Annoying creationists

[kleinman]

Annoying Creationists

The difference between what you have done and what I have done is that I have posted the data and parameters use to obtain the data. I have a large spreadsheet with all the data and parameters used to obtain the data from ev. We are not playing poker where you can bluff to win this debate, you have to produce the data and show how you obtained it. I have done this with ev and what this data shows is that the number of selection pressures profoundly slow the evolutionary process. Real measurable examples of mutation and selection show the same thing.

All default settings except:

4096 bases
24 Mutations per genome
Pause ONLY on Rseq >= Rfreq
Result: Convergence in 13,094 generations.
----
Same experiment except
Set spurious bindings inside binding site region to 0
Set spurious bindings outside binding site region to 0
Result: No convergence after 35,000 generations. None, zippo, nada!

So kjkent1, what is the lesson you want to teach from this single case? What is the selection pressure for Rseq >= Rfreq? Didn’t you know there is no selection pressure for Rseq >=Rfreq? Did the mistakes for this case go to zero? How about for the other experiment, did the mistakes go to zero? Perhaps you should continue your search for an example from ev where from the random initialization of the program you find a case where Rseq>=Rfreq, then you could claim it takes zero generations for convergence.

The "perfect" creature is not perfect unless it is free of both missing and spurious bindings. Setting a mistake count to zero prevents the program from clearing that mistake from the genome.

Any experiment conducted with a mistake count set at zero will never evolve a "perfect creature." If you turn on "stop on perfect creature," the creature that is evolved is not perfect, BECAUSE it still contains errors!!! What ev reports is an error, because you have introduced a bug into the program.

After all this time, you still don’t understand the mutation and selection sorting process. You can still obtain a perfect creature without selection, the probability is miniscule but it is probable. You can also obtain a creature with Rseq >= Rfreq without selection but the probability is also miniscule. The point that you refuse to understand is that these sorting/optimization problems become profoundly slow as the sorting requirements become more complex. Simple sorting conditions that require only a small number of mutations at the appropriate loci are the easiest to satisfy; complex sorting conditions which require many mutations at numerous different positions on the genome are much, much more difficult to satisfy. That is the lesson which ev teaches and that is the lesson which real examples of mutation and selection teaches. Transforming a reptile into a bird is a far more complex sorting/optimization problem than ev’s simple example. Besides the fact that there are no selection conditions that would do this, even if you could imagine the selection conditions, this sorting/optimization problem would take vastly more generations than ev’s simple sorting/optimization problem. Combination selection pressures profoundly slow the mutation and selection sorting/optimization process.

If you can't see this, then you're mentally ill, Alan. Everyone here understands this concept but you. Do you have a learning disability or what?

Whatever learning disability I may have, it doesn’t compare with your disability in mathematics.

Sol, this article demonstrates exactly that combination selection pressures profoundly slow the evolution of resistance.

What are you talking about? It has nothing to do with evolution. All they found is that for some reason (which they don't understand) some bacteria are susceptible to that combination of antibiotics, and some aren't. Presumably there's some biochemical explanation.

Certainly it has everything to do with evolution. These problems are all about a population finding a trajectory to a local optimum on a fitness landscape. When you have combination selection pressures, it interferes with the population finding a trajectory to a local optimum. That is what the mathematics shows and that is what the empirical evidence shows. That’s how the mutation and selection sorting/optimization problem works.

Could you define "profoundly slow " ? Is it different than really slow or very slow or maybe just stop?

Sure I’ll define “profoundly slow” for you; it’s too slow for the theory of evolution to be mathematically possible. Now if you read the thread, you will get some mathematical examples of this definition.

Why don’t you mention that the majority of the examples of aneuploidy are harmful.

Because it isn't true. If it were true, there would be virtually no polyploidisation events known. In the real world, however, as much as 80% of all flowering plants are believed to have both diploid and various polyploid populations. In animals, this number is less (this has been suggested to be because there is less selfing in animals, but I don't know if this is sufficient explanation), but nonetheless it occurs. Again, in Lumbriculus variegatus most populations I have looked at seem to be of various non-diploid ploidy levels.

That explains the “Invasion of the Body Snatchers”, now do you want to explain how polyploidisation speeds up the evolutionary process, especially since in animals it is extremely harmful.

Sure you can prove something by disproving something else

No, you can't. As usual you demonstrate your utter ignorance of how things work.

Sure I know how mutation and selection works. I have the mathematical and empirical evidence which shows that combination selection pressures profoundly slow the mutation and selection sorting/optimization process.

it called the process of elimination

That only works when you know exactly how many options you have.

So let’s see, we have abiogenesis and evolution as one option, creation as a second option and the option you can’t think of. That should cover all the possible options.

and the theory of evolution has been eliminated.

It has ? Well, that's odd, because we've got a poster on this thread who's been claiming the same thing, and so far he hasn't been able to push his theory past rhetoric.

Oh, wait. That's you!

All that mathematical and empirical evidence which shows how mutation and selection actually works, it’s so annoying to you evolutionists.

So now we got here either by creation or something you can’t think of.

Nice try, moonbat. It's YOUR onus to prove creation. I don't have to lift a finger.

Moonbat? I don’t have to lift a finger either to prove creation; right now my job is to continue to post the evidence that the theory of evolution by mutation and selection is mathematically impossible. And you know what Belz, it’s really easy to find the evidence. Isn’t that annoying?

You evolutionists do love you speculations and extrapolations.

I don't suppose you'll speculate when I ask you how the universe was created ? How the soul operates ? What it does ? Why God made everything so that it looks like evolution works ?

The difference here is that evolutionists like to call their speculations and extrapolations “science”. The problem for you evolutionists is that when mathematics and accurate measurement of how the mutation and selection sorting/optimization process works, it makes your speculations and extrapolations mathematically impossible.

I swear I'm going to release a new version of Evj that does not use the term perfect creature. And I'm going to do it soon.

That’s a good idea Paul, it is confusing terminology but it’s not going to change the mathematical fact of life that combination selection pressures profoundly slow the evolutionary process. Your Rcapacity label is not very informative either. Why don’t you call it the Robfuscation value, or perhaps the Rincomprehensible value.

In order to make the mutation and selection sorting/optimization process more comprehensible, here are so more examples of how it works.
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11981365&dopt=AbstractPlus

CONTEXT: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. OBJECTIVE: To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. DESIGN: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. MAIN OUTCOME MEASURE: HIV-1 status of the infant. RESULTS: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. CONCLUSION: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.

Patrick E Duffy, Carol Hopkins Sibley. The Lancet. London: Dec 3-Dec 9, 2005. Vol. 366, Iss. 9501; pg. 1908

Jambou and colleagues' paper is a wake-up call; resistance to artemisinins may indeed be selected by uncontrolled use of artemisinins as monotherapy or in conjunction with ineffective partner drugs. We ignore this warning at the risk of a rapid demise of ACTs that are currently just being tested and deployed.

http://www3.interscience.wiley.com/cgi-bin/abstract/112773693/ABSTRACT?CRETRY=1&SRETRY=0

Multi-drug resistant hepatitis B virus (HBV) has been reported in hepatitis B patients who received sequential antiviral therapy. In vitro studies showed that HBV constructs with mutations resistant to lamivudine and adefovir have marked reduction in sensitivity to combination of lamivudine and adefovir, whereas constructs with mutations resistant to either drug remain sensitive to the other drug. We conducted this study to determine whether mutations conferring resistance to multiple antiviral agents co-locate on the same HBV genome in vivo and to describe the evolution of these mutations. Sera from six patients who had been found to have multi-drug resistant HBV mutations to lamivudine + adefovir, lamivudine + hepatitis B immunoglobulin (HBIG), or lamivudine + entecavir on direct sequencing were cloned after nested polymerase chain reaction (PCR). Analysis of 215 clones from 11 samples with multi-drug resistant mutations on direct sequencing showed that 183 (85%) clones had mutations to both therapies on the same genome; 31 clones had lamivudine-resistant mutants only. Clonal analysis of serial samples from three patients showed progressive evolution from all clones with lamivudine-resistant HBV mutations only to mixtures of clones that have multi-drug resistant mutations and clones that have lamivudine-resistant HBV mutations only, and ultimately all clones having multi-drug resistant HBV mutations. In conclusion, mutations conferring resistance to multiple antiviral agents co-locate on the same viral genome, suggesting that combination therapy directed against mutants resistant to each treatment may not be adequate in suppressing multi-drug resistant HBV. De novo combination therapy may prevent the emergence of multi-drug resistant mutants. (HEPATOLOGY 2006;44:703-712.)

Now I hope that all of you can remember something to be thankful for today. You all have a happy thanksgiving carving up a turkey and I’ll be back next week to continue carving up the theory of evolution turkey.

 

[Kotatsu]

That explains the “Invasion of the Body Snatchers”, now do you want to explain how polyploidisation speeds up the evolutionary process, especially since in animals it is extremely harmful.

What? It is not extremely harmful in animals, as evidenced by the fact that as many as 20% of all annelids have at least one polyploid form, and many have several. You simply ahve no idea about anything, do you?

 

[joobz]

I swear I'm going to release a new version of Evj that does not use the term perfect creature. And I'm going to do it soon.

~~ Paul

While you are at it, can you include a list of model assumptions made in evj and explain that ANY extrapolation that is made that exceeds the bounds of the assumptions is inherently wrong?

 

[Belz...]

Sure you can prove something by disproving something else

No, you can't. As usual you demonstrate your utter ignorance of how things work.

Sure I know how mutation and selection works.

Er... we were talking about the scientific method. Are you paying attention ?

I'm more and more of the opinion that you are either mentally ill, somehow, or a chatbot who just picks random words in my sentences and tries to answer as best you can. Nobody could be that thick.

it called the process of elimination

That only works when you know exactly how many options you have.

So let’s see, we have abiogenesis and evolution as one option, creation as a second option and the option you can’t think of. That should cover all the possible options.[/QUOTE]

Kleinman, if you had ever gone to school, which you haven't because you're either in an institute or a computer program, you'd know that that's completely irrelevant. The probaiblity of one isn't dependent upon the probability of the other.

All that mathematical and empirical evidence which shows how mutation and selection actually works, it’s so annoying to you evolutionists.

What mathematical evidence ? I've never seen a single equation from you.

What empirical evidence ? All the ones you've mentioned disprove your theory.

Of course, if you weren't a chatbot, you'd have a memory of these things.

I don’t have to lift a finger either to prove creation; right now my job is to continue to post the evidence that the theory of evolution by mutation and selection is mathematically impossible.

Then don't try to ascribe a probability to something you're not trying to prove, especially when you're not programmed to apply logic.

And you know what Belz, it’s really easy to find the evidence. Isn’t that annoying?

No, just sad that you think this is so. How much RAM are you using ?

The difference here is that evolutionists like to call their speculations and extrapolations “science”.

We call those "hypotheses".

The problem for you evolutionists is that when mathematics and accurate measurement of how the mutation and selection sorting/optimization process works, it makes your speculations and extrapolations mathematically impossible.

Even when such sorting/optimisation processes are shown to you to work differently ?

 

[kjkent1]

So kjkent1, what is the lesson you want to teach from this single case? What is the selection pressure for Rseq >= Rfreq? Didn’t you know there is no selection pressure for Rseq >=Rfreq? Did the mistakes for this case go to zero? How about for the other experiment, did the mistakes go to zero? Perhaps you should continue your search for an example from ev where from the random initialization of the program you find a case where Rseq>=Rfreq, then you could claim it takes zero generations for convergence.

Alan, I don't no what's wrong with you, but you should consider getting professional help. If not psychological counseling, then at least take a computer programming class.

The reason why the mistakes quickly go to zero when you set the mistake count to zero is because ev NO LONGER COUNTS THOSE MISTAKES!

I hope that was simple enough for you. Your hypothesis, at least as far as ev is concerned, is based on your misunderstanding of how the software is constructed. Setting a mistake count to zero, means that ev won't recognize the existence of the mistake that would have otherwise been counted, and thus ev will report no mistakes, even though the mistakes are still there.

The genome that is created by ev when a mistake count is zeroed is a genome that does not represent a "perfect creature," i.e., one absent any mistakes.

The only accurate measurement of perfection in ev, once a mistake count is zeroed is the convergence from Rseq -> Rfreq. And since that convergence never occurs unless all three mistak counts are non-zero, your concluding that a creature is quickly created perfect is simply absurd.

Have someone teach you computer programming, because if you actually stepped through the program code, you would understand that you are making a spectacular mistake!

Happy Thanksgiving.

 

[rocketdodger]

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11981365&dopt=AbstractPlus

This abstract says nothing about evolution you fool. FAIL

Patrick E Duffy, Carol Hopkins Sibley. The Lancet. London: Dec 3-Dec 9, 2005. Vol. 366, Iss. 9501; pg. 1908

From http://www.thebody.com/content/art13284.html:

Arteminisin is one of the most potent and fast acting malaria treatments available, killing up to 99.99 percent of parasites.

Gee, I wonder why combination therapy using Arteminisin and other such antimalarial drugs slows evolution... maybe because they destroy the population? FAIL

http://www3.interscience.wiley.com/cgi-bin/abstract/112773693/ABSTRACT?CRETRY=1&SRETRY=0

http://en.wikipedia.org/wiki/Lamivudine

http://en.wikipedia.org/wiki/Adefovir

http://en.wikipedia.org/wiki/Entecavir

All three drugs are viral inhibitors. And we know what immunoglobulins do.

Gee, I wonder why combination therapy using these treatments slows evolution.. maybe because they completely inhibit the population? FAIL

 

[Belz...]

Dodger, maybe you'd benefit from some time off this thread.

Maybe we all would.

 

[Dr Adequate]

Whatever learning disability I may have, it doesn’t compare with your disability in mathematics.

But kleinman, do you not realise that the mental handicap that makes you unable to do mathematics also makes you incompetent to judge the mathematical abilities of others?

No, you don't, do you?

No-one can help you until you acknowledge that you have a problem. Admitting that you "may" have a learning difficulty is, I guess, a tentative first step towards accepting reality, but you've got a long way to go.

We're all here for you, though in my case only at weekends. If there's any really basic, easy, simple, straightforward mathematical principle you want explaining for the hundred-and-first time, don't hesitate to ask. Only this time, do try to listen to the answer.

 

[rocketdodger]

Dodger, maybe you'd benefit from some time off this thread.

Maybe we all would.

No doubt.

 

[Paul C. Anagnostopoulos]

Ah, you wimps. I've been here for 6,709 posts.

~~ Paul

 

[Belz...]

You're not impressing anyone, Paul. I've been here for 6710 !

 

[Dr Adequate]

I thought of another hypothesis to explain kleinman ... do you suppose that a right-sided stroke could have this effect?

 

[Belz...]

People with right-side strokes can learn to overcome this disability, so no.

 

[Dr Adequate]

People with right-side strokes can learn to overcome this disability ...

(a) Not all of them; (b) only if they try.

 

[Belz...]

The point is, they CAN.

 

[sol invictus]

Certainly it has everything to do with evolution. These problems are all about a population finding a trajectory to a local optimum on a fitness landscape. When you have combination selection pressures, it interferes with the population finding a trajectory to a local optimum. That is what the mathematics shows and that is what the empirical evidence shows. That’s how the mutation and selection sorting/optimization problem works.

It has as much to do with evolution as it does with petri dishes: without either, the experiment would have been impossible. But the result is simply that bacteria which are more resistant (than standard strains) to one antibiotic are less resistant to it combined with another.

So? What does that have to do with the rate of evolution under multiple pressures?

I think you are very, very confused.

 

[kleinman]

Annoying Creationists

I hope you all had a wonderful thanksgiving. It seems though that you evolutionist still haven’t figured out how mutation and selection actually works so let’s have some leftover theory of evolution turkey. We are serving up the heart of the theory, mutation and selection. For those of you who still haven’t figured out how mutation and selection works, it is a sorting/optimization problem which is extremely sensitive to the number of selection conditions. A single selection condition which targets a single gene is the easiest case for a population to evolve resistance to that selection conditions. Each additional selection condition applied simultaneously makes it much more difficult for the population to evolve to these combined selection conditions. This is what Dr Schneider’s peer reviewed and published model or random point mutation and natural selection shows and this is what hundreds of real empirical examples of mutation and selection shows. Now let’s see how you evolutionists counter these mathematical and empirical facts of mutation and selection.

That explains the “Invasion of the Body Snatchers”, now do you want to explain how polyploidisation speeds up the evolutionary process, especially since in animals it is extremely harmful.

What? It is not extremely harmful in animals, as evidenced by the fact that as many as 20% of all annelids have at least one polyploid form, and many have several. You simply ahve no idea about anything, do you?

Well now Kotatsu, not only have you explained “Invasion of the Body Snatchers”, you have now explained why annelids are more evolutionarily advanced than humans.

I swear I'm going to release a new version of Evj that does not use the term perfect creature. And I'm going to do it soon.

While you are at it, can you include a list of model assumptions made in evj and explain that ANY extrapolation that is made that exceeds the bounds of the assumptions is inherently wrong?

Finally joobz acknowledges whose simulation of mutation and selection is showing that combination selection pressures profoundly slow the evolutionary process. It goes to show you even an alchemical engineer can learn something if you work with him long enough.

Paul, let’s see Dr Schneider and you list the assumptions that would eliminate the mathematical fact of life that the more complex the selection conditions the slower the process goes and at the same time Dr Schneider can take the rate of information gain on a 256 base genome and extrapolate that to a 3 gigabase genome.

Paul, the problem for you is not the term “perfect creature”. We can get past that confusing use of terminology. The problem for you evolutionists is how the mutation and selection sorting/optimization process works both mathematically and empirically. There is no way that you can extrapolate this process to explain how common descent could be achieved.

Er... we were talking about the scientific method. Are you paying attention ?

I'm more and more of the opinion that you are either mentally ill, somehow, or a chatbot who just picks random words in my sentences and tries to answer as best you can. Nobody could be that thick.

Belz, is that all you can do, to resort to name calling? If you can’t give an alternative to abiogenesis and evolution or creation as the way we came to be, admit it. In the mean time, I’ll continue to demonstrate with real examples of mutation and selection how this process works when there are combined selection pressures. Dr Schneider’s peer reviewed and published model of random point mutations and natural selection already demonstrates how the process works mathematically. That is how the scientific method works.

So kjkent1, what is the lesson you want to teach from this single case? What is the selection pressure for Rseq >= Rfreq? Didn’t you know there is no selection pressure for Rseq >=Rfreq? Did the mistakes for this case go to zero? How about for the other experiment, did the mistakes go to zero? Perhaps you should continue your search for an example from ev where from the random initialization of the program you find a case where Rseq>=Rfreq, then you could claim it takes zero generations for convergence.

Alan, I don't no what's wrong with you, but you should consider getting professional help. If not psychological counseling, then at least take a computer programming class.

The reason why the mistakes quickly go to zero when you set the mistake count to zero is because ev NO LONGER COUNTS THOSE MISTAKES!

Kjkent1, when you reduce down the number of selection conditions and the number of generations required for convergence for a 16k genome with all three selection conditions goes from over 5,000,000 generations to at most a couple hundred generations for any of the single selection condition cases demonstrates that you need to learn how to count, let alone take a computer programming class.
From http://www.thebody.com/content/art13284.html:

Arteminisin is one of the most potent and fast acting malaria treatments available, killing up to 99.99 percent of parasites.

Gee, I wonder why combination therapy using Arteminisin and other such antimalarial drugs slows evolution... maybe because they destroy the population? FAIL

Rocketdodger, you missed this quote from the same citation:

Jambou and colleagues' paper is a wake-up call; resistance to artemisinins may indeed be selected by uncontrolled use of artemisinins as monotherapy or in conjunction with ineffective partner drugs. We ignore this warning at the risk of a rapid demise of ACTs that are currently just being tested and deployed.

What you don’t understand Rocketdodger is that the remaining 0.01 percent of the population that isn’t killed can much more easily evolve resistance to a single selection pressure than it can against combination pressures. Dr Schneider’s computer simulation shows that even a population of 64 can easily evolve resistance to a single selection pressure in a small number of generations. This is how the mathematics of mutation and selection works. You don’t need huge populations to evolve against single selection pressures. It is when you combine selection pressures that you profoundly impair a populations’ ability to evolve against both conditions simultaneously.

Whatever learning disability I may have, it doesn’t compare with your disability in mathematics.

But kleinman, do you not realise that the mental handicap that makes you unable to do mathematics also makes you incompetent to judge the mathematical abilities of others?

Adequate, I don’t have to judge your mathematical abilities on the topic of mutation and selection, you rightly judged yourself to be incompetent on the topic. Here is what you said about yourself:

And I, sir, am a mathematician, and I may be the greatest expert in the UK on certain aspects of non-associative algebras, and on absolutely nothing else ... oh, certain aspects of neoclassical economics ... uses of geometry in design ... OK, there are lots of things I'm an expert on ... none of which are relevant to our great struggle between truth and bullcrap.

So, now that we know that you have abandoned mathematical logic and reason for your mathematically irrational and illogical theory of evolution belief system, what do you have to say?

We're all here for you, though in my case only at weekends. If there's any really basic, easy, simple, straightforward mathematical principle you want explaining for the hundred-and-first time, don't hesitate to ask. Only this time, do try to listen to the answer.

So what is your advice on the theory of evolution by mutation and selection? You give us a silly graph.

The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.

And then Adequate goes on to say this:

More optimisation takes more time. This is what my model shows. This is what ev shows. This is what reality shows. This is freakin' obvious.

Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution?

And

So far as I know, no-one has done the experiment.

and

and too bad you don’t have any empirical examples of your silly graph ...

As I have explained to you, I produced the model because I've not heard of this precise experiment being done.

So Adequate, you give us a silly illogical and irrational graph without a real example of what you are trying to demonstrate, you have lost contact with reality when you embraced the mathematically impossible theory of evolution.

Dodger, maybe you'd benefit from some time off this thread.

Maybe we all would.

No doubt.

The problem for you evolutionists is not this thread; your problem is that you have lost contact with the mathematical and empirical truth of how the mutation and selection sorting/optimization process actually works.

Ah, you wimps. I've been here for 6,709 posts.

Perhaps you have a wider binding site width and they have a smaller Rcapacity value than you. Now don’t be so hard on your fellow evolutionists. If I recall you took a break or two to watch the sun over the primordial soup.

Certainly it has everything to do with evolution. These problems are all about a population finding a trajectory to a local optimum on a fitness landscape. When you have combination selection pressures, it interferes with the population finding a trajectory to a local optimum. That is what the mathematics shows and that is what the empirical evidence shows. That’s how the mutation and selection sorting/optimization problem works.

It has as much to do with evolution as it does with petri dishes: without either, the experiment would have been impossible. But the result is simply that bacteria which are more resistant (than standard strains) to one antibiotic are less resistant to it combined with another.

So? What does that have to do with the rate of evolution under multiple pressures?

I think you are very, very confused.

It has everything to do with evolution under multiple pressures. Certainly, some combinations of drugs will interfere with the action of each other. Drugs that act during the reproduction phase such as the beta-lactams will not be as effective when used with drugs that interfere with protein synthesis thus making it less likely that the population would be reproducing. In these cases you are not using the drugs in combination. One drug is affecting a particular part of the population life cycle and the other drug is affecting a different phase of the life cycle. In addition, the combinations used in these studies were below therapeutic levels.
http://pubs.acs.org/cen/news/85/i15/8515notw7.html

Using the right combination of antibiotics could curtail the development of drug-resistant bacteria, a new study shows.

Systems biology assistant professor Roy Kishony and grad students Remy Chait and Allison Craney at Harvard Medical School demonstrate that certain combinations of doxycycline and ciprofloxacin favor the growth of doxycycline-sensitive bacteria over doxycycline-resistant ones (Nature 2007, 446, 668). The combination is "suppressive," meaning that its bacteria-killing effect is weaker than that of the individual drugs.

The researchers tested the combinations against Escherichia coli strains that differ only in the presence or absence of a tetracycline efflux pump, which provides a common mechanism of resistance to tetracycline, doxycycline, and related antibiotics. In assays that measured selection for the gene responsible for this resistance, they found strong selection for doxycycline-resistant strains when they treated bacteria with doxycycline alone or in combination with erythromycin, which has a synergistic effect with doxycycline.

In contrast, the doxycycline-ciprofloxacin combination selects against the doxycycline-resistant bacteria at some concentrations. The resulting persistence of doxycycline-sensitive strains is counterintuitive. "The selection against resistance stems from the interaction between the antibiotics and is therefore largely independent of the underlying mechanistic way by which the bacteria become resistant," Chait says.

The observed effects work against only doxycycline-resistant bacteria. The authors suggest that such a strategy will work best with combinations of drugs where each one suppresses the other.

The clinical relevance of the findings is still uncertain. [size=+2]The current work involves antibiotic doses below therapeutic levels. "The suppressive condition that allowed for the observation of the effect is never used clinically," says Shahriar Mobashery, an antibiotic expert at the University of Notre Dame. Nevertheless, the study is "interesting conceptually," he says, and the phenomena "deserve further study and explanation."[/SIZE]

Kishony's group plans to study higher drug concentrations that fully inhibit both the sensitive and resistant bacteria. [size=+2]"We hope that these findings may suggest avenues of research into new treatment strategies employing antimicrobial combinations with improved selection against resistance," Chait says.

[/SIZE]
Ultimately, these authors recognize that combination therapies interfere with the evolution of resistance. Here are a couple of more examples which demonstrate how the mutation and selection sorting/optimization problem actually works, that is that combination selection pressures profoundly slow the populations’ ability to evolve against these selection pressures simultaneously.

A Fungal Achilles' Heel
Joseph Heitman. Science. Washington: Sep 30, 2005. Vol. 309, Iss. 5744; pg. 2175, 2 pgs Evolution of drug resistance in pathogenic fungi. Antimicrobial azole drugs (fluconazole) inhibit the activity of lanosterol 14-α-demethylase (Erg11) and block the production the membrane sterol ergosterol, inhibiting growth. Hsp90 and calcineurin are required for fungal cells to tolerate fluconazole, or to acquire and maintain drug resistance. Exposure to an Hsp90 inhibitor (geldanamycin) or calcineurin inhibitors (cyclosporin A or FK506) can enhance the effect of fluconazole, preclude or delay the onset of drug resistance, and reverse drug resistance.

Remarkably, Hsp90's function in drug resistance is exerted through calcineurin, a serine-threonine-specific protein phosphatase that is controlled by calcium and calmodulin, a calcium-binding protein. Calcineurin is the target of cyclosporin A and FK506, immunosuppressive drugs that revolutionized organ transplant therapy by inhibiting T cell activation (3). Calcineurin is essential for virulence of several pathogenic fungi including C. albicans and Cryptococcus neoformans (4-8) and also enables fungal cells to tolerate drugs that block ergosterol biosynthesis, even clinically derived resistant isolates (8, 9). Cowen and Lindquist marshalled genetic and epistasis evidence to implicate calcineurin as a relevant target for Hsp90 action in promoting drug resistance. This model is supported by prior biochemical and drug combination studies that revealed a direct physical and mechanistic relationship between Hsp90 and calcineurin in mediating drug tolerance (10, 11).

These discoveries have the potential to dramatically advance antimicrobial therapy. Azoles are fungistatic and not fungicidal, and therefore they inhibit the growth of fungal cells but do not kill them. Yet concomitant inhibition of either Hsp90 or calcineurin renders fluconazole and other drugs that target ergosterol biosynthesis fully lethal to fungal microbes (see the figure). This raises the prospect of developing potent drug combinations that enhance the intrinsic activity of drugs that target ergosterol biosynthesis while obviating (or at least reducing) the development of drug resistance. Small-molecule inhibitors and high-resolution x-ray crystal structures are known for both calcineurin and Hsp90 (12, 13). Cyclosporin A and FK506 have been in clinical use for one to two decades, whereas the Hsp90 inhibitor geldanamycin is in clinical trials as a novel chemotherapy agent. Geldanamycin appears to be well tolerated in humans, which bodes well for additional clinical indications as a potential antimicrobial agent (14). A variety of active geldanamycin analogs have been synthesized, broadening the potential to identify molecules with improved antimicrobial spectra, reduced side effects, or oral bioavailability. Given a recent report that geldanamycin combined with cyclosporin A exerts a synergistic toxic activity against P. falciparum (11), this potential therapeutic regime might be applicable to fungi and parasites.

The phenothiazinium chromophore and the evolution of antimalarial drugs
Mark Wainwright, Leonard Amaral. Tropical Medicine and International Health. Oxford: Jun 2005. Vol. 10, Iss. 6; pg. 501
Abstract (Summary)
The phenothiazinium salt methylene blue [3,7-bis(dimethylamino)phenothiazinium chloride] is the oldest known synthetic antimalarial drug, its clinical efficacy having been reported in 1891. The role of methylene blue in the evolution of the modern antimalarial armoury is often unappreciated, yet it can be linked directly to standard drugs such as chloroquine and its congeners. Also, in the face of increasing plasmodial resistance to modern antimalarials, phenothiazinium derivatives have again featured as lead compounds in drug research. The precise mode of action of methylene blue and its commercial analogues against Plasmodium spp. remains a cause for conjecture, having been variously described as nucleic acid intercalation, food vacuole basification, parasite redox cycle interference and haem polymerization inhibition. That the activity of the series may be due to more than one route - i.e. a multifactorial activity - underlines the utility of these compounds in antimalarial research either as single drugs or as adjuvants (partners in a drug combination), particularly in the face of resistant parasitic strains.[PUBLICATION ABSTRACT]
That’s how the mutation and selection sorting/optimization problem works, single selection conditions targeting single genes are the easiest conditions for a population to evolve against, as soon as you use combination pressures which target more than a single gene, the process is profoundly slowed. That’s how mutation and selection sorting/optimization work mathematically and that’s how mutation and selection sorting/optimization work empirically.

 

[Belz...]

Belz, is that all you can do, to resort to name calling?

Er... what name calling ?

If you can’t give an alternative to abiogenesis and evolution or creation as the way we came to be, admit it.

I can't think of an alternative.

That doesn't help you, though. And the fact that you don't understand why speaks volumes.

In the mean time, I’ll continue to demonstrate with real examples of mutation and selection how this process works when there are combined selection pressures.

Except that every example you've provided assumes evolution happens...

Dr Schneider’s peer reviewed and published model of random point mutations and natural selection already demonstrates how the process works mathematically. That is how the scientific method works.

How abouy Adequate's and Dodger's respective models ?

 

[joobz]

Finally joobz acknowledges whose simulation of mutation and selection is showing that combination selection pressures profoundly slow the evolutionary process. It goes to show you even an alchemical engineer can learn something if you work with him long enough.

Every model has assumptions. Paul's conclusions have remained within the bounds of the model's limitations. Perhaps you'd like to offer justifications for the ones you've made?


Don't worry, I really don't expect an answer from you. You've proven that you are incapable of presenting anything of substance.

 

[delphi_ote]

By "diversity" you mean a few amino acid substitutions?! You realize the number of DNA mutations that requires is on the order of 10s, right? Is this really your argument? You don't understand how mutation could change a handful of amino acids over the course of millions of years?

This is officially the dumbest thing you've said in this entire thread.

Hmm... it's been a week and no response? How sad!