Monday, May 25, 2015

Authors Should Explain Why bcl2 and P53 Genes Are Not Important To Skin Lightening in Neandertals? A Problem in The Methodology of Harvard Paper

[What is the purpose of this thread? In actuality, this thread shares commonality with the other theories I have proposed in these blogs, relating to causality, and is therefore relevant to the other theories I have discussed here. Part of science is testing alternative, new, if not existing hypotheses, and so this discussion is also relevant to that issue in a broader sense. This relates to the existing causality in organisms, the selection model and its "effects" on the presence of traits and/or genes, and so this discussion is highly relevant to the causality of that model. In my opinion, the bcl-2/p53 gene issue" is a good test of their central hypothesis. But a far better theory which at least may encompass such complex phenomenon would be one grounded in thermodynamics, and that begins with the correct view of thermodynamics relative to machines, and living things, in a new theory, Virtual Closed Systems]

I do enjoy a lively science discussion. Especially fending off nasty troll attacks whilst attempting to engage the author(s) in the errors of their papers. That is why I'm still waiting for the source authors of the Disqus article I posted about earlier, over here, to reply to a relatively straightforward scientific question regarding a significant issue with their methodology. I don't care much for "we've done it this way all along" reply, that sort of mind set, though of great befit to dogmatists, would have us believing in pre-Copernican astronomy and all other sort of 'weird shit', also known more technically, as non-science.
But there is also I believe good reason to criticize this paper if only because of its rushed sense of delving into a subject with minimal data, (It's far more complex than identifying just a couple of genes) and bespeaks an agenda that goes beyond science, and so another aim here is to simply point out that other than having done the sequencing, I don't believe they are even close to making any case for what they're concluding. Isn't the subject far too complex for the limited information available?, why the necessity to rush to sketchy unfounded conclusions? Here's the paper:

According to the article: "The paper doesn’t specify why these genes (SLC24A5 and SLC45A2) might have been under such strong selection. But the likely explanation for the pigmentation genes is to maximize vitamin D synthesis, said paleoanthropologist Nina Jablonski of Pennsylvania State University...or, evolving pale skin that absorbs UV more efficiently or favoring lactose tolerance to be able to digest the sugars and vitamin D naturally found in milk. [2]"

I also note that a well meaning scientist, a geneticist, attempted to answer the question, but unfortunately tried to lead us away from the issue by invoking an argument that disqualified the question (certainly a good attempt, well done!). He wanted to assume that it wasn't an issue because, he didn't believe it was an issue. "These genes" he said, couldn't possibly be changing, because if they did, it would be fatal, meaning non-inheritable. A fine bit of logic if it was correct. But here's at least one reason that fails. There are many subtle mutations of these genes I brought up, and that is precisely why they are important to causing so many variations in how people, today, respond to cancer. Look no further than the extensive work done on bcl-2 mediation and up-regulation of cancer resistance to drugs among others. And we know some are at risk for cancer under all sorts of conditions, while others might not be, and  the gene P53 is one that essentially "turns on" cancer. I heard nothing further. One can argue that P53 and bcl-2 don't mutate under any circumstance, but that contradicts the other evidence outside of evo-biology, in cancer research, that these are important genes in mediating cancer. So then we are simply talking about the specific regulating genes, why aren't these factored in? The problem of their methodology has not gone away by naming some other genes, which they fail to mention. I could just as easily argue that Vitamin D genes are also regulated by other genes, which are also not mentioned in their paper.

So we can see that the claim here in their paper and elsewhere, that skin lightened to yield more Vitamin D production, is offset by the potential increase in skin cancer risk to the individual. At the very least if one claims one variable changed, i.e. a gene for Vitamin D production, they need to show why these other variables, genes for brcl-2 or P53 stayed the same. That's a basic methodology of science. These genes absolutely were present in Neanderthals, as they are very important basic genes. So where's the genomic sequencing that might support this?

Disqus authors, and that includes source authors benefiting from the publicity of their papers, do in fact, respond to comments on their blogs, and this comment I posted there was virtually the same day it was posted onto the site, so it was plenty "fresh". And though the atmosphere on their particular press-release is "dog eat dog" that's no excuse for not replying and they should enter the fray they created and permitted, just like all the rest. I posted essentially the same question on their archive site bioRxiv, but have had no response. One would think that out of seventeen or so authors on the paper, one might have the time...

If we imagine skin lightening, in ancient Neanderthals and Homosapiens, early humans who migrated to Europe, thus de-protecting itself from the sun's harmful rays, it would be logical to ask how this might increase skin cancer rates and if this would not outweigh the apparent "benefits" of more Vitamin D? But even if both had to change, how do we know, from a theoretical standpoint, which of these was the most important? A true believer in his ability to discern Vitamin D production in skin as the single most important reason for ascendance should also be able to reasonably explain why the 19,997 other genes were NOT so significant in that same alleged outcome, just as one is forced to do in any other science. As the two other genes I brought but by way of example, are directly involved in the body's response to skin cancer as well as other cancers, that is really the other question here, the methodology used to discern one gene's influence over another.

We are to somehow ignore the direct biochemical contributions of these genes or at least regulating genes for P53 and bcl-2 effects in cancer survival in ancient peoples, while we pretend that a gene for Vitamin D, is the important factor. It's been argued that evolution needs to eventually be more quantitative like the other sciences (see R. Highfield 2013, Edge "What Theory Needs To Be Retired?). But that isn't really at issue here, methodology, the basis of causal analysis of the problem, should not be at a different standard for one science field or another. Chemists and physicists do not have a magic eraser that can be used to wipe out causative factors that are important to the general thesis, that may obviously be contradictory, why then should these scientific authors not be held to the same standards?

1. The question I posted to the author's on the bioRxiv site:
My question is regarding the methodology behind the paper, an "upstream" issue as to why the authors chose to select only certain genes such as the SLC...A5 and SLC...A2 as opposed to looking at many other genes that may have been available in the samples. A central working hypothesis is that these genes in question gave some advantage, that led to skin lightening and possibly greater Vitamin D production. The question is, how can other genes like bcl-2 and P53 genes be excluded as being extremely important, to "Eight thousand years of Nat Selection..." since these are critical to modulating cancer susceptibility (see Genta studies etc on cancer) and would be it seems, more activated when skin lost pigmentation? Would the risk of higher cancer rates not offset advantage of Vitamin D production? It is not a mutually exclusive issue, it is a matter of why as I ask above, the methodology does not require looking at these other critical genes in the skin, and their impact. So how can they be excluded from the study?

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