged in areas in which chloroquine had been added to table salt on a large scale as population based malaria prophylaxis. Chloroquine resistance spread rapidly in areas in which, for lack of resources for microscopy, all fevers were treated with chloroquine.

> >
> > Nor can you explain away the fact that "evolutionists" have been teaching the evolution of drug resistance as a canonical example of "rmns" for decades and that standard microbiology textbooks present the "multiplication rule of probabilities" as a rationale for combination drug therapy fr almost as many decades.
> Of course, selection pressures can cause directional selection when they are used inappropriately. But the simple-minded argument made by you and biologists is to stop using antibiotics to prevent the selection of resistant variants. You do that at the expense of withholding antibiotics from those who need them.

Not sure why you say that. Nobody recommends withholding antibiotics from patients who need them.

>Your lack of clinical experience reveals your lack of understanding of the risks associated when using this strategy of preventing drug resistance. And your lack of understanding of this problem goes beyond this. You don't understand who are the most at risk of getting resistant infections. You had an opportunity to do this in your study but you didn't do the work.
> >
> > Many factors cause the emergence and spread of drug resistance: overuse of antibiotics by physicians eager to please their patients, large-scale use of antibiotics in agriculture, incomplete treatments with antibiotics, counterfeit antibiotics with much lower doses than shown on the package, availability of antibiotics without prescription in many countries.
> These are all secondary issues. First, you need to understand how drug resistance occurs. Then you can develop protocols that would minimize these secondary issues. You don't know how drug resistance occurs because you think it occurs by survival of the fittest. Study and understand the Kishony experiment and use that understanding to develop more durable protocols for any patient regardless of their immune status.

What makes you think immmune status was an issue in my paper? In the first place AIDS has only a modest effect on malaria parasitemia, much more moderate than the effect of AIDS on TB or leishmaniasis or toxoplasmosis. In the second place, hyperparasitemia was an exclusion criteria for the study, precisely because different treatments are required for patients with or at risk of severe malaria. So if you are imagining that the treatment failures were patients with hyperparasitemia and more replications allowing them to develop resistance, you're mistaken.

>You would have a better understanding if you had actually practiced clinical medicine. Have you actually done an H&P since you left med school? The way you talk, I think not.
> >
> > And your model does nothing whatsoever to help. You, yourself prescribe monotherapy in circumstances in which you clinical experience, not your model, tells you it will probably work. You, yourself, have no way of estimating the probability of mutation to a resistant phenotype until it happens in practice. You talk about how Group A strep can be still be treated with penicillin monotherapy because resistance has not evolved after decades of such treatment, but you forget that at one point people thought Strep pneumoniae couldn't evolve resistance to penicillin because it had not done so yet, even after decades of penicillin monotherapy.
> And if you had ever practiced clinical medicine, you would understand why monotherapy usually works. The reason is that an otherwise healthy person, their immune system is a big factor in the success of monotherapy. But if I treat someone with immune suppression of one form or another, I'll use two or three drug therapy. But you missed the opportunity to understand this factor because when you published your paper on treatment failure, you didn't study the patients who got these resistant infections.

Except that in many situations monotherapy doesn't work in immunocompetent people, and your model isn't helpful in identifying those cases.

Not sure what you mean by "didn't study the treatment failures." Of course we did. And, though you may have missed it, the treatment failures were all cured with second line therapy.

>That is sloppy incomplete work from someone who doesn't have a good idea of the problem he is dealing with, either on a theoretical basis or a clinical basis. Why don't you blame the problem of malaria resistance on over-zealous doctors giving their patients' malaria treatment just to make them happy?

Practicioners (often not doctors) who dole out anti-malarials indiscriminately for cases of fever are indeed part of the problem.

[Alan Kleinman MD PhD]

So why don't you learn something from this? The use of single drug therapy either for treatment or prophylaxis is the fastest way to select for drug-resistant variants. But the blunder you make would not be solved by withholding treatment from those who need it, it is in the way you use these selection pressures. And from a clinical point of view, in a malaria-endemic region, and without other diagnostic tools, assuming someone has malaria is not a bad assumption. After all, if they didn't have malaria, why would this treatment contribute to drug-resistant malaria? You are not very logical.

>
> > >
> > > Nor can you explain away the fact that "evolutionists" have been teaching the evolution of drug resistance as a canonical example of "rmns" for decades and that standard microbiology textbooks present the "multiplication rule of probabilities" as a rationale for combination drug therapy fr almost as many decades.
> > Of course, selection pressures can cause directional selection when they are used inappropriately. But the simple-minded argument made by you and biologists is to stop using antibiotics to prevent the selection of resistant variants. You do that at the expense of withholding antibiotics from those who need them.
>
> Not sure why you say that. Nobody recommends withholding antibiotics from patients who need them.

So then why would you make the claim that doctors give patients antibiotics to make them happy? Have you ever made a clinical judgment in your entire medical career? I think not. There is an old adage used in clinical medicine, you treat patients, not lab tests. And you watch their clinical response to treatment. That's how you practice good clinical medicine. But you don't understand this.

>
>
> >Your lack of clinical experience reveals your lack of understanding of the risks associated when using this strategy of preventing drug resistance. And your lack of understanding of this problem goes beyond this. You don't understand who are the most at risk of getting resistant infections. You had an opportunity to do this in your study but you didn't do the work.
> > >
> > > Many factors cause the emergence and spread of drug resistance: overuse of antibiotics by physicians eager to please their patients, large-scale use of antibiotics in agriculture, incomplete treatments with antibiotics, counterfeit antibiotics with much lower doses than shown on the package, availability of antibiotics without prescription in many countries.
> > These are all secondary issues. First, you need to understand how drug resistance occurs. Then you can develop protocols that would minimize these secondary issues. You don't know how drug resistance occurs because you think it occurs by survival of the fittest. Study and understand the Kishony experiment and use that understanding to develop more durable protocols for any patient regardless of their immune status.
>
> What makes you think immmune status was an issue in my paper? In the first place AIDS has only a modest effect on malaria parasitemia, much more moderate than the effect of AIDS on TB or leishmaniasis or toxoplasmosis. In the second place, hyperparasitemia was an exclusion criteria for the study, precisely because different treatments are required for patients with or at risk of severe malaria. So if you are imagining that the treatment failures were patients with hyperparasitemia and more replications allowing them to develop resistance, you're mistaken.

Your understanding of immune status is pathetic. There are many factors which contribute to immune status, age of the patient, co-morbities such as diabetes, cancer, and other diseases, nutritional status, medications such as steroids, immune suppressant therapies,... If you had any idea of these factors, you would understand why drug resistance is a greater problem in hospitals where patients tend to be debilitated than out in the community where patients tend to be healthier. But even in the community, there is a spectrum of patients with different levels of immune competence. But you don't understand this and which type of patients are more likely to get drug-resistant infections.

>
> >You would have a better understanding if you had actually practiced clinical medicine. Have you actually done an H&P since you left med school? The way you talk, I think not.
> > >
> > > And your model does nothing whatsoever to help. You, yourself prescribe monotherapy in circumstances in which you clinical experience, not your model, tells you it will probably work. You, yourself, have no way of estimating the probability of mutation to a resistant phenotype until it happens in practice. You talk about how Group A strep can be still be treated with penicillin monotherapy because resistance has not evolved after decades of such treatment, but you forget that at one point people thought Strep pneumoniae couldn't evolve resistance to penicillin because it had not done so yet, even after decades of penicillin monotherapy.
> > And if you had ever practiced clinical medicine, you would understand why monotherapy usually works. The reason is that an otherwise healthy person, their immune system is a big factor in the success of monotherapy. But if I treat someone with immune suppression of one form or another, I'll use two or three drug therapy. But you missed the opportunity to understand this factor because when you published your paper on treatment failure, you didn't study the patients who got these resistant infections.
>
> Except that in many situations monotherapy doesn't work in immunocompetent people, and your model isn't helpful in identifying those cases.

Like I say, your understanding of immunology doesn't reach the level of a first-year medical student. Have you ever heard of immunoglobin subclass deficiencies? There are lots of reasons that some people respond differently to infections than others but this concept is not even on your radar screen and when you had an opportunity to study why some of the people in your study failed treatment, you didn't do the analysis. That's why I think you suck as a researcher.

>
> Not sure what you mean by "didn't study the treatment failures." Of course we did. And, though you may have missed it, the treatment failures were all cured with second line therapy.

Oh really, what was the age of the patients who failed treatment? What other health problems did these patients have that failed treatment? What other medications where they taking in addition to the treatment medications? You don't care about these kind of questions because you don't know how to practice clinical medicine.

>
> >That is sloppy incomplete work from someone who doesn't have a good idea of the problem he is dealing with, either on a theoretical basis or a clinical basis. Why don't you blame the problem of malaria resistance on over-zealous doctors giving their patients' malaria treatment just to make them happy?
>
> Practicioners (often not doctors) who dole out anti-malarials indiscriminately for cases of fever are indeed part of the problem.

And there are practitioners like you who don't know how to dole out anti-malarial drugs and select for resistant variants as well. These untrained practitioners are smart enough to know that these people probably have malaria and the fact that resistant variants are appearing is proof of that. They just don't know how to use these selection pressures in a way to minimize the selection of resistant variants, and neither do you. Your publication on treatment failure is proof of that.

[Bill Rogers]

On Thursday, April 5, 2018 at 10:00:03 PM UTC-4, Alan Kleinman MD PhD wrote:
> On Thursday, April 5, 2018 at 6:15:03 PM UTC-7, Bill Rogers wrote:

<snip>

> > Yes, resistance to anti-malarials is largely due to overuse of anti-malarials (as you'd know if you'd read more than a single, minor paper in the field). Chloroquine resistance first emerged in areas in which chloroquine had been added to table salt on a large scale as population based malaria prophylaxis. Chloroquine resistance spread rapidly in areas in which, for lack of resources for microscopy, all fevers were treated with chloroquine.
> So why don't you learn something from this? The use of single drug therapy either for treatment or prophylaxis is the fastest way to select for drug-resistant variants. But the blunder you make would not be solved by withholding treatment from those who need it, it is in the way you use these selection pressures. And from a clinical point of view, in a malaria-endemic region, and without other diagnostic tools, assuming someone has malaria is not a bad assumption.

...........

>After all, if they didn't have malaria, why would this treatment contribute to drug-resistant malaria? You are not very logical.

If virtually all members of a population have detectable, but subtherapeutic, levels of chloroquine at any given time (as a result either of chloroquine supplementation in table salt, or use of chloroquine to treat all fevers), what do you think will happen to the malaria parasites in that population? It's a population-wide Kishony experiment, perfectly set up for sequential selection of resistance to increasing chloroquine doses.


<snip the rest; there are plenty of other folks willing to trade insults with you>

[Andre G. Isaak]

In article <a52689c4-27e1-4b08...@googlegroups.com>,

Remember that Herr Dr. Dr. doesn't believe that anything nonlethal
counts as a selection pressure.

Andre

--
To email remove 'invalid' & replace 'gm' with well known Google mail service.

[Alan Kleinman MD PhD]

Why Billery can learn. It is a blunder to use single drugs (especially at low levels for long-term) for prophylaxis of infectious diseases. What do you think will happen to immune-compromised patients who are given single drug antibiotics as prophylaxis of infections.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948664/
Just how much do physicians and biologist understand about combination therapy for the treatment of infections for the prevention of emergences of resistant variants?

>
>
> <snip the rest; there are plenty of other folks willing to trade insults with you>

Yea, we've had enough of your hot air.

[Alan Kleinman MD PhD]

You got it backwards. It is you that thinks that selection pressures are never lethal or impair the replication of any variants in a population. Oh, there is one selection pressure that doesn't kill or impair the reproduction of some or all members of the population. It is Noexistium, that's the selection pressure that turns fish into mammals.

[Panthera Tigris Altaica]

oh, yes.

[Alan Kleinman MD PhD]

[Panthera Tigris Altaica]

[jillery]

On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>You got it backwards. It is you that thinks that selection pressures are never lethal or impair the replication of any variants in a population. Oh, there is one selection pressure that doesn't kill or impair the reproduction of some or all members of the population. It is Noexistium, that's the selection pressure that turns fish into mammals.

So where do you think mammals came from? Your black bag? A cabbage
patch? The stork?


--
I disapprove of what you say, but I will defend to the death your right to say it.

Evelyn Beatrice Hall
Attributed to Voltaire

[Alan Kleinman MD PhD]

On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
> On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >You got it backwards. It is you that thinks that selection pressures are never lethal or impair the replication of any variants in a population. Oh, there is one selection pressure that doesn't kill or impair the reproduction of some or all members of the population. It is Noexistium, that's the selection pressure that turns fish into mammals.
>
>
> So where do you think mammals came from? Your black bag? A cabbage
> patch? The stork?

If Barbie understood mathematics, Barbie would understand that rmns didn't do it. But Barbie doesn't understand mathematics.

[Wolffan]

On 07 Apr 2018, Alan Kleinman MD PhD wrote
(in article<3a07bd31-ace2-48e2...@googlegroups.com>):

> On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
> > On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
> > wrote:
> >
> > > You got it backwards. It is you that thinks that selection pressures are
> > > never lethal or impair the replication of any variants in a population.
> > > Oh, there is one selection pressure that doesn't kill or impair the
> > > reproduction of some or all members of the population. It is Noexistium,
> > > that's the selection pressure that turns fish into mammals.
> >
> >
> > So where do you think mammals came from? Your black bag? A cabbage
> > patch? The stork?
> If Barbie understood mathematics, Barbie would understand that rmns didn't do
> it. But Barbie doesn't understand mathematics.

You have failed to show your work. You have succeeded in showing that
you’re an arrant coward. And a liar and a fraud.

[Alan Kleinman MD PhD]

Wolfie and fraidy cat are mathematically incompetent frauds and liars who couldn't recognize a calculation if it was posted on a billboard in 10' high letters. Their ignorance harms people with drug-resistant infections, herbicide-resistant weeds, pesticide-resistant insects and less than durable cancer treatments.

[Wolffan]

On 07 Apr 2018, Alan Kleinman MD PhD wrote

(in article<eb9d0f74-e090-477c...@googlegroups.com>):

[Alan Kleinman MD PhD]

> Wolfie and fraidy cat are frauds and liars. Their ignorance harms people with drug-resistant infections, herbicide-resistant weeds, pesticide-resistant insects and less than durable cancer treatments.

[Wolffan]

On 07 Apr 2018, Alan Kleinman MD PhD wrote

(in article<6e3f768a-e2b8-4382...@googlegroups.com>):

Squeak for me, Feather Fetish Boy!

[Bob Casanova]

On Sat, 7 Apr 2018 07:04:46 -0700 (PDT), the following
appeared in talk.origins, posted by Alan Kleinman MD PhD
<klei...@sti.net>:

>On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
>> On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
>> wrote:
>>
>> >You got it backwards. It is you that thinks that selection pressures are never lethal or impair the replication of any variants in a population. Oh, there is one selection pressure that doesn't kill or impair the reproduction of some or all members of the population. It is Noexistium, that's the selection pressure that turns fish into mammals.
>>
>>
>> So where do you think mammals came from? Your black bag? A cabbage
>> patch? The stork?

>If Barbie understood mathematics, Barbie would understand that rmns didn't do it. But Barbie doesn't understand mathematics.

Irrelevant insults aside, you seem to have a problem with
the meaning of "Please explain your belief", and seem to
think a valid response is "You can't understand". It's not.

So please explain where mammals came from, and where
feathers came from, when neither mammals nor feathers
existed prior to the Mesozoic Era.
--

Bob C.

"The most exciting phrase to hear in science,
the one that heralds new discoveries, is not
'Eureka!' but 'That's funny...'"

- Isaac Asimov

[Wolffan]

On 07 Apr 2018, Bob Casanova wrote
(in article<mt3icdlutn91vig08...@4ax.com>):

> On Sat, 7 Apr 2018 07:04:46 -0700 (PDT), the following
> appeared in talk.origins, posted by Alan Kleinman MD PhD
> <klei...@sti.net>:
>
> > On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
> > > On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
> > > wrote:
> > >
> > > > You got it backwards. It is you that thinks that selection pressures are
> > > > never lethal or impair the replication of any variants in a population.
> > > > Oh, there is one selection pressure that doesn't kill or impair the
> > > > reproduction of some or all members of the population. It is Noexistium,
> > > > that's the selection pressure that turns fish into mammals.
> > >
> > >
> > > So where do you think mammals came from? Your black bag? A cabbage
> > > patch? The stork?
>
> > If Barbie understood mathematics, Barbie would understand that rmns didn't
> > do it. But Barbie doesn't understand mathematics.
>
> Irrelevant insults aside, you seem to have a problem with
> the meaning of "Please explain your belief", and seem to
> think a valid response is "You can't understand". It's not.

The Feather Fetish Boy _cannot_ make a valid response. He’s painted himself
into a corner, no doubt using a feather duster.

>
>
> So please explain where mammals came from, and where
> feathers came from, when neither mammals nor feathers
> existed prior to the Mesozoic Era.

I hereby predict that he won’t make a substantive reply to this, either.

Hey! Feather Fetishist! Squeak for me! You’re a really reliable, and
extremely amusing, squeaky toy! Squeak, boy, squeak!

[Alan Kleinman MD PhD]

On Saturday, April 7, 2018 at 3:15:02 PM UTC-7, Wolffan wrote:
> On 07 Apr 2018, Bob Casanova wrote
> (in article<mt3icdlutn91vig08...@4ax.com>):
>
> > On Sat, 7 Apr 2018 07:04:46 -0700 (PDT), the following
> > appeared in talk.origins, posted by Alan Kleinman MD PhD

> > :
> >
> > > On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
> > > > On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
> > > > wrote:
> > > >
> > > > > You got it backwards. It is you that thinks that selection pressures are
> > > > > never lethal or impair the replication of any variants in a population.
> > > > > Oh, there is one selection pressure that doesn't kill or impair the
> > > > > reproduction of some or all members of the population. It is Noexistium,
> > > > > that's the selection pressure that turns fish into mammals.
> > > >
> > > >
> > > > So where do you think mammals came from? Your black bag? A cabbage
> > > > patch? The stork?
> >
> > > If Barbie understood mathematics, Barbie would understand that rmns didn't
> > > do it. But Barbie doesn't understand mathematics.
> >
> > Irrelevant insults aside, you seem to have a problem with
> > the meaning of "Please explain your belief", and seem to
> > think a valid response is "You can't understand". It's not.
>
> The Feather Fetish Boy _cannot_ make a valid response. He’s painted himself
> into a corner, no doubt using a feather duster.
> >
> >
> > So please explain where mammals came from, and where
> > feathers came from, when neither mammals nor feathers
> > existed prior to the Mesozoic Era.
>
> I hereby predict that he won’t make a substantive reply to this, either.
>
> Hey! Feather Fetishist! Squeak for me! You’re a really reliable, and
> extremely amusing, squeaky toy! Squeak, boy, squeak!

Silly Wolfie is very boring. Your posts are what the PgDn button is made for. Stick with howling at the moon.
PgDn

[Wolffan]

On 07 Apr 2018, Alan Kleinman MD PhD wrote
(in article<021126b0-26bd-4890...@googlegroups.com>):

then why are you squeaking for me, Feather Fetish Boy?

>
> Stick with howling at the moon.
> PgDn

You have failed to show your work. You have succeeded in showing that

[jillery]

On Sat, 7 Apr 2018 07:04:46 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
>> On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
>> wrote:
>>
>> >You got it backwards. It is you that thinks that selection pressures are never lethal or impair the replication of any variants in a population. Oh, there is one selection pressure that doesn't kill or impair the reproduction of some or all members of the population. It is Noexistium, that's the selection pressure that turns fish into mammals.
>>
>>
>> So where do you think mammals came from? Your black bag? A cabbage
>> patch? The stork?
>If Barbie understood mathematics, Barbie would understand that rmns didn't do it. But Barbie doesn't understand mathematics.

So you have no idea where mammals came from, and you just post
non-sequitur spam because you have no idea what you're talking about.
That's what lying trolls do.

[Bob Casanova]

On Sat, 07 Apr 2018 11:40:41 -0700, the following appeared
in talk.origins, posted by Bob Casanova <nos...@buzz.off>:

>On Sat, 7 Apr 2018 07:04:46 -0700 (PDT), the following
>appeared in talk.origins, posted by Alan Kleinman MD PhD
><klei...@sti.net>:
>
>>On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
>>> On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
>>> wrote:
>>>
>>> >You got it backwards. It is you that thinks that selection pressures are never lethal or impair the replication of any variants in a population. Oh, there is one selection pressure that doesn't kill or impair the reproduction of some or all members of the population. It is Noexistium, that's the selection pressure that turns fish into mammals.
>>>
>>>
>>> So where do you think mammals came from? Your black bag? A cabbage
>>> patch? The stork?
>
>>If Barbie understood mathematics, Barbie would understand that rmns didn't do it. But Barbie doesn't understand mathematics.
>
>Irrelevant insults aside, you seem to have a problem with
>the meaning of "Please explain your belief", and seem to
>think a valid response is "You can't understand". It's not.
>
>So please explain where mammals came from, and where
>feathers came from, when neither mammals nor feathers
>existed prior to the Mesozoic Era.

Still waiting...

Where did mammals and feathers come from, when neither
existed prior to the Mesozoic Era?

Wiggle, wiggle...

[Bob Casanova]

On Sat, 07 Apr 2018 18:13:56 -0400, the following appeared
in talk.origins, posted by Wolffan <akwo...@gmail.com>:

>On 07 Apr 2018, Bob Casanova wrote
>(in article<mt3icdlutn91vig08...@4ax.com>):
>
>> On Sat, 7 Apr 2018 07:04:46 -0700 (PDT), the following
>> appeared in talk.origins, posted by Alan Kleinman MD PhD
>> <klei...@sti.net>:
>>
>> > On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
>> > > On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
>> > > wrote:
>> > >
>> > > > You got it backwards. It is you that thinks that selection pressures are
>> > > > never lethal or impair the replication of any variants in a population.
>> > > > Oh, there is one selection pressure that doesn't kill or impair the
>> > > > reproduction of some or all members of the population. It is Noexistium,
>> > > > that's the selection pressure that turns fish into mammals.
>> > >
>> > >
>> > > So where do you think mammals came from? Your black bag? A cabbage
>> > > patch? The stork?
>>
>> > If Barbie understood mathematics, Barbie would understand that rmns didn't
>> > do it. But Barbie doesn't understand mathematics.
>>
>> Irrelevant insults aside, you seem to have a problem with
>> the meaning of "Please explain your belief", and seem to
>> think a valid response is "You can't understand". It's not.
>
>The Feather Fetish Boy _cannot_ make a valid response. He’s painted himself
>into a corner, no doubt using a feather duster.

Yeah, we all see that. But it's fun to watch him squirm.

>> So please explain where mammals came from, and where
>> feathers came from, when neither mammals nor feathers
>> existed prior to the Mesozoic Era.
>
>I hereby predict that he won’t make a substantive reply to this, either.

Now *that's* a prediction which doesn't require psi
talent...

>Hey! Feather Fetishist! Squeak for me! You’re a really reliable, and
>extremely amusing, squeaky toy! Squeak, boy, squeak!

[Andre G. Isaak]

In article <vgkkcdt8ma2rmqe0j...@4ax.com>,

The alleged Mesozoic was supposedly more than 6,000 years ago. I doubt
he accepts this.

[Wolffan]

On 08 Apr 2018, Andre G. Isaak wrote
(in article<agisaak-E02F31...@news.eternal-september.org>):

All of the alleged evidence for a ‘Mesozoic era’ was clearly fabricated
by members of the reptiles-grow-feathers cult who can’t understand the
crown jewel of all mathematics, rmns.

[Andre G. Isaak]

In article <0001HW.207AAA7801...@news.supernews.com>,

Oh man, why did you have to go and post that?

Now the illuminati will have to kill you.

[Alan Kleinman MD PhD]

On Sunday, April 8, 2018 at 12:40:03 PM UTC-7, Andre G. Isaak wrote:
> In article <vgkkcdt8ma2rmqe0j...@4ax.com>,
> Bob Casanova <nos...@buzz.off> wrote:
>
> > On Sat, 07 Apr 2018 11:40:41 -0700, the following appeared
> > in talk.origins, posted by Bob Casanova <nos...@buzz.off>:
> >
> > >On Sat, 7 Apr 2018 07:04:46 -0700 (PDT), the following
> > >appeared in talk.origins, posted by Alan Kleinman MD PhD

> > >:
> > >
> > >>On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
> > >>> On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
> > >>> wrote:
> > >>>
> > >>> >You got it backwards. It is you that thinks that selection pressures are
> > >>> >never lethal or impair the replication of any variants in a population.
> > >>> >Oh, there is one selection pressure that doesn't kill or impair the
> > >>> >reproduction of some or all members of the population. It is Noexistium,
> > >>> >that's the selection pressure that turns fish into mammals.
> > >>>
> > >>>
> > >>> So where do you think mammals came from? Your black bag? A cabbage
> > >>> patch? The stork?
> > >
> > >>If Barbie understood mathematics, Barbie would understand that rmns didn't
> > >>do it. But Barbie doesn't understand mathematics.
> > >
> > >Irrelevant insults aside, you seem to have a problem with
> > >the meaning of "Please explain your belief", and seem to
> > >think a valid response is "You can't understand". It's not.
> > >
> > >So please explain where mammals came from, and where
> > >feathers came from, when neither mammals nor feathers
> > >existed prior to the Mesozoic Era.
> >
> > Still waiting...
> >
> > Where did mammals and feathers come from, when neither
> > existed prior to the Mesozoic Era?
>
> The alleged Mesozoic was supposedly more than 6,000 years ago. I doubt
> he accepts this.

I certainly don't accept this notion that mammals came from fish and reptiles grow feathers and wings, rmns cannot do transformations like this. It's the multiplication rule of probabilities that prevents this. It doesn't matter how many squillions of years you want to claim for it to occur.

[Alan Kleinman MD PhD]

On Saturday, April 7, 2018 at 9:25:03 PM UTC-7, jillery wrote:
> On Sat, 7 Apr 2018 07:04:46 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >On Friday, April 6, 2018 at 9:10:03 PM UTC-7, jillery wrote:
> >> On Fri, 6 Apr 2018 05:46:10 -0700 (PDT), Alan Kleinman MD PhD
> >> wrote:
> >>
> >> >You got it backwards. It is you that thinks that selection pressures are never lethal or impair the replication of any variants in a population. Oh, there is one selection pressure that doesn't kill or impair the reproduction of some or all members of the population. It is Noexistium, that's the selection pressure that turns fish into mammals.
> >>
> >>
> >> So where do you think mammals came from? Your black bag? A cabbage
> >> patch? The stork?
> >If Barbie understood mathematics, Barbie would understand that rmns didn't do it. But Barbie doesn't understand mathematics.
>
>
> So you have no idea where mammals came from, and you just post
> non-sequitur spam because you have no idea what you're talking about.
> That's what lying trolls do.

I know mammals didn't come from fish, that's a big fish story.

[Panthera Tigris Altaica]

I notice that you haven't said where mammals came from. And that you still have not shown your work.

[Andre G. Isaak]

In article <abbdac3a-2d5b-41f5...@googlegroups.com>,

Your 'multiplication rule of probabilities' carries no weight whatsoever
until you actually provide some experimental evidence for it.

The standard scientific view that all tetrapods (not just mammals) has
been backed up not just by the fossil record but also by many thousands
of papers from a wide range of fields including genetics, comparative
anatomy, embryology and palaeontology, just to name a few.

Any sane person is going to favour the consensus position which is
backed up by mountains of evidence over the word of a single crackpot
with a single equation who doesn't appear willing to provide evidence
that that equation is supported by even a single empirical example and
who instead spends their time coming up with schoolyard nicknames for
his various detractors.

[Alan Kleinman MD PhD]

But I have explained correctly how rmns works but you don't understand this because you don't understand introductory probability theory.

[Alan Kleinman MD PhD]

On Monday, April 9, 2018 at 8:30:03 AM UTC-7, Andre G. Isaak wrote:
> In article <abbdac3a-2d5b-41f5...@googlegroups.com>,

The evidence is everywhere but since you are having a hard time seeing it, I'll repost some examples:
"Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins", https://pdfs.semanticscholar.org/7d94/c58d1e7bd4f732486bbb0f5681ada85d9333.pdf
I used this empirical example to derive the equations for a single selection pressure targeting a single gene. https://www.ncbi.nlm.nih.gov/pubmed/25244620
Then there is Billery Rogers paper; "Failure of artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria in southern Cambodia", https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628668/ .
I used this empirical example to derive the governing equations for multiple simultaneous selection pressures.
https://www.ncbi.nlm.nih.gov/pubmed/27501057
This paper explains how large a population required for multiple simultaneous beneficial mutations in order to adapt to the selection conditions.
Then we have the Kishony experiment, the Lenski experiment, the successful use of 3 selection pressures for treating hiv, the successful use of combination herbicides to prevent the emergence of herbicide-resistant weeds, the successful use of combination pesticides to prevent the emergence of pesticide-resistant insects, the use of combination cancer treatment to give more durable cancer treatments...
Now you might have difficulty understanding these empirical examples if you don't have a good grasp on the mathematics of stochastic processes. But since rmns is a stochastic process, you will have to understand introductory probability theory to understand the physics of rmns.

>
> The standard scientific view that all tetrapods (not just mammals) has
> been backed up not just by the fossil record but also by many thousands
> of papers from a wide range of fields including genetics, comparative
> anatomy, embryology and palaeontology, just to name a few.

This is an old story based on a lack of understanding of the mechanism of genetic transformation. Palaeontologists cherry-pick the fossil record to fit a preconceived notion. But it is obvious, there is no reasonable way that rmns can transform fish into mammals and make reptiles grow feathers and wings.

>
> Any sane person is going to favour the consensus position which is
> backed up by mountains of evidence over the word of a single crackpot
> with a single equation who doesn't appear willing to provide evidence
> that that equation is supported by even a single empirical example and
> who instead spends their time coming up with schoolyard nicknames for
> his various detractors.

You mean mountains of speculation and I have no problem opposing this consensus when it leads to multi-drug resistant microbes, multi-herbicide resistant weeds, multi-pesticide resistant insects and less than durable treatments for cancer. While the reptiles grow feathers crowd piles up their speculation, they fail to correctly understand the accounting rules which govern rmns.

[Panthera Tigris Altaica]

You have not shown your calculations. You flatly refuse to do so.

[Bob Casanova]

On Sun, 08 Apr 2018 13:37:15 -0600, the following appeared
in talk.origins, posted by "Andre G. Isaak"
<agi...@gm.invalid>:

Ummm...point.

[Bob Casanova]

On Sun, 08 Apr 2018 10:34:12 -0700, the following appeared

[Vincent Maycock]

On Mon, 9 Apr 2018 09:07:32 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

snip

> Palaeontologists cherry-pick the fossil record to fit a preconceived notion.

Any evidence for this assertion? Examples? Citations?

[Panthera Tigris Altaica]

Just as he will never, ever, post his calculations, he will never, ever, post any evidence for anything he asserts.

[Alan Kleinman MD PhD]

On Monday, April 9, 2018 at 10:35:03 AM UTC-7, Vincent Maycock wrote:
> On Mon, 9 Apr 2018 09:07:32 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> snip
>
> > Palaeontologists cherry-pick the fossil record to fit a preconceived notion.
>
> Any evidence for this assertion? Examples? Citations?

What exactly is the Archiedumbtrex fossil other than a cherry-picked fossil which fits your comparative anatomy concept? Have you sequenced the genome of this fossil and done the DNA identification? Where are your citations? It is time for your 19th-century concept of science to enter the 21st century.

[Vincent Maycock]

On Mon, 9 Apr 2018 11:44:51 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>On Monday, April 9, 2018 at 10:35:03 AM UTC-7, Vincent Maycock wrote:
>> On Mon, 9 Apr 2018 09:07:32 -0700 (PDT), Alan Kleinman MD PhD
>> wrote:
>>
>> snip
>>
>> > Palaeontologists cherry-pick the fossil record to fit a preconceived notion.
>>
>> Any evidence for this assertion? Examples? Citations?
>
>What exactly is the Archiedumbtrex fossil

_Archaeopteryx_ is clearly a transitional form between dinosaurs and
birds, no matter how dumb you think it is.

>other than a cherry-picked fossil which fits your comparative anatomy concept?

LOL! "My comparative anatomy concept"?

Are you saying you don't think some creatures don't resemble some
others more so than they do others?

And if cherry-picking has gone on, where are the fossils that weren't
picked?

And who has been doing the picking? Me? Paleontologists?

And are you aware that there are more transitional fossils than just
_Archaeopteryx_?

> Have you sequenced the genome of this fossil and done the DNA identification?

No, we don't have DNA from _Archaeopteryx_, but that's not necessary;
the morphology of the form is pretty clear.

Also, are you aware that DNA studies of other creatures *have* been
done and in general support comparative anatomy, as well as giving us
a better understanding of how evolution created the wealth of
different life forms we see around us?

> Where are your citations?

https://en.wikipedia.org/wiki/Archaeopteryx

[Alan Kleinman MD PhD]

On Monday, April 9, 2018 at 1:35:03 PM UTC-7, Vincent Maycock wrote:
> On Mon, 9 Apr 2018 11:44:51 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >On Monday, April 9, 2018 at 10:35:03 AM UTC-7, Vincent Maycock wrote:
> >> On Mon, 9 Apr 2018 09:07:32 -0700 (PDT), Alan Kleinman MD PhD
> >> wrote:
> >>
> >> snip
> >>
> >> > Palaeontologists cherry-pick the fossil record to fit a preconceived notion.
> >>
> >> Any evidence for this assertion? Examples? Citations?
> >
> >What exactly is the Archiedumbtrex fossil
>
> _Archaeopteryx_ is clearly a transitional form between dinosaurs and
> birds, no matter how dumb you think it is.

So you don't mind telling us what the selection pressure was, the genes targeted and the mutations required to transform a non-feather producer to a feather producing replicator.

>
> >other than a cherry-picked fossil which fits your comparative anatomy concept?
>
> LOL! "My comparative anatomy concept"?
>
> Are you saying you don't think some creatures don't resemble some
> others more so than they do others?

Comparative anatomy is useless in determining relatedness. Modern science uses genetic testing to determine relatedness.

>
> And if cherry-picking has gone on, where are the fossils that weren't
> picked?

Like I say, you choose fossils that fit your belief system without ever taking into account the mechanism of genetic transformation. hiv can't evolve efficiently to three selection pressures targeting just two genes. How is a reptile to transform the multiple genetic loci, the proteins, and control modules to make scales into feathers when the fastest evolving replicator known cannot evolve to combination therapy?

>
> And who has been doing the picking? Me? Paleontologists?

There are lots of people who have convinced themselves that this logic is correct but they have never considered the mechanisms of genetic transformation in their categorization scheme.

>
> And are you aware that there are more transitional fossils than just
> _Archaeopteryx_?

Are you aware of how rmns works? Before you find a fossil and claim that it is transitional, learn about the mechanisms of evolution. It might help you from grossly overspeculating.

>
> > Have you sequenced the genome of this fossil and done the DNA identification?
>
> No, we don't have DNA from _Archaeopteryx_, but that's not necessary;
> the morphology of the form is pretty clear.

"Pretty clear"? The way rmns works can be predicted with mathematical certainty. And this is verified with repeatable experiments.

>
> Also, are you aware that DNA studies of other creatures *have* been
> done and in general support comparative anatomy, as well as giving us
> a better understanding of how evolution created the wealth of
> different life forms we see around us?

"In general"? You take a few genetic matches and claim relatedness while ignoring the huge number of genetic differences.

[Vincent Maycock]

On Mon, 9 Apr 2018 13:53:35 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>On Monday, April 9, 2018 at 1:35:03 PM UTC-7, Vincent Maycock wrote:
>> On Mon, 9 Apr 2018 11:44:51 -0700 (PDT), Alan Kleinman MD PhD
>> wrote:
>>
>> >On Monday, April 9, 2018 at 10:35:03 AM UTC-7, Vincent Maycock wrote:
>> >> On Mon, 9 Apr 2018 09:07:32 -0700 (PDT), Alan Kleinman MD PhD
>> >> wrote:
>> >>
>> >> snip
>> >>
>> >> > Palaeontologists cherry-pick the fossil record to fit a preconceived notion.
>> >>
>> >> Any evidence for this assertion? Examples? Citations?
>> >
>> >What exactly is the Archiedumbtrex fossil
>>
>> _Archaeopteryx_ is clearly a transitional form between dinosaurs and
>> birds, no matter how dumb you think it is.
>So you don't mind telling us what the selection pressure was,

Insulation, which was co-opted for aerodynamic purposes.

>the genes targeted and the mutations required to transform a non-feather producer to a feather producing replicator.

You've told me that someone told you that it's like 7 or 8 genes
involved. Are you sure this couldn't happen, if the modifications
didn't all happen simultaneously?

>> >other than a cherry-picked fossil which fits your comparative anatomy concept?
>>
>> LOL! "My comparative anatomy concept"?
>>
>> Are you saying you don't think some creatures don't resemble some
>> others more so than they do others?
>Comparative anatomy is useless in determining relatedness.

So you think all creatures resemble each other equally?

> Modern science uses genetic testing to determine relatedness.

Which evolutionary biologists use as well, but you dismiss them for no
good reason.

>> And if cherry-picking has gone on, where are the fossils that weren't
>> picked?
>Like I say, you choose fossils that fit your belief system

And where are the ones that don't fit my "belief system"?

> without ever taking into account the mechanism of genetic transformation. hiv can't evolve efficiently to three selection pressures targeting just two genes. How is a reptile to transform the multiple genetic loci, the proteins, and control modules to make scales into feathers when the fastest evolving replicator known cannot evolve to combination therapy?

If the intensity of selection were low, it could happen. It might not
affect the trajectories, but you yourself said it would affect
*something.*

>> And who has been doing the picking? Me? Paleontologists?
>There are lots of people who have convinced themselves that this logic is correct but they have never considered the mechanisms of genetic transformation in their categorization scheme.
>>
>> And are you aware that there are more transitional fossils than just
>> _Archaeopteryx_?
>Are you aware of how rmns works? Before you find a fossil and claim that it is transitional, learn about the mechanisms of evolution. It might help you from grossly overspeculating.
>>
>> > Have you sequenced the genome of this fossil and done the DNA identification?
>>
>> No, we don't have DNA from _Archaeopteryx_, but that's not necessary;
>> the morphology of the form is pretty clear.
>"Pretty clear"?

Very clear, yes.

> The way rmns works can be predicted with mathematical certainty.

Unless you made a mistake somewhere. It happens, even to the best of
mathematicians.

> And this is verified with repeatable experiments.

You don't have any quantitative comparisons between the experiments
and your math.

>> Also, are you aware that DNA studies of other creatures *have* been
>> done and in general support comparative anatomy, as well as giving us
>> a better understanding of how evolution created the wealth of
>> different life forms we see around us?
>"In general"? You take a few genetic matches

What makes you think it's just a "few" genetic matches?

[Panthera Tigris Altaica]

You are attacking someone else's position. You are not providing evidence for your own. I suspect that you cannot provide evidence for your own. If you can, please provided it. With the full and complete support, especially including all of your calculations.

[Alan Kleinman MD PhD]

On Monday, April 9, 2018 at 2:20:03 PM UTC-7, Vincent Maycock wrote:
> On Mon, 9 Apr 2018 13:53:35 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >On Monday, April 9, 2018 at 1:35:03 PM UTC-7, Vincent Maycock wrote:
> >> On Mon, 9 Apr 2018 11:44:51 -0700 (PDT), Alan Kleinman MD PhD
> >> wrote:
> >>
> >> >On Monday, April 9, 2018 at 10:35:03 AM UTC-7, Vincent Maycock wrote:
> >> >> On Mon, 9 Apr 2018 09:07:32 -0700 (PDT), Alan Kleinman MD PhD
> >> >> wrote:
> >> >>
> >> >> snip
> >> >>
> >> >> > Palaeontologists cherry-pick the fossil record to fit a preconceived notion.
> >> >>
> >> >> Any evidence for this assertion? Examples? Citations?
> >> >
> >> >What exactly is the Archiedumbtrex fossil
> >>
> >> _Archaeopteryx_ is clearly a transitional form between dinosaurs and
> >> birds, no matter how dumb you think it is.
> >So you don't mind telling us what the selection pressure was,
>
> Insulation, which was co-opted for aerodynamic purposes.

This is the old speculation. Which biologic (reactions) pathways are affected by temperature variation?

>
> >the genes targeted and the mutations required to transform a non-feather producer to a feather producing replicator.
>
> You've told me that someone told you that it's like 7 or 8 genes
> involved. Are you sure this couldn't happen, if the modifications
> didn't all happen simultaneously?

That's the number I got from a link from Edward Max. But aren't far more biological pathways affected by temperature variation? And until the insulation grew, wouldn't many biological reactions be affected?

>
> >> >other than a cherry-picked fossil which fits your comparative anatomy concept?
> >>
> >> LOL! "My comparative anatomy concept"?
> >>
> >> Are you saying you don't think some creatures don't resemble some
> >> others more so than they do others?
> >Comparative anatomy is useless in determining relatedness.
>
> So you think all creatures resemble each other equally?

I think that relatedness based on genetic sequencing is far more accurate than anything that can be done by comparative anatomy. Any attempt at determining relatedness based on gross anatomy at best is only a crude approximation. And if don't take into account the mechanisms of genetic transformation, that crude approximation becomes rank speculation.

>
> > Modern science uses genetic testing to determine relatedness.
>
> Which evolutionary biologists use as well, but you dismiss them for no
> good reason.

That's because evolutionary biologists are selective in their use of genetics. For example, I've heard the argument that humans and chimps produce identical insulin and therefore must be related. But on closer examination, it is found that the pre-proinsulin molecules differ by two amino acids. And is the enzyme which cleaves the pre-proinsulin identical between humans and chimps? And you can go on looking at each allele at each loci and you will start to understand the mathematical problem you have in getting all these genetic changes in a million generations.

>
> >> And if cherry-picking has gone on, where are the fossils that weren't
> >> picked?
> >Like I say, you choose fossils that fit your belief system
>
> And where are the ones that don't fit my "belief system"?

You don't pick those cherries.

>
> > without ever taking into account the mechanism of genetic transformation. hiv can't evolve efficiently to three selection pressures targeting just two genes. How is a reptile to transform the multiple genetic loci, the proteins, and control modules to make scales into feathers when the fastest evolving replicator known cannot evolve to combination therapy?
>
> If the intensity of selection were low, it could happen. It might not
> affect the trajectories, but you yourself said it would affect
> *something.*

rmns does not depend on the intensity of selection. It depends on the ability of a variant to amplify to improve the probability of a beneficial mutation occurring. And for a mutation rate of e-9, it takes e9 replications for that beneficial mutation to occur. And that's for a single targeted selection pressure. Thermal stress targets virtually every metabolic pathway.

>
> >> And who has been doing the picking? Me? Paleontologists?
> >There are lots of people who have convinced themselves that this logic is correct but they have never considered the mechanisms of genetic transformation in their categorization scheme.
> >>
> >> And are you aware that there are more transitional fossils than just
> >> _Archaeopteryx_?
> >Are you aware of how rmns works? Before you find a fossil and claim that it is transitional, learn about the mechanisms of evolution. It might help you from grossly overspeculating.
> >>
> >> > Have you sequenced the genome of this fossil and done the DNA identification?
> >>
> >> No, we don't have DNA from _Archaeopteryx_, but that's not necessary;
> >> the morphology of the form is pretty clear.
> >"Pretty clear"?
>
> Very clear, yes.

Clear as mud. So tell us, aren't reptiles under thermal stress today?

>
> > The way rmns works can be predicted with mathematical certainty.
>
> Unless you made a mistake somewhere. It happens, even to the best of
> mathematicians.

The math is quite simple, Billery Rogers calls it juvenile. And the correlation with the empirical evidence is accurate and every successful treatment of hiv confirms this math.

>
> > And this is verified with repeatable experiments.
>
> You don't have any quantitative comparisons between the experiments
> and your math.

Read my response to Andre on this subject. Kishony uses the same numbers for his experiment that my math predicts.
https://www.youtube.com/watch?v=Irnc6w_Gsas
Using the mutation rate Kishony gives for his experiment gives the same number of predicted replications from the math that I've presented for each beneficial mutation that Kishony reports.

>
> >> Also, are you aware that DNA studies of other creatures *have* been
> >> done and in general support comparative anatomy, as well as giving us
> >> a better understanding of how evolution created the wealth of
> >> different life forms we see around us?
> >"In general"? You take a few genetic matches
>
> What makes you think it's just a "few" genetic matches?

Study the reports in detail. So called "junk-DNA" is ignored. You can't just use portions of genomes which appear homologous, you must compare the entire genome. Cherry-picking fossils has taught biologists a bad habit when comparing genomes.

[Vincent Maycock]

On Mon, 9 Apr 2018 15:05:19 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>On Monday, April 9, 2018 at 2:20:03 PM UTC-7, Vincent Maycock wrote:
>> On Mon, 9 Apr 2018 13:53:35 -0700 (PDT), Alan Kleinman MD PhD
>> wrote:
>>
>> >On Monday, April 9, 2018 at 1:35:03 PM UTC-7, Vincent Maycock wrote:
>> >> On Mon, 9 Apr 2018 11:44:51 -0700 (PDT), Alan Kleinman MD PhD
>> >> wrote:
>> >>
>> >> >On Monday, April 9, 2018 at 10:35:03 AM UTC-7, Vincent Maycock wrote:
>> >> >> On Mon, 9 Apr 2018 09:07:32 -0700 (PDT), Alan Kleinman MD PhD
>> >> >> wrote:
>> >> >>
>> >> >> snip
>> >> >>
>> >> >> > Palaeontologists cherry-pick the fossil record to fit a preconceived notion.
>> >> >>
>> >> >> Any evidence for this assertion? Examples? Citations?
>> >> >
>> >> >What exactly is the Archiedumbtrex fossil
>> >>
>> >> _Archaeopteryx_ is clearly a transitional form between dinosaurs and
>> >> birds, no matter how dumb you think it is.
>> >So you don't mind telling us what the selection pressure was,
>>
>> Insulation, which was co-opted for aerodynamic purposes.
>This is the old speculation. Which biologic (reactions) pathways are affected by temperature variation?

We're not talking about *those* pathways right now, just feathers.

>> >the genes targeted and the mutations required to transform a non-feather producer to a feather producing replicator.
>>
>> You've told me that someone told you that it's like 7 or 8 genes
>> involved. Are you sure this couldn't happen, if the modifications
>> didn't all happen simultaneously?
>That's the number I got from a link from Edward Max. But aren't far more biological pathways affected by temperature variation? And until the insulation grew, wouldn't many biological reactions be affected?

They would be affected, but evidently not enough to kill them all off.

>> >> >other than a cherry-picked fossil which fits your comparative
anatomy concept?
>> >>
>> >> LOL! "My comparative anatomy concept"?
>> >>
>> >> Are you saying you don't think some creatures don't resemble some
>> >> others more so than they do others?
>> >Comparative anatomy is useless in determining relatedness.
>>
>> So you think all creatures resemble each other equally?
>I think that relatedness based on genetic sequencing is far more accurate than anything that can be done by comparative anatomy.

So "less accurate" is the same thing as "useless"?

> Any attempt at determining relatedness based on gross anatomy at best is only a crude approximation.

Which DNA studies have confirmed spectacularly in many cases.

>And if don't take into account the mechanisms of genetic transformation, that crude approximation becomes rank speculation.
>>
>> > Modern science uses genetic testing to determine relatedness.
>>
>> Which evolutionary biologists use as well, but you dismiss them for no
>> good reason.
>That's because evolutionary biologists are selective in their use of genetics. For example, I've heard the argument that humans and chimps produce identical insulin and therefore must be related. But on closer examination, it is found that the pre-proinsulin molecules differ by two amino acids. And is the enzyme which cleaves the pre-proinsulin identical between humans and chimps?

These days we have more information about the genomes of humans and
chimps, so we don't have to rely on insulin molecules.

> And you can go on looking at each allele at each loci and you will start to understand the mathematical problem you have in getting all these genetic changes in a million generations.

That's what's called an "argument from incredulity," and is not good
logic.

>> >> And if cherry-picking has gone on, where are the fossils that weren't
>> >> picked?
>> >Like I say, you choose fossils that fit your belief system
>>
>> And where are the ones that don't fit my "belief system"?
>You don't pick those cherries.

Yes, but what *are* they, explicitly?

>> > without ever taking into account the mechanism of genetic transformation. hiv can't evolve efficiently to three selection pressures targeting just two genes. How is a reptile to transform the multiple genetic loci, the proteins, and control modules to make scales into feathers when the fastest evolving replicator known cannot evolve to combination therapy?
>>
>> If the intensity of selection were low, it could happen. It might not
>> affect the trajectories, but you yourself said it would affect
>> *something.*
>rmns does not depend on the intensity of selection. It depends on the ability of a variant to amplify to improve the probability of a beneficial mutation occurring. And for a mutation rate of e-9, it takes e9 replications for that beneficial mutation to occur. And that's for a single targeted selection pressure. Thermal stress targets virtually every metabolic pathway.

Presumably, those metabolic pathways had already evolved by the time
birds evolved from dinosaurs.

>> >> And who has been doing the picking? Me? Paleontologists?
>> >There are lots of people who have convinced themselves that this logic is correct but they have never considered the mechanisms of genetic transformation in their categorization scheme.
>> >>
>> >> And are you aware that there are more transitional fossils than just
>> >> _Archaeopteryx_?
>> >Are you aware of how rmns works? Before you find a fossil and claim that it is transitional, learn about the mechanisms of evolution. It might help you from grossly overspeculating.
>> >>
>> >> > Have you sequenced the genome of this fossil and done the DNA identification?
>> >>
>> >> No, we don't have DNA from _Archaeopteryx_, but that's not necessary;
>> >> the morphology of the form is pretty clear.
>> >"Pretty clear"?
>>
>> Very clear, yes.
>Clear as mud. So tell us, aren't reptiles under thermal stress today?

If the right mutations don't come along, they won't evolve insulation.
They'll have to find other ways to adapt.

>> > The way rmns works can be predicted with mathematical certainty.
>>
>> Unless you made a mistake somewhere. It happens, even to the best of
>> mathematicians.
>The math is quite simple,

And some mathematicians can make even simple errors.

> Billery Rogers calls it juvenile. And the correlation with the empirical evidence is accurate and every successful treatment of hiv confirms this math.
>>
>> > And this is verified with repeatable experiments.
>>
>> You don't have any quantitative comparisons between the experiments
>> and your math.
>Read my response to Andre on this subject. Kishony uses the same numbers for his experiment that my math predicts.
>https://www.youtube.com/watch?v=Irnc6w_Gsas
>Using the mutation rate Kishony gives for his experiment gives the same number of predicted replications from the math that I've presented for each beneficial mutation that Kishony reports.

Are you sure he was using your mathematics when he did this? It seems
like more of a coincidence that he was talking about billions and
billionths.

>> >> Also, are you aware that DNA studies of other creatures *have* been
>> >> done and in general support comparative anatomy, as well as giving us
>> >> a better understanding of how evolution created the wealth of
>> >> different life forms we see around us?
>> >"In general"? You take a few genetic matches
>>
>> What makes you think it's just a "few" genetic matches?
>Study the reports in detail. So called "junk-DNA" is ignored.

Why would junk DNA be ignored? That would be the best kind of DNA to
use, since it would be resistant to homoplasy.

>You can't just use portions of genomes which appear homologous, you must compare the entire genome. Cherry-picking fossils

Actually, that hasn't happened.

[erik simpson]

Fossils are generally very rare, and believe me, paleontologists make the most
of what has been found. Cherry-picking is nonexistent.

[Alan Kleinman MD PhD]

On Monday, April 9, 2018 at 3:50:02 PM UTC-7, Vincent Maycock wrote:
> On Mon, 9 Apr 2018 15:05:19 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >On Monday, April 9, 2018 at 2:20:03 PM UTC-7, Vincent Maycock wrote:
> >> On Mon, 9 Apr 2018 13:53:35 -0700 (PDT), Alan Kleinman MD PhD
> >> wrote:
> >>
> >> >On Monday, April 9, 2018 at 1:35:03 PM UTC-7, Vincent Maycock wrote:
> >> >> On Mon, 9 Apr 2018 11:44:51 -0700 (PDT), Alan Kleinman MD PhD
> >> >> wrote:
> >> >>
> >> >> >On Monday, April 9, 2018 at 10:35:03 AM UTC-7, Vincent Maycock wrote:
> >> >> >> On Mon, 9 Apr 2018 09:07:32 -0700 (PDT), Alan Kleinman MD PhD
> >> >> >> wrote:
> >> >> >>
> >> >> >> snip
> >> >> >>
> >> >> >> > Palaeontologists cherry-pick the fossil record to fit a preconceived notion.
> >> >> >>
> >> >> >> Any evidence for this assertion? Examples? Citations?
> >> >> >
> >> >> >What exactly is the Archiedumbtrex fossil
> >> >>
> >> >> _Archaeopteryx_ is clearly a transitional form between dinosaurs and
> >> >> birds, no matter how dumb you think it is.
> >> >So you don't mind telling us what the selection pressure was,
> >>
> >> Insulation, which was co-opted for aerodynamic purposes.
> >This is the old speculation. Which biologic (reactions) pathways are affected by temperature variation?
>
> We're not talking about *those* pathways right now, just feathers.

But that's the reality, thermal stress affects virtually every metabolic pathway because the function of enzymes is temperature dependent. What makes you think that one selection pressure comes along to produce feathers, another comes along to produce wings, a third selection condition comes along to produce flight muscles, and another selection comes along to produce pneumatic bones and so on. What portion of the genome would not have to be transformed to turn a reptile into a bird?

>
> >> >the genes targeted and the mutations required to transform a non-feather producer to a feather producing replicator.
> >>
> >> You've told me that someone told you that it's like 7 or 8 genes
> >> involved. Are you sure this couldn't happen, if the modifications
> >> didn't all happen simultaneously?
> >That's the number I got from a link from Edward Max. But aren't far more biological pathways affected by temperature variation? And until the insulation grew, wouldn't many biological reactions be affected?
>
> They would be affected, but evidently not enough to kill them all off.

I don't think you understand what thermal stress does to animals, especially if you superimpose starvation, predation, disease... What makes you think that selection pressure in natural are imposed like the selection pressures of the Kishony experiment?

> >> >> >other than a cherry-picked fossil which fits your comparative
> anatomy concept?
> >> >>
> >> >> LOL! "My comparative anatomy concept"?
> >> >>
> >> >> Are you saying you don't think some creatures don't resemble some
> >> >> others more so than they do others?
> >> >Comparative anatomy is useless in determining relatedness.
> >>
> >> So you think all creatures resemble each other equally?
> >I think that relatedness based on genetic sequencing is far more accurate than anything that can be done by comparative anatomy.
>
> So "less accurate" is the same thing as "useless"?

If you are going to claim that fish are related to mammals and reptiles are related to birds, yes, it is useless.

>
> > Any attempt at determining relatedness based on gross anatomy at best is only a crude approximation.
>
> Which DNA studies have confirmed spectacularly in many cases.

Take a look at Charles Brenner's work and see if you can put the genomes of humans and chimps and see if they are related or determine a MRCA.

>
> >And if don't take into account the mechanisms of genetic transformation, that crude approximation becomes rank speculation.
> >>
> >> > Modern science uses genetic testing to determine relatedness.
> >>
> >> Which evolutionary biologists use as well, but you dismiss them for no
> >> good reason.
> >That's because evolutionary biologists are selective in their use of genetics. For example, I've heard the argument that humans and chimps produce identical insulin and therefore must be related. But on closer examination, it is found that the pre-proinsulin molecules differ by two amino acids. And is the enzyme which cleaves the pre-proinsulin identical between humans and chimps?
>
> These days we have more information about the genomes of humans and
> chimps, so we don't have to rely on insulin molecules.

That's right and virtually every gene differs between humans and chimps. And you only have a million generations to make the transformation.

>
> > And you can go on looking at each allele at each loci and you will start to understand the mathematical problem you have in getting all these genetic changes in a million generations.
>
> That's what's called an "argument from incredulity," and is not good
> logic.

So give us a rational explanation of how this type of transformation can occur.

>
> >> >> And if cherry-picking has gone on, where are the fossils that weren't
> >> >> picked?
> >> >Like I say, you choose fossils that fit your belief system
> >>
> >> And where are the ones that don't fit my "belief system"?
> >You don't pick those cherries.
>
> Yes, but what *are* they, explicitly?

I guess you are right on this point because there are people who think humans are related to bananas. Of course, that's not based on gross anatomy.

>
> >> > without ever taking into account the mechanism of genetic transformation. hiv can't evolve efficiently to three selection pressures targeting just two genes. How is a reptile to transform the multiple genetic loci, the proteins, and control modules to make scales into feathers when the fastest evolving replicator known cannot evolve to combination therapy?
> >>
> >> If the intensity of selection were low, it could happen. It might not
> >> affect the trajectories, but you yourself said it would affect
> >> *something.*
> >rmns does not depend on the intensity of selection. It depends on the ability of a variant to amplify to improve the probability of a beneficial mutation occurring. And for a mutation rate of e-9, it takes e9 replications for that beneficial mutation to occur. And that's for a single targeted selection pressure. Thermal stress targets virtually every metabolic pathway.
>
> Presumably, those metabolic pathways had already evolved by the time
> birds evolved from dinosaurs.

Presumption and speculation. So how do you think rmns works? Do you have a mathematical explanation that is verifable by repeatable experiment?

>
> >> >> And who has been doing the picking? Me? Paleontologists?
> >> >There are lots of people who have convinced themselves that this logic is correct but they have never considered the mechanisms of genetic transformation in their categorization scheme.
> >> >>
> >> >> And are you aware that there are more transitional fossils than just
> >> >> _Archaeopteryx_?
> >> >Are you aware of how rmns works? Before you find a fossil and claim that it is transitional, learn about the mechanisms of evolution. It might help you from grossly overspeculating.
> >> >>
> >> >> > Have you sequenced the genome of this fossil and done the DNA identification?
> >> >>
> >> >> No, we don't have DNA from _Archaeopteryx_, but that's not necessary;
> >> >> the morphology of the form is pretty clear.
> >> >"Pretty clear"?
> >>
> >> Very clear, yes.
> >Clear as mud. So tell us, aren't reptiles under thermal stress today?
>
> If the right mutations don't come along, they won't evolve insulation.
> They'll have to find other ways to adapt.

What's the probability of the right mutations coming along?

>
> >> > The way rmns works can be predicted with mathematical certainty.
> >>
> >> Unless you made a mistake somewhere. It happens, even to the best of
> >> mathematicians.
> >The math is quite simple,
>
> And some mathematicians can make even simple errors.

That's why it must be peer reviewed before it is published. Errors can still occur. If you think there is an error in my math, where is it. If you think there is an error in the physics, where is the empirical example that works differently from this math?

>
> > Billery Rogers calls it juvenile. And the correlation with the empirical evidence is accurate and every successful treatment of hiv confirms this math.
> >>
> >> > And this is verified with repeatable experiments.
> >>
> >> You don't have any quantitative comparisons between the experiments
> >> and your math.
> >Read my response to Andre on this subject. Kishony uses the same numbers for his experiment that my math predicts.
> >https://www.youtube.com/watch?v=Irnc6w_Gsas
> >Using the mutation rate Kishony gives for his experiment gives the same number of predicted replications from the math that I've presented for each beneficial mutation that Kishony reports.
>
> Are you sure he was using your mathematics when he did this? It seems
> like more of a coincidence that he was talking about billions and
> billionths.

I doubt he was using my math. There are many references which put the mutation rate for e coli at about e-9. I suspect that Kishony has a pretty good idea of the population sizes for his colonies. He certainly didn't say thousands or trillions for his colony sizes. One of the basic things that microbiologist do is colony counts.

>
> >> >> Also, are you aware that DNA studies of other creatures *have* been
> >> >> done and in general support comparative anatomy, as well as giving us
> >> >> a better understanding of how evolution created the wealth of
> >> >> different life forms we see around us?
> >> >"In general"? You take a few genetic matches
> >>
> >> What makes you think it's just a "few" genetic matches?
> >Study the reports in detail. So called "junk-DNA" is ignored.
>
> Why would junk DNA be ignored? That would be the best kind of DNA to
> use, since it would be resistant to homoplasy.

"Junk DNA" gets ignored because it doesn't fit the presumptions.

>
> >You can't just use portions of genomes which appear homologous, you must compare the entire genome. Cherry-picking fossils
>
> Actually, that hasn't happened.

Oh really? So why are there so many different estimates for the similarity of human and chimp DNA?

[erik simpson]

You really are a spectacularly ignorant fraud.

[Panthera Tigris Altaica]

Yes, he is.

[Alan Kleinman MD PhD]

It is stupid space cases like you who are totally ignorant of the basic science and mathematics of rmns. And your ignorance causes multi-drug resistant microbes, multi-herbicide resistant weeds, multi-pesticide resistant insects and less than durable cancer treatments. And the math is so simple, a grade-schooler could understand it but you don't, dumb cluck.

[erik simpson]

Not only are you hopelessly ignorant of the fossil record, you're also
hopelessly ignorant of DNA phylogeny, which you tout above "mere comparative
anatomy". Your Biblical preconceptions blind you to any objective scientific
methods.

[Panthera Tigris Altaica]

You have never demonstrated the accuracy of any of the above. You have never taken the first step towards doing so: posting your calculations to t.o. Why should anyone believe one word you post when you cannot, you _will not_, provide a single iota of support for them?

[Alan Kleinman MD PhD]

On Monday, April 9, 2018 at 5:35:03 PM UTC-7, erik simpson wrote:

> Not only are you hopelessly ignorant of the fossil record, you're also
> hopelessly ignorant of DNA phylogeny, which you tout above "mere comparative
> anatomy". Your Biblical preconceptions blind you to any objective scientific
> methods.

If you want to believe that fish turn into mammals and reptiles grow wings and feathers, you have the right to believe that nonsense. But it is stupid people like you who have failed to correctly describe how rmns works. And your stupidity harms the medical field and agriculture. Why don't you study the data on rmns. You might learn something about the multiplication rule of probabilities. Dumb cluck space case.

[erik simpson]

No, you're the dummy. Your vaunted DNA shows beyond doubt (to anyone except
the feeble-minded and the stubbornly ignorant) that not only are birds reptiles
who grew feather, but earlier they were fish 9the same fish we're descended
from). Earlier still, we have a common ancestor with bananas. I don't know
how you got a medical degree without taking any biology courses, but you
obviously found a way. I guess you must be a somewhat competent physician, and
you don't need a license to practice science, or wouldn't have one.

[jillery]

On Mon, 9 Apr 2018 07:30:16 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>I know mammals didn't come from fish


I didn't ask where mammals didn't come from, troll.

--
I disapprove of what you say, but I will defend to the death your right to say it.

Evelyn Beatrice Hall
Attributed to Voltaire

[Vincent Maycock]

On Mon, 9 Apr 2018 16:35:39 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>On Monday, April 9, 2018 at 3:50:02 PM UTC-7, Vincent Maycock wrote:

snip

>> So "less accurate" is the same thing as "useless"?
>If you are going to claim that fish are related to mammals and reptiles are related to birds, yes, it is useless.

Why would those things make it useless rather than just "less
accurate"?

>> > Any attempt at determining relatedness based on gross anatomy at best is only a crude approximation.
>>
>> Which DNA studies have confirmed spectacularly in many cases.
>Take a look at Charles Brenner's work and see if you can put the genomes of humans and chimps and see if they are related or determine a MRCA.
>>
>> >And if don't take into account the mechanisms of genetic transformation, that crude approximation becomes rank speculation.
>> >>
>> >> > Modern science uses genetic testing to determine relatedness.
>> >>
>> >> Which evolutionary biologists use as well, but you dismiss them for no
>> >> good reason.
>> >That's because evolutionary biologists are selective in their use of genetics. For example, I've heard the argument that humans and chimps produce identical insulin and therefore must be related. But on closer examination, it is found that the pre-proinsulin molecules differ by two amino acids. And is the enzyme which cleaves the pre-proinsulin identical between humans and chimps?
>>
>> These days we have more information about the genomes of humans and
>> chimps, so we don't have to rely on insulin molecules.
>That's right and virtually every gene differs between humans and chimps. And you only have a million generations to make the transformation.

Aren't most of the differences neutral? How does your mathematics
deal with that?

>> > And you can go on looking at each allele at each loci and you will start to understand the mathematical problem you have in getting all these genetic changes in a million generations.
>>
>> That's what's called an "argument from incredulity," and is not good
>> logic.
>So give us a rational explanation of how this type of transformation can occur.

Insulation to aerodynamics, like I said before.

>> >> >> And if cherry-picking has gone on, where are the fossils that weren't
>> >> >> picked?
>> >> >Like I say, you choose fossils that fit your belief system
>> >>
>> >> And where are the ones that don't fit my "belief system"?
>> >You don't pick those cherries.
>>
>> Yes, but what *are* they, explicitly?
>I guess you are right on this point because there are people who think humans are related to bananas. Of course, that's not based on gross anatomy.

Humans *are* related to bananas. You're using an argument from
incredulity again.

I mean, obviously there are life forms more closely related to bananas
than we are, but we do share a common ancestor with bananas, if you go
back in time far enough.

snip

>> Are you sure he was using your mathematics when he did this? It seems
>> like more of a coincidence that he was talking about billions and
>> billionths.
>I doubt he was using my math.

So what numbers from your math have been found in the Kishony
experiment?

>There are many references which put the mutation rate for e coli at about e-9. I suspect that Kishony has a pretty good idea of the population sizes for his colonies. He certainly didn't say thousands or trillions for his colony sizes. One of the basic things that microbiologist do is colony counts.
>>
>> >> >> Also, are you aware that DNA studies of other creatures *have* been
>> >> >> done and in general support comparative anatomy, as well as giving us
>> >> >> a better understanding of how evolution created the wealth of
>> >> >> different life forms we see around us?
>> >> >"In general"? You take a few genetic matches
>> >>
>> >> What makes you think it's just a "few" genetic matches?
>> >Study the reports in detail. So called "junk-DNA" is ignored.
>>
>> Why would junk DNA be ignored? That would be the best kind of DNA to
>> use, since it would be resistant to homoplasy.
>"Junk DNA" gets ignored because it doesn't fit the presumptions.

No, it's creationists who like to ignore junk DNA, because they don't
think God would put "junk" into the genome.

>> >You can't just use portions of genomes which appear homologous, you must compare the entire genome. Cherry-picking fossils
>>
>> Actually, that hasn't happened.
>Oh really? So why are there so many different estimates for the similarity of human and chimp DNA?

What does that have to do with cherry picking fossils?

[Alan Kleinman MD PhD]

On Monday, April 9, 2018 at 9:50:02 PM UTC-7, jillery wrote:
> On Mon, 9 Apr 2018 07:30:16 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >I know mammals didn't come from fish
>
>
> I didn't ask where mammals didn't come from, troll.

We all know the mythology that you believe. It's just mathematically irrational. You know, that really hard subject Barbie.

[Alan Kleinman MD PhD]

On Tuesday, April 10, 2018 at 6:40:03 AM UTC-7, Vincent Maycock wrote:
> On Mon, 9 Apr 2018 16:35:39 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >On Monday, April 9, 2018 at 3:50:02 PM UTC-7, Vincent Maycock wrote:
>
> snip
>
> >> So "less accurate" is the same thing as "useless"?
> >If you are going to claim that fish are related to mammals and reptiles are related to birds, yes, it is useless.
>
> Why would those things make it useless rather than just "less
> accurate"?

Because you are making a claim about rmns which is irrational. Before you start making claims about the types of genetic transformations that can occur, you should have a good idea of how the mechanisms of genetic transformation work. There are few biologists that would argue that recombination is the way fish turn into mammals and rightly so because recombination without error will not create new alleles. So what are the other options? Some kind of lateral transfer of genetic material? But that doesn't stand up logically because that genetic material has to come from someplace. So what is the other option and how does that option work to accumulate the genetic changes to make such transformations. If the field of biology hadn't abandoned hard mathematical science, this should have been a key question to answer.

>
> >> > Any attempt at determining relatedness based on gross anatomy at best is only a crude approximation.
> >>
> >> Which DNA studies have confirmed spectacularly in many cases.
> >Take a look at Charles Brenner's work and see if you can put the genomes of humans and chimps and see if they are related or determine a MRCA.
> >>
> >> >And if don't take into account the mechanisms of genetic transformation, that crude approximation becomes rank speculation.
> >> >>
> >> >> > Modern science uses genetic testing to determine relatedness.
> >> >>
> >> >> Which evolutionary biologists use as well, but you dismiss them for no
> >> >> good reason.
> >> >That's because evolutionary biologists are selective in their use of genetics. For example, I've heard the argument that humans and chimps produce identical insulin and therefore must be related. But on closer examination, it is found that the pre-proinsulin molecules differ by two amino acids. And is the enzyme which cleaves the pre-proinsulin identical between humans and chimps?
> >>
> >> These days we have more information about the genomes of humans and
> >> chimps, so we don't have to rely on insulin molecules.
> >That's right and virtually every gene differs between humans and chimps. And you only have a million generations to make the transformation.
>
> Aren't most of the differences neutral? How does your mathematics
> deal with that?

Even if they are neutral, do the math for just the two differences in pre-proinsulin. Unless these differences are just random variations, how do these differences exist between humans and chimps for virtually the entire population? Each selective difference with a mutation rate of e-9 is going to require e9 replications for there to be a reasonable probability of the next beneficial mutation occurring and that's if only a single beneficial mutation occurs which improves fitness. If the selection conditions require multiple mutations to improve fitness, that population size goes up exponentially. There is a reason why all the examples of rmns involve huge populations with the ability of these populations to recover from the initial insult of the selection pressure. The few variants that survive that stress can rapidly recover the population size necessary for rmns to work. The entire population size of humans on earth today is barely large enough for rmns to works for just a couple cycles of rmns. But that means that those few lucky members who have those beneficial mutations would have to have billions of offspring for the next cycle of rmns to work. You have a real mathematical problem for your theory but it is good news for the medical field and agriculture in dealing with drug-resistance, herbicide-resistance, pesticide-resistance and finding more durable cancer treatments. Once you have a correct understanding of a phenomenon, you have a better understanding of how to deal with the consequences of that phenomenon. Before people understood Newton's laws, they could still build bridges but with a good understanding of these laws, bridge construction markedly improved.

>
> >> > And you can go on looking at each allele at each loci and you will start to understand the mathematical problem you have in getting all these genetic changes in a million generations.
> >>
> >> That's what's called an "argument from incredulity," and is not good
> >> logic.
> >So give us a rational explanation of how this type of transformation can occur.
>
> Insulation to aerodynamics, like I said before.

That's hand waving and you know it. But I don't blame you. You used to be able to say that rmns did it, but that argument is gone.

>
> >> >> >> And if cherry-picking has gone on, where are the fossils that weren't
> >> >> >> picked?
> >> >> >Like I say, you choose fossils that fit your belief system
> >> >>
> >> >> And where are the ones that don't fit my "belief system"?
> >> >You don't pick those cherries.
> >>
> >> Yes, but what *are* they, explicitly?
> >I guess you are right on this point because there are people who think humans are related to bananas. Of course, that's not based on gross anatomy.
>
> Humans *are* related to bananas. You're using an argument from
> incredulity again.

Well then don't stay in a refrigerator because you will spoil faster.

>
> I mean, obviously there are life forms more closely related to bananas
> than we are, but we do share a common ancestor with bananas, if you go
> back in time far enough.

You can't even give a rational explanation how reptiles grow wings and feathers. What is the selection pressure that would turn a banana into a biologist?

>
> snip
>
> >> Are you sure he was using your mathematics when he did this? It seems
> >> like more of a coincidence that he was talking about billions and
> >> billionths.
> >I doubt he was using my math.
>
> So what numbers from your math have been found in the Kishony
> experiment?

There are two ways you can get the numbers that Kishony uses. You can get the numbers from the probability curves in my publications (or you could derive the equations yourself and do the calculation) or you can use the mean value for the binomial distribution. rmns is a binomial probability problem, does the beneficial mutation occur or does it not occur.

>
> >There are many references which put the mutation rate for e coli at about e-9. I suspect that Kishony has a pretty good idea of the population sizes for his colonies. He certainly didn't say thousands or trillions for his colony sizes. One of the basic things that microbiologist do is colony counts.
> >>
> >> >> >> Also, are you aware that DNA studies of other creatures *have* been
> >> >> >> done and in general support comparative anatomy, as well as giving us
> >> >> >> a better understanding of how evolution created the wealth of
> >> >> >> different life forms we see around us?
> >> >> >"In general"? You take a few genetic matches
> >> >>
> >> >> What makes you think it's just a "few" genetic matches?
> >> >Study the reports in detail. So called "junk-DNA" is ignored.
> >>
> >> Why would junk DNA be ignored? That would be the best kind of DNA to
> >> use, since it would be resistant to homoplasy.
> >"Junk DNA" gets ignored because it doesn't fit the presumptions.
>
> No, it's creationists who like to ignore junk DNA, because they don't
> think God would put "junk" into the genome.

And you think there is DNA in genomes that has no function? Why would a replicator waste energy replicating DNA that has no use? I think we are just scratching the surface on understanding DNA. You have yet to scratch the surface on understanding how rmns works.

>
> >> >You can't just use portions of genomes which appear homologous, you must compare the entire genome. Cherry-picking fossils
> >>
> >> Actually, that hasn't happened.
> >Oh really? So why are there so many different estimates for the similarity of human and chimp DNA?
>
> What does that have to do with cherry picking fossils?

We have the genomes of both humans and chimps so instead of cherry-picking fossils in order to claim they came from a common ancestor, show us how such a genetic transformation can be done in a million generations. What you are having a hard time grasping is the huge population sizes necessary for rmns to work. e9 replication per beneficial mutation in the Kishony experiment under ideal conditions. For the Lenski experiment to work requires about e11 replications for each beneficial mutation. Neither chimps not humans ever achieve population sizes like those required for the Lenski experiment. Do you understand what bracketing a solution is?

[jillery]

On Tue, 10 Apr 2018 06:47:56 -0700 (PDT), Alan Kleinman MD PhD
<klei...@sti.net> wrote:

>On Monday, April 9, 2018 at 9:50:02 PM UTC-7, jillery wrote:
>> On Mon, 9 Apr 2018 07:30:16 -0700 (PDT), Alan Kleinman MD PhD
>> wrote:
>>
>> >I know mammals didn't come from fish
>>
>>
>> I didn't ask where mammals didn't come from, troll.
>We all know the mythology that you believe. It's just mathematically irrational. You know, that really hard subject Barbie.

The really hard question here is for you to answer where you think
mammals come from. It's just as hard as for you to show your
calculations which show how your mathematical formula predicts the
outcomes of the Kishony and Lenski experiments. These are always hard
questions for lying trolls like you.

[Alan Kleinman MD PhD]

On Tuesday, April 10, 2018 at 8:10:03 AM UTC-7, jillery wrote:
> On Tue, 10 Apr 2018 06:47:56 -0700 (PDT), Alan Kleinman MD PhD

> wrote:
>
> >On Monday, April 9, 2018 at 9:50:02 PM UTC-7, jillery wrote:
> >> On Mon, 9 Apr 2018 07:30:16 -0700 (PDT), Alan Kleinman MD PhD
> >> wrote:
> >>
> >> >I know mammals didn't come from fish
> >>
> >>
> >> I didn't ask where mammals didn't come from, troll.
> >We all know the mythology that you believe. It's just mathematically irrational. You know, that really hard subject Barbie.
>
>
> The really hard question here is for you to answer where you think
> mammals come from. It's just as hard as for you to show your
> calculations which show how your mathematical formula predicts the
> outcomes of the Kishony and Lenski experiments. These are always hard
> questions for lying trolls like you.

Take and pass an introductory course in probability theory and you might understand Barbie. Then again, you may not.

[Mark Isaak]

On 4/10/18 7:40 AM, Alan Kleinman MD PhD wrote:
> On Tuesday, April 10, 2018 at 6:40:03 AM UTC-7, Vincent Maycock wrote:
>> On Mon, 9 Apr 2018 16:35:39 -0700 (PDT), Alan Kleinman MD PhD

>>> Oh really? So why are there so many different estimates for the similarity of human and chimp DNA?
>>
>> What does that have to do with cherry picking fossils?
> We have the genomes of both humans and chimps so instead of cherry-picking fossils in order to claim they came from a common ancestor, show us how such a genetic transformation can be done in a million generations.

The number of differences between human and chimpanzee is within a range
that can be explained entirely by genetic drift, with no selection
necessary.

The different estimates for similarity come in part from measuring
different things -- base substitutions or genes, e.g.

--
Mark Isaak eciton (at) curioustaxonomy (dot) net
"Ignorance, allied with power, is the most ferocious enemy justice can
have." - James Baldwin

[Alan Kleinman MD PhD]

On Tuesday, April 10, 2018 at 9:45:03 AM UTC-7, Mark Isaak wrote:
> On 4/10/18 7:40 AM, Alan Kleinman MD PhD wrote:
> > On Tuesday, April 10, 2018 at 6:40:03 AM UTC-7, Vincent Maycock wrote:
> >> On Mon, 9 Apr 2018 16:35:39 -0700 (PDT), Alan Kleinman MD PhD
> >>> Oh really? So why are there so many different estimates for the similarity of human and chimp DNA?
> >>
> >> What does that have to do with cherry picking fossils?
> > We have the genomes of both humans and chimps so instead of cherry-picking fossils in order to claim they came from a common ancestor, show us how such a genetic transformation can be done in a million generations.
>
> The number of differences between human and chimpanzee is within a range
> that can be explained entirely by genetic drift, with no selection
> necessary.

Ok graduate student in population genetics who got nothing out of his course, explain away. Tell us how drift caused two amino acid differences in pre-proinsulin between humans and chimps. Tell us how many generations this took. And then you can explain every difference between every other gene between humans and chimps. Show your work.

>
> The different estimates for similarity come in part from measuring
> different things -- base substitutions or genes, e.g.

We already know how you measure things, you use a yardstick.