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Why would I want my doctor to have studied evolution?

From Dr. Michael Egnor:

No Nobel prize in medicine has ever been awarded for work in evolutionary biology. In fact, I think it’s safe to say that the only contribution evolution has made to modern medicine is to take it down the horrific road of eugenics, which brought forced sterilization and bodily harm to many thousands of Americans in the early 1900s. That’s a contribution which has brought shame—not advance—to the medical field.

So ‘Why would I want my doctor to have studied evolution?’ I wouldn’t. Evolutionary biology isn’t important to modern medicine. That answer won’t win the ‘Alliance for Science’ prize. It’s just the truth.

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142 Responses to Why would I want my doctor to have studied evolution?

  1. I have to say, just for the sake of correctness, that Dr. Egnor is wrong about this. Evolutionary biology and population genetics are in fact even becoming more important to medecine. The tools to identify disease genes in populations often rely on methods developed by evolutionary biologists.

    For example, see this page at the Broad Institute at MIT/Harvard:

    http://www.broad.mit.edu/mpg/

    From this, I quote:

    Population genetics

    Patterns of genetic variation shed light on recombination, demography, admixture, and evolutionary selection in the human population. In turn, knowledge about human population history helps inform studies in medical genetics.

  2. Why does Egnor refer to the neo-Darwinist theory of evolution as simply “evolution?”

    Egnor believes in evolution, but at http://www.pandasthumb.org they’re calling him a creationist, because of his careless use of terminology.

    ID theorists believe in evolution, they are not creationists. But ant-ID groups insist ID is creationism, and that it opposes evolution.

    I wish both sides would clarify their terminology

  3. bdelloid, if you read Dr. Engor’s entire article, you will read,

    I do use many kinds of science related to changes in organisms over time. Genetics is very important, as are population biology and microbiology. But evolutionary biology itself, as distinct from these scientific fields, contributes nothing to modern medicine.

  4. “No Nobel prize in medicine has ever been awarded for work in evolutionary biology.”

    Out of curiousity, does this count:
    http://nobelprize.org/nobel_pr.....index.html

    I’m not disagreeing with the main premise of the article nor rejecting the letter in its entirety. Althought, our current flu vaccines are made based on the common strand from previous years and we supposedly figure out that from phylogenetic trees or so I’ve seen.:-)

  5. bfast,

    First, the reference I made was about population genetics. And this is precisely a subset of the field of evolutionary biology.

    Second, I don’t really understand what he means by “evolutionary biology itself” independent of “population biology”. There is no precise distinction at all between these fields. In fact, what does he mean by “population biology” ? Population genetics ? Ecology ? Sociology ? Anthropology ?

  6. I wish both sides would clarify their terminology

    It seems to me that fuzzy terminology works to the benefit of the materialists; hence it is unlikely to change anytime soon. The term’s relation to the concept of change over time via natural selection serves as an anchor, and is co-opted into big “E” evolution, aka neo-Darwinian evolution.

    To deny NDE then is to deny all definitions of evolution, which makes it easy to pigeon-hole NDE deniers into the creationist camp.

    I have noticed the ID crowd uses the term “neo-Darwinian evolution” to make the appropriate distinction, although it doesn’t seem to resonate with the gen pop yet, and thus works effectively to the advantage of the NDE camp.

    It is interesting to note that even creationists believe in evolution, with a little “e,” that species change over time. I myself am a creationist and a strong supporter of ID.

    Creationism, in my view, seeks to interpret observations of nature based on the special revelation found in the Bible, while ID remains in the realm of general revelation, i.e., those things observable in nature alone, with no SR starting point.
    Creationism will deny material origins of life, as well as the concept of common descent. ID on the other hand has no problem with common descent, only material origins, and that natural selection acting on random mutations can account for the diversity of living organisms.

    It would seem that from a procedural standpoint, neo-Darwinism has more in common with creationism than ID does; in that both creationism and NDE spring from a priori commitment to a philosophical viewpoint, and ID does not. Both creationism and neo-Darwinism must fit all data into a predetermined philosophical scaffold, where ID is free to follow the evidence where it leads.

    Evolution is the accepted term by those adhering to NDE, and it’s definition is well understood as not being limited to biological selection within species.

    Please forgive the length of this post, and the pedestrian definitions herein.

  7. 1, bdelloid wrote:

    The tools to identify disease genes in populations often rely on methods developed by evolutionary biologists

    I find that hard to believe.

    Before you can identify a disease gene you first have to identify the disease. Next you have to decide whether it’s a genetic disease or not (assuming it hasn’t already been identified as such) usually by looking at the distribution of the disease within any given extended family. Doctors generally do all that. Finally, if the inheritance pattern makes it look as though the disease is probably transmitted genetically, and if there is some good reason to go to the expense of identifying the gene involved, the geneticists will be called in. Then they can do tests they’ve devised (during their research on genetics) on people at risk of having inherited these genes so that the afflicted can make decisions concerning whether or not to have children, when the total colectomy or bilateral mastectomy should be scheduled and so on and so forth.

    Evolutionary biologists may, I suspect, use the information gathered by population geneticists (using tools developed by ordinary geneticists) to make evolutionary inferences regarding how allele frequencies and distributions came to be the way they are now. That is, they are not scientists so much as they are scientifically trained philosopher historians who make inferences from information provided by scientists doing real research in many fields.

    On the other hand, as someone who trained in medicine, when I think of evolutionary biologists I think of people who decided things such as that the appendix is a vestigial organ in human beings – a left over from, say, the rumen of cows – or that the coccyx is all that is left of our ape-like ancestor’s tail. These are the people who decided that such organs must be vestigial, are therefore not necessary for individual human survival and can be removed without consequence. But it turns out that the coccyx is important for holding our insides up. And it turns out that the appendix contains lymphoid tissue and could be important for preserving us from the effects of orally ingested pathogens. These facts were probably discovered by physiologists, anatomists, histologists, gastroenterologists, orthopaedic surgeons and so on. I very much doubt that evolutionary biologists had anything to do with this increase in our knowledge about the human body and the way it works.

  8. 1, bdelloid

    “The tools to identify disease genes in populations often rely on methods developed by evolutionary biologists.”

    You should first define what do you understand as “evolution”. Genetic variation ? Novel function ? Novel organs ? Extinction ?

    IOW, if a method is developed by an evolutionary biologist, that doesn’t mean that this guy just waited for a million years to pass and just observe some new methods emerged from Mother Nature… No, this guy used his INTELLIGENCE to test, to DESIGN, to develop a new method… Just because he is an evolutionist, doesn’t mean that what he observed is “evolution in action”… May well be that he BELIEVED he saw… That’s religion.

    Don’t mix genetic variation matter with origin of life matter…

  9. What Dr Egnor is saying is that it is very unnecessary to medicine whether or not, for example, chimps and humans shared a common ancestor.

    That is because that premise is not demonstratable in a lab nor in the wild.

    Medicine, on the other hand, has to be demonstratble in a lab and in the wild. If not it doesn’t get released to the public.

  10. bdelloid,

    You are talking about micro-evolution and no one in ID doubts micro-evolution. The fact that you use your examples actually supports the ID position. Go to the following link and read comment #28

    http://www.uncommondescent.com.....me-online/

    We go through this process every couple days here when someone challenges ID and all they can come up with is micro-evolution like it is some big thing.

    Thank you for making the ID position.

  11. Two things,

    First, maybe one of the moderators delete the repeating messages. We have all done it by mistake some times.

    Second, can someone explain how can you refer to another UD thread without ending up in the moderaton filter. The only way I know is to copy the url and paste it in the message but every time it ends up in the abyss for awhile.

  12. bdelloid:

    “The tools to identify disease genes in populations often rely on methods developed by evolutionary biologists.”

    Yes, and this work is based on the law of segregtion as discovered by Mendel, a priest. What’s this got to do with Darwin, or Darwinian theory? I’m sure doctors take classes on Genetics. I took one as well, and it was all about inheritance, not about Darwinism.

  13. I saw a post earlier that was bragging about the large percentage of Doctors that dont’ accept evolution. (30+%) Yet this post is saying that evolution doesn’t need to be studied by Doctors because they have no use for it (let’s just assume that’s true even though I disagree), similar to the way plumbers don’t have a use for it. If that’s the case, why would any of us care what percentage of Doctors or plumbers accepted evolution theory?

  14. Fross,

    I think the answer is obvious, Namely, that the doctors study biology in depth to do their jobs. Plubers don’t. Duh!

  15. Plumbers not Plubers.

  16. Fross,
    Medicine is applied biology,
    Engineering is applied physics,
    Software engineering (my field) is applied logic.

    I think there is a strong correlation between engineering and the big bang theory, and medicine and evolutionary biology. The big bang theory rarely enters into the practal application of physics that engineers care about, as evolutionary biology rarely enters into medicine. An engineer, however, as a richer, thicker view of what must transpire for the big bang to happen than does the non-engineer. Likewise the doctor has a richer, thicker view of what must transpire for biological evolution to happen.

    Now here’s the rub. I bet bones that a survey of engineers would find a high acceptance of the big bang theory. Engineers are not uniting to say, “no way — I am an engineer with a rich, thick understanding of what had to have happened for the big bang to take place — it didn’t happen!” Yet a significant number of doctors are saying the equivalent, “No way — I am an applied biologist, with a rich, thick understand of what had to have happened for the neo-Darwinian evolution to have taken place — it didn’t happen!”

    The plumber says, “I just passed gas, is that a big bang, or evolution?”

  17. Okay,

    For someone who is currently studying medicine right now (literally i have a test on friday), a reason why you don’t want your doctoring studying evolution is

    1) It has no practical application to our field.

    2) You don’t want ppl who have limited time to expend there energy on a useless endeavor.

    3) Evolution doesn’t provide useful explanations. For instance there are muscarinic receptors (part of theparasympathetic system) on blood vessels, but no PS innervation. What’s the answer in the NDE paradigm

    1) Its an evolutionary anomaly w/ an unknown history of why its there and how it effects survival.

    Design paradigm

    1) Let’s figure out why its there and minimize any adverse effects that may come from using PS stimulants, or use it to our advantage.

  18. Edit

    sorry not “doctoring”

    and I meant no PS innervation on the Blood vessels themselves if you didnt catch that

  19. “Yes, and this work is based on the law of segregtion as discovered by Mendel, a priest. What’s this got to do with Darwin, or Darwinian theory?”

    The modern process of hunting down and identifying disease alleles as well as related population/pharmacogenomic studies are *much* more sophisticated than simply understanding the principles of segregation. In fact, independent segregation can be grossly violated by meiotic drive loci, which are only properly understood in the context of natural selection and evolution. State of the art medical genetics techniques integrate concepts like the the formation and breakdown of haplotypes (groups of linked alleles) over evolutionary time periods in ancestral humans, as well as admixture between ancient populations, stochastic fluctuation of allele frequencies, etc,etc. Call it microevolution if you will, but it’s evolution, and it ultimately traces back to Darwin’s insights. Egnor would seem to imply that these genetics areas can be surgically isolated and sanitized from “evolution” as such. That comes across as false to anyone actively working in these fields. It is false on both practical terms and in terms of the historical development of the methods, and this indicates to me a)his complete ignorance on the matters of genetics in question–which, if he’s like the physicians I am familiar with, represents a likely scenario or b) his willful bending of the definition of “evolution” to exclude anything of medical utility.

    Again, we are not arguing about deep macroevolution vs. recent microevolution; Egnor is speaking about the relevance of “evolution” as such to modern medicine and medical genetics. And if we are to treat that word as it is normally used, it encompasses both micro and macroevolution so the incorrectness of his statements is not mitigated by rehearsing the differences in micro vs. macro-evolution. If he wanted to distinguish micro from macro-evolution he could have; instead, he chose dismiss evolution in one big lump.

  20. great_ape,

    No one disputes micro-evolution. There is no argument there. There is no argument over the concept of natural selection or other factors that affect the distribution of alleles from generation to generation in a population. We all know the argument is over something else.

    Do you think NCSE or PZ Meyers would calm down if everyone at ID said we have no problem with micro-evolution or natural selection. Everyone at NCSE knows that ID accepts micro-evolution, natural selection etc. and PZ Meyers and his associates know the same. Larry Moran knows that. Dawkins knows that.

    So why all the heat. Everyone knows that the meaning of evolution that is being fought over is how novel alleles are generated and the origin of life itself. So when the words are brought up in a contentious discussion that and that alone is the topic that is really being discussed.

    Now other topics do come up that are not the generation of new alleles. For example, how fast can alleles fix themselves in a population is one that is often discussed but that is not the real issue. This has relevance if novel alleles have enough time to become fixed and become separate species to match what is seen in the fossil record but the real discussion is always over the origin of new alleles.

  21. Call it microevolution if you will, but it’s evolution, and it ultimately traces back to Darwin’s insights. Egnor would seem to imply that these genetics areas can be surgically isolated and sanitized from “evolution” as such.

    I don’t care to give a subtle, nuanced reply. I’ll only point out that Darwin believed in blended inheritance; he thought that the environment in some way affected reproductive organs, which in turn caused variation. Where would NS and supposed “evolution” be without DNA, without modern genetic principles? Nowhere. One can begin to understand the “fitness” value of supposed NS and “evolution” from allele frequencies and transmission and such, but an understanding of the underlying mathematical principles would lead you in that direction on their own.

    Let me not dismiss Darwin in his entirety, but, please, is he some kind of savior of biology? Isn’t he,as Egnor points out, really just the father of eugenics?

  22. great_ape, at the risk of being repetitive, let me re-quote Dr. Engor:

    I do use many kinds of science related to changes in organisms over time. Genetics is very important, as are population biology and microbiology. But evolutionary biology itself, as distinct from these scientific fields, contributes nothing to modern medicine.

    As you are suggesting that the good Dr. is in error because portions of biology which are in the “evolutionary biology” camp have medical application, portions that the good Dr. acknowledged before you set him straight, I figure the repeat is justified.

    If you take evolutionary biology, subtract “Genetics is very important, as are population biology and microbiology”, in the remainder you will find the portion of evolutionary biology that Dr. Engor rejects.

  23. “If you take evolutionary biology, subtract “Genetics is very important, as are population biology and microbiology”, in the remainder you will find the portion of evolutionary biology that Dr. Engor rejects.”
    –bfast

    I was aware of that particular quote from Egnor. Your paraphrase of it, which I believe is precisely what he intended to say, is just what I take issue with. That sort of subtraction is unwarranted in my opinion and can serve no other purpose than a rhetorical one.

    If say “evolution is useless to medicine…although X,Y,Z are not..” The implication is that X,Y,and Z are not part of evolution proper. That’s false. And I suspect if you backed Egnor in a corner, he’d admit it. But of course, his rhetorical aim is to score a point and be dismissive of evolution as a whole by saying the first part of the statement…”evolution is useless..” …never mind that his latter qualifications render the statement fairly empty.

    I think Jerry is right, the real issue in contention is not microevolution, but deeper macroevolution issues. (Although I do think that Jerry’s perhaps a bit too optimistic about how many folks on the ground in ID find even microevolution acceptable.)

    When folks–even if their target is ultimately (RM+NS => information)– lambast evolutionary biology as a whole, and when in doing so they convey erroneous ideas and are overly dismissive of important concepts, then they need to be responded to according to their statements’ face value. We can’t
    just assume “oh, he’s just attacking the idea of the increase of information via RM+NS so take anything he says about “evolution” as such with a grain of salt.”

    “So when the words are brought up in a contentious discussion that and that alone is the topic that is really being discussed.” –jerry

    I think it is dangerous to not be explicit about precisely what is debated in these contexts. Whatever the intentions of the speaker, it can only serve to confuse and mislead those who aren’t “in the know.” And I suspect, from some of the comments that I read, that there are far less people “in the know” than you and I would like to believe. And they don’t make any nuanced distinction between macro and micro-evolution. Every negative statement against evolution is another score for the team.

    Would PZ and company be satisfied if ID supporters, as a group, officially endorsed micro-evolution? I seriously doubt it. But it would go a long way towards clarifying the debate and finding some common ground for reasonable folks to work from. As I see it now, the YECs thrive on the current confusion and that leads to no good for anyone.

  24. great_ape.

    I often make the claim that ID subsumes NDE in the sense that nothing in the science or the findings of NDE is antithetical to ID. Those in ID may object rather strenuously to some of the conclusions that specific researchers make but not necessarily to their findings or methodology.

    They may also object to some of their philosophy of science too.

    In other words, ID just extends NDE by assuming that the origin for some new alleles or life forms is not due to random events or lawful processes of nature. No one objects to natural selection which is one of the most over hyped processes in the history of science.

    I wonder which of the fellows of CSC if any would object to the position that ID subsumes NDE. I know from Behe’s comments that he is in agreement with this. I understand there are many here who may not agree with this but I wonder if any of the major players would actually disagree.

    Many people here routinely bash NDE without really separating out what is perfectly fine from what is seen as objectionable. I blame many who espouse NDE as the main source for this when they go far beyond what the data allows in order to make unwarranted scientific conclusions as well as metaphysical conclusions. It is not hard to find this both in the history of Darwinism or its current offshoots, in the textbooks and with present day advocates of the theory. Starting with Darwin himself, they all saw this theory as a means for undermining traditional religion and they did not hesitate to state it and use it to reduce or eliminate the influence of religion.

  25. I think Jerry is right, the real issue in contention is not microevolution, but deeper macroevolution issues. (Although I do think that Jerry’s perhaps a bit too optimistic about how many folks on the ground in ID find even microevolution acceptable.)

    Several years ago, I would have grudgingly conceded microevolution to NDEists, mostly because of Denton’s acceptance of it. Grudgingly, because to concede it makes arguing against the unlikelihood of RM+NS that much more difficult. But that admitted, I now find that the more literature I read, the more I think through its implications, RM+NS even at the “micro” level seems questionable. Bacterial SOS responses can hardly be called “random”, for example. And is “breeding” really RM+AS?

    So, I have questions. But it’s not simply to deny Darwin his due, but because science seems to be telling me something different.

    I pose a question for you, great ape: why does sickle-cell anemia exist? (Watch out, I may have an ace up my sleeve).

  26. “I understand there are many here who may not agree with this but I wonder if any of the major players would actually disagree.” –jerry

    I’d also be interested to know.

    “I blame many who espouse NDE as the main source for this when they go far beyond what the data allows in order to make unwarranted scientific conclusions as well as metaphysical conclusions.” -jerry

    You have a point. Those that over-extend what is factually known about NDE’s role in biological history vs. what is only inferred (with varying degrees of confidence) share in the blame.
    No matter how many times or how loud certain things are shouted, many evolutionary “facts” remain inferences and not raw facts per se. Some inferences are simply much better grounded than others. More to blame, IMO, are those who are on personal crusades against religion, spirituality, etc. The frustrating part is that this is ultimately only a small, albeit very vocal, part of the community. Yet they stir many folks in religious circles into thinking a Jihad is required. There is no agenda to undermine religion in evolutionary biology. Or again, if there is, nobody sent me the memo.

  27. “I pose a question for you, great ape: why does sickle-cell anemia exist? (Watch out, I may have an ace up my sleeve” –PaV

    And here I was, about to leave when you dangle this morsel in front of me. I presume you know the classic explanation for the sickle-cell allele persistence. I can’t recall anything major developing lately in that area–although admittedly things sneak by from time to time. Alright, I’ll bite. Sickle cell persists because, in its heterozygous state, the recessive allele that is responsible for it confers partial resistance to malaria. Something about the shape of the blood cell is unpalatable for the parasite in a certain stage of its development. (a bit hazy here) This is also consistent with the fact that the sickle cell allele is found in geographic regions where malaria is common.

    That’s the standard story last I checked. Tell me something interesting. (Preferably something that doesn’t entail punishing the evil-doers.)

  28. This is also consistent with the fact that the sickle cell allele is found in geographic regions where malaria is common.

    Well, here’s my ace up my sleeve. I just finished watching “The Great Global Warming Swindle” video. In it, one of the world’s foremost authorities on malaria debunks GW claims that GW will spread malaria to more northern climates by noting that the worst outbreak of malaria occurred in Russia; in fact, in a very cold region of Russia.

    This, in turn, throws a damper on the conventional Darwinian wisdom for why sickle-cell anemia exists, which is that is confers a “fitness” advantage. Now, if malaria can occur anywhere on the globe, even colder regions, then maybe the only reason that it is found in certain populations is simply because of the in-breeeding of those populations, and no more. And perhaps the only reason it still is found anywhere is simply because it is only the homozygous form that is deadly. IOW, it exists in the heterozygous form simply because it’s not lethal enough to eliminate it–NOT because it confers any advantage. It would be interesting to research how the common, Darwinian understanding of sickle-cell anemia came to be.

  29. http://wps.prenhall.com/esm_fr.....2-,00.html

    It was Haldane. And he was guessing. Look closely at the statistics for Africa, with “S” allele and “AA” homozygotes. The data seems to indicate no real advantage/disadvantage to the “S”/”AA” carriers.

  30. When most people talk about evolution they do so in the context of Common Descent linked to “culled genetic accidents”.

    However when some people then say they disagree with evolution (in that sense) some whacko will, always and without fail, bring up variations within a population in an attempt to discredit that “denier”.

    And before we start talking about micro vs. macro we need a good definition of both. Because as it stands today even YECs accept macroevolution and have since at least the time of Linneaus.

    macroevolution

    In evolutionary biology today, macroevolution is used to refer to any evolutionary change at or above the level of species. It means at least the splitting of a species into two (speciation, or cladogenesis, from the Greek meaning “the origin of a branch”, see Fig. 1) or the change of a species over time into another (anagenetic speciation, not nowadays generally accepted [note 1]).

    Linneaus put the Created Kind at the level of Genus.

    BTW Great_Ape any chance of you showing us the scientific data that accounts for the physiological and anatomical differences observed between chimps and humans? On another site you were so sure of yourself but you never supported your assertions.

    Is that how you discuss things?

  31. Quick question: How can someone that believes the Earth has only been around for ten thousand years believe in macro evolution? That would entail so many inconsistencies and contradictions as to render the belief a bit absurd.

  32. jmcd, with the line between macro and micro set at the species level, the YEC crowd must accept some macroevolution. Noah’s ark was by no means capable of holding all species. If it only had to hold all families, for instance, it would be a lot easier. But that would mean that there was only one species of cat represented on the ark. With lions, tigers, cheetahs, leopards, house cats and all, the species boundary must have been crossed many times.

    That said, I find it a bit silly to have the line between macro and micro on the species level. To me the great challenge for evolution is the development of new structures — knee joints, etc., and new organs — lungs, etc. It is at this level that I most expect that ID will prove to provide the only explanation.

  33. Thank you bFast. That was an excellent explanation.

    It all comes back to “designed to evolve” vs.”evolved via culled genetic accidents”.

    IOW JMCD, if the organisms had the information for variation already in their genomes all it would take is some new niches to bring it out.

    And this would be especially so if on Noah’s Ark (for example) each pair was as gentically different (high degree of heterozygosity) as successful reproduction could allow.

    This is discussed in “Noah’s Ark: A Feasibility Study”.

    NOTE:

    I am NOT arguing for YEC or Noah’s Ark. All I am doing is to show that the accpeted definition of macroevolution just adds more confusion to the debate than it does to show what is being debated.

  34. Look closely at the statistics for Africa, with “S” allele and “AA” homozygotes” –PaV

    What precisely do you mean by “look closely”? Is that your general impression of the numbers or did you calculate the statistics? There is the implication, if you you read further down the article, that the statistics come out as showing a positive advantage for the S allele (it only has to be a modest advantage to be propped up and not lost to negative selection or drift)
    But I haven’t done the stats myself either so I can’t say.

    “In it, one of the world’s foremost authorities on malaria debunks GW claims that GW will spread malaria to more northern climates by noting that the worst outbreak of malaria occurred in Russia; in fact, in a very cold region of Russia.” –PaV

    Isolated instances of malaria outbreaks in northern climes do not refute or even detract from the natural selection hypothesis for S-allele malaria resistance for multiple reasons:

    #1) just because the mutation *might* prove advantageous in a Russian population or elsewhere in the Northern region doesn’t mean that they will (a)possess the appropriate S-alleles or b)experience a new (de novo) S-allele mutation. There are any number of mutations that undoubtedly *would* prove beneficial to members of a population, but that does not imply that those individuals would actually *possess* or *acquire* them.

    #2) even ignoring #1, which can’t be ignored, it would require a relatively constant selective pressure (relatively constant malaria exposure) to maintain the S-alleles. I did not see this film, but I suspect it is not the case that malaria outbreaks in these Northern regions are common and/or continual. That is different from a tropical climate or subtropical climate where it is a persistent aspect of existence.

  35. “BTW Great_Ape any chance of you showing us the scientific data that accounts for the physiological and anatomical differences observed between chimps and humans?” –Joseph

    Not terribly likely, as I’m not even sure what that question means exactly (i.e. what level of detail you’re looking for or what would satisfy you).

    “On another site you were so sure of yourself but you never supported your assertions.” Joseph

    We were discussing a slightly different issue. You claimed that you couldn’t imagine how **any** amount of genetic change could account for the physiological/anatomical differences between humans and chimps. That was a poorly thought-out claim on the grounds of basic biology alone–all questions of evolution aside. I explained to you why it was faulty. My position hasn’t changed.

  36. In first and second year medicine, we had to do a number of courses to indoctrinate us into Darwinism. I am sure that this was done to counter the obvious design inference that we inevitably gathered from everything else we learned in anatomy, physiology, embriology, biochemistry, pharmacology … the list goes on and on.

    I was glad to hear the best Darwinists had to serve up to us. Unlike Richard Dawkins who found out at the aga of 9, I was not convinced in my twenties that the most powerful idea in history was more than the most powerful delusion in history.

    I am sure my patients do not suffer from my non conformity.

  37. great_ape:
    What precisely do you mean by “look closely”? Is that your general impression of the numbers or did you calculate the statistics? There is the implication, if you you read further down the article, that the statistics come out as showing a positive advantage for the S allele (it only has to be a modest advantage to be propped up and not lost to negative selection or drift)
    But I haven’t done the stats myself either so I can’t say.

    Looking at the statistics, I was quite surprised. I expected to see ratio of infected (I) to uninfected (U) that would be radically different between the S-allele carriers and the AA-homozygotes. But what you see is that the ratios are generally not that far away from each other (except when the test size was small), and you never saw instances where, e.g., one ratio was above 1 and the othe below 1. Similarly, the data show populations where the ratio of I/U is greater than 1 (#s 2,5,6,8,&9). That’s half of the ten populations they studied. So, does the S-allele help at all? The only “help” comes from the fact that the AA populations has a higher ratio.

    But then there’s this–which is easily observable from the data: some of these ratios are quite equal between the S-carriers and the AA’s. Notice:

    Pop.#4: S. Ghana: S-allele I/U= 0.32; AA-homozyg: I/U= 0.47

    and, then,

    Pop. #10 S. Ghana: S-allele I/U= 0.38; AA-homozyg: I/U= 0.42.

    But, here’s the whopper!!!

    Pop. #6 Nigeria: S-allele: I/U= 3.17; AA-homozyg: I/U= 3.23!!!!!

    Yes, that’s right, the AA-homozygotes had a “slight” advantage, i.e., 3.23/3.17= 0.02 selective advantage.

    Well, there you have it: in the LARGEST SAMPLE SIZE of all the given populations, the AA-homozygotes statistically have a selective advantage over the S-allele carriers. [[great-ape: (from above) "(it only has to be a modest advantage to be propped up and not lost to negative selection or drift)"]]

    You see, just more Darwinian garbage. Haldane speculates, scientists investigate, and then (WRONGLY) interpret the data to fit their preconceived Darwinian idea!! I’m forced to add that you, as well, have fallen for it.

    As Twain said, “There’s lies, damn lies, and statistics”. Look at the numbers: Population #4: S-allele: I/U= 0.32; Population #6: S-allele: I/U= 3.17. Do you see how far off the numbers are?!?!! It is obvious to anyone who spends more than five minutes time on these numbers, and, more importantly doesn’t come at them with a Darwinian bias, that the numbers—for the purpose of calculating “selective advantage”— are simply MEANINGLESS! Something far different is afoot in these numbers. Why is Nigeria so different from Ghana? Is it hospitialization? Is it food supply? I don’t know what causes the difference, but when ratios become that skewed, then it is obvious that an “S-allele selective advantage” has NOTHING to do with it.

    But, of course, you can do the calculation, and then tell everyone how sickle-cell anemia confirms Darwinism!

  38. “But, of course, you can do the calculation, and then tell everyone how sickle-cell anemia confirms Darwinism!” -PaV

    Someone in you guys’ camp should probably spell this one out for PaV. I fear I lack the necessary restraint this evening.

  39. I’ve quickly looked over the numbers, and, yes, in the case of Nigeria the numbers speak otherwise. In any event, it was only meant to rub it in some. Nonetheless, my point is still made: Africans carrying the S-allele in Nigeria are infected in a 3 to 1 ratio, while those in S. Ghana are infected in a 1 to 3 ratio. If, indeed, the S-allele has a selective value in making people less prone to malarial infection, then how do you propose to explain these results? I haven’t the foggiest notion of how these numbers support the notion that sickle-cell anemia confers resistance to carriers.

  40. PaV,

    Read through the entire tutorial (linked above) in which you found these numbers carefully . I does a fairly good job of illustrating one way to calculate statistics for the malaria data, and discusses the logic behind the calculation. Pay particular attention to the part about coin flipping. In short, you first need to set up a null hypothesis. In this case the null hypothesis is that there is no effect of the S-allele on incidence of infection (probability of a given individual being infected with malaria). What is the expectation under this hypothesis? You allele status (S/*) or (A/A)) will *not* be related the frequency of infection in a subpopulation. Restated, assuming an appropriately random sample, in any given population examined (Nigeria, Ghana, etc), the sub-group that has the S-allele and the sub-group that doesn’t have the S-allele should have an equal chance of being infected with malaria. Just like there is an equal chance of getting heads or tails when flipping a coin. Here, they’ve looked at ten populations. In each population, you need to calculate the frequency of infection of those people with the S-allele and the frequency of infection among those without it. [note: this is, in each subpopulation and in each allelic subgroup (i.e. calculate separately S/* and A/A), the number of infected individuals divided by the sum of both the infected and uninfected individuals)

    Under our null hypothesis (no effect of S-allele) the S-allele group’s infection frequency should sometimes be higher than the AA-allele group and sometimes lower. Let’s call cases where S-group is higher “tails” and cases where S-group incidence of infection is lower “heads.” Under the null hypothesis, the system should behave just like a coin flip. Yet what do we see in the data? Roughly equal heads and tails. I put the numbers in Excel and did it myself just to be sure: in each and every case, infection rate for the AA-group is higher than for the S-group. That’s ten heads in a row. That’s rather significant. Looking at various ratios in particular populations, as you did, can be misleading when you haven’t formally framed the question and decided what your hypothesis is and how you’re going to test it vs. chance. The big picture clearly shows a *lower incidence of infection* for the S-allele carrying group. That’s the take-home message. But don’t take my word for it. I suspect there are a number of folks lurking here that will tell you just the same.

  41. “Yet what do we see in the data? Roughly equal heads and tails.” –me

    Oops; the second sentence quoted should have gone before the first in my statistics post. Makes much more sense that way. Don’t know how I managed that one…

  42. See: Darwinist chastised for spinning “just so” stories, but he still brings home the bacon

    Indeed, after 50 years of investigation, we can’t convincingly demonstrate selection for most of the red-blood-cell diseases, other than sickle-cell anaemia, that are probably coevolving with the strong selective force of malaria. Other best-case scenarios for human genetic adaptation, such as adult lactase persistence and skin colour, are also incomplete.

    Selection happens, but there are numerous problems in it’s efficacy in mammalian populations, not the least of which are those outlined in Sanford’s GeneticEntropy.

    Sanford rightly argues that advantages can be drowned out by noise (i.e. random bad luck).

  43. Considering the topic, perhaps it would have been more appropriate to bold

    Indeed, after 50 years of investigation, we can’t convincingly demonstrate selection for most of the red-blood-cell diseases, other than sickle-cell anaemia, that are probably coevolving with the strong selective force of malaria. Other best-case scenarios for human genetic adaptation, such as adult lactase persistence and skin colour, are also incomplete.

  44. “Sanford rightly argues that advantages can be drowned out by noise (i.e. random bad luck).” -Sal

    This is correct… but just for the record, people should know that this idea of “drowning out” was not a novel insight on Sanford’s part. This is part of basic population genetics. The beauty of sampling statistics, though, is that even modest (e.g. mammalian) breeding population sizes yield fairly good approximations of the total allele frequency in the entire population. As a result, wild fluctuations in allele frequencies from “random bad luck” are not generally expected. As a further consequence, even alleles with smallish selective benefits will proceed (pretty much) deterministically to fixation. Kimura showed probability of fixation is approximated by:
    p(fixation) = (1 – exp(-4Nsq) / (1 -exp(-4Ns))

    Where q is the initial allele frequency, N the breeding population size, and s the selection coefficient (roughly, relative benefit). This includes “random bad luck,” whose influence is inversely proportional to population size. Try some numbers out and you’ll see that the initial frequency is critical. Once an allele reaches 1% frequency, even in a population as small as 10000 individuals, an allele conferring 0.5% advantage has a probability of fixing of over 98%.

  45. I believe Malaria can fix sickle-cell anemia if all other factors are equal.

    When we observe anti-biotic resistance in a petri dish we have strong selective forces and control in making “all other factors equal”.

    What may be happening with the fixing of sickle-cell anemia in the wild is the issue of the strength of selection and the other factors.

    As a further consequence, even alleles with smallish selective benefits will proceed (pretty much) deterministically to fixation. Kimura showed probability of fixation is approximated by:
    p(fixation) = (1 – exp(-4Nsq) / (1 -exp(-4Ns))

    There was the “no selection box” in Sanford’s book. At some point, if the selection force is so dilute, it can not be a factor, the trait will be appropriately modeled as neutral. It’s like trying to listen to someone whispering to you across a crowded noisy room.

    There were many conceptions sketched out in Sanford’s book that would be worth exploring theoreticaly and empricially. I think it’s pre-mature to be making certain conclusions….

    Somewhat off topic, but for what it’s worth, here is a monkey wrench article:
    Remote Sheep Population Resists Genetic Drift
    Science Daily

    Stories like this suggest Solexa technolgy will reveal the fact our conceptions of even evolution today are probably more off the mark than we are will to admit. Until then, it might be advisable to be cautious in our conclusions.

  46. “BTW Great_Ape any chance of you showing us the scientific data that accounts for the physiological and anatomical differences observed between chimps and humans?” –Joseph

    Great_Ape:
    Not terribly likely, as I’m not even sure what that question means exactly (i.e. what level of detail you’re looking for or what would satisfy you).

    Give us what you have. IOW what was it that satisfied you that humans and chimps shared a common ancestor?

    Do we know what, if anything, can account for the rearrangement of toes? (chimps have an opposable big toe)

    Do we know what, if anything, can account for bipedal, upright walking? (spine attaches differently to the skull, legs are different, rib cage different, etc.)

    And those are just two examples.

    The point being without that data all you have is faith inm your imagination.

    Great_Ape:
    You claimed that you couldn’t imagine how **any** amount of genetic change could account for the physiological/anatomical differences between humans and chimps.

    Umm That was NOT my claim. My claim was that NO ONE can account for the physiological and anatomical differences observed between chimps and humans. And reality supports that claim.

    Great_Ape:
    That was a poorly thought-out claim on the grounds of basic biology alone–all questions of evolution aside.

    It is a cliam supported by reality. IOW if anything is faulty it is your responses.

  47. great_ape:

    Roughly equal heads and tails. I put the numbers in Excel and did it myself just to be sure: in each and every case, infection rate for the AA-group is higher than for the S-group. That’s ten heads in a row. That’s rather significant. Looking at various ratios in particular populations, as you did, can be misleading when you haven’t formally framed the question and decided what your hypothesis is and how you’re going to test it vs. chance. The big picture clearly shows a *lower incidence of infection* for the S-allele carrying group. That’s the take-home message. But don’t take my word for it. I suspect there are a number of folks lurking here that will tell you just the same.

    Your analysis just blindly looks at statistics. I won’t bother to quote Twain again.

    Look at the numbers for S. Ghana and Nigeria again. One can explain the significant difference between the two countries this way: in S. Ghana, malaria hasn’t been virulent, while in Nigeria, it has. But then in Nigeria we see that there is almost NO difference between the S-carriers and the AA-homozygotes. If, indeed, the S-allele has some advantage, then why in an area that is apparently being ravaged by malaria do we see no difference in infection rates? Do you have an answer for that? And, beware, I have another ace up my sleeve. ;)

    This whole exploration of sickle-cell anemia and “microevolution” is turning out to be just like my search for a Darwinian explanation for “macroevolution”: “Where’s the beef?” So far it simply looks like another “just-so” story. Why should I be surprised?

  48. “Your analysis just blindly looks at statistics.” –PaV

    That’s the idea. Frame the question properly, make a hypothesis, and dispassionately determine if there is a significant effect there that is not expected by chance. There is always some degree of noise in the data. This may manifest itself in the fact that there is less difference between the two allele groups in Nigeria than you might expect. Your argument is essentially equivalent to arguing that europeans are not really taller than chinese because, golly gee, how would you explain Yao ming…

    I’m guessing you have never had a formal statistics course of any sort. The entire point of developing the science of statistics is to avoid the kind of fuzzy arguments that you’re trying to make about your impressions of the numbers when looking at particular data points. That’s not how it’s done and for good reason. And that has nothing to do with biology; that’s not how it’s done in *any* field. Twain’s quote is funny, yes, but the field of statistics was not abandoned after it was made. The fact of the matter is that, without formal statistics, it’s a lot *easier* to lie and also a lot easier to be just plain wrong.

  49. great_ape:
    “Your argument is essentially equivalent to arguing that europeans are not really taller than chinese because, golly gee, how would you explain Yao ming…”

    I’m afraid that is not the case at all. Your argument seems to be that, yes, we should look blindly at the data, crunch the numbers, and let the numbers speak for themselves. Are you aware of the highly correlated connection between who wins the Super Bowl and how the Stock Market fares in that same year? That’s statistics. Should be conclude from this high correlation that the two phenomena are connected?

    Now, as the “ace up my sleeve”, here’s a quote from a PBS story:

    ” A Mutation Story:

    A gene known as HbS was the center of a medical and evolutionary detective story that began in the middle 1940s in Africa. Doctors noticed that patients who had sickle cell anemia, a serious hereditary blood disease, were more likely to survive malaria, a disease which kills some 1.2 million people every year. What was puzzling was why sickle cell anemia was so prevalent in some African populations.”

    You see, this whole exercise is using the wrong kind of data. It shouldn’t be using infection rates, but malarial survival rates. And, do you further see, that it didn’t matter to them, and it didn’t matter to you. You simply wanted to “crunch the numbers”! (Every student who completed the exercise could then tell their friends: “Yes, indeed, the S-allele does confer ‘selective advantage’, and I can prove it statistically!”) On the other hand, I noticed the obvious: the S-allele wasn’t much of a defense against getting infected.

    With computers, and statistics, it’s the same aphorism: “junk in; junk out”.

    A final note: I’ve looked high and low doing searches for relevant data here, and could find none really. Does data exist? Where is it? I’m hoping someone can answer these questions. This whole thing smells of Kettlewell’s moths.

    P.S. I study statistics when I have to; otherwise its’ quite boring.

  50. “It shouldn’t be using infection rates, but malarial survival rates.”
    –PaV

    Survival rates would be nice data to have, but I’m going to speculate that the most fool-proof way to avoid death by malaria is to never become infected with malaria in the first place.

    “On the other hand, I noticed the obvious: the S-allele wasn’t much of a defense against getting infected.” –PaV

    Who can hope to prevail against reasoning such as this? I’ve nothing else to say on the matter. Perhaps someone else can provide illumination.

  51. Survival rates would be nice data to have, but I’m going to speculate that the most fool-proof way to avoid death by malaria is to never become infected with malaria in the first place.

    You’d be wrong-ish. Everyone in malaria endemic areas gets infected at some point during their life. Adults that grew up in these regions are less susceptible to severe malaria than visitors (don’t forget your anti-parasitics!).

    To send an ace your way, I can tell you that in malaria endemic regions, the freuqency of the S allele is higher in adults than in children. Here’s another puzzler to think about: Malaria mortality is not stongly corelated with malaria transmission.

  52. “You’d be wrong-ish. Everyone in malaria endemic areas gets infected at some point during their life.” –HodorH

    Point taken; I admittedly know very little about malaria epidemiology. I imagine the reduced probability of being infected at any given time-slice of one’s life, over the long-haul, is positively correlated with the probability of not dying from malaria. Although, biologically speaking, the same factors that make a person’s cells less likely to support initial infections (i.e. the property of resistance) would likely–if an infection did nevertheless ensue–mitigate just how rampant it could become and thus reduce the chance of mortality. So maybe survival rates among S-allele carriers vs. noncarriers are the main factor here, and the correlation observed between s-allele carriers and low rates of infection is just a by-product of the underlying biology? This could possibly explain the puzzle you pose about the incongruence between mortality rates and transmission rates, but see below, b/c I’m not sure I understood your puzzle exactly.

    Also, if you could link to a source for those child vs. adult S-allele frequencies, that would be great, as it’s difficult to think of a more straightforward way to illustrate natural selection occurring in this case.

    “Here’s another puzzler to think about: Malaria mortality is not stongly corelated with malaria transmission.” -HodorH

    I’m wondering if I properly understand your wording here. Is this correlation you speak of between the number of malaria deaths in a region and the number of verified transmission events between any infected individuals? Or is the correlation between only those individuals that die and the individuals they transmit to? Or are these correlations involving properties of different strains of malaria? Or is it something else?

  53. great_ape: “Who can hope to prevail against reasoning such as this? I’ve nothing else to say on the matter. Perhaps someone else can provide illumination.”

    You are speaking as if your interpretation of the data has proven right. Is there a reason for that?

  54. great_ape,
    There’s an old review chock full of good stuff, “New insights into the epidemiology of malaria relevant for disease control” Snow RW Marsh K,Br Med Bull. 1998;54(2):293-309.

    The relevant portion for the transmission::mortality comparison:

    In an earlier attempt to examine the relationship between transmission
    intensity and the risks of fatal outcome, we abstracted all the data related to malaria-specific childhood mortality recorded in communities
    where estimates of the intensity of P. faldparum exposure had been
    documented through entomological investigations (Fig. I)15. These data
    have proved of limited value in defining an empirical relationship
    between intensity of transmission and death from malaria for a number
    of reasons, including the insensitivity of indirect techniques for
    ascertaining cause of death1617; the problems in defining host-parasite
    exposure through the entomological inoculation rate; and confounding
    factors such as the presence or absence of effective clinical management
    for malaria between the sites and over time. The latter cannot be
    underestimated: at Keneba in The Gambia18 and Mlomp in Senegal19,
    childhood mortality was reduced to remarkably low levels through the
    provision of well funded, well staffed and comprehensive essential
    clinical services. Conversely, the emergence of resistance to Africa’s
    leading anti-malarial, chloroquine, has led to significant rises in severe
    disease and mortality20. Nevertheless, Figure 1 does highlight several important points: (i) there is an amazingly limited amount of data on one of the most fundamental relations in the epidemiology of malaria; and (ii) under the lowest transmission intensities mortality must rise
    sharply, where after the relationship remains unclear.

    The accompanying graph shows no correlation between transmission and mortality.

    I’ll try to dig up the sickle cell stuff I mentioned, but that was from a lecture a couple years ago, so I don’t have that data on hand.

  55. I was just reviewing this discussion, and I realized that something might not be clear to everyone: Malaria is transmitted by mosquito, not from person to person. If that was obvious to everyone, sorry for the extraneous comment.

  56. “You are speaking as if your interpretation of the data has proven right. Is there a reason for that?” -PaV

    Here’s my advice. Print out the malaria data, get into your car or truck, and drive it to the nearest religiously affiliated college or university. One where you can be certain that the statistics professor does not accept darwinian evolution. Show him or her the data, and have them explain to you exactly why you’re wrong. There is nothing I can say to you that will convince you.

  57. “Malaria is transmitted by mosquito, not from person to person.” –HodorH

    Yikes. For a moment that had slipped my mind while I was thinking about how it spreads across a population. I was working with ether in the lab this week; that’s the only excuse I have.

  58. Here’s one describing the effect of S allele on malaria infections, though it’s not the droids paper I was looking for:

    Longitudinal study of Plasmodium falciparum infection and immune responses in infants with or without the sickle cell trait.

    * Le Hesran JY,
    * Personne I,
    * Personne P,
    * Fievet N,
    * Dubois B,
    * Beyeme M,
    * Boudin C,
    * Cot M,
    * Deloron P.

    Institut National de la Sante et de la Recherche Medicale, Unite 13 Institut de Medecine et d’Epidemiologie Africaine, Paris, France.

    BACKGROUND: Individuals may be homozygous (SS) or heterozygous (AS) sickle cell gene carriers or have normal adult haemoglobin (AA). Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known. METHODS: We followed two cohorts of children. The first was enrolled at birth (156 newborn babies) and the second at 24-36 months old (84 children). Both cohorts were followed for 30 months; monthly for parasitological data and half yearly for immunological data. RESULTS: In the first cohort, 22%, and in the second 13% of children were AS. Whatever their age parasite prevalence rates were similar in AA and AS individuals. Mean parasite densities increased less rapidly with age in AS than in AA children, and were significantly lower in AS than in AA children >48 months old. The AA children tended to be more often admitted to hospital than AS children (22% versus 11%, NS). Both anti-Plasmodium falciparum and anti-Pfl55/RESA antibody rates increased more rapidly in AA than in AS children. Conversely, the prevalence rate of cellular responders to the Pfl55/RESA antigen was similar in AA and AS children during the first 2 years of life, then it was higher in AS than in AA children. CONCLUSIONS: Sickle cell trait related antimalarial protection varies with age. The role of the modifications of the specific immune response to P. falciparum in explaining the protection of AS children against malaria is discussed.

  59. great_ape:

    “Show him or her the data, and have them explain to you exactly why you’re wrong. There is nothing I can say to you that will convince you.”

    Do you remember that old bromide about when you point your finger at someone, there’s three fingers pointing back at you?

    From two different studies that HodorH has posted:

    1.) “we abstracted all the data related to malaria-specific childhood mortality recorded in communities
    where estimates of the intensity of P. faldparum exposure had been
    documented through entomological investigations (Fig. I)15. These data
    have proved of limited value in defining an empirical relationship
    between intensity of transmission and death from malaria for a number
    of reasons,….”

    2.) “Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known.”

    Isn’t it clear yet that there isn’t any connection between the S-allele and any selective advantage, that it’s only part of the Darwinian imagination, that there is no data to support it? Another Darwinian “just-so” story. Why can’t you accept that?

  60. PaV,
    Did you stop reading the first excerpt at the point where you added the ellipses? Did you look at the data in the second paper before dismissing it? It says the mechanisms are poorly known because that is the justification for the research.

    Additionally, I found a rather mathy paper finding selection coefficients for the S allele during my search for Mr. Ape. Would you like to analyze that one?

  61. “Isn’t it clear yet that there isn’t any connection between the S-allele and any selective advantage, that it’s only part of the Darwinian imagination, that there is no data to support it? Another Darwinian “just-so” story. Why can’t you accept that?” –PaV

    Pav,

    Okay, I think this last post of yours goes over the top and gives you away. You’re clearly parodying the antics of some in the more obstinate and unscrupulous pundits. Very cute, but you’re wasting folks’ time on both sides of the aisle. It’s simply asking too much to have me believe that someone could consistently render grammatically correct English in the fashion you have and yet be as oblivious as you’re coming across. It’s one thing to cherry-pick quotes out of context to fit your position. It’s quite another to do so when the people you’re arguing with have the same text you’re quoting right in front of them and can see it contradicts you.

  62. HodorH: This should be interesting for you:

    “The high frequency of the sickle allele in some parts of Africa is understood to be a consequence of high malarial endemicity. One corollary of this is that the sickle allele frequency should be declining in populations of African ancestry that are no longer exposed to malaria. We have previously shown that there has been no change in sickle allele frequency in malaria-free Jamaica between two large-scale neonatal screening exercises conducted in 1973-1981 and 1995-2003.

    http://www3.interscience.wiley.....8;SRETRY=0

    As to the paper you found, I’d be happy to look at it. It seems from my searching that nothing much is known with any certainty. It looks more and more–just as the quote above points out–there’s absolutely nothing to the supposed connection between malaria and sickle cell anemia. The more likely scenario, at this point, might have more to do with the complexity of haemoglobin, and that SNP’s of various types (I have one myself) happen without fatal consequences, and that these SNP’s simply just live on in the population. I don’t see any evidence to the contrary. It seems as if Darwinian faith in such things as selective advantage is the only thing that keeps this alive.

  63. great_ape:

    “It’s simply asking too much to have me believe that someone could consistently render grammatically correct English in the fashion you have and yet be as oblivious as you’re coming across.”

    Condescension will get you nowhere. I’m afraid you’re the one who is oblivous. Look at my last post, and the quote I’ve posted. So far I’ve shown that the data in the study about S-allele ‘selective advantage’ that you thought was reliable was completely irrelevant. Now I’ve demonstrated that S-allele frequency hasn’t changed in the absence of the “natural-selector”, i.e., malaria. So who’s oblivious. It’s just another Darwinian sham, no more, and you choose to fall for it.

  64. Folks:

    I have watched this thread, and think it will be helpful at his point to add a few points, as one who hails from Jamaica.

    In Jamaica, Sickle Cell Trait is fairly commonly known to be associated with medical problems, though of course less than those of full-blown Sickle Cell Anaemia. (Oddly, that did not come up in my O level biology class in which the subject of the NS-based alleged protective nature of the trait was raised.) I learned of it as a university student, from my fellow students. [I should note in memoriam, that one of my friends, a lovely young lady, died as a student from Sickle Cell Anaemia.]

    1] Sickle Cell Trait:

    Here, note from Dr John Kark:

    Sickle cell trait usually is not regarded as a disease state because it has complications that are either uncommon or mild. Nevertheless, under unusual circumstances serious morbidity or mortality can result from complications related to polymerization of deoxy-hemoglobin S. Such problems include increased urinary tract infection in women, gross hematuria, complications of hyphema, splenic infarction with altitude hypoxia or exercise, and life-threatening complications of exercise, exertional heat illness (exertional rhabdomyolysis, heat stroke, or renal failure) or idiopathic sudden death (1-4). Pathologic processes that cause hypoxia, acidosis, dehydration, hyperosmolality, hypothermia, or elevated erythrocyte 2,3-DPG can transform silent sickle cell trait into a syndrome resembling sickle cell disease with vaso-occlusion due to rigid erythrocytes. . . . .

    In addition some disease associations have been noted with sickle cell trait which might not result from polymerization of hemoglobin S but from linkage to a different gene mutation. The association of hemoglobin S with cases of renal medullary carcinoma, early end stage renal failure in autosomal dominant polycystic kidney disease, and surrogate end points for pulmonary embolism are not necessarily the result of hemoglobin S polymerization. Complications from sickle cell trait are important because about three million people in the United States have this genotype, about 40 to 50 times the number with sickle cell disease.

    So, that is the first thing I would want my med student friends to know,that SC trait can cause serious medical conditions. (That does not fit the meme that SCT protects from malaria and does little or no no harm. The second impression is plainly misleading. Let’s look at the first, next.)

    Pause . . .

    GEM of TKI

  65. Continuing . . .

    2] From an Atlanta GA fact sheet:

    We also learn that:

    One of 12 Blacks in the United States has Sickle Cell Trait. It is a myth that only blacks have sickle cell conditions . . . . There are over 700 different types of hemoglobin. Many of these serve as a protection against Falciparum Malaria. They are not contagious and can only be passed from parent to child. It is important for you to know your hemoglobin type.

    So, this is not a race in which there are two horses but 700.

    If the selection pressure were strong enough, neither SS nor SA types would win, as both are associated with adverse conditions, that would tend to eliminate, at least if the relevant timespan on Malaria were on the usual projected evolutionary timescale. For, even Wiki notes on SCT, that: “People who have the sickle cell trait have reduced susceptibility to malaria, due to natural selection for the heterozygote advantage. However, people with the sickle cell trait can still contract severe cases of malaria.”

    It also notes: “Malaria has infected humans for over 50,000 years, and may have been a human pathogen for the entire history of our species.[1] Indeed, close relatives of the human malaria parasites remain common in chimpanzees, our closest relatives.[2]”

    I would also want my med student friends to know these too, instead of a simplistic just so story.

    3] The “statistricks” games . . .

    There are half-truths, blatant lies and statistricks. That’s because “while figgers don’t lie, liars can figger.” This, too, I would want my med student friends to know – and a good course in critical thinking and on the nature, strengths, limitations and ethical issues over the scientific approach have more relevance than a lot of time on NDT. [I haven't mentioned our usual joke on campus on telling who is a med student – the one who usually looks like s/he hasn't slept for the past week or so. That is, there is a relevance and time available constraint here.]

    PaV and HH have highlighted between them, that something is wrong in the presentation of the statistics in the relevant case study in the textbook. HH’s excerpt in no 58 — which comes from a 1999 peer reviewed journal article [long after the story we are discussing gained wide circulation and general acceptance] — is telling, unless it is demonstrably false: “Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known.”

    So, which is it: has htre story gained currency based on solid evidence but i the teeth of absence of it? Has there been subsequent to 1999, the provision of the missing evidence and mechanisms? Absent this last, I would therefore render a Scotch verdict on this case of claimed NDT microevolution at work [and note, by partial loss of genetic information, not creating new functional information . . .]: case not proven.

    BTW, all of this is in a context where microevolution per se is not an issue across NDT, ID and YEC advocates – the complexity threshold is not crossed in cases of information loss and consequences, or in cases where we are not looking at the creation of 500 bits of information or equivalent, by chance that leads to novel biofunctionality and/or systems and/or plans — but the issue is: is this case well warranted? Looks to me, no.

    So, I would then let my med student friends hear that his is claimed, but there are these statistical concerns and limitations, so here are the points that are relevant to medical praxis [cf 1 and 2 above.] That is a lot more useful than indoctrination in evolutionary materialist ideology presented in the name of “science.”

    Trust that helps

    GEM of TKI

  66. H’mm:

    So, I guess I DO want med students to know about NDT and its applications to medicine after all — including the just so story problem and issues over substantiation, as well as the problems over eugenics and the ethics of the value of human life.

    GEM of TKI

  67. PaV:
    Here’s the paper:
    Quantitative aspects of the relationship between the sickle-cell gene and malaria.

    Parasitol Today. 1997 Mar;13(3):107-11

    The Jamaican paper looks interesting, it tells us that malaria may not be the only factor in the persisitance of the S allele. But it does not rule out a selective advantage of the S allele in malaria endemic regions.

  68. “Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known.” -linked article

    As HodorH pointed out earlier, the authors here are (awkwardly, IMO) trying to engender a sense that more study is needed as a means of explaining the motivation for their research. It is evident from the literature (notice in particular, the articles that reference the article itself) that the underlying biology for the protection is poorly understood, but the protective effect itself, as determined by several metrics, seems well established by data analysis. Why they chose to say here that it merely *could* have a protective effect is beyond me to explain… other than poor word choice. Of course, *why* they make this questionable statement is a moot point because later on in the same article you’re citing they CONCLUDE: “CONCLUSIONS: Sickle cell trait related antimalarial protection varies with age” So the very source you’re quoting, again, contradicts you’re point if you actually finish reading it.

    “If the selection pressure were strong enough, neither SS nor SA types would win, as both are associated with adverse conditions, that would tend to eliminate, at least if the relevant timespan on Malaria were on the usual projected evolutionary timescale.” -kairosfocus

    The above is wrong.
    #1) You appear to be confusing individual’s genotype with the alleles themselves; the ultimate competition over what may or may not fix is between the two alelles S and A, not the genotypes SA and SS. #2) Alleles with negative consequences *can* persist indefinitely when they occur in combinations with other alleles that are advantageous. Look up “balancing selection” and “overdominance”.

    There are half-truths, blatant lies and statistricks. That’s because “while figgers don’t lie, liars can figger.” –kairosfocus

    If I could make scientific arguments by simply repeatedly invoking aphorisms, it would make my professional life much simpler. But that’s not how it works. That is rhetoric, not rational scientific discourse. It serves no other purpose than direct attention away from the pertinent details.

    “PaV and HH have highlighted between them, that something is wrong in the presentation of the statistics in the relevant case study in the textbook.” –kairosfocus

    The case study does not make a statement about the underlying biology involved, nor does it claim to *prove* anything. It simply asks the question of whether the data are consistent with the hypothesis S/* genotypes exhibit a protective effect. Based on standard, agreed upon statistical methods of analysis, they do. Now, it could be the case that this statistical significance is less relevant to the maintenance of the S-allele in populations than the *survival* advantage. (See my speculations about the relationship between infection protection and ultimate survival above.) In which case, the presentation would need to be changed to be more informative. Nevertheless, the significance holds. The data is what it is and supports the hypothesis. The truth may ultimately be more complex, but in any plausible scenario, carriers of the S-allele are *somehow* benefiting from over their non-S peers, otherwise the deleterious nature of the S-allele make it far less prevalent than it is or possibly completely remove it from the population.

    “BTW, all of this is in a context where microevolution per se is not an issue across NDT, ID and YEC advocates ” –kairosfocus

    So I am repeatedly told. Clearly i have no problem with microevolution. Jerry has no problem with microevolution. Behe has no problem with microevolution. Yet it’s obviously an issue for PaV, and that’s what’s relevant at the moment.

  69. “We have previously shown that there has been no change in sickle allele frequency in malaria-free Jamaica between two large-scale neonatal screening exercises conducted in 1973-1981 and 1995-2003.”
    –jamaican paper

    As for the jamaican paper, the link didn’t work for me, but I am incredulous that they would expect to see a statistically significant decrease in allele frequencies over what is effectively within *A SINGLE GENERATION TIMESPAN* That’s very very bad population genetics, particularly when considering the type of selection coefficient you’re likely dealing with. For example, a bottleneck resulting in increase disease allele frequencies (such as in Ashkenazi Jews, Acadians, etc) had resulted in above-average disease allele frequencies for hundreds of years (well, nearly 200 for acadians). Over time, the frequencies would be expected to go descend–if the population doesn’t completely disperse through admixture–yet over any period of one or a few generations, you wouldn’t necessarily see a decrease; you may, due to stochasticity, possibly even get an *increase* some generations. This does *not* mean, however, that these diseases don’t have negative fitness consequences.

  70. Okay, I was able to read the abstract for the jamaican paper.
    They actually made a simulation for how the frequency would be expected to decline over time. That’s good. What they found was, over the longer time period since leaving Africa, the frequency of the first cohort is consistent with the model expectations. Thus it supports the idea of malaria protection from the S-allele as explaining its persistance. Yet when they look at the change between the two *recent* cohorts, it doesn’t change as much as they’d *expect*. Yet this is a ridiculously short period of time and noise is a factor. Did they adequately account for the noise or the possibility that their parameters are incorrect? I can’t say because I can’t access the paper from home. But at the very least, the paper provides *ambiguous* evidence for the S-allele malaria protection connection.

  71. I find this discussion curious. There must be a whole literature on sickle cell anemia. There must be a significant sub-portion devoted to the genetic aspects of it and why heterozygote survives better. I have a hard time understanding how all the people who have studied this could be wrong about what is happening.

    Like any theory there are probably plenty of anomalies but it seems to stretch the imagination to think the whole community who is interested in this disease has missed something so basic which voids the genetic aspects of it.

  72. jerry: ” find this discussion curious. There must be a whole literature on sickle cell anemia. There must be a significant sub-portion devoted to the genetic aspects of it and why heterozygote survives better.”

    So I supposed, until I started looking around.

  73. “The above is wrong.” –me

    kairosfocus,

    I may have misunderstood your statement above about the SA and SS types. If you were simply saying that SS and SA wouldn’t be beneficial and the S would be selected out if having a single S in a genotype was nearly 100% detrimental (i.e. reduces fitness to almost zero), then that would indeed be true in that eventuality. But as is clear, and as you have indicated, this is not the case. I apologize if I was too hasty and not generous enough in my interpretation of your statements. My response was factual, if misdirected, and may still prove to be a useful clarification for someone following.

  74. great_ape:

    “I can’t say because I can’t access the paper from home. But at the very least, the paper provides *ambiguous* evidence for the S-allele malaria protection connection.”

    Yet, from what little we have from the abstract, one gets the sense that they’re backing into the solution they want. What I mean is that their conclusion is that if they raise the selection value for the SS-homozygote, then the model they’re using shows a selective advantage for the heterozygote. So, then, what’s the point of “blindly” doing statistics, if you just turn around and “tweak” the value for one of the input values. It reminds me of: “junk in; junk out.”

  75. “There must be a significant sub-portion devoted to the genetic aspects of it and why heterozygote survives better.” –jerry

    The biological reasons for *why* heterozygotes survive better appears much less well understood than I initially thought. So I was surprised as well in that regard. But the genetic/statistical evidence *that* they have reduced infection rates and enhanced survival is plentiful. So the community is not suffering from a mass delusion when they claim that heterozygotes confer resistance to malaria. I was hoping that someone in this field would chime in since this is outside my area, but that is not happening thus far.

  76. Here’s the first half of an abstract for a paper from 1983:

    “In a sample of 424 pregnant Zambian women a series of tests was carried out: sickle cell test, haemoglobin estimation and screening of a thick blood smear for malarial parasites. More anaemia was found in the primigravidae than in the multigravidae. The haemoglobin level was found to be lower with primigravidity and, independently of this gravidity effect, also with malaria. Taking into account the higher malaria frequency in primigravidae, this group must be considered as a high risk group for development of anaemia. There was no significant interaction between sickle cell trait, anaemia and malaria.” (my emphasis)

    I’m not quite sure what they mean by “interaction”, but I’m supposing they mean some sort of ‘correlation’.

    This is from PubMed, going all the way back to 1983.

  77. “What I mean is that their conclusion is that if they raise the selection value for the SS-homozygote, then the model they’re using shows a selective advantage for the heterozygote.” –PaV

    I presume they are deriving their selection coefficient independently from a previous empirical study. One can estimate this value from actual (i.e. real) genotype frequencies. Again, I can’t be sure ’cause I can’t read the entire text. They seem to find that using this coefficient, the first data set is consistent but the change between the two cohorts is not consistent. They then argue that it may be due to an increase in S-allele fitness that is *not* malaria-dependent.

    In other words, the part where they tweaked the selection value in the model to match their data is the part that supports *your* position.

  78. I have looked in pubmed as well. In particular, try a search joining “anemia”, “malaria”, and “resistance.”

    What I stumble across when searching pubmed are gems such as these:

    Williams TN.
    Curr Opin Microbiol. 2006 Aug;9(4):388-94. Epub 2006 Jul 3
    Human red blood cell polymorphisms and malaria.

    Min-Oo G, Gros P.
    Cell Microbiol. 2005 Jun;7(6):753-63.
    Erythrocyte variants and the nature of their malaria protective effect.

    Shear HL, Roth EF Jr, Fabry ME, Costantini FD, Pachnis A, Hood A, Nagel RL.
    Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria.
    Blood. 1993 Jan 1;81(1):222-6.

    Colombo B, Felicetti L. Admission of Hb S heterozygotes to a general hospital is relatively reduced in malarial areas.
    J Med Genet. 1985 Aug;22(4):291-2.

    These articles and more point to solid data connecting the genotype to resistance. And no, I will not arbitrarily extract quotes that support my position from them because the papers themselves, in their *entirety*, either analyze data or review analyses of data that *conclude* there is a connection between resistance and genotype. That’s what matters. Not ambiguous sentences extracted from their contexts.

  79. This is from the wikipedia site and looks like a pertinent review

    How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria
    Dominic P. Kwiatkowski

    Am J Hum Genet. 2005 August; 77(2): 171–192.

  80. great_ape:

    They seem to find that using this coefficient, the first data set is consistent but the change between the two cohorts is not consistent. They then argue that it may be due to an increase in S-allele fitness that is *not* malaria-dependent.

    I understand them as saying that when they compared actual frequencies between two different neo-natal screenings, which took place twenty years apart, that the S-allele did not decrease in frequency, and that the only way that they could get their model’s predicted decrease to match the non-significant decrease of S-allele frequency was by assigning a “recent” (meaning ‘twenty years later’, not in the original testing) higher fitness value to the HbSS homozygotes.

    Here’s what the abstract says:

    “We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction. Close agreement between predicted and observed values was only achieved by simulating a recent, marked increase in HbSS fitness. Thus, the unexpected persistence of the sickle allele in Jamaica may reflect the fact that the actual fitness among SS individuals is higher than that previously realized.”

    They thus render it a case of “retrodicting”, and not “predicting”—since their “predictions” failed!

    To my mind’s eye, given that there are so many different types of ‘heterozygotes’ for hemoglobin—sickle cell, thalassemia, dust antigen, HLA, etc., etc.—the more sensible interpretation is not that ALL of these confer any kind of ‘heterozygote advantage’, but simply that when it comes to hemoglobin its complex structure permits a number of heterozygotes appearing without lethality. IOW, the recessive homozygotes are not sufficiently lethal as to eliminate them from a population entirely, so there remains a kind of ‘residual’ allele frequency. That’s my hunch.

  81. H’mm

    Seems I should follow up a few points:

    1] G-A: If I could make scientific arguments by simply repeatedly invoking aphorisms, it would make my professional life much simpler.

    You will see that I noted the above just once, and provided a context, namely that the “race” is broader than just one genetic variant. That is why I gave several excerpts and remarks on what I think medical students [and the general public!] should know about.

    2] The case study does not make a statement about the underlying biology involved, nor does it claim to *prove* anything. It simply asks the question of whether the data are consistent with the hypothesis S/* genotypes exhibit a protective effect.

    You will observe, I provided a context, which shows that there are material facts missing, including personal observation in a context where sickle cell trait and anaemia are major public health problems. Thus, my remarks on the deleterious effects of SCT [which weakens the individuals so affected and may materially reduce development capability, cf even Wiki's discussion as linked, consistent with my observations of individuals straggling with it].

    It is worth a further note from Wiki:

    Malaria . . . causes disease in approximately 400 million people every year and is the cause of between one and three million deaths annually, mostly among young children in Sub-Saharan Africa. Malaria is not just a disease commonly associated with poverty, but is also a cause of poverty and a major hindrance to economic development. . . . . Malaria has infected humans for over 50,000 years, and may have been a human pathogen for the entire history of our species . . . . Malaria is thought to have been the greatest selective pressure on the human genome in recent history.[48] This is due to the high levels of mortality and morbidity caused by malaria, especially the P. falciparum species.

    In short, the race should over the timespan suggested have been won long since by something else. For, at say 25 y/gen, we are looking at 40 gen/ky i.e., 2000 generations. And, if we are looking at 1 +MY, that number goes to 40,000 generations. [And since we are really looking at the loss of infants, the replacement time is probably far faster; as we know that families have “replacement: and “spare” children to compensate for expected infant mortality. Indeed,t his is the reason behind the population boom when public health progress first educes death rates, then the subsequent demographic transition when people realise that there is no need for “spares” and “replacements.”]

    Pausing . . .

    GEM of TKI

  82. Continuing . . .

    3] . . . this is a ridiculously short period of time and noise is a factor.

    This brings out the point. What the study showed, as you noted, was:

    1] over the longer time period since leaving Africa, the frequency of the first cohort is consistent with the model expectations.

    2] when they look at the change between the two *recent* cohorts, it doesn’t change as much as they’d *expect*.

    Now, how many 1 – 5 year olds do you suspect were born in Jamaica to be present in [1973-1981] – [15 to 25 years] and [1995-2003] – [15 to 25 years]? How many were eliminated by Malaria in the early 1950′s or so? [By the 1970's it was not a serious public health issue, Dengue of course was, on occasion.] There was plainly a base in the population large enough to give meaningful numbers, especially given that Jamaica’s population was probably 1 + mn in the 50′s and then 2+ mn in the early to mid 70′s. [The growth rate has tapered off, with emigration and birth control as material factors.].

    Further, while Jamaica has had many problems, it has long had a serious and effective public health system, which has gathered good statistics, and over the span from the 1950′s on has hosted a major teaching and medical research hospital tied to The University of the West Indies that has done excellent, world-class public health research. In particular, now I have found an abstract, TMRU is a world famous research centre. So, your “noise” dismissal is highly questionable.

    Indeed, observe PaV’s onward excerpt, in No 80:

    Close agreement between predicted and observed values was only achieved by simulating a recent, marked increase in HbSS fitness. Thus, the unexpected persistence of the sickle allele in Jamaica may reflect the fact that the actual fitness among SS individuals is higher than that previously realized

    The authors themselves conclude: our models suggest that without substantial changes in current screening and counseling practice, there will be little “natural” reduction in sickle allele frequency for several hundred years. Better estimates of relative fitness will be helpful in refining these predictions and may aid in assigning health care priorities in Jamaica and the African Diaspora.

    Now, that goes to the heart of the issue, as we are here looking at a question on the eliminability of SS in the population.

    The report, “Predicted declines in sickle allele frequency in Jamaica using empirical data,” further, was peer reviewed to appear in Am J Hematol. 2006; 81(11):817-23 (ISSN: 0361-8609), and so it is quite likely that the main, “unexpected” results cited were statistically significant [save as they noted!], i.e. there was a [flat] observed trend line and there was enough data to show whether or not the expected trend was matched by observations. Evidently, it was not, though as observed, the initial numbers were generally consistent with the model.

    PaV then goes on to note relative to a point I highlighted above:

    given that there are so many different types of ‘heterozygotes’ for hemoglobin —sickle cell, thalassemia, dust antigen, HLA, etc., etc.—the more sensible interpretation is not that ALL of these confer any kind of ‘heterozygote advantage’, but simply that when it comes to hemoglobin its complex structure permits a number of heterozygotes appearing without lethality. IOW, the recessive homozygotes are not sufficiently lethal as to eliminate them from a population entirely, so there remains a kind of ‘residual’ allele frequency.

    In short, the overall evidence points to the precise pattern identified in the French paper long since noted above: “Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known.”

    4] Apology.

    Accepted, with a note.

    For, you will see that I made a two-part post, with a PS, observing first that my remarks are based on being in a relevant context. Specifically, I noted based on observations and living in a context, backed up by medical authority, that SA is ALSO associated with potentially serious medical complications, and that it is generally associated with negative effects that hinder the potential of the victims to thrive. In a “race” with something like 700 horses, across the relevant span, it is reasonable to consider that it should be eliminated, if malaria is the number one pressure on the population and if since it mainly kills off 1 – 5 year olds, people will have more babies to compensate for those lost. [My grandparents had 9 and 12 children, circa 1920's – 30's; the 12 being in the context of two lost as infants. Not sure if Malaria could have been a factor.]

    Accordingly, on what med students should learn, I noted:

    the first thing I would want my med student friends to know,that SC trait can cause serious medical conditions. (That does not fit the meme that SCT protects from malaria and does little or no no harm. The second impression is plainly misleading . . .) . . . .

    I would . . . let my med student friends hear that [t]his [NDT-based protective pattern] is claimed, but there are these statistical concerns and limitations, so here are the points that are relevant to medical praxis

    5] The biological reasons for *why* heterozygotes survive better appears much less well understood than I initially thought. So I was surprised as well in that regard. But the genetic/statistical evidence *that* they have reduced infection rates and enhanced survival is plentiful. So the community is not suffering from a mass delusion when they claim that heterozygotes confer resistance to malaria.

    Observe the overall context: there is a multi horse race, it is not just on SS, SA, AA. Thus,t he force of PaV’s remark in 80 and my earlier remarks in 64 – 65.

    But the bottomline is already present, i.e. you have come out where PaV and I have also come out: there is a lot more to the story than the simple NDT just-so one popularly presented. And, that is what med students should learn.

    GEM of TKI

  83. PS: I add that from the “predicted but not observed declines in Jamaica” study, there is also an issue of HOMOZYGOTE SS viability thus “protective” effect, or at least sufficient non-lethality to survive and persist in the population. [Note too, the reference to counselling, i.e. to hoped-for artificial selection; aka microevolution by intelligent design. H'mm, isn't that what Darwin used as a "substitute" for NS in his own studies and reported on in Origin?]

    This point on SS, too, does not fit the simple just so story. Let us note: that empirical datum was sufficiently newsworthy among students of haematology to be publishable in a major peer-reviewed journal in 2006.

    GEM of TKI

  84. “They thus render it a case of “retrodicting”, and not “predicting”—since their “predictions” failed!” -PaV

    Yes, their predictions failed for the specific and rather brief period from the 70s to the 90s. They did not fail for the larger span of history since the initial colonization.

    “IOW, the recessive homozygotes are not sufficiently lethal as to eliminate them from a population entirely, so there remains a kind of ‘residual’ allele frequency.” –PaV

    We are specifically discussing sickle-cell alleles and genotypes. Lethality, remember, is only part of the picture; there is also loss in overall reproductive fitness. The fact that homozygous recessive sickle-cell genotypes are less reproductively successful cannot be ignored. The frequency of the S-allele, barring other considerations, ultimately, should go down. How fast depends on numerous factors.

    The point you’re both failing to appreciate is that a longterm trend (colonization to now) is much easier to observe than one over a couple decades. It was the one over the couple of decades that failed to fit their model. Only then do they “retrodict” and insert a new parameter to explain *why* it failed. In my opinion, their retrodiction was a gross error because you can’t expect to see a significant decrease in allele frequency over those ~2 decades. That’s barely time for a generation turnover. Once you factor in noise, etc, I have no idea why they would even *think* they’d see a decrease here. And then, the icing on the cake is that, to make their new theory work, they have to assume the magical S-benefit is only *recent*. That makes the second part of the paper and all the talk about “no natural reduction” even sillier.

    Also, we are not only trying to explain why the S-allele *persists*, but also why it persists at such *high frequencies* in those regions plagued with malaria as opposed to other regions. This is an important point that your “just lingering and not very harmful” theory does not adequately address.

  85. “There was plainly a base in the population large enough to give meaningful numbers….”

    Large numbers, yes, but meaningful? Recall that the statistical question involves a trend over time. And nothing is plain or obvious here about the analysis. Bias in the “sampling” of next generation’s alleles due to natural selection will be both subtle and subject to a number of noise sources, and it is not straightforward to predict how fast this should happen, or, more importantly, what criteria are necessary to *detect* it happening.

    I simply question the wisdom behind the authors’ interpretation of their results. Did they, for instance, examine random intervals during the longer model period and ask how often they find periods of ~20-30 years where *no* significant decrease was predicted even though the overall (longterm) decrease is clear? (I’m assuming the model was a stochastic computer simulation). I bet they would find numerous time intervals where, by chance, no decrease in allele frequency was observed in the simulation). Yet they choose to invoke another parameter, a novel and unknown genetic benefit, along with a *change* in what’s going on biologically in recent decades, to explain the absence of significance over this short time period. Very questionable reasoning IMO.

    “Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known.”

    Once more, quoting an expression of doubt from a single paper from several years ago, particularly when the paper goes on to *show* a quantifiable protective effect of the S-allele across age groups is highly questionable.

    “Observe the overall context: there is a multi horse race, it is not just on SS, SA, AA. Thus,t he force of PaV’s remark in 80 and my earlier remarks in 64 – 65.” –kairosfocus

    We are specifically discussing the fate of sickle-cell alleles and their relationship to malaria. Certainly there is additional biological complexity, but you merely drag it in without giving any clear indication of how they directly impact the issue at hand. Let’s revisit something in your earlier post, where you suggest SA genotype is too deleterious and should be eliminated in such a horse race. You neglected to highlight this particular passage, so I will:

    “Nevertheless, under unusual circumstances serious morbidity or mortality can result from complications related to polymerization of deoxy-hemoglobin S.”

    Note the part about unusual circumstances. I read unusual circumstances as being particular rare. Once again, it is important to read the entirety of the material you’re referring and comprehend it. Do not simply highlight the parts that seem agreeable. The doctors in the study you referenced were justifiably discussing a real medical *possibility* concerning SA that the medical community should be aware of. They specifically note, however, that the circumstances under which SA complications arise are *unusual*. This indicates that your argument that the SA genotype should have lost the race or been trampled by horses or whatever is without substance.

  86. Following up:

    1] GA: their predictions failed for the specific and rather brief period from the 70s to the 90s . . . . a longterm trend (colonization to now) is much easier to observe than one over a couple decades . . . . ~2 decades. That’s barely time for a generation turnover.

    First, the researchers used the evolutionary population scenario to project trends across the period in question,and found statistically significant results that contradicted the predictions on the trend line: it was flat not trending down. Further to this, the studies were conducted on screenings in the 1970s – 80s and 1990s – 2000s. The findings withstood peer review, well enough to be published.

    Moreover, mothers giving birth to children circa 1973 would have been born ~ 15 – 30+ or so years earlier, probably during the end of the era in which Malaria was a problem. (Here based on the spreading of DDT, but reckoning that mosquito control before that would have had impacts.)

    This also immediately implies that the data span a 50+-year period, which is an appreciable fraction of the history of the dominant African population of Jamaica. For, in C18, the typical expected incremental slave lifespan in Jamaica was reportedly ~ 5 years, and the trade was officially ended in 1807 – 8. So, we are looking at maybe 250 years, for the importation of the genetic bulk of the population.

    Thus, we are looking at a snapshot of the population dynamics over about 20 – 25% of the existence of that population in Jamaica, and starting at the time when we have the ending of the malarial era ranging into something like three generations of births in the post Malaria era, as [given the unfortunate patterns of reproduction that massively prevail] many of the women involved would be unwed teen mothers. (Indeed, I should be saying 12 – 14 years or so at the lower end, but I believe that this is significantly less than 5%. These are LARGE SCALE, routine screenings, where there are probably ~ 10′s of thousands of births per year. 5% of 10^4 = 500. If I am an order of magnitude high, that would still capture enough to be within credible statistics. E.g. 8 * 50 = 400, so the short cycle tail of the distribution should include enough to validate the claim that three generations of births are significantly represented, maybe more, as women in their 40s are often enough still in the reproductive population in Jamaica. So, 1973 – 40 = 1933 is also a relevant number to the span of the study.)

    “Rather brief” is therefore credibly a material misrepresentation. So is “ barely time for a generation turnover.“

    2] They did not fail for the larger span of history since the initial colonization . . .

    The numbers at the beginning of the period were generally consistent with expected incidence of ACT etc, but the material point is that they did not trend down as ALSO predicted y the models.

    Now, as this is a recent study [2006 pub date], one wishes for corroboration through other studies in Jamaica and elsewhere, but this is the first step to empirical disconfirmation. It is sufficiently strong a result that the authors make a clinical recommendation designed to foster voluntary action by the counselled to shift the trend.

    3] Lethality . . . is only part of the picture; there is also loss in overall reproductive fitness.

    Precisely, and that is what I pointed out in remarks above. Namely there is reason to believe that heterozygous and homozygous presence of S is harmful, but not sufficiently so to trigger an elimination from the population. Then when we incorporate the rest of the 700 horses, we see that the pictureisa log more complex than the just so story makes out. And that is what med students and the public need to know.

    4] we are not only trying to explain why the S-allele *persists*, but also why it persists at such *high frequencies* in those regions plagued with malaria as opposed to other regions.

    Here is what the peer reviewed study – I hope THIS link is stable — actually found:

    The high frequency of the sickle allele in some parts of Africa is understood to be a consequence of high malarial endemicity. One corollary of this is that the sickle allele frequency should be declining in populations of African ancestry that are no longer exposed to malaria. We have previously shown that there has been no change in sickle allele frequency in malaria-free Jamaica between two large-scale neonatal screening exercises conducted in 1973-1981 and 1995-2003 . . . We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction. Close agreement between predicted and observed values was only achieved by simulating a recent, marked increase in HbSS fitness. Thus, the “unexpected” persistence of the sickle allele in Jamaica may reflect the fact that the actual fitness among SS individuals is higher than that previously realized.

    Thus the study was, on a peer reviewed assessment basis, good enough to discriminate significant and non-significant trends over the span. The result was, within statistical significance, flat – and flat in a POST-MALARIA, overwhelmingly African derived population.

    Pausing . . .

    GEM of TKI

  87. Filter problems . . .

  88. Okay:

    I think I may get through some real brief points without details etc . . .

    1] Reproductive age range is about 12 – 45 in Ja so three plus generations and a span from 1930s on is in the screened population, not just 20 years, and one gen.

    2] The peer reviewed material was good enough to pick up a trend as predicted but the trend was not observed, and that in a post malaria pop that should have a down trend. Data was not sig different from flat, leading to suggested clinical interventions.

    3] The Atlanta brochure, from a reputable source, highlights that There are over 700 different types of hemoglobin. Many of these serve as a protection against Falciparum Malaria.

    4] That means that the number of horses in the race is a relevant issue, not just dragged in. Second to last beats last but does not necessarily come first!

    5] The same brochure warns SCT victims against atm press equiv to 8 k ft or more, and surgery. Those are not “rare” issues.

    So there is more than the just so story that med students should know about.

    GEM of TKI

  89. Got that through.

  90. great_ape:

    Yes, their predictions failed for the specific and rather brief period from the 70s to the 90s. They did not fail for the larger span of history since the initial colonization.

    I didn’t get the impression that a study was done from ‘colonization’ until the 1973-76 time period. How would they have ascertained the allele frequency of those original populations? And if their model showed that over a twenty year time period the S-allele didn’t decline quickly enough, then going back in time, starting with the 1973-76 levels, it seems logical that their model would have had to start with unusually high levels of the S-allele in order to arrive at the 1973 levels. As far as malaria, has the Caribbean been free of malaria for all these centuries, or for only the last 50 years or so? I’m not sure, but it might have been only with the advent of DDT that they were able to get rid of the mosquitoes.

    As to this particular paper, I think it’s a follow-up paper. My impression is that they took the numbers from the first time perios, applied a model, and calculated what the second time period numbers should be and found they were higher than the model predicted. Now, as a follow-up, in this paper they’re saying the discrepancy can be accounted for by assuming a higher SS fitness, which, as I said before, is ‘retrodicting’.

  91. “I didn’t get the impression that a study was done from ‘colonization’ until the 1973-76 time period. How would they have ascertained the allele frequency of those original populations?” –PaV

    I assume that this longer term study was done because they say that the early cohort’s data *is* consistent with the model. But what was the model of? I suspect they used the current allele statistics in the regions affected by malaria from which jamaican’s imigrated as the starting frequencies. Then studied the time period following. I will try to hunt down a pdf of the paper to confirm this.

  92. #1 “1] Reproductive age range is about 12 – 45 in Ja so three plus generations and a span from 1930s on is in the screened population, not just 20 years, and one gen.” –kf

    Matters not. In population genetics terms this is roughly a generation and a drop in the bucket of time. This is a technical issue so unless you have knowledge/training in this that can explain why what I was taught is wrong, I suggest you trust me here.

    #2. “and that in a post malaria pop that should have a down trend….”

    The first cohort did show a downward trend, presumably since the colonization. I admittedly don’t know much about Jamaican history, but I will try to get the pdf to verify my interpretation.

    #3 & 4. “The Atlanta brochure, from a reputable source, highlights that There are over 700 different types of hemoglobin. Many of these serve as a protection against Falciparum Malaria.”

    This is a good point, and *could* be relevant, depending on the frequencies of the alleles in question *and* whether or not they are alleles at the same gene locus. There are numerous variations across a population but many are very low frequencies. In terms of your horse race analogy, they are hamsters.

    5] The same brochure warns SCT victims against atm press equiv to 8 k ft or more, and surgery. Those are not “rare” issues. –kf

    In most malaria-infected regions, I don’t imagine exposure to heights over 8000 feet is a frequent occurence. I could be wrong.

  93. PaV and GA:

    1] DDT made a big difference everywhere. So did major public health initiatives. Until that happened the Caribbean was a tropical deathtrap, not a tourist paradise. (I recall the plaques in St Michael’s Cathedral B’dos to the UK regiments stationed there — they tended to lose a LOT even when no war was on. Disease.]

    2] Given the range of reproductive age, ~ 12 – 45, the 20 year apart samples capture 3 + generations of births. [Here I am looking at both mothers and their infants.] That takes us back to the 1930s, which I think we can reasonably accept was malarial, pending more specific data. [Guyana still is in remote parts, to my knowledge.]

    3] Slave average life expectancy on arrival was ~ 5 y in C18, and the trade was stopped after about 1807 – 8. So the genetic base of the population is about 250 years old on the outside. 70 years is almost 1/3 of that. (Slaves did not come from any one area.)

    4] Sickle Cell is a significant and fairly common public health problem in Ja, and has long been so. So the incidence is on the evidence, high.

    5] The key point from the first paper was that it has been flat between the 70′s-80s and the 90s-00s, not falling as expected from the same model that matched the level in the first case. This one suggests a mechanism for the unexpected result.

    That mechanism and the associated context are where the challenges lie, and they point out that med students need a lot more than just the simple story.

    GEM of TKI

  94. GA:

    You may be right on how “generation” is defined in your field, but I am speaking from direct observation of my homeland, and as one whose work often requires analysis of empirical data.

    So, I must insist: given that the reproductive age is ~ 12 – 45, sadly on the lower end [part of Jamaica's major social problems], the samples will have naturally captured mothers born from the 1930′s on up to in the case of 2003, the edge of the 1990s, and will have also captured 3+ generations of births, up to 2003.

    If your technical defns cannot capture that factor they are based on wrong assumptions, period.

    If I were looking at trend lines on genetic patterns, I would be very interested in birth dates and generations, not just calendar time when the samples were taken, and in mothers not just their kids. So, I repeat, the samples from 1973 to 2003 inclusive credibly capture a range of births from the 1930s to the 2000′s, if infants and their mothers are in the screen [which is what would be clinically feasible in Jamaica].

    Thus, 3+ biological generations will be reflected in the data. Birth certificates and associated public data [there is but one central islandwide records office that compiles such from parishes, districts and hospitals] would allow a cross-check too. (With enough time and money, patterns in families could be traced . . . thanks to a gift of the Mormon church on genealogy stuff.)

    I would then split the samples by cohorts on birth timelines back to the 1930′s and correlate the genetic data with that, giving trendlines from the 1930s to the 2000s, maybe clumped decadally if the overall sample sizes are too small for annual or half decade clustering.

    Maybe you have a better answer but that is what looks reasonable to me. (Perhaps you can come up with a better technique that gives better data from these “large” samples, but I would accept nothing less than that much information squeezed out of the easily available and cross-checkable data.)

    Thus, I can see that the two snapshots credibly can capture trends from the time when Malaria would have likely been still a problem, up to the past half century in which it has for sure been off the PH picture.

    H’mm: I would want med students to know how to creatively squeeze information out of data too.

    Trust this helps

    GEM of TKI

  95. G-A –There are half-truths, blatant lies and statistricks. That’s because “while figgers don’t lie, liars can figger.” –kairosfocus . . . If I could make scientific arguments by simply repeatedly invoking aphorisms, it would make my professional life much simpler.

    G-A, he made an argument that took three posts and touched on numerous points. It’s neither fair nor accurate to say he’s arguing by aphorism.

  96. “G-A, he made an argument that took three posts and touched on numerous points. It’s neither fair nor accurate to say he’s arguing by aphorism.” –tribune

    I was responding to not only his use of aphorism but also to PaV’s above where he invoked Twain’s and others multiple times.

    I have, finally, gained access to the full paper that most of this discussion has been based on, and I’ll be sending another post discussing it this evening.

  97. kairosfocus,

    The relevant historical details concerning jamaica are much appreciated.

    I would like, for a moment, to take a step back and assess what is and is not in agreement here. I am beginning to feel as though we are “losing the forest for the trees” in this discussion and some perspective is necessary. If there is a point listed below which is not accepted, please indicate which.

    1. Frequencies of the S-allele, which causes sickle-cell anemia in its homozygous state are, as a matter of empirical fact, higher in malaria-prone regions than elsewhere. This is based on real genotype data, explains why African-americans have higher sickle-cell incidents, and I presume no one is questioning this fact here.

    2. Haldane proposed, well before it could be empirically tested, that the reason for the high frequency of the S-allele in these populations was due to a protective benefit against malaria provided by the S-allele in its homozygous state.

    3. More than one testable prediction can be made based on Haldane’s hypothesis. I detail them below:

    3a. There should be a decreased incidence of infection of malaria for SA carriers *and/or*
    a decreased incidence of mortality from malaria for SA carriers.

    3b. If a population in a malaria-endemic area were to relocate to a non-malaria region, the S-allele frequencies would decline. Restated, if the selective pressure preserving the S-allele were removed, the deleterious nature of the SS homozygote would cause the allele frequency of S to decline in the population.

    Tests of empirical evidence thus far:

    –> 3a. Consistent with this hypothesis, statistically, is the data PaV first linked to. All populations show a lower incidence of infection for S-containing genotypes than for non-S phenotypes.
    This represents a comfortably significant statistical effect, indicating *something* is going on between the variables of infection and genotype.

    –>3a (also). Other studies, referenced by HodorH, indicate that the genotype frequencies for those containing S are *higher* in adults than in children. This is straightforward and powerful evidence for the removal of non-S-allele containing individuals from the population in regions with endemic malaria.

    –3b. Concerning evidence for the allele decline after a population relocation, I will continue in another post below, as it is more complex.

    In sum, so far, several empirical tests have failed to exclude Haldane’s evolutionary (or microevolutionary) hypothesis based on predictions directly resulting from this hypothesis. This is a pretty good case so far. This is how science works.

  98. CORRECTION:
    “…provided by the S-allele in its homozygous state.” –me

    That should be heterozygous state…

  99. 3c.

    Okay, I have the details of the Hanchard et al. 2006 paper mentioned above.

    A few pertinent points:

    1. The allele frequency data for the study is from *neonatal* screening. As such, the 1973 cohort begins with individuals born in 1973 and ends with those born in 1981. The same applies to the 1995-2005 cohort.

    2. As I anticipated from the abstract, there are *two* components to the simulation. One is the prediction of allele frequency decline from

    3. They note in their methods, when discussing the fitness of genotypes modelled, that there is “good evidence that malarial mortality is the major contributor to differences in relative fitness between AA and AS where malaria is hyperendemic [Note: referencess Aido et al 2002 and Williams et al 2005]. So please note that the authors of this paper concede as established, one of the major points in contention here.

    3. When DDT was introduced to Jamaica is, by and large, irrelevant here. The authors show empirical data indicating that the mean death-rate for mortality via malaria from 1886-1927 was 40.8 per 100,000 in Jamaica. This is compared to mean rates of 500-1000 per 100,000 *currently* in the regions of Africa from which the populations came. In effect, the selection from malaria in Jamaica was negligible compared to Africa. This is a premise of the study. After the population relocated, the selective effect deriving from malaria was effectively removed.

    4. As I anticipated from the abstract, there are *two* components of the simulation. In the first component, allele frequencies of the *first* cohort 1973-1981 are compared to what they would be after 7 roughly 30-year generations since relocation of the population to Jamaica. Using a starting allele frequency based on the *current* allele frequencies found in the regions of origin in Africa. They ranged this parameter over a window that included multiple African regions contributing individuals. They then compared how the allele frequency was predicted to decline until the 1973-1981 period with the *actual* 1973-1981 genotype data. This part of the simulation was *consistent* with their model, indicating that the allele frequency fell *as expected* over the 7 generations until 1973-1981, just as Haldane’s hypothesis predicted it should when the positive benefit (malaria resistance) was nullified and only the negative consequences of the S-allele remained.

    In the *second* phase of the simulation, they looked at the last generation(s) from 1973-1981 thru 1995-2003. The further decline expected by their model during *this specific time period* was not observed. The dwell on this point considerably, as I detail below.

    [pause here...]

  100. Pardon my numerical numbering issues above…

    Continuing…

    The decline in the final generation in the simulation is greater than what is actually observed.

    They dwell on this point because it is the most incongruent with expectation, and they can get the most “newsworthy” mileage from it.
    In order to make the data *fit*, they have to increase the fitness of the S-allele during the *last* generation.

    They offer several possible explanations, and ultimately give many caveats, which is as it should be.

    #1. The model is wrong. (too simple, parameters off, etc.) They clearly do are not favorably inclined towards this explanation.

    #2. (my personal favorite) Better healthcare has rendered the S-allele less lethal in the modern period (post-1960 or so), reducing the rate of decline of S alleles in the last generation. On one interpretation, this is why their “retrodictive” increasing of the S-fitness parameter for the last generation(s) makes it more consistent with he data.

    –The authors don’t buy this explanation, however, because they don’t think sickle-cell lethality was *that* much improved in the modern era. They offer weak argument IMO, however, for why this should be believed. Specifically, they cite the incredible improvements in survival in the 70s thru the 90s as evidence things could *not* have been improving much in the 50s and 60s. This, to me, seems a poor reason to dismiss possibility #2 when no sickle-cell mortality data from the 1950s and 1960s were examined examined.

    [pause.]

  101. (continuing from above)

    #3 The authors suggest increased transmission of S-allele to offspring may be a contributing factor in the S-allele’s persistence and maintenance above and beyond malaria resistance. The effect has been noted in a previous Brazilian study. However, they note that this effect is a minor player. They suggest that *maybe*, with malaria out of the picture, this effect might manifest itself to bolster the S-allele further than it might be expected. This is followed by a disclaimer, indicating that the reviewers thought it was bologna and wished it removed or severely weakened.

    #4. Finally, they correctly suggest that since the S-allele frequency is not naturally falling as expected in recent years, it is a problem that may not take care of itself and more effort will be necessary to diagnose, genetically council couples, etc, to reduce sickle-cell incidence.

    In conclusion, I have two issues. 1) I question how much whether noise may have prevented them seeing a decline in S-frequency over the last generation (i.e. between the 1973/1983 and 1995/2003 cohorts). 2) Even if this is correct, I question why they so readily dismiss the possibility that the improved S-allele relative fitness that slowed the S-allele decline in the last generation was not attributable to health care and other modern improvements. Instead, they dwell on the notion that it is due to some inexplicable new S-allele advantage. Maybe they thought they’d get more funding that way? I couldn’t say.

    In either case, the majority of the timeline is *consistent* with Haldane’s prediction. Thus it can be added two the multiple other predictions that held up. It is only the last generation period that breaks the pattern and, I believe, there is good reason to believe this is because of modern innovation that mitigated the lethality of the S-allele, thereby slowing its decline.

    I hope this has brought some clarity.

  102. ““Rather brief” is therefore credibly a material misrepresentation. So is “ barely time for a generation turnover.“” –kairosfocus

    We are coming, as you recognized, from two very different perspectives. Models of the sort they are employing typically use *non-overlapping* generations. (I checked, they are indeed simulating 9 non-overlapping generations since the first slaves were transported) That is, each 20-30yrs span represents a single generation turnover. This, of course, is a gross over-simplification of reality. But overlapping generations are a nightmare to model and, from what I understand, non-overlapping generations capture the demographic picture adequately *most* of the time. So when I say that 1973-2005 is a drop in the bucket of time, I mean: a)than it only represents 1-2 *sampling* events in the model. Thus there are only 1-2 events for selection to do its thing. I know that in most allele frequency models, across that timespan, you might even see the exact *opposite* trend compared to what is occurring overall. Their model shows a deterministic trend downwards. But the *empirical* datapoint could be drifting erratically over the same period because if 2 sampling events are what’s going on in model-world, and if model-world captures real-world reasonably well, then two sampling events doesn’t leave much room to smooth out random noisy bumps in allele frequencies.

    b)These sorts of allele frequency simulations are typically done over 10s of 1000s of years (if not longer) so that is why I find it a bit odd for them to be thinking on such short timescales. In particular, I find it odd for them to be so comfortable with modeling such short timescales (in human generations; bacteria and drosophila are another story). I think the authors were both creative and bold to try testing the hypothesis this way, I just think they should have been far more skeptical about what they could reasonably determine from the period of 1973-2005. Frankly, if I were them, I’d just be incredibly grateful that I saw the expected decline from the colonization to the 1973-1983 cohort. Yet hats off to them if they have indeed noticed that the decline is flattening out. Though I disagree with their interpretation of *why* it might be flattening out, it is clear to me that more counseling and other intervention is needed if their 1973 thru 2005 results hold up to further scrutiny.

  103. GA, PaV and others:

    Okay. Seems that the first post in the sequence that was blocked yesterday made it overnight . . . [I didn't try to post the other two parts]

    Also, appreciation GA for pulling the paper [I do not currently have access to EBSCO host etc]. The evident use of infants only, in a context where mothers etc to the 1930′s would have naturally been available, is probably a reflection of funding constraints on the health service – a pity, but a reality. [NB: sufficient of cohorts to the 1920's are still available among the aged to get some indications for a multidecadal trend line, but this is of course a clock ticking away at this point.

    Your point on the relatively low incidence of reported Malaria deaths in Jamaica is also taken on board, though a parish by parish breakdown may have revealed a key pattern – there are several relatively large scale swampy, low-lying areas [Near the Hellshire region, the Black River Morass, Parts of Westmoreland stand out in my mind, and many areas that are not like that, so a more detailed breakdown may be helpful. But, they are using W African rates as proxies . . . easier and cheaper. BTW, there is an implication that low enough selection pressure has no observable effect.]

    I also note that even with screening of infants, if we are looking at a trend line that is visible on 20 years span, selecting infants based on maternal age at birth in annual cohorts is going to reflect trends too: kids born to 15 yo’s vs 45 yo’s. Birth certificates in Jamaica (thus a fortiori routinely available data in hospitals and clinics) will have that information. [Note here your citing of HH on how the trends on S are claimed to be visible adult/child in one generation span.] So, there are credible ways to do follow up work on those trend lines. But, money is a constraint again doubtless.

    Now, on key points to be followed up:

    1] Going back on “rare”

    The Atlanta fact sheet [I am suspecting h-links on the filter problem, so kindly look back at no 65] actually warned SA folks as follows:

    Persons who have Sickle Cell Trait should be aware of the following:

    1] They are advised against flying in unpressurized aircraft at an altitude above 8,000 feet
    2] They are advised against going deep-sea diving or high mountain climbing, due to the possibility of sickling of the red blood cells
    3] If they should see blood in his/her urine (hematuria), he/she should see a doctor immediately
    4] Persons should let their anesthesiologist and doctors know their condition it they need to have any type of surgery

    There are over 700 different types of hemoglobin. Many of these serve as a protection against Falciparum Malaria. They are not contagious and can only be passed from parent to child. It is important for you to know your hemoglobin type.

    In short, even brief exposure to relatively high altitudes is problematic. That would hold for mot only flying, but going to market in the hills to sell produce, etc. [In British territories, the wealthy tended to live in seaport towns, in Spanish ones, they often preferred to live in higher cooler –- relatively Malaria-free – areas].

    Surgery etc are also not very rare, for public health and pop trend concerns. [A seriously deleterious or deadly condition is sufficient of a bad outcome, that even for lowish probabilities, one needs to be warned and cautious.]

    Third, we are evidently in a multi-horse race, in a context where Malaria is said to be the major selection pressure on the human genome in recent times. That raises the underlying point PaV and I have made, that this is not a two or three horse race, so if pop dynamics have ex hypothesi had time and capacity to play out to select for S, it would also have had time to select for OTHER protective traits that are not so damaging. And, that means the genetic race should have been won by something else, if protective effect is the critical driving force.

    2] Thus . . .

    it seems to me PaV has long since [also relative to the abstract] made the key take-home [or, at least take-to clinic] lesson points above, in 80:

    [1] when they compared actual frequencies between two different neo-natal screenings, which took place twenty years apart, that the S-allele did not decrease in frequency, and that the only way that they could get their model’s predicted decrease to match the non-significant decrease of S-allele frequency was by assigning a “recent” (meaning ‘twenty years later’, not in the original testing) higher fitness value to the HbSS homozygotes. . . . .

    [2] given that there are so many different types of ‘heterozygotes’ for hemoglobin—sickle cell, thalassemia, dust antigen, HLA, etc., etc.—the more sensible interpretation is not that ALL of these confer any kind of ‘heterozygote advantage’, but simply that when it comes to hemoglobin its complex structure permits a number of heterozygotes appearing without lethality. IOW, the recessive homozygotes are not sufficiently lethal as to eliminate them from a population entirely, so there remains a kind of ‘residual’ allele frequency.

    Pausing . . .

  104. Continuing . . .

    The above got through, partial confirming of h-link hyp . ..

    3] Moreover . . .

    Given the young age at first birth in a lot of Jamaica’s population, the 20-30 year separation of the two screenings is also a pretty good proxy for your adult/child decline in frequency of S, in no 97, 3a. So, the flatness trend observed is probably not insignificant, even across the span of only one generation. [I am still pointing to the potential of sampling mothers and their children and using date of mother's birth . . .]

    So, on looking at your 100, the key point seems to be a bit of a split on the narrower point: S frequency does decline over 7 or so gens, but stabilises over the last 1 – 2. Note too, how they are coming out on the age of Ja’s pop base about where I was: 30 * 9 = 270 y.

    And, I note that mortality from SCA etc is STILL a problem.

    The 50′s – 60′s were an early transitional era in Jamaica’s health care and infrastructure in general, and on general familiarity with Jamaica’s development and health care picture, I am very willing to accept the implication of the authors that the bulk of improvement in both care and resulting mortality statistics due to that etc happened 70′s – 80′s, based on patterns of infrastructure development in the 50′s to early 70′s and the sharp rise in penetration of personnel over the later span [especially in the 70's – early 80's], tied to development of education systems and policies to man the infrastructure and carry forward the many health and development projects, some of which my Mom worked on in the Bureau of Health Education late 60′s – mid 70′s.

    It is of course the cohort of the 50′s – 60′s whose births would be showing up in the 70′s – 80′s, and this second cohort whose children would be showing up in the 90′s to 00′s. Thus, the adult generation, child generation downward trend effect should be evident in the samples. The authors therefore properly highlight the observed fact that it does not.

    4] On generations, samples and noise:

    You have accepted that the non-overlapping generation approximation is a useful heuristic. That fits with the point that maternal birthdate is relevant as I noted earlier. But, cost is always a factor that leads to simplification in research work.

    A range of about 15 – 45 years does average to about 30 years, and in my own family’s direct line, 6 generations carries me back roughly to turn of C19, so the approximation is valid for my family on average. [But, there are several cases of multigenerational teen mothers in my [fairly large!] wider family. So, at death, one of my grandfathers had Great-Great grandchildren at 95; 5 generations born in 95 years is less than 20 years average.]

    I am not very impressed by “noise” claims in a context of LARGE samples, taken over half a decade or more. Jamaica has probably 10E4 or better births per year.

    If there is a trend line, and the model [however proxy-riddled and crude] has been more or less validated [across 7 gens], in a context where there is enough sensitivity in the sampling processes to pick up S- frequency falls between adults and children in a population, then there is enough data to see the onward trend if there is one. The observation is, no, there is no trend statistically significantly different from flat. [And, they are probably well beyond the point where the law of large numbers kicks in.]

    So, subject to further data, we are looking at . . .

    [Provisional] Conclusions:

    1] There is reason to believe that there are many varieties of haemoglobin, up to 700. A significant fraction of these are believed to be protective against Malaria.

    2] Of these, sickle cell trait and anaemia are believed to be somewhat protective [the statistical debate between Pav and GA shows there is some dispute here and there may be interfering factors].

    3] Supportive of the protectiveness hypothesis, is the observed/inferred declining trends in Jamaica etc, but with asterisks on observed flatness in this case.

    4] However, as GA has just pointed out, the trend lines are best seen in light of 1000′s of gens. That raises the immediate point that the selective pressure on humanity from malaria may not be as long-term as has been imagined, though there is reason to believe that Malaria has been around as long as we have been around swampy regions. (Indeed, across such a long term span, other variants of haemoglobin would be more likely to win the race . . . YEC advocates may therefore want to follow up this one as a test of just how long humans have been around . . . )

    5] More seriously, the case raises significant questions on the testability and confirmed status of NDT in yet another highlighted example of claimed microevolution. Unfortunately, this is a familiar pattern, from Finch’s beaks to peppered moths and so on . . .SCOTCH VERDICT: Case not proven

    6] On the underlying problem, NDT-driven Macroevolution, we have not even got close to the 500-bit minimum threshold for generating genetic information from “lucky noise” to begin to test that we have empirical reason to believe that RM + NS can create body plan level biodiversity, including credibly irreducibly complex systems. E.g., not only haemoglobin but the other molecules, then the cell types, tissues and organs and control systems required for animals with a blood based circulatory system. The gaps dominate the evidence in short. Of course, across chance, necessity and agency we know that agency routinely generates such functionally specified, complex and often fine tuned, information ands systems. So, inference to design is a very live issue.

    GA, that brings us back to the point where we were previously, esp since there has been no onward facilitation by was it Patrick . . .

    GEM of TKI

  105. Still having a problem . . .

    GEM

  106. Concluding

    [Provisional] Conclusions:

    1] There is reason to believe that there are many varieties of haemoglobin, up to 700. A significant fraction of these are believed to be protective against Malaria.

    2] Of these, sickle cell trait and anaemia are believed to be somewhat protective [the statistical debate between Pav and GA shows there is some dispute here and there may be interfering factors].

    3] Supportive of the protectiveness hypothesis, is the observed/inferred declining trends in Jamaica etc, but with asterisks on observed flatness in this case.

    4] However, as GA has just pointed out, the trend lines are best seen in light of 1000′s of gens. That raises the immediate point that the selective pressure on humanity from malaria may not be as long-term as has been imagined, though there is reason to believe that Malaria has been around as long as we have been around swampy regions. (Indeed, across such a long term span, other variants of haemoglobin would be more likely to win the race . . . YEC advocates may therefore want to follow up this one as a test of just how long humans have been around . . . )

    5] More seriously, the case raises significant questions on the testability and confirmed status of NDT in yet another highlighted example of claimed microevolution. Unfortunately, this is a familiar pattern, from Finch’s beaks to peppered moths and so on . . .SCOTCH VERDICT: Case not proven

    6] On the underlying problem, NDT-driven Macroevolution, we have not even got close to the 500-bit minimum threshold for generating genetic information from “lucky noise” to begin to test that we have empirical reason to believe that RM + NS can create body plan level biodiversity, including credibly irreducibly complex systems. E.g., not only haemoglobin but the other molecules, then the cell types, tissues and organs and control systems required for animals with a blood based circulatory system. The gaps dominate the evidence in short. Of course, across chance, necessity and agency we know that agency routinely generates such functionally specified, complex and often fine tuned, information ands systems. So, inference to design is a very live issue.

    GA, that brings us back to the point where we were previously, esp since there has been no onward facilitation by was it Patrick . . .

    GEM of TKI

  107. I believe we have indeed returned to a similar impass as before, but I believe an objective observer would have no difficulty judging the matter.

    Finally, some remarks on your concluding points.

    1. 700 horses. Without knowing more about these 699 allelic competitors, such as frequency, fitness, degree of malaria resistance conferred, etc, it is impossible to assess if or how well they would compete with the S-allele.

    2. Let us be perfectly clear here; there was no *statistical* debate between myself and PaV. I actually calculated the statistics; PaV used no formal analysis whatsoever other than stating his impression of the numbers. That is not science or anything resembling it.

    3] “Supportive of the protectiveness hypothesis, is the observed/inferred declining trends in Jamaica etc, but with asterisks on observed flatness in this case.”

    3. Please distinguish *where* the curve was flat from where the prediction fit, which is the majority of the time period in question >= 75%.

    4. I fail to see the logic of #4. Perhaps you could succintly restate it.

    5. I feel #5, given 1-3 and possibly 5, is an assertion that is not consistent with the data presented.

    6. Well outside the bounds of this discussion, so I won’t comment.

    In sum, from my perspective, I think only your 700 horses argument has potential, but much information and development would be necessary to give enough substance to it to warrant conclusion #5.

  108. On point 5 above, that should read given 1-3 and possibly 4.

  109. Natural selection in action in malaria though it is not Darwinian but Intelligent Design micro-evolution

    http://news.wired.com/dynamic/.....TE=DEFAULT

  110. Hi all,

    sorry to intrude at the end of such an interesting discussion, but I have been away for a few days, so I had to catch up…

    I am intrigued by the subject of microevolution, because, although I could well not have problems with it in principle, I would like to understand better what is meant by the term. Indeed, I feel that I could share some of PaV’s problems with microevolutionary scenarios, but I have to make some important distinctions.

    I have read the previous posts about S haemoglobin and malaria with interest, but I don’t understand well where is the problem. In general, I can agree with most of Great Ape’s summaries in posts 97 and followings, in the sense that:

    a) I can accept that there is a statistically significant correlation between the S trait and malaria infection, both geographically and as incidence data, although it can be true that further studies can be useful to confirm better the correlation itself.

    b) It seems, also according to the data cited by kairosfocus, that the interpretation of such a correlation as evidence of an “evolutionary” persistence of the S trait due to selective pressure is less obvious. In other words, the correlation exists, but the causal model proposed by Haldane is not necessarily the best explanation. I want to mention here that a statistical correlation is no evidence, in itself, of a specific causal model. The choice of the model and its empirical evaluation is a methodological problem, and statistics can only provide numerical data in support of the inferences made by the researchers. So, if the negative correlation between the prevalence of the S trait and the incidence of malaria can be evidence of a protective effect of the S trait in malaria infection, it is not necessarily evidence of a selective effect of malaria on the S trait. Indeed, the cited discordances in the Jamaica study are against this second inference (that is, Haldane’s theory).

    c) Anyway, I can accept Haldane’s theory without problems, if it will be supported by facts. Even if it were so, I still don’t understand well in what sense it should be considered evidence of “microevolution”.

    I will try to explain better this last point. It seems to me that we can comment on 3 important models which are often cited by Darwinists as examples of “microevolution”, or even of “macroevolution”. Part of this discussion was already done with both great ape and kairosfocus in another thread. The 3 models are:

    1) Bacterial resistance to antibiotics, in the (minor) form due to point mutations which modify single structures which are the target of the antibiotic.

    2) Mosquito resistance to OP pesticides due to point mutations in Ace1 gene.

    3) Human (partial) resistance to malaria due to point mutations in the beta haemoglobin chain.

    As you can see, the 3 models are very similar, for at least three different reasons:

    a) A point mutation is the cause of the three conditions.

    b) The mutation is always a variation in the sense of a “loss of information”, with some more or less severe “fitness cost”. The cost is more difficult to evaluate in bacterial resistance (also because there are very different targets involved), has been shown in mosquito mutations, and is obvious in the human S trait. In other word, in all three models we are dealing with something which can be correctly called a genetic “disease”, and more specifically a mendelian disease (point mutation in a gene).

    c) The “advantage” provided by the mutation is always related to the loss of information, which “interferes” with a specific, “intelligent” aggression from some agent (antibiotics, pesticides, plasmodia). In other words, the “disease” provides an indirect “escape” from some enemy, because it changes (in a degenerative sense) the target of the aggression. This is clear in all three conditions.

    Let’s discuss better the S haemoglobin – malaria model, just to slow more in detail my points. S haemoglobin is a variant haemoglobin with a single aminoacid substitution in the beta chain. While many single aminoacid substitutions in the haemoglobin chain do not interfere with the protein function, that is not the case with S haemoglobin. S haemoglobin, indeed, is a very unstable molecule, and it tends to precipitate inside the red blood cell (where the haemoglobin concentration is extremely high), especially in conditions of hypoxia. The instability of the molecule is the cause of the severe disease in the homozygous state, and of the mild disease in the heterozygous state, where the quantity of S haemoglobin is lower, because the other allele is normal. So, the point is: S haemoglobin is a “severely less functional” molecule, it precipitates in the red blood cell and is a cause of the sickle deformation of the cell and of its precocious death, with all the pathological consequences. So, you can see that in no way S haemoglobin can be considered an “evolution” of A haemoglobin. That’s exactly the reason why it confers some protection from malaria infection: although the specific mechanism is not well known, indeed it can easily be argued that the presence of the “diseased” S haemoglobin in the red blood cell is a handicap fro the intracellular cycle of the malaria parasite. In other words, S haemoglobin is so much “less functional” that even parasites do not tolerate it!

    So, even if it were true that the S trait has been “selected” by the pressure of the malaria infection, where is the “microevolution”? At best, we can speak of “facilitation in persistence of a disease because of a second, competing disease”. What has evolved? What has been selected” Where is the “new information”.
    Please, note that even if we considered these models as examples of evolution, it would be just “minimal” evolution: always and only point mutations, single bit variations. Obviously, CSI or IC are not at stake here.

    But even so, I have real difficulties to consider them as examples of “minimal” evolution. To me, they are just disease, like the many other mendelian diseases which we must daily diagnose and, to some extent, cure. Do you really mean that carriers of recessive diseases such as drepanocytosis or thalassemia are the beginning of a new species, or even of a significant positive variation in our species? Why?

    Please, someone from the Darwinist group (great ape, listen) show me a single case of a really “positive” acquisition, even from a point mutation, and then we can start speaking of minimal or microevolution.
    And then, show me a model of positive acquisition of function through many (let’s say 100) selectable single bit substitutions, and then we can start speaking of macroevolution. And I mean “start”.
    Otherwise, we shall always remain at the level of unsupported fantasies…

  111. great_ape:
    “1. Frequencies of the S-allele, which causes sickle-cell anemia in its homozygous state are, as a matter of empirical fact, higher in malaria-prone regions than elsewhere. This is based on real genotype data, explains why African-americans have higher sickle-cell incidents, and I presume no one is questioning this fact here.”

    Yes, I’m questioning it. Where is the data? How well documented is it?

    great_ape: “3. More than one testable prediction can be made based on Haldane’s hypothesis. I detail them below:

    3a. There should be a decreased incidence of infection of malaria for SA carriers *and/or*
    a decreased incidence of mortality from malaria for SA carriers.”

    Why would sickle-cell anemia prevent malaria? Mosquitos deposit the parasite in the blood system; only a small percentage of the RBC are affected, which the body is constantly attacking and destroying, leaving perfectly healthy RBCs to be infected. Further, if you want to say that the “fact” that the S-allele frequencyis higher in adults than in children, suggesting that this is a “slam dunk” for heterozygote advantage, then understand that at the same time it completely dismantles the case for the S-allele preventing infection. You can’t have your cake and eat it too. Oops, another aphorism. Please excuse me.

    great_ape:
    “3. They note in their methods, when discussing the fitness of genotypes modelled, that there is “good evidence that malarial mortality is the major contributor to differences in relative fitness between AA and AS where malaria is hyperendemic [Note: referencess Aido et al 2002 and Williams et al 2005]. So please note that the authors of this paper concede as established, one of the major points in contention here.”

    But “good evidence” is not the same as “convincing evidence”, or even “proof”. Maybe it’s just a “hunch” that they have, like Haldane.

    G-A: “Using a starting allele frequency based on the *current* allele frequencies found in the regions of origin in Africa. They ranged this parameter over a window that included multiple African regions contributing individuals. ”

    So, they were guessing.

    G-A “This part of the simulation was *consistent* with their model, indicating that the allele frequency fell *as expected* over the 7 generations until 1973-1981, just as Haldane’s hypothesis predicted it should when the positive benefit (malaria resistance) was nullified and only the negative consequences of the S-allele remained.”

    How do you know that we’re dealing with “malarial resistance”? Are you guessing?

    G-A “In the *second* phase of the simulation, they looked at the last generation(s) from 1973-1981 thru 1995-2003. The further decline expected by their model during *this specific time period* was not observed.”

    Isn’t this interesting: when they’re guessing what the allele frequencies were, and how fast they might decline, the model works. Then when you have two REAL points in time, all of a sudden the model DOESN’T work. Very interesting.

    G-A “#4. Finally, they correctly suggest that since the S-allele frequency is not naturally falling as expected in recent years, it is a problem that may not take care of itself and more effort will be necessary to diagnose, genetically council couples, etc, to reduce sickle-cell incidence.”

    For me, this is the crux of the matter. If, indeed, the S-allele, because of its heterozygote advantage is being “selected” for, then absent the environmental element which renders the heterozgyote more “fit”, the allele, since it is so “unfit” in the homozygote, should disappear. But, we don’t see that. There appears to be a “bottom” which, in the absence of data, could have been around for a long time. Now, on the other hand, if the S-allele simply makes malaria less virulent—which, indeed, appears to be the case—then, in the presence of epidemic levels of malaria more of the S-alleles would survive and S-allele frequency would rise, and, in its absence, the frequency would fall. Now, I don’t consider this NS, but simple stochastic genetic behavior. What we have is a “defective” hemoglobin molecule that has, as an unintended consequence, some remedial effect in the case of malaria. If, indeed, this were NS at work, then in malaria free areas, over the long run, this allele should vanish—IOW, NS would “punish” it. But you see, this study strongly suggests this isn’t the case. The Hardy-Weinberg Law seems to be taking over.

    G-A “Instead, they dwell on the notion that it is due to some inexplicable new S-allele advantage. Maybe they thought they’d get more funding that way? I couldn’t say.”

    The answer as to why they do this is quite simple, really: they’re Darwinists, and that’s what Darwinists do, they dream up possibilities–emphasis on the dream part.

    G-A “In either case, the majority of the timeline is *consistent* with Haldane’s prediction. Thus it can be added two the multiple other predictions that held up. It is only the last generation period that breaks the pattern and, I believe, there is good reason to believe this is because of modern innovation that mitigated the lethality of the S-allele, thereby slowing its decline.”

    What “predictions that held up”? Isn’t that what we’re discussing? You propose that the data from Africa on infection rates supports Haldane’s hypothesis, even when the largest sample shows an almost indistinguishable difference in infection rates between S-allele carriers and non-S carriers, and even when the supposed studies showing that there is a big difference between S-allele levels in children and in adults contradicts this hypothesis (and where are these studies exactly? Have we seen them?) Now you want to say that the study your quoting from supports this theory because of a supposed decline in S-allele carriers ( I say “supposed” since we don’t know if the S-allele levels declined in the first generation that African blacks were in malaria free Jamaica, or whether it was spread out over all seven, or, if, in fact, the Africans that came over had low S-allele levels in the first place. This study can’t ferret any of that out), but the only part of the study that compares real, known data to other real, known data, doesn’t conform to their model—which, I’m sure, is based on “Haldane’s hypothesis”. So, it is premature (and perhaps presumptous)on your part to conclude that there’s ‘even more evidence’ for Haldane’s “guess”.

    What’s very clear to me, and should be very clear to all, is that, once again, what Darwinists proclaim as “fact”, when looked at in detail, looks suspect, if not wrong.

    G-A “So when I say that 1973-2005 is a drop in the bucket of time, I mean: a)than it only represents 1-2 *sampling* events in the model. Thus there are only 1-2 events for selection to do its thing. I know that in most allele frequency models, across that timespan, you might even see the exact *opposite* trend compared to what is occurring overall.”

    But you see, there’s this problem. If they have “modeled” this population for 9 generations, and the model “fits” the data from the first cohort, then, if you’ve been correct for 9 generations, why would you be wrong all of a sudden for the very next, “single” generation? Again, we’re dealing with real, known data, and that real, known data doesn’t want to “fit” the model. You, as well as the authors, don’t think the model’s wrong. I happen to think it is (as I’ve stated above). Time will tell.

    G-A “Frankly, if I were them, I’d just be incredibly grateful that I saw the expected decline from the colonization to the 1973-1983 cohort.”

    How could it possibly be wrong? All the numbers are assumed! If it doesn’t work, assume new numbers until it “fits”. But, that said, I, too, am grateful for their work because at least now we will have real, longitudinal data to work with instead of assumption heaped upon assumption.

  112. Comment in filter . . .

  113. H’mm:

    Let n me at least try to get though this much quickly [also, testing the filter]:

    ___________

    4] distinguish *where* the curve was flat from where the prediction fit, which is the majority of the time period in question >= 75%.

    I am not so sure the model fitted the first 3/4s so much as much as it was calibrated relative to the assumptions of decline and the observations in the earlier study, with the decline thesis being assumed and seen as “verified” by the low incidence of S. I find this seems to be hinted at in the following phrasing in the abstract:

    To evaluate the determinants of, and derive expected values for, sickle allele frequency in Jamaica, local empirical data were used to estimate the parameters of deterministic models of allele frequency decline. We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction. Close agreement between predicted and observed values was only achieved by simulating a recent, marked increase in HbSS fitness.

    The onward projection was that the trend should more or less continue, but: the “unexpected” persistence of the sickle allele in Jamaica may reflect the fact that the actual fitness among SS individuals is higher than that previously realized. In turn, that fits in more with PaVs thought that the basic point is that variants that are sufficiently non-lethal [“survival of the fittest”] will be retained in the pop. You will note that in my last comment I split the difference, seeing that both theses may have a point: some protective effect, some residual naturally persistent survival level. I am also asking why is there not another horse that has won the race, if it has been ongoing for as long as the evo models of human origins assert.

    _____________

    GEM of TKI

  114. gpuccio:

    c) The “advantage” provided by the mutation is always related to the loss of information, which “interferes” with a specific, “intelligent” aggression from some agent (antibiotics, pesticides, plasmodia). In other words, the “disease” provides an indirect “escape” from some enemy, because it changes (in a degenerative sense) the target of the aggression. This is clear in all three conditions.

  115. Much has been written since my last post; I will try to respond, where possible, in the next day or so.

    But one thing quickly for gpuccio:

    “But even so, I have real difficulties to consider them as examples of “minimal” evolution. ” –gpuccio

    In this case, I think your issue is largely semantic. For myself, and many others, evolution in its most straight-forward sense begins at the level of population genetics, where a beneficial trait increases in frequency and ultimately fixes in the population. What began as rare becomes characteristic. Thus selection at the level of the population is evolution, or microevolution. The S-allele case discussed above has a twist because, if Haldane is correct, the negative effects of the homozygote S genotype prevent the S-allele from fixing. However, the forces at work are, at heart, that which Darwin outlined as the basic algorithm of natural selection. Which is why I think natural selection/microevolution is appropriate nomenclature.

  116. I’ll be waiting.

  117. Just a brief note and request for a favor. There are IMO several things wrong with PaV’s recent (longish) post above. There are very basic problems there that transcend the evolution vs. ID debate. They deal with scientific methodology and basic scientific literacy. I feel it shouldn’t be my sole responsibility to address each issue in detail, and it would be very fruitful for everyone if folks other than myself corrected some of the more egregious statements. Just because he ultimately shares the same position as you doesn’t mean you can’t challenge individual assertions. If there were a darwinist/evolutionist on this thread, I’d feel free–if not compelled–to criticize anything they posted that I believed incorrect.

  118. great_ape:

    I am always available to discuss serenely scientific problems, especially if pertaining to method. I have read the discussions between you and PaV, and I have already tried to sum up my point of view in my previous post. I deeply respect both PaV and you, and with both of you I have had more than one satisfactory exchange. That does not imply that I necessarily agree with anybody else’s point of view. For instance, although I can certainly share many of PaV’s arguments, I do believe in statistical methodology, provided it is used well, while, if I understand well, he seems to be more skeptical about that subject. Indeed, scientific methodology and statistics are one of my main interests.
    Regarding your discussions about the S trait, I must confess that I was not very interested in the details, for two reasons: first, I have not checked all the available data source; second, my impression was that the object of the discussion was essentially irrelevant, because, as I have already stated in my previous post, the S trait, in my opinion, can tell us nothing about microevolution.
    Anyway, I will try to state again my tentative ideas on the subject, which consists of two separate hypotheses:

    a) S trait carriers are more rarely infected by malaria. As I have said, I tend to believe that, but I have not chacked all the available data, and I am not particularly motivated to do that. I have done a quick calculation in excel on the numbers you linked about africa, taken as a whole, performing a simple chi square, and the resulting p for the null hypothesis was very low, so I am statistically satisfied, but I have no idea if the data are methodologically correct, so I cannot give a final judgement. Anyway, let us say that we have a very likely association between the S trait condition and some protection from malaria infection, and we have also a possible explanatory model (a defective hemoglobin could well be a habdicap for the intracellular growth of the plasmodium). So, on this point I would tentatively agree with great ape, both in method and conclusions.

    b) S trait has persisted in time because of the selective pressure due to its positive effect on malaria infection risk. This second hypothesis is in no way a logical consequence of the first one, and has to be proved empirically. I am not sure we have evidence of it, although in principle I have no difficulty in admitting it could be true. But many models could be true, but are not true. Apart from the lack of strict evidence (but, again, I have not checked all the available data), I have some basic problems with “easy” explanations like that, which in part are similar to reservations expressed by PaV. One important factor is that we have many potential variables, in red blood cell phenotype and metabolism, which seem to influence susceptibility to malaria infection, and therefore the model is potentially very complex. A second important consideration is that we have a lot of other mendelian diseases which have persisted for very long times without any “microevolutionary” model to explain them. As far as I know, our understanding of the intrinsic mechanisms of generation and persistence of genetic diseases is still very superficial.

    So, to some up: with all the reservations due to my incomplete knowledge of the subject, my idea is that a) is probably true, while b) could be true, but is only a tentative hypothesis.

    But the important thing is that anyway b), even if it were true, is not an example of microevolution. You say that my issue is mainly semantic. Well, it is. Semantic is very important for me, because bas semantic is often a screen for bad thinking, and for hidden lies, like natural selections which don’t “select” anything, or micorevolutions which don’t “evolve” anything.

    So, lacking a clear definition of what microevolution should be, I will start form the following definition (from answers.com):

    “Microevolution = Evolution resulting from a succession of relatively small genetic variations that often cause the formation of new subspecies.”

    Not very satisfying, indeed. So I will add your definition, which I like more:

    “For myself, and many others, evolution in its most straight-forward sense begins at the level of population genetics, where a beneficial trait increases in frequency and ultimately fixes in the population”

    Well, I will only comment that, according to those definitions, and especially yours, the S trait model is not an example of microevolution. The reasons:

    1)Here we have no beneficial trait. As I have already said, S hemoglobin can in no way be considered a beneficial trait. It is a poorly functional molecule, indeed a “toxic” variant of normal hemoglobin (it is unstable, it precipitates in the RBC causing its deformation and ultimate death). In the homozygous form, it is quite incompatible with a long and healthy life, and in its heterozygous form it can be tolerated only because the normal allele can synthesize normal A hemoglobin, and is anyway a cause of problems and symptoms for the carrier.

    2) The trai, anyway, has never become “fixed” in the population (thanks God!), in the sense of increasing its frequency and becoming the main allele. Even after a very long time, and even in countries where malaria infection is endemic, the S trait is a minor variation: it just survives, like many other mendelian diseases; it causes much suffering, but, luckily, it has created no new subspecies.

    So, if we want to discuss microevolution (and I am really intersted in that) I think you (I mean great ape, or anyone volunteering) shoud provide, in my opinion, some other, pertinent model.

  119. great_ape,

    I want to express my appreciation for your participation here having to defend your position while being outnumbered.

    However, PaV has a degree in biology from a secular school. I wouldn’t be too quick to label him as illiterate in science.

    I myself have said I think sickle-cell anemia might be fixed and was fully convinced of it before this thread began, so in a sense I had been favorable to your position on the issue.

    But in the course of this thread, I must concede I now think my initial position could be wrong. Fixing a mutation that is inherently deleterious is not easy. The pluses have to outweigh the negatives, and until that can be quantified, I would think all other factors being equal that a deleterious mutation would be selected against, not for.

    I do value your civil participation here and hope you continue to be a part of the UD community.

    But let’s be scientific about this. As a controlled reference environment (where there is no malaria) what is the selection force against sickle-cell anemia? That will give how much selection force for sickle-cell anemia must be provided in a malaria environment. What would be the conditions that would be needed to make a definitive estimate? I don’t think the definitions of controlled conditions and sufficient sampling size have even been defined.

    I would presume, the weaker the selection force, the larger the sample size is needed to establish the selection force exists to some level of confidence. Is that correct?

    Salvador

  120. By the way, was this other paper ever cited in the above discussion?

    Hum Biol. 2001 Aug;73(4):583-6.

    Protection afforded by sickle-cell trait (Hb AS): what happens when malarial selection pressures are alleviated?

    Hoff C, Thorneycroft I, Wilson F, Williams-Murphy M.

    Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, USA.

    Abstarct:

    A study of reproductive outcome in Mobile, AL was conducted among a large maternal cohort with sickle-cell disease (Hb SS), sickle-cell trait (Hb AS), and no hemoglobinopathies (Hb AA). It was found that mean gravidity and live births among Hb AS women were significantly higher than among Hb AA women. These findings were surprising since it is generally held that once malarial pressure is alleviated, any reproductive advantage that might be conferred by Hb AS would disappear and fertility levels would reach levels similar to or slightly less than that of Hb AA women. A search of the literature was subsequently conducted and a large cohort study of an African-derived population was found in the United Kingdom. Results from this study also showed that parity was significantly higher among Hb AS women compared to Hb AA women. If survivorship is similar among Hb AS and Hb SS women, findings from these two studies raise doubts whether directional selection is occurring against the Rb S allele in nonmalarial environments. Balancing selection may still be occurring.

  121. Salvador,

    I’m not sure why you’d think the sickle-cell S-allele would necessarily fix or be lost rather than reaching an equilibrium with non-S (A). Recall that the presence of the S-allele in *two* separate genotypes SA and SS, one of which is beneficial and one of which is detrimental, yields a dynamic where the negative nature of the SS type pulls down hard on S frequencies, but the positive SA type causes it to increase. How fast the S-allele frequency is moving up or down depends on several factors, including the relative frequency of S. (The higher the S-allele frequency, the higher the probability of deleterious SS homozygotes, leading to more rapid removal of S) You can solve for an equilibrium here where neither allele fixes. This is more or less what I think is occurring in malaria endemic regions.

    As to your question about estimating the degree of selection against S-allele (without malaria’s influence), it’s a good question. This would indicate how strong the malaria benefit of S would need to be to counter its effects. I need to check further into the details.

    “I would presume, the weaker the selection force, the larger the sample size is needed to establish the selection force exists to some level of confidence. Is that correct?” –Salvador

    I’d restate it as “the weaker the selection force, the larger the population size needs to be to counter the influence of stochastic genetic drift, such that the allele would *deterministically* decrease in frequency (all else being equal.)”

  122. great_ape wrote:

    I’m not sure why you’d think the sickle-cell S-allele would necessarily fix or be lost rather than reaching an equilibrium with non-S (A).

    You are correct. I mis-spoke. “Fixed” is the inccorect term. Thanks.

    Sal

  123. “However, PaV has a degree in biology from a secular school. I wouldn’t be too quick to label him as illiterate in science.” –PaV

    I didn’t mean to suggest he is altogether illiterate. I do have considerable doubts about his familiarity with how science and scientific discourse is generally conducted. I find it extremely difficult to hold an intelligible conversation with someone with whom so very little common ground can be found. Statistics is a pillar of scientific discourse. (And yes, I know that the framework and assumptions are important). There are some basic criteria, which, once we abandon them, we might as well just be stating how we “feel” about the various concepts.
    It was my assumption that others here in the community would find many of his assertions and implications equally problematic. Basically, in sociological terms, I was looking for the community to help lay down some ground rules for what is taken as given and what is not. Skepticism is healthy. Seeking to undermine every premise offered is not healthy. It’s one thing to be outnumbered here. It’s another thing to be outnumbered and have to illustrate, on top of everything else, that Africans from malaria-endemic regions have a higher rate of sickle-cell anemia. For that kind of thing I expected other reasonably objective voices to lend a hand for the sake of maintaining a fruitful conversation.
    [end complaining]

  124. “I am not so sure the model fitted the first 3/4s so much as much as it was calibrated relative to the assumptions of decline and the observations in the earlier study, with the decline thesis being assumed and seen as “verified” by the low incidence of S.” –kairosfocus

    The paper’s methods state the following, “an estimate for the relative fitness of women with HbSS was computed as the product of the number of predicted live births and the probability of survival to puberty…there is a delay in onset of puberty and first pregnancy among HbSS compared to HbAA individuals; thus survival to age 15 years approximates survival to puberty. An estimate for the relative fitness of men with HbSS was computed as the product of survival to puberty and one minus the cumulative probability of complete erectile dysfunction by the age of 15 years.”

    It’s not clear to me from their methods section if they use local data or other studies for calibration. (Presumably if they completely used local empirical data, their model should have more accurately predicted the *recent* allele decline, which is the opposite of what happened)

    Basically, when I say the model “fit” for the first 3/4 of the time period, I mean that, using those parameters, the 1973-1983 cohort allele frequencies were within the range expected if they had been declining according to the model’s dynamic. Again, if this were an artifact of the fact they were using empirical Jamaican data, you’d expect to see the opposite of what they found.

    As to your horse race analogy. The more I think about it, the more I think there may be something to it. First, let me say that it really ultimately depends on the details of the other horses. It may well be that even though those alternative, less lethal allele types confer resistance to malaria as well, they may not do so as effectively/efficiently etc, as the S-allele. It also may be that they weren’t available (i.e. present) in the appropriate populations. As the army folks say, a good plan now is better than the best plan a day too late. Just because we know of a multitude of variations of Hb doesn’t mean those variants are/were present in malaria-endemic regions. Currently, for example, there is a heavy European bias in our genetic variation data. So the details of the competing horses are key. That said, there may be something to this increased AS transmission and infant health that “props up” the S-allele more so than its competitors. It has a head start in the race. Depending on just *how much* selection for malaria resistance is occurring, and *how much* selection against sickle -cell is occurring this head start for S may or may not be necessary for its persistence in the population. So it truly comes down to the numbers here. Yes, non-lethal variants can linger in the population as PaV suggested, but *deleterious* variants generally only linger at very low frequencies. (where homozygotes are very rarely seen outside of inbreeding) Here, we have populations where a known significantly deleterious allele (S) is at a relatively high frequency. So it’s clear something else is going on; the question is what. For me the malaria resistance is evidently part of the story. I am now, however, somewhat more open to the idea that there’s another element in the equation.

  125. A few points:

    gpuccio,

    I appreciate your thoughtful comments. There are a few things I (conveniently) take as given because I extend a basic level of trust to my fellow scientists. If I did not, we would never get anywhere. When there appears sufficient reason for more skepticism, I’ll provide it. I accept the premise that Africans from endemic malaria regions have higher S-allele incidents. I have read several scholarly articles to that effect, have heard it on TV, etc. So I have as much confidence in this as I do that Japan exists, even though I’ve never been there. Same goes for the protective effect of the SA genotype for malaria. Same for the reduction in fitness for the SS genotype (i.e. sickle-cell). Now I can reference papers for those things, but some would not be happy until they had all the raw data in their hands. (And some still wouldn’t be happy until they collected it themselves.) I don’t have time for all that so I work with certain reasonable premises, as, I imagine, most everyone does.

    You are right, the protection from SA is more “definitive” than the malaria natural selection hypothesis for *why* S-allele persists in the population at high frequency. But consider the fact that this only seems to be the case in malaria-endemic regions. Inference to best explanation, with a few other juicy tidbits (such as the child vs. adult genotype assymetry) thrown in to assist. Like I said earlier, I’m open to the idea that something else, in addition, helps prop up the S-allele, but I need to think through that further and, ultimately, it comes down to numbers. This *other* influence does not explain why the S-allele is more frequent in malaria-endemic regions and why it is found much more rarely elsewhere. That is the reason I remain skeptical as to how much influence this “propping up” force ultimately has. It clearly doesn’t exert itself strongly outside of malaria-endemic regions. Which makes one wonder how much it exerts within.

    “A second important consideration is that we have a lot of other mendelian diseases which have persisted for very long times without any “microevolutionary” model to explain them.” –gpuccio

    Good thought, but these mendelian diseases you mention are largely (a) recessive, such that, at low frequencies, they can “hide” in their heterozygote state silently. (b) complex, such that penetrance is not high (MS, Alzheimer’s, Parkinson’s, Schizophrenia, etc.) That is, a constellation of things determines if they’ll manifest or not. (c) As in the case of alzheimers (by and large) manifestation occurs after reproductive age and thus has negligible effects on reproductive fitness. Natural selection, in this case, can no longer provide any assistance.

    [pause]

  126. thanks for the paper reference, gpuccio. There was mention in the Jamaican paper of other curious findings about AS vs. AA relative transmission and fitness.

    the details of this particular study confuse me a little. They claim that directional selection may no longer be occurring against S, but what about SS homozygotes (i.e. sickle-cell), for which they show no maternity data for? Am I missing something? …. ack, okay, so they’re suggesting you can’t call it directional (as in one-directional) since there appears to be some force selecting *for* the AS genotype. So it’s balancing selection. Although they’re not sure. It would be interesting to see how strong this AS bias is compared to the deleterious of SS homozygotes.

  127. “Semantic is very important for me, because bas semantic is often a screen for bad thinking, and for hidden lies, like natural selections which don’t “select” anything, or micorevolutions which don’t “evolve” anything.” –gpuccio

    I understand. But for you I detect “evolve” must correspond to something akin to “create” or “build.” That is an association you have formed, for understandable reasons, but not one which is consistent with how the term “microevolution” is used amongst biologists. To “evolve” simply indicates “change”. Sometimes change can be “constructive” in nature, sometimes it’s simply change. That is why neutral evolution of alleles is still “molecular evolution” even though nothing is selected for. Thus microevolution, in my understanding, is the change of a trait in a population, typically, but not necessarily, under the influence of natural selection. It need not be so grand as to “build” anything. It may simply tweak or help in some way.

    By the way, I’d be happy to discuss microevolution, information, etc. futher, but this particular thread is getting a bit unwieldy. Perhaps an opportunity will arise elsewhere.

    answers.com:
    ““Microevolution = Evolution resulting from a succession of relatively small genetic variations that often cause the formation of new subspecies.””

    I have problems with their answer.
    Firstly, the “formation of subspecies” part is unnecessary. And just what a “subspecies” is is a can of worms I don’t even wish to come close to. The first part is okay, but I think one or two changes should be sufficient. No building required, in my mind, just change.

    [pause...]

  128. “Well, I will only comment that, according to those definitions, and especially yours, the S trait model is not an example of microevolution. The reasons…”

    Fair enough. I should perhaps instead have said that [I believe] the forces (balancing selection) explaining the S-allele genotype and frequencies are of a similar *nature* as those involved in the process of microevolution.

    As I have already said, S hemoglobin can in no way be considered a beneficial trait.” –gpuccio

    Not a beneficial trait in *any* way? When combined with a normal allele it appears to confer appreciable malaria resistance. That’s a benefit, any way you slice it. It’s not an *elegant* way to confer resistance, but it’s a *way*. Hence a benefit in the appropriate context (genetic and environmental). Context is key.

  129. great_ape: “I didn’t mean to suggest he is altogether illiterate. I do have considerable doubts about his familiarity with how science and scientific discourse is generally conducted.”

    Yes, well, you see, the problem is is that “science and scientific discourse” have given us Darwinism as a “fact”. Sorry, Darwinism is not science, it’s more ideology.

    great_ape:”Statistics is a pillar of scientific discourse. (And yes, I know that the framework and assumptions are important). There are some basic criteria, which, once we abandon them, we might as well just be stating how we “feel” about the various concepts.”

    Statistics has its place in science, no doubt. But it has its limits. Yes, “junk in–junk out”. Yes, an aphorism. You seem to just say: “Give me the numbers. I’ll do my magic (plug it into Excel), voila, the answer.” Is that science?

    Now, as to the the data on malarial infection, I’ve already pointed out that in the *largest* sample (by far!), the numbers were almost identical. That should be a red flag. Then, let’s add this: what the S-allele seems to do is make malaria less severe (and one can suppose less lethal). If this is true, are there some S-allele carriers who respond so mildly to malaria that they are not reported; i.e., they end up not going to a clinic, not receiving medical care or treatments, which would cause the number of infected S-allele carriers to be undereported. Add that possiblity to the data for Nigeria, and it’s very questionable, then, what, exactly, were looking at.

    You seem to just take the data at face value. Let me say that looking at the data, doing simple calculations in my head, yes, it’s quite obvious what Excel will show. I concede that the data–as given–would, if number-crunched, show a selective advantage for the S-allele. So what. I don’t need statistics to tell me that. But that’s not the important question here. The important question here is: how reliable is this data? Stated another way: statistics is blind: it doesn’t care what numbers it’s crunching. Hence, it is absolutely essential that good data be used, that it be screened.

    From a post by HodorH, here’s an example of what I mean:

    “These data have proved of limited value in defining an empirical relationship between intensity of transmission and death from malaria for a number of reasons, including the insensitivity of indirect techniques for ascertaining cause of death1617; the problems in defining host-parasite exposure through the entomological inoculation rate; and confounding factors such as the presence or absence of effective clinical management for malaria between the sites and over time. The latter cannot be underestimated: at Keneba in The Gambia18 and Mlomp in Senegal19, childhood mortality was reduced to remarkably low levels through the provision of well funded, well staffed and comprehen-sive essential clinical services.”
    This is an example of serious scientific effort.

    You blindly accept numbers and use statistical methods and say: “This is how science is done.” I say, let’s look at this data, it looks suspcious, and your response is: “I have considerable doubts about your familiarity with how science and scientific discourse is generally conducted.”

    great-ape: “It’s another thing to be outnumbered and have to illustrate, on top of everything else, that Africans from malaria-endemic regions have a higher rate of sickle-cell anemia.”

    Funny, I don’t really remember that being discussed that much. The discussion was rather over whether the S-allele protected Africans from infection or not. It was also about a study that showed no appreciable change in S-allele frequency from one generation to another in a malaria free area. You said this was probably due to “noise”. And if they had found a small decrease in allele frequency and I suggested that was “noise”, tell me, honestly, what would your reaction have been?

  130. Hi All

    Let me first join Sal in expressing appreciation for the manner in which GA has participated in this and previous threads. In fact, if memory serves, he is by far and away the most civil NDT and/or evo mat advocate I have encountered online over the past two years or so.

    Now, on points worth a note – duly noting on the “still in filter” comment the way:

    1] GA, 121: the presence of the S-allele in *two* separate genotypes SA and SS, one of which is beneficial and one of which is detrimental

    I think based on already cited remarks by clinicians, and my own observations in Jamaica as I actually met people with SC problems, the highlighted first half of that claim is not so. SCT is associated with symptoms and vulnerabilities that are anything but beneficial. It may confer some protection from malaria, but on the cited evidence, so do a lot of other variants on the protein, so the logical question is why hasn’t another horse “won” the race.

    In fact, another horse HAS won the race – S is evidently a distinct minority even among notoriously malaria prone populations. [So the issue is really why deleterious mutations endure in the population, i.e the problem is within the general issue of genetic diseases, in itself a challenge to the evolutionary dynamics by which innovations are supposed to “take over” populations.]

    2] Statistics is a pillar of scientific discourse. (And yes, I know that the framework and assumptions are important) . . . Seeking to undermine every premise offered is not healthy.

    In fact, the issue is deeper than that. Scientific explanations are per epistemological constraints on empirical knowledge through generally inductive reasoning, inherently provisional, and requires a judgement of trust. But as the paradigms and scientific revolutions concept shows, there is often an issue of worldviews involved too, and also agendas. Science is no freer from such factors than the people involved. In that context, statistics is not better than the assumptions, models and quality of data involved. Sadly, in many cases, cost to collect key data is also a major constraint.

    In this case though we must note that the data come from two “large” screening studies [and I note the AL study that did sample mothers . . .], in a context where there are credibly well over 10E4 live births per year. It is credible that the samples are an appreciable fraction of that total. The result, on two empirical data points a generation apart [thus capturing two generations], was that within statistical nullity, there is no down trend. There is apparently at least one other study out there that gives a similar result. Another study now brought forth seems to show higher fecundity among AS women. As is not as harmless as has been made out. We also credibly know that there are up to 700 genetic horses in the race. [Cf from suppressed post: here] So the simple Haldane story is probably simplistic. PaV’s summary is that evidently things that are not sufficiently lethal to be weeded out will remain in the population. That is almost a truism, and the further point that there is no consistent level of S in similar malaria-prone regions is also significant.

    Indeed, your remarks above on competing forces and stabilisation in the population are IMHO coming around to that.

    Pausing . . .

  131. Continuing . . .

    3] GA, 124: It’s not clear to me from their methods section if they use local data or other studies for calibration. (Presumably if they completely used local empirical data, their model should have more accurately predicted the *recent* allele decline, which is the opposite of what happened)

    From the Abstract, as cited by me in the point that got through, no 113:

    . . . local empirical data were used to estimate the parameters of deterministic models of allele frequency decline. We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction.

    Seems to me they DID use local empirical data to estimate the parameters of the NS-driven model that would drive the decline. But, on observing the actual data, they found the outcome flat within statistical significance.

    4] when I say the model “fit” for the first 3/4 of the time period, I mean that, using those parameters, the 1973-1983 cohort allele frequencies were within the range expected if they had been declining according to the model’s dynamic.

    Entirely consistent with my remark that it seems they more or less CALIBRATED the model to fit the data as at 1970′s or so, i.e. by deriving an estimated original rate with the current W African regions as a proxy for the source circa 250 y a. Then they adjusted semi-empirically as physicists would say. But then with this “deterministic” model, the onward projection failed. THAT is what they are noting.

    And, let us observe from above that we know that from other studies, shifts in S between adult and child generations are detectable. You yourself cited this above.

    5] horse race analogy . . . it really ultimately depends on the details of the other horses . . . It also may be that they weren’t available (i.e. present) in the appropriate populations

    In short, the picture is more complex than is usually presented, and there is now a question on the efficacy of mutations to create new biofunctional molecules in populations under environmental stress. [Recall, Wiki has noted that this may be the most significant genetic pressure on the human genome in recent times . . .]

    5] non-lethal variants can linger in the population as PaV suggested, but *deleterious* variants generally only linger at very low frequencies. (where homozygotes are very rarely seen outside of inbreeding) Here, we have populations where a known significantly deleterious allele (S) is at a relatively high frequency. So it’s clear something else is going on; the question is what. For me the malaria resistance is evidently part of the story. I am now, however, somewhat more open to the idea that there’s another element in the equation.

    In short, we are moving to a consensus, that he simple story is a bit too simple. So, while med students indeed should be exposed to NDT mechanisms, they should also be exposed to the issues and complexities of the real world – including the gaps and conundrums faced by NDT. (Maybe, too, that is part of why the recent surveys show that doctors are strongly inclined not to take NDT at face value – direct awareness of the messiness of the real world in materially important contexts.)

    Pausing . . .

  132. Continuing . . .

    6] GA 125: the protection from SA is more “definitive” than the malaria natural selection hypothesis for *why* S-allele persists in the population at high frequency. But consider the fact that this only seems to be the case in malaria-endemic regions.

    The second half is on the Jamaica evidence [and that of the other study mentioned, possibly?] under current empirical challenge. S is apparently persisting beyond what credibly acceptable NDT models project. So much so, a clinical intervention is being recommended. So, there is at least preliminary evidence that the story is messier than we “expected” based on NDT models.

    7] 127, to GP: for you I detect “evolve” must correspond to something akin to “create” or “build.” That is an association you have formed, for understandable reasons, but not one which is consistent with how the term “microevolution” is used amongst biologists. To “evolve” simply indicates “change” . . . . I’d be happy to discuss microevolution, information, etc. futher, but this particular thread is getting a bit unwieldy. Perhaps an opportunity will arise elsewhere.

    We now come to the many variations in meaning of the term “evolution.” I note that on a major interpretation of NDT, micro-evolutionary population shifts are held to cumulate to body-plan level systemic innovations sufficient to account for biodiversity in current and fossil biotas. Thus, it is material to observe that creativity of this chance + necessity driven mechanism is not an immaterial factor.

    In this context, the shift to the concept that evolution is not necessarily creative or progressive is technically true but IMHCO apt to become little more than a subterfuge under pressure of challenge. I note that in particular, the tendency to brush aside the implications of the challenge of getting to information from lucky noise in the face o f the issue of complex bio-functional information required for innovations, to me marks a defensive move of a paradigm in trouble.

    8] 128: I should perhaps instead have said that [I believe] the forces (balancing selection) explaining the S-allele genotype and frequencies are of a similar *nature* as those involved in the process of microevolution

    Consensus approaches . . .

    9] When combined with a normal allele it [S] appears to confer appreciable malaria resistance. That’s a benefit, any way you slice it. It’s not an *elegant* way to confer resistance, but it’s a *way*. Hence a benefit in the appropriate context (genetic and environmental)

    Of course, the 700 [and more] horses issue appears, and the observed and commonplace fact that the SA form is associated with significant and relatively frequent pathologies also, are material. What I would like to see is the causal explanation of why SA women seem have more kids in AL.

    10] PaV, 129: in the *largest* sample (by far!), the numbers were almost identical. That should be a red flag . . . . if they had found a small decrease in allele frequency and I suggested that was “noise”, tell me, honestly, what would your reaction have been?

    This is a significant, empirically anchored point. It needs to be followed up, especially as there seems to be at least one other similar case out there. And, acknowledgement that the re are significant numbers of strange, i.e. unexpected, empirical findings relative to NDT-driven expectations. In short, shouldn’t we be rethinking, given that Malaria is rated as perhapsthe single highest evolutionary pressure on the human pop in recent times?

    11] let’s add this: what the S-allele seems to do is make malaria less severe (and one can suppose less lethal). If this is true, are there some S-allele carriers who respond so mildly to malaria that they are not reported; i.e., they end up not going to a clinic, not receiving medical care or treatments, which would cause the number of infected S-allele carriers to be undereported. Add that possiblity to the data for Nigeria, and it’s very questionable, then, what, exactly, were looking at.

    This is a very good question/issue indeed, and well worth following up. Sarly, there i s a factor not much in the discussion – all of this costs a lot of money,a nd the funding goes tot he predominant paradigm as a rule. So, we must be aware of paradigm-bias in what becomes accepted scientific knowledge in any given era.

    GEM of TKI

  133. kairosfocus:

    “In short, we are moving to a consensus”

    That’s also my feeling. I am very happy that the discussion here has proved very constructive, even with everybody keeping his fundamental views. That’s the merit of all.
    Thank you again, kairosfocus. for adding your usual clarity and wider approach to the debate. You have also literally stolen words from my mouth (in the sense that I was going to say exactly some of the things you highlighted).

    Great ape, I am very happy with your final considerations, with which I can very well agree, maintaining the slight differences on some important points which should by now be clear.

    I agree that the discussion here has been very long. Just have patience, and let me add a couple of innocent thoughts, which could be useful fot future discussions (which I really hope we will have together):

    Consensus 1: Statistics is important, but we must know how to use it. But method is important too, and we must know how to use it. Statistical and methodological analysis are two different, complementary things. Great ape has stressed statistics, PaV has stressed method. Respecting their different emphasis on the specific details, I think that both are sincerely and correctly motivated in doing that. That said, I want to thank kairosfocus for adding the “prevailing paradigm/scientific revolution” perspective, which is very dear to my heart. So let’s remember that, while scientific method is certanly important, some anarchistic guys like me can be sympathetic with Feyerabend’s views agains it, at least to some degree.

    Consensus 2: S hemoglobin and malaria. I think we all have learned interesting things, and the subject is obviously open to research (you have certainly noticed that the papers about the variations in malaria free populations are all very recent!). So I am happy that PaV’s “provocation” opened the discussion on this specific point. Kairosfocus has already done a good job remembering the negative aspects of the S hemoglobin even in heterozygous form. Just a note to great ape: mendelian disease is a term reserved to single gene diseases, whose heredity follows the mendelian paradigm. In that sense, S cell disease is a recessive (indeed, partially recessive) mendelian disease, exactly like all other recessive diseases, such as beta thalassemia, cystic fibrosis, and many others. The other diseases you mention are multifactorial, poligenic diseases, and they do not follow mendelian rules of heredity. In my opinion, the problem remains of how so many mendelian “single gene” diseases, both recessive and dominant, have persisted in some form of equilibrium in absence of apparent selective pressure, without disappearing or being fixed by genetic drift, or similar “mechanisms”.

    Consensus 3: So, forgetting the details of the S hemoglobin-malaria scenario, what do we do with the concept of “microevolution”? I have much appreciated the following comments by great ape:

    “But for you I detect “evolve” must correspond to something akin to “create” or “build.” That is an association you have formed, for understandable reasons, but not one which is consistent with how the term “microevolution” is used amongst biologists. To “evolve” simply indicates “change”. Sometimes change can be “constructive” in nature, sometimes it’s simply change. That is why neutral evolution of alleles is still “molecular evolution” even though nothing is selected for. Thus microevolution, in my understanding, is the change of a trait in a population, typically, but not necessarily, under the influence of natural selection. It need not be so grand as to “build” anything. It may simply tweak or help in some way.”

    I think here we can really agree. If “microevolution” is defined in such a minimal way, that is as a molecular change where nothing is built or, in the case of neutral evolution, nothing is selected, I have no problem with it. It is a model which is perfectly possible, but still it remains only a model, unless convincing empirical evidence can be found. So, it should be evaluated in each single context, to judge its true relevance.
    I still maintain that such a minimal form of possible genetic change should be called “micro-variation”, and not “micro-evolution”, but who am I to challenge the semantic whims of the scientific community? Alas, I stay convinced that semantics is important, and that such an “unnatural” extension of the meaning of “evolution” in common scientific language has definite ideological connotations.
    But, apart from that, the problem is that “microevolution” is not only supposed to mean the minimal form of variation where, as you say, nothing is built and/or nothing is selected. Microevolution is usually believed to be able to build and/or select. It is usually believed to be the “building-block” of macroevolution. In other words, if “microevolution” did not build anything (as I believe to be the truth), where could macroevolution come from? In the general model, macroevolution is supposed to arise from repeated events of microevolution. But if you build nothing, you cannot sum up a pile of nothings to obtain something (and something big indeed!).
    So, even not discussing here the necessity for macroevolution to be “deconstructable” as a sum of simple microevolutionary events, each of them selectable, I think that at least we should try to identify and verify (or falsify) a few “microevolutionary” events which really build something. In other words, find a few examples of single documented mutations which have “built” something in the sense of a new function, and not simply destroyed a pre-existing function conferring indirect advantages versus environmental aggressors which were specifically targeted at that function.

    But, as you have noticed, this thread has become very long. If you want, we can start again the discussion in some future occasion.

  134. great_ape: But for you I detect “evolve” must correspond to something akin to “create” or “build.” That is an association you have formed, for understandable reasons, but not one which is consistent with how the term “microevolution” is used amongst biologists. To “evolve” simply indicates “change”. Sometimes change can be “constructive” in nature, sometimes it’s simply change.”

    gpuccio: still maintain that such a minimal form of possible genetic change should be called “micro-variation”, and not “micro-evolution”, but who am I to challenge the semantic whims of the scientific community? Alas, I stay convinced that semantics is important, and that such an “unnatural” extension of the meaning of “evolution” in common scientific language has definite ideological connotations.

    Here’s something posted at physorg.com today about ‘Ancestral Eve and tooth decay bacteria’:

    “As humans migrated around the world and evolved into the different races and ethnicities we know today,” Caufield said, “this oral bacterium evolved with them in a simultaneous process called coevolution.”

    I, in agreement with gpuccio,(and kairosfocus I would think) am troubled by the kind of equivocation that seems to be part and parcel, i.e., typical, of Darwinism. As the quote I provide illustrates, the word “evolve” is being used equivocally. IOW, the only way that ‘bacteria’ can co-evolve is if the host ‘evolves’ as well. Humankind is that host. So now, here comes—per force—the statement that humanity “evolved” into different “races” and ethnicities. This is the kind of thing that Darwinists say all the time, unreflectively, and it only causes science to become muddled. Oftentimes when I am reading a scientific article I actually have to *translate* what the scientists are saying since the language they use and the actual results they’re attempting to describe don’t match up. It is my sense that in the current debate, the Darwinian side, rather than attempting to avoid equivocations, actually is adding to the numerous equivocations that are already out there. To me, this only makes a daunting task all the harder.

    As an example of an equivocation that’s just out there, and seems hopeless to be resolved, is in regard to the “beneficial effects” of an otherwise deleterious mutation. When great_ape responded thusly….

    Not a beneficial trait in *any* way? When combined with a normal allele it appears to confer appreciable malaria resistance. That’s a benefit, any way you slice it. It’s not an *elegant* way to confer resistance, but it’s a *way*. Hence a benefit in the appropriate context (genetic and environmental). Context is key.

    … my thoughts were: “Is blindness beneficial? Not really. But in the context of an electrical blackout, yes, indeed, it does have its advantages.” How do we move beyond such a relativistic assessment of beneficial/deleterious? In this regard, I appreciate gpuccio’s recurring question of how much ‘function’ is being added. This type of question might provide some adequately objective way of gauging ‘benefit’ versus ‘harm’, thus allowing us to at least avoid this equivocal use of “beneficial.”

    Finally, I think this thread has gone on about as long as it can so while still being constructive. (Although I’ll keep looking back to see if others are choosing to continue) I, too, feel that I’ve learned a lot. And great_ape’s challenges have forced me to more rigorously think through certain ideas. I’m thankful for that. I’m also thankful for the kind of summaries that both gpuccio and kairosfocus have provided.

  135. I agree the thread has run its course. A few final points, though.

    1. The sickle cell allele in malaria-endemic regions in Africa ranges from 5-20% in frequency depending on the region (around 8% for African-Americans). This data is obtained from sickle-cell medical info around the internet; I unfortunately can’t find a good article from home, but I trust this figure is in the ballpark. For an allele that’s as harmful as S is in its homozgygous state (and sometimes in its heterozygous as kairosfocus points out) this is highly unexpected and demands explanation. This is not something that’s just stochastically lingering by chance, as some have suggested.

    2. kairosfocus, indeed they seem to have used local jamaican data to calibrate their model. Yet there is nothing whatsoever I can find that suggests they calibrated it so as to *fit* the first cohort. I’m not clear how or even why they would choose to orchestrate the fit you suggest. That would completely undermine their experimental design. And such a fit (if it was their intention) only makes it more difficult to explain their data, as they now have to explain why there was a *change* in the allele dynamics after the first cohort was reached. Generally, this “fitting” idea you suggest is precisely what people try to avoid by using empirically-derived parameters. The only manipulation they do is *subsequent* to the initial model test, when they try to discern what *would* have needed to be true of the fitness parameter to make the model fit the last period from 1973-2003. That is my understanding.

    3. gpuccio, kairosfocus, let us continue the microevolution and associated nomenclature discussion on a future thread.

    4. “What I would like to see is the causal explanation of why SA women seem have more kids in AL.” –kairosfocus

    I too would be very interested to know.

    5. “How do we move beyond such a relativistic assessment of beneficial/deleterious?” –PaV

    A fair question. This is achieved in evolutionary biology by generally considering a trait’s “benefit” or “relative fitness” as a function of relative reproductive success of the trait’s carriers. That is what is what is either explicitly or implicitly being done in the studies we are discussing here.

    Finally…

    7. “in fact, another horse HAS won the race – S is evidently a distinct minority even among notoriously malaria prone populations. ” –kairosfocus

    Yes, but as I pointed out above, 5-20% frequency of the S-allele is *not* the miniscule minor frequency you’d expect from a recessive genetic disorder of that severity. THAT is what has raised a flag all these years that something else must be going on. And hence the malaria theory. Mendelian diseases that survive in populations, depending on their severity, persist at much lower frequencies. Consider cystic fibrosis and similar mendelian diseases and how many people you know have them. Now consider that in some regions of Africa, approximately q^2 or (.20)*(.20) people are expected to be born with the disease. That’s 1 out of every 25 people.

    But as you all have noted, we can at least agree that the picture is not quite as simple as it is often presented. Yet, to my mind, the take-home message from the malaria/sickle-cell stands, in essence, as an important illustration of the concept of balancing selection as well as helping us understand why a deleterious trait might be found at *unexpectedly high* frequencies.

    I too have appreciated the unfortunately all-to-uncommon civil discussion, and I’ve learned a few things and brushed up on a few others.

    (By the way, gpuccio, thanks for the correction; I should definitely *not* have included discussion of complex diseases (alzheimers, etc.) when we were specifically discussing simple mendelian diseases. A particularly inexcusable oversight on my part. I rather hope this is attributable to my haste and not the premature manifestations of a genetically complex neurodegenerative disease.)

  136. “Now consider that in some regions of Africa, approximately q^2 or (.20)*(.20) people are expected to be born with the disease. That’s 1 out of every 25 people” –me

    I am referring to sickle-cell anemia here as “the disease.” I should have been more clear.

  137. Hi All

    Indeed, this thread has now come to a mutually respectful consensus on key points. GP, in 133, has summed up pretty well. Feyerabend is in fact one of my personal intellectual mini-heroes [or, should I say antiheroes . . .], and he is right to raise the issue of microevolution as the claimed building block of macroevolution, but one dogged by information-generation challenges as discussed previously and mentioned above. PaV correctly guesses in 134, that I find myself troubled by the equivocation that haunts terminology in this field.

    (One of the very first things I learned in 4th form Physics was the definition of a definition: a precise, accurately descriptive statement. I am forever and gratefully indebted to my first full Physics teacher, Mr Anthony Craven, for his focus on clarity and exactness of expression. I hope that in my onward studies and career, I have lived up to his hopes and dicta.)

    I think, DV, I will soon feature this thread in my own blog as an example of how a critically aware discussion of evolutionary issues can be undertaken without rancour and what happens as a result. For that, G-A must receive kudos.

    I will note on a few points as per G-A’s last response justabove:

    1] Local Jamaican data:

    Yes, they used such data. What makes me think they twiddled to get a match to the 1970s cohort is the remark :We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction.

    Had the calibration data been truly independent of the 1970s cohort, I am confident they would have said, “predicted,” not “broadly consistent.”

    Nothing is wrong with that semi-empirical approach, once one recognises what one is doing: the 1935 Weizacker liquid drop semi-empirical nuclear mass model is famous in Physics. There are certain dynamical considerations and assumed initial conditions, and then we tune the parameters to get a match to a known empirical point. Then, we project and test to see if the model has predictive not just generally explanatory power. Note the distinction I am making here between explanation in general terms and actual predictive power [or retrodicting power]. (BTW, such an approach is how climate models are developed and tuned, then run – and hence in part the controversies and limitations, as SD and GD etc love to highlight on their favourite off-topic. Similarly, here in Montserrat, our public is this week debating the pros and cons of a recent super-computer simulation on a possible lateral blast explosion of the growing lava dome, that could engulf Salem, the nearest currently occupied village. The model is basically an extension of the blast that happened Dec 26, 1997 that wiped out several evacuated villages in the South. But, evacuations are expensive and disruptive . . .)

    When they moved on from explanation to prediction, things fell apart, preliminarily showing that the model is too simplistic. And that is what is at the crux of our own discussion. Going further, we are seeing a situation where damaging changes to the genome are stabilising in the population, in this case at a rate of several percent – instead of being swept out as one or more of the remaining 600+ horses wins the race. So, there are other dynamics that are credibly at work. YECs may wish to question whether the real world timeline has had time to get to an outright win instead of a split difference. Those who view NS as perhaps less efficient than sometimes presented [PaV], will challenge the idea that the best horse wins outright.

    Perhaps what is happening is that the genome is deteriorating under impact of noise and those variations that are not utterly lethal or destructive to reproductive capacity are preserved one way or another, more or less leading to a more or less stabilised situation? [Here, “stability” can include oscillations via limit cycles etc.]

    But the point is that med students need to know that data come first, that theories and models have limitations, and that we need to be open to being wrong, and so make the effort to put forth creative ideas that may be wrong, but are fruitful along the way . . .

    GEM of TKI

    PS cf here on hyps, models and theories.

  138. Oh yes:

    I should comment a bit on 0.2^2 ~ 0.04, which is of course still a small minority, though not as low as with other similar genetic diseases.

    (Recall, we are looking at environments where malarial mosquitoes were/are abundant and hungry, and where across time, little could be done to prevent being bitten.)

    Even in such environments, which were presumably in several cases also relatively reproductively isolated for many generations, we did not see S dominating the population. That is why I spoke of other horses winning the race, and note PaV’s remark in 80:

    given that there are so many different types of ‘heterozygotes’ for hemoglobin—sickle cell, thalassemia, dust antigen, HLA, etc., etc.—the more sensible interpretation is not that ALL of these confer any kind of ‘heterozygote advantage’, but simply that when it comes to hemoglobin its complex structure permits a number of heterozygotes appearing without lethality. IOW, the recessive homozygotes are not sufficiently lethal as to eliminate them from a population entirely, so there remains a kind of ‘residual’ allele frequency. That’s my hunch.

    So, yes there may be some empirically demonstrable protective effect against malaria in S-distorted haemoglobin — in this case balanced off by a disease that is serious in SS form and what we may call mildly present with damaging consequences and potential consequences in SA form – but there are other possible horses in the race. In particular, people with more “normal” haemoglobin – forms that appear to be vulnerable to malaria — actually do predominate even in the teeth of what has been called the most stringent selection pressure on the human genome in “recent” times. One that wiki characterises as:

    one of the most common infectious diseases and an enormous public-health problem . . . . has infected humans for over 50,000 years, and may have been a human pathogen for the entire history of our species.[1] Indeed, close relatives of the human malaria parasites remain common in chimpanzees, our closest relatives.[2] References to the unique periodic fevers of malaria are found throughout recorded history . . . .

    causes about 350–500 million infections in humans and approximately one to three million deaths annually[13] . . . The vast majority of cases occur in children under the age of 5 years;[14] pregnant women are also especially vulnerable . . . Precise statistics are unknown because many cases occur in rural areas where people do not have access to hospitals or the means to afford health care. Consequently, the majority of cases are undocumented.[13] . . . . Malaria is presently endemic in a broad band around the equator, in areas of South America, South and Southeast Asia, parts of the Middle East and Oceania, and much of Africa; however, it is in sub-Saharan Africa where 85– 90% of malaria fatalities occur . . . . Malaria is not just a disease commonly associated with poverty, but is also a cause of poverty and a major hindrance to economic development . . . economic impact includes costs of health care, working days lost due to sickness, days lost in education, decreased productivity due to brain damage from cerebral malaria, and loss of investment and tourism.[14] In some countries with a heavy malaria burden, the disease may account for as much as 40% of public health expenditure, 30-50% of inpatient admissions, and up to 50% of outpatient visits.[25] . . . . Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia caused by hemolysis, hemoglobinuria, and convulsions. . . . For reasons that are poorly understood, but which may be related to high intracranial pressure, children with malaria frequently exhibit abnormal posturing, a sign indicating severe brain damage.[27] Malaria has been found to cause cognitive impairments, especially in children. It causes widespread anemia during a period of rapid brain development and also direct brain damage from cerebral malaria to which children are more vulnerable.[28] . . . . Consequences of severe malaria include coma and death if untreated—young children and pregnant women are especially vulnerable . . . . Severe malaria can progress extremely rapidly and cause death within hours or days.[29] In the most severe cases of the disease fatality rates can exceed 20%, even with intensive care and treatment.[30] In endemic areas, treatment is often less satisfactory and the overall fatality rate for all cases of malaria can be as high as one in ten.[31] Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.[32]

    We can easily see why such an awful disease would put serious genetic pressure on the affected population. That means that there would be a huge, fast-building genetic reward for something that confers resistance, which should therefore rapidly dominate the population. But, S simply has failed to do so. Other horses have won the race, despite their handicaps. Why?

    As we try to look at that why, the story as seen above, gets complicated real fast – starting with data patterns. So, it is fair comment to note that there seems to be a lot more to the story than meets the casual eye. And, that is what med students should know.

    GEM of TKI

  139. PPPS: The case of the Duffy antigen is an interesting parallel. Of this Wiki notes:

    Plasmodium vivax malaria uses the Duffy antigen to enter blood cells. However, it is possible to express no Duffy antigen on red blood cells (Fy-/Fy-). This genotype confers complete resistance to P. vivax infection. The genotype has not been found in Chinese populations [nb China is of course in the Malaria belt], has rarely been found in white populations, but is found in 68% of black people. This is thought to be due to very high exposure to P. vivax in Africa in the past.

    I think that gives a bit of further context; especially on what winning a genetic horse race can look like. (Including of course mutation through evident loss of information.)

    It is worth noting that the selection forces seem to have worked that extensively in the face of a LESS serious form of the disease, one that would have had far less damaging impact on reproductive potential:

    The parasite Plasmodium vivax is the most frequent and widely distributed cause of benign, but recurring (tertian), malaria. It is one of four species of parasite that commonly cause malaria infection in humans. It is less virulent than Plasmodium falciparum, the deadliest of the four, and seldom fatal.

    Or, is it that the founder african population[s] just happened to be predominantly of the relevant genetic variant?

    [In short, we again see the problems of "scientifically" reconstructing the past . . . we have to look at relative plausibility of competing explanations, not "proofs."]

    GEM of TKI

  140. Finally for now:

    I also ran across HLA-B53. This, from NIH, seems worthy of following up:

    Another version of the HLA-B gene, HLA-B53, has been shown to help protect against severe malaria. HLA-B53 is most common in West African populations, where malaria is a frequent cause of death in children. Researchers suggest that this version of the HLA-B gene may help the immune system respond more effectively to the parasite that causes malaria.

    In looking for stuff on prevalence, I came across this, in a Sept 2000 NEJM review paper:

    In the Gambia, infection with Plasmodium falciparum, which causes malaria, is extremely common, although the mortality rate among children with malarial anemia or cerebral malaria is low. Both complications are believed to be the consequence of a failure to clear the parasites from the blood, leading to increased hemolysis and blockage of cerebral blood vessels by parasitized erythrocytes. HLA typing of the relevant population revealed the presence of the HLA-B*53 allele at a frequency of approximately 25 percent among healthy persons or children with mild malaria (the allele is rare in non-African populations). By contrast, the frequency of HLA-B*53 among patients with severe malaria was approximately 15 percent. The comparison suggests that possession of the HLA-B*53 allele reduces the risk of death from severe malaria by approximately 40 percent. Presumably, the HLA-B53 molecules bind very efficiently certain peptides produced by processing the malarial circumsporozoite protein and present them to CD8+ T cells, whose progeny attack the liver-stage parasites. Such cytotoxic T cells have indeed been found in patients with malaria, and circumsporozoite peptides have been eluted from the HLA-B*53 molecules of these patients. 40 Protection against severe malarial anemia is also afforded by possession of the class II HLA-DRB1*1302/DQB1*0501 haplotype. In other sub-Saharan populations, different class I and class II alleles are involved in the resistance to severe malaria.

    This gives us at least some prelim numbers on general prevalence [for which healthy persons and/or mild malaria is probably a reasonable proxy] and on differential presence among pops with mild/severe malaria. While this variation is obviously relatively common in African pops and rarish elsewhere, why did it not outright win the genetic race in Gambia etc, instead of latching [if it has latched . . . YECs note] at the sort of 20% level level we are seeing?

    This 1994 Colloquium paper is also worth a look, to see the conventional account in summary form, including a brief ref to HLA-B53 and other interesting cases.

    This story has much more to it than meets the eye . . .

    GEM of TKI

  141. I have watched this debate as I am sure many others have and the interesting thing besides the general level of civility is how little there is to support the Darwin paradigm. Though I do not know much about the details of genetics it is possible to follow the gist of the arguments and make some conclusions.

    Genetics is obviously an extremely important discipline when focused on medicine and diseases and how they are passed on generation to generation. We should never underestimate this. But when genetics is applied to evolution on a grander scale than just explaining the changes of allele frequencies over time it comes up empty.

    Natural selection is definitely a mechanism of genetics but it is an extremely limited one. Otherwise we would be looking at an endless laundry list of its effects. Instead we are focused on a few case of degeneration that lead to a posiitive benefit.

  142. Jerry:

    Thanks for the kind remarks. THe civility is in no small measure due to the approach taken by G-A, and we must all be thankful to him for his time and gentlemanly conduct.

    For the sake of clarity, it may be worth excerpting Wiki briefly on how S-type mutations may protect against malaria:

    The best-studied influence of the malaria parasite upon the human genome is the blood disease, sickle-cell disease. In sickle-cell disease, there is a mutation in the HBB gene, which encodes the beta globin subunit of haemoglobin. The normal allele encodes a glutamate at position six of the beta globin protein, while the sickle-cell allele encodes a valine. This change from a hydrophilic to a hydrophobic amino acid encourages binding between haemoglobin molecules, with polymerization of haemoglobin deforming red blood cells into a sickle shape.

    Individuals homozygous for the mutation have full sickle-cell disease and rarely live beyond adolescence. However, this allele has sustained gene frequencies in populations where malaria is endemic of around 10%. This is because individuals heterozygous for the mutated allele, known as sickle-cell trait, have a low level of anaemia but also have a greatly reduced chance of malaria infection. The existence of four haplotypes of sickle-type hemoglobin suggests that this mutation has emerged independently at least four times in malaria-endemic areas, further demonstrating its evolutionary advantage in such affected regions.

    There are also other mutations of the HBB gene that produce haemoglobin molecules capable of conferring similar resistance to malaria infection. These mutations produce haemoglobin types HbE and HbC which are common in Southeast Asia and Western Africa, respectively.

    Proteins fold based in part on water-soluble and water-insoluble amino acid elements. In this case the point substitution of hydrophilic for hydrophobic encourages an undesirable cross-linking. The resulting effect is that here is in the SA form a mild and in the SS a serious form o the sickle cell condition. One result is that evidenty malarial pathogens have problems penetrating an indhabiting such cells. But their primary functionality is also damaged.

    People with SS, in primitive situations, die young. SA types are prone to various health problems and vulnerabilities. They also tend to give birth to children who suffer the SS condition. [SA x SA --> 25% SS, 50% SA, 25% AA. Compensating for the resulting "weak" health of offspring may partly explain the observation in AL that SA mothers tend to have more children.]

    The complexities come in as we see the rest of 700 variants on haemoglobin, and on the anomalies relativge to the Haldane NDT-style model, that S seems more persitent than the simple model predicts. I have just put up two more variants that show just how diverse the situation is with malaria. For, it seems the “best” example of a protective mutation that “wins” the genetic horserace, protects against the milder form of the disease, and a variety of Haemoglobin that protects against severe malaria, has not won the race, though it does not seem to have immediately noteworthy major damaging effects. [NB: the more virulent form seems to have multiple pathways to invade blood cells. That makes it far more complicated to deal with than Pv, the more mild type protected against by omitting Duffy's antigen.]

    Thus, med students need to hear a quite nuanced story. And, we the public should not be given a simplistic picture on malaria and sicle cell disease.

    All the best

    GEM of TKI

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