Talk:Eutherian fetoembryonic defense system hypothesis/Archive 1

My edits

I came across this page when looking for other articles to include as "see alsos" on the "Immunity during Pregnancy and Infancy" section of the Immune system article I have been working on. While I found the content of this article to be of interest, the layout was confusing and the wording a bit too technical for a typical reader. I then went about editing the article, only to discover (when checking to see what else liked here) that this article has been the subject of some discussion. I hope that my edits do not interfere with any attemps to manage this article. It was all in good faith. Cheers--DO11.10 04:20, 15 October 2006 (UTC)

Style, notability, logic

I'm intrigued to read about this line of investigation, but I have a few problems with how this article is written, and how related material has been added elsewhere. The editor User:Clarkgf is apparently one of the principal authors of the research in question, and I hope he will not take this as personal criticism; it mostly has to do with how an encyclopedia differs from a scientific journal.

Basically this article is a summary of three papers published in 1997 and 2001, which introduced the hypothesis, proposed a name for it, and suggested how it might apply to a particular disease. The article takes a while to get to the key points that distinguish the hypothesis from previous models (the function of specific glycoproteins, etc.) but that's a question of editing. And there are some critical unsourced claims that are, to my non-expert eye, far from self-evident - like the claim that "the profile of the major oligosaccharides linked to CA125 and the major surface glycoprotein of HIV-1 (gp120) almost perfectly overlap", and the statement that human gametes have no MHC/HLA (which, according to at least one review of literature [1], is far from certain) - and the discussion of alternate models is so brief and cryptic that it makes eu-FEDS sound like the only sane option; but those things can be addressed in editing too.

The real problem is that neither Google nor PubMed show any references to the hypothesis (under that name) other than those three papers themselves. Now I know that notability can be a gray area on Wikipedia, and peer-reviewed publication obviously lends some weight, but note that the WP guideline on fringe theories talks about the desirability of being discussed in a respected publication, not just published in one. If no one but the authors is talking about it (yet), I suggest that it is not notable. It may be entirely correct and still not belong here (yet).

I'm not starting a request for deletion yet because I'm not sure I understand the field well enough to be searching for the right things. If I'm wrong and the article is appropriate, then I'll try to take some action on the style and sourcing complaints above.

Regardless, I think the sections on how the hypothesis applies to AIDS and SIV are problematic. The article in footnote 7 is very interesting (full text is available - I added a PubMed link; please do that whenever you can) but over my head; unfortunately the summary here is not helpful - it seems to be just saying that HIV is an example of a pathogen that is not suppressed effectively by the immune system, and that therefore HIV might be using mechanisms suggested by this hypothesis, which out of context is just a wild guess. The material added to Simian immunodeficiency virus is even worse, taking a totally unremarkable principle (many viruses are well adapted to a particular host in which they do not cause disease) and claiming that it supports the eu-FEDS theory, based on an unsourced and unexplained "mirroring" of the maternal immune response, and an extremely counterintuitive if not incorrect claim (also unsourced) that massive CD4+ depletion does not count as an immunopathology. I'm deleting those statements for now. ←Hob 05:16, 27 October 2006 (UTC)

Response from Clarkgf

User:Clarkgf posted the following to my user talk page. I have asked him to direct this discussion to the article talk page in the future. My responses are indented within the text. ←Hob 01:21, 31 October 2006 (UTC)

Hi, I am responding to your discussion of the article on the eu-FEDS hypothesis. I would guess that you are certainly not an expert, and are confused because you really do not understand the literature or the gaping holes in the existing models for AIDS pathogenesis. Before you change anything however, you should think about what you are doing, however. For example, you do not sit on an NIH AIDS study section that now funds research on this hypothesis. This study section accepted ALL of these arguments as TRUE because they are the real experts, and they appreciate the complexity of AIDS pathogenesis. The literature backs up every statement here. I just did not get around to putting in the references for the other linkages there.

But since you might confuse some intelligent non-experts about the real issues here, I will get back to you soon with a complete rebuttal. If you are a reasonable person, you will reverse your changes, and be a credit to your profession. Otherwise, you will just be another person that got in the way. clarkgf

I may be confused or have a lack of understanding, but it is not the case that only NIH-funded researchers can edit Wikipedia articles - and cutting back article content when there is a lack of editorial consensus is not "getting in the way". This article, like all of them, is a work in progress, and we really don't give total deference to any particular editor based on professional credentials (especially since we have very little ability to verify that anyone is who he/she claims to be). Articles must be justified only in terms of what is in the article, including the specific citations given. Please see Wikipedia:Verifiability. Also, please see Wikipedia:No personal attacks. ←Hob 02:26, 31 October 2006 (UTC)

---

(added later:)

More references will come tomorrow, but for today I have addressed some of the issues you raised.

Expression of major histocompatibility markers on human sperm or egg

Careful experiments indicate that human sperm and eggs do not express either HLA class I or class II molecules, as noted in a review article that is purely focused on this topic. It is not credible to give equal weight to older papers when newer publications using superior technology are available. If sperm are not purified and washed, they can be contaminated with other cells in semen that are class I/II positive.

If newer studies are available then please cite them. Currently, your citations on this particular point are from 1991 and 1960. The review of literature I mentioned above is from 1999, and cites material that is mostly after 1991. I'm not saying you are wrong, but on Wikipedia you can't ask the readers (or other editors) to take your word for anything. Everything in the article needs to be either the current consensus position in the field, or clearly indicated as the conclusion of someone in particular. ←Hob 02:26, 31 October 2006 (UTC)

Induction of tolerance to SIV compared to other viruses

There are usually two responses to viral infection: (i) complete destruction of the virus and all virally infected cells (referred to as sanitizing immunity); or (ii) extensive viral destruction followed by restriction of the viral DNA/RNA to a specific organ or tissue without any protein expression (i.e. latency). Latent viruses can only re-emerge if the immune system is suppressed by another infection. No virus induces viremia without causing severe pathological effects. The only notable exception is of course SIV infection of its natural hosts.

Citations please. Hepatitis C is one other notable exception that comes to mind. ←Hob 02:26, 31 October 2006 (UTC)

To compare typical latent viral infections to SIV infection of its natural hosts is like suggesting that the earth’s moon and Jupiter are the same size. Tolerance to SIV in its natural hosts is therefore completely unnatural. Since SIV has an extremely limited genome, it could not evoke tolerance by suppressing different immune pathways. Logically, SIV can only escape the host's immune response by integrating itself into a system of tolerance that already exists. There is only one system that can invoke this type of tolerance, and that occurs during reproduction.

Acceptance in the literature

The Internet does not apply to scientific articles. Some of the most highly cited articles in existence have only a single internet link. An article is often discussed in a paper, and cited. Therefore the key number you are looking for is not the number of hits on websites, but the number of citations that an article receives. You would find that these hypothetical papers have been cited over 100 times by authors other than the principals behind the model. In addition, this topic has been reviewed more recently in a major book on reproductive immunology known as the Immunology of Pregnancy. So to say it is a "fringe subject" is quite inappropriate.

I didn't say it was a fringe subject; I just asked you to read some Wikipedia policies, one of which had that phrase in its title. And yes, I do understand the role of citations in scientific literature. I'm not using a simple Google search, I'm using PubMed, and I'm not finding anything. If there are hundreds of references by others to this hypothesis, perhaps you could point out one or two. ←Hob 02:26, 31 October 2006 (UTC)

Destruction of naïve CD4+ T cells

It is obvious from the plethora of studies on the AGMs and the SMs that the increased turnover of CD4+ T cells following viral infection is NOT the cause of AIDS. The rate of CD4+ T cell turnover in these monkeys is identical to patients with full blown AIDS. This fact was also shown in humans in the 1990s (references coming). No, the key is that HIV-1 appears to both activate and suppress the human immune response at the same time. That is a neat trick that tumor cells also perform.

Are you claiming that the rate of CD4+ T-cell destruction does not correlate with the development of AIDS at all? In my (limited) understanding, that is very far from being a consensus viewpoint; that doesn't mean it can't be discussed on WP, but it shouldn't just be tossed off as if it is common knowledge, and you will definitely want to confer with editors on the AIDS and HIV articles as well. "References coming" is not a very useful approach when editors raise questions like this. ←Hob 02:26, 31 October 2006 (UTC)

More is on the way. —The preceding unsigned comment was added by Clarkgf (talk • contribs) .

Response 2 from Clarkgf

I am sorry if I offended you in any way. That was wrong. AIDS is a complex topic and there are many "aha" moments even for experts in the area. I have said things at meetings that surprised and shocked some experts, but later they recant and say that they did not know specifically about that point. I do not want to offend anyone, but teach them, so that we can finally overcome AIDS and cancer too. So let us address the issues you presented above.

If newer studies are available then please cite them. Currently, your citations on this particular point are from 1991 and 1960. The review of literature I mentioned above is from 1999, and cites material that is mostly after 1991. I'm not saying you are wrong, but on Wikipedia you can't ask the readers (or other editors) to take your word for anything. Everything in the article needs to be either the current consensus position in the field, or clearly indicated as the conclusion of someone in particular. ←Hob 02:26, 31 October 2006 (UTC)

I believe that the best investigator in the world in this area is Gottfried Dohr. He wrote an excellent review article in 1998 where he discussed in detail all the problems with the earlier studies that erroneously showed that sperm were MHC positive [2]. He maintains that the precursor cells are positive, but that during development sperm lose their MHC markers. Though there are few newer papers (because clinically it is now obvious using appropriate MHC specific antibodies and highly purified sperm) there is now little disagreement that sperm are MHC negative cell types. —Preceding unsigned comment added by Clarkgf (talk • contribs)

A week has gone by and you have made no edits to the article, you're just arguing about it on talk pages. Citations supporting the article need to be in the article. ←Hob 20:14, 31 October 2006 (UTC)

I didn't say it was a fringe subject; I just asked you to read some Wikipedia policies, one of which had that phrase in its title. And yes, I do understand the role of citations in scientific literature. I'm not using a simple Google search, I'm using PubMed, and I'm not finding anything. If there are hundreds of references by others to this hypothesis, perhaps you could point out one or two. ←Hob 02:26, 31 October 2006 (UTC)

No, the operative word here is citation. In effect, do other authors cite your paper? Pubmed will not help you there. If you have less than 10 citations, then your topic is on the fringe. If more, then the topic is not on the fringe. This fact can be confirmed o the ISI Web of Knowledge citation source. So let us simply consider the number of citations of the two review articles that are directly related to eu-FEDS (or its precursor name the human fetoembryonic defense system hypothesis; the name was later changed to include all placental mammals). We will not consider citations to other papers that support this model:

Clark GF, Oehninger S, Patankar MS, et al. A role for glycoconjugates in human development: The human feto-embryonic defence system hypothesis

HUMAN REPRODUCTION 11 (3): 467-473 MAR 1996 Times Cited: 59

Clark GF, Dell A, Morris HR, et al. Viewing AIDS from a glycobiological perspective: potential linkages to the human fetoembryonic defence system hypothesis

MOLECULAR HUMAN REPRODUCTION 3 (1): 5-13 JAN 1997 Times Cited: 25 —Preceding unsigned comment added by Clarkgf (talk • contribs)

For those of us without ISI access (i.e. most editors and readers of Wikipedia), could you please list several of these citations? Also, it would be helpful if you would read Wikipedia guidelines on how to use talk pages - in particular, how to indent replies below the relevant text and how to sign posts. Thank you. ←Hob 20:14, 31 October 2006 (UTC)

Are you claiming that the rate of CD4+ T-cell destruction does not correlate with the development of AIDS at all? In my (limited) understanding, that is very far from being a consensus viewpoint; that doesn't mean it can't be discussed on WP, but it shouldn't just be tossed off as if it is common knowledge, and you will definitely want to confer with editors on the AIDS and HIV articles as well. "References coming" is not a very useful approach when editors raise questions like this. ←Hob 02:26, 31 October 2006 (UTC)

I am afraid that the answer to this question is yes. The increased turnover of naive CD4+ T cells is not the cause of AIDS, as outlined in a recent review article. [3]. In the abstract to this review, the following correct phrase is included:

"Recent attempts to understand HIV-1 pathogenesis have set aside the view that CD4+ T-cell depletion is effected solely by HIV-1-mediated killing in favor of a more complete explanation that also includes T-cell dynamics and, more specifically, chronic immune activation as a central factor in HIV-1 pathogenesis."

You see, the experts acknowledge two major problems with CD4+ T cell destruction. First, the rate of decline of CD4+ T cells is too slow for the real culprit to be the overt destruction of naïve CD4+ T cells (the major cell population that is affected by cytolysis). Another major problem is that no one has ever demonstrated that there is any difference in the cytopathicity of SIV for CD4+ T cells in their natural hosts. As previously outlined, essentially complete tolerance is observed in the natural hosts even as CD4+ T cell destruction mirrors what occurs in HIV-1 infected patients. And that is why this very simple explanation is so problematic, and why unfortunately the current AIDS article is incorrect based on our current scientific understanding. Even in encyclopedias, we need to be accurate.--Clarkgf 15:41, 1 November 2006 (UTC)

We have wandered pretty far afield here from article content - if there is specific text in the current AIDS article that you think is "incorrect", you need to correct it or at least point it out. Anyway, I am well aware that direct killing of infected CD4+ T cells is no longer thought to be the major mechanism in HIV pathogenesis; I never said it was, and the AIDS and HIV articles don't say so either - they just say that there are both direct and indirect mechanisms, including some degree of destruction by cytotoxic T cells (your points about the destructive effects of immune system activation in HIV disease are, as far as I know, fairly uncontroversial at this point). None of which is to say that your hypothesis is wrong with regard to SIV - just that this particular argument, as you presented it in the article, is partly based on attacking an oversimplified straw-man notion, and lumping together the general problem of CD4+ T cell loss with questions about specific mechanisms in a misleading way... and in any case, that kind of speculation about recent research just doesn't belong here. But I would like to keep discussion of the SIV article on its own talk page if possible. ←Hob 21:57, 4 November 2006 (UTC)

Responses to Other Points

Citations please. Hepatitis C is one other notable exception that comes to mind. ←Hob 02:26, 31 October 2006 (UTC).

Please supply a reference indicating that HepC induces the viremia like SIV in its natural hosts without pathological effects or shortening the life span of infected individuals. I would like to read that paper.

A week has gone by and you have made no edits to the article, you're just arguing about it on talk pages. Citations supporting the article need to be in the article. ←Hob 20:14, 31 October 2006 (UTC)

I have changed the eu-FEDS article now to include all the references I think are necessary. I also removed the comment about human sperm expressing the same carbohydrate sequences as Helicobacter pylori. That is only published now in abstract form, and it will take some time for it to become a part of the biomedical literature. But there is no doubt that very unusual carbohydrate sequences that are profusely expressed on human sperm also coat the surface of H. pylori. And unfortunately, these same carbohydrate sequences are also profusely expressed on the surface of 90% of all human cancers, but only as those cancers progress to the end stage where they are uniformly fatal. I will reference these observations in the eu-FEDS article when those data on the sperm profiling are published. Now I would appreciate it if you would reverse the changes that were made in those other articles. I think that there are now some very logical reasons to believe that these linkages are extremely important--Clarkgf 15:39, 2 November 2006 (UTC)

Thank you for the additional references; I look forward to following them up. I also added a response to your user talk page, on some points that don't have to do with this article directly. ←Hob 22:00, 4 November 2006 (UTC)

RFC

I have added a request for comment at Wikipedia:Requests for comment/Maths, science, and technology#Clinical and medical topics to solicit opinions from other editors. I would particularly like to hear from editors in medical/biological fields, because some of User:Clarkgf's statements hinge on questions of what is in the scientific literature, and I no longer have easy access to medical journals. Specifically:

• I questioned the notability of this hypothesis, to which Clarkgf responded that his papers have been cited over 100 times in peer-reviewed literature. I don't want to request deletion of the article if it is in fact notable, but I have no way to check this.
• Some related material was added in Simian immunodeficiency virus, including a "see also" link to this article. Some of the comments above relate to Clarkgf's justification for this, based on claims about the behavior of SIV in different animals, and questions about the degree and cause of CD4+ cell destruction. Some of his statements and interpretations seem questionable to me but I may be misreading the literature.
• If the article is to be kept, I think it still needs work from an NPOV standpoint (e.g. to avoid making judgements about what is or is not an "interesting" fact), but I'm having trouble thinking of appropriate wording that accurately summarizes and attributes the hypothesis without making unsupported speculations; Clarkgf seems committed to keeping it just as it is, and has stated that I don't know enough about the field, so other editors' comments would be helpful.

Thanks. ←Hob 23:18, 4 November 2006 (UTC)

User:Hob asked for a reference for this hypothesis. It took a long time to find one published by a world class expert (Bette Korber) that is also available to everyone on the Internet, but there is one available [4]. This review involves the significance of shifts in HIV or SIV genomes and the implications of such findings for viral pathogenesis. This article is specifically focused on shifts in glycosylation and the implications arising from this work.

I did not ask for a reference "that is also available to everyone on the Internet", just any reference that is evidence of other scientists discussing your hypothesis. That article certainly does cite your work, but only for the very broad statement that "AIDS progression may be related to the glycobiology of the virus"; there is absolutely no reference to the eu-FEDS hypothesis and its specific claim that certain glycoproteins help pathogens to evade immune response because they are similar to a mechanism used to protect a gestating fetus, which is the subject of this article. Such a citation does not lend notability to the theory. I have in front of me a long list of citations of your articles (Google Scholar turns out to be very good for this sort of thing); I can only get abstracts of most of them, so I don't know the context of the citations, but in the cases where I've been able to check, they have been on specific points like this and do not constitute discussion or acceptance of this hypothesis. ←Hob 19:07, 6 November 2006 (UTC)

You have some very different ideas about what a reference is. Apparently, for you the acronym has to be completely spelled out, even though the concept is explained in the context of the statement leading up to the reference! I am sorry, but in my view this argument now reeks of the semantics of "legal eagles". But then again, the concept of "no personal attacks" somehow coexists in your mind with direct inferences that this model is simply a "wild guess" lacking any semblance of logic or evidence in its favor! I have never faced any attack like the one leveled here from any of my colleagues or even my competitors. Diplomatic this discourse is NOT! My colleagues in science would certainly be more reserved and measured. Perhaps it is because, in spite of any personal reservations they may have about this paradigm, they know in the back of their minds that this hypothesis has an excellent chance of being proven correct.

After today, I will not respond to any more of your comments.I have had enough.--Clarkgf 22:39, 6 November 2006 (UTC)

I'm sorry that you feel attacked; that is not my intent. As I have suggested before, I think you should read the Wikipedia guidelines concerning verifiability, and the difference between a personal attack and a disagreement over article content and references. I don't know how to explain this any better, but I will try again: your model might be absolutely correct in every way and be a staggeringly important discovery, but that has very little bearing on whether this particular article text is appropriate Wikipedia content. What we do here is to summarize verifiable facts about subjects that are deemed by consensus to be notable, and there is a very high bar for that when it comes to hypotheses. If your colleagues really are discussing your theory extensively in the literature, then it is likely notable. But the single example you have given so far is not, as far as I can tell, a good example of that.

As for whether my description of the citation in question is accurate, I will leave that to other editors to decide, since the article is readily available through the link above. It's not just that it doesn't say "eu-FEDS": it makes no mention at all, in summary or paraphrase or in any way that I can see, of your theory about the role of glycoproteins in protecting the fetus from immune response, which (according to your own summary in the article) is the key distinguishing feature of the theory. It simply cites you as a reference for the statement that "cell-specific glycosylation profiles may affect immune susceptibility, and AIDS progression may be related to the glycobiology of the virus". ←Hob 02:34, 7 November 2006 (UTC)

Still waiting for the response on the HepC and its persistence without pathogenesis.

Well if you're interested in scoring points off me, feel free to take that one because I have no time to dig up articles for you. And since I didn't make any claims about hepatitis C pathogenesis in a Wikipedia article, I don't really have to. Anyway - it may well be a bad analogy, it depends on whether you mean no pathogenic effect or just no development of symptomatic disease, but it's hardly uncommon for people to go 30-40 years with mildly elevated LFTs and no development of cirrhosis, and die of unrelated causes; most of the damage is not a direct effect of the virus, but a byproduct of immune response, which in many hosts is quite weak. All of which makes it harder to see what is so remarkable about your SIV example when you put it in such broad terms - but again, that is hardly the main point here. ←Hob 19:07, 6 November 2006 (UTC)

Again, making statements without providing references. Not the Wiki way, even in a discussion like this one. Interesting that several investigators (e.g. Kurth and Norley) have worked on this "trivial" question for the past seventeen years. Interesting that immunologists scratch their heads when confronted with this observation in the appropriate contextual setting. And it is interesting that every time a speaker discusses this topic at an AIDS meeting, everybody follows every word of his/her talk. Next time I will question such investigators about how they can be so clueless that as to spend so much of their time and effort on this completely trivial non-issue. Too bad that many working on this "not quite so able" topic also believe that any model for AIDS pathogenesis must also explain this paradox. Those dumb scientists, what do they know?--Clarkgf 22:39, 6 November 2006 (UTC)

I don't know what you think "the Wiki way" means, but again, the subject of this article is not hepatitis C. I may have used a poor analogy in my comment on this talk page, but again, what is in question is the basis for the statements you added to the articles - specifically, whether monkeys who show no ill effects from SIV are still losing CD4+ cells at the same rate as human AIDS, which is not what the cited articles appear to say (and, if it were true, would hardly seem like an example of no pathogenesis). That is an entirely different question from whether this is an important field of research. ←Hob 02:34, 7 November 2006 (UTC)

It is difficult to follow the logic of all the arguments here. It is very challenging to completely understand a broad hypothesis like the one presented in this article. It may be difficult if not impossible for an editor or even a set of editors to come to a consensus, because normally hardly anyone attempts to cross so many areas of research (reproduction, pathogenesis, classical virology, retrovirology, glycobiology, proteomics, genomics, etc.) at the same time. That is what broad hypotheses try to do, but that is why they generate such acute responses as observed in this discourse. No matter what happens here, in the end this debate should be available for posterity.--Clarkgf 07:45, 6 November 2006 (UTC)

Again you're confusing an encyclopedia with a scientific journal. The purpose of writing articles here is not to carry on a debate, or to point to promising new directions for inquiry. Editors are able to achieve consensus here very often in complicated fields where we're short on expert advice, by sticking to the rule that when in doubt we must be cautious and say only what is verifiable. ←Hob 19:07, 6 November 2006 (UTC)

Again you are confusing a hypothesis with a factual article. A theory is not the same as a group of facts that are well established. Einstein was for many a scientist with very fringe ideas until observations made during a solar eclipse proved that the sun's gravity could bend light rays as his model predicted. Then he became more famous than the Beatles. What you are saying is that his theory would never have made a Wiki article before that eclipse, though they could explain many non-Newtonian observations that were completely evident at that time. But his work should have been accepted if he had taken the time to present it in an understandable format. --Clarkgf 22:39, 6 November 2006 (UTC)

Comparing oneself to Einstein, and claiming that your colleagues "know in the back of their minds" that you are right, is not a good way to win confidence in this forum. ←Hob 02:34, 7 November 2006 (UTC)

I am making an exception for User Hob for this vastly misleading passage. It is now clear that this reviewer is putting words in my mouth. I clearly said that my colleagues know that it is very possible that this model is correct. Otherwise I would never have been NIH funded to pursue this line of research. If there was just one scientist on the review panel for this application (known as a study section) that disagreed as vehemently as this reviewer did, there would have been no way that these studies would have been funded! Not only that, but this grant was funded in the first round of its application, which is like the chance of being struck by lightning (ask any NIH funded investigator to verify this fact). By contrast, these comments (though somehow deemed "diplomatic" by this reviewer) basically imply that this hypothesis is nothing more than the rantings of a village idiot! Somebody is massively wrong here, and I do not believe it is me.

As for the comparison to Einstein, this passage is again extremely misleading. I was simply saying that he faced a similar uphill climb for the acceptance of his model for relativity. At this particular point in time, there is no other hypothetical model that attempts to explain all of the different observations that are made during the development of AIDS, or the induction of tolerance to SIV in its natural hosts. This reviewer thinks that this model is not noteworthy, and that is this reviewer's right. I respectfully disagree with this assessment. Any reasonable model that employs rational arguments to address one of the most critical health issues of our time should be immediately noteworthy. That is my final word on this matter. Let the chips fall where they may.--Clarkgf 16:59, 7 November 2006 (UTC)

That is a very reasonable common-sense definition of "notable", but it is not what "notable" means on Wikipedia. As for diplomacy, please see your user page. In general it is best here to stick to responding to the specific points being made, or even better, to stick to talking about the actual article text and proposing ways it might be revised or clarified—something I have really failed to do so far. When other editors join in here, maybe that will be easier. ←Hob 18:40, 7 November 2006 (UTC)

The following response is duplicated from the user page:

For anyone who is reading this passage, sorry, but I am a world class expert in this area of research. Some issues have been raised about the validity of my statements. Proof for NIH funding can be found by going to the NIH CRISP web site [5] and entering Clark, Gary under investigator name. Notability was also suggested to be a major issue. The Gordon Research Conferences are the oldest and most prestigious meetings on science and engineering in the world, and they represent the leading edge of scientific thinking. I gave a talk at a Gordon Conference last year in Ventura, CA with the following title: "The immune-reproductive nexus: the key to understanding many human pathologies?" This talk was centered around the eu-FEDS hypothesis that relates pathogenesis to the induction of tolerance to the developing eutherian. Evidence confirming this seminar can be found at [6]. This confirmation should invalidate any claims made suggesting that this hypothesis is not being accepted, or that it involves some "wild guess" by the village idiot or insane person.--Clarkgf 23:31, 9 November 2006 (UTC)

The Difference Between True and Notable

This has dragged me back from an informal wikibreak brought on by far too much to do at work, so I'll be brief. It seems to me, although no one has exactly said this on either side, that the issue in the debate over this article is whether or not the eu-FEDS hypothesis is the correct model for this that and the other. Simply put, that issue has nearly no relevance to the matter at hand. I am not myself a doctor. I am not a medical researcher. My last science classes were in high school. As such, I am in no place whatsoever to evaluate emerging medical theories. That is the job of the NIH, scientific journals, and other experts. It is not the job of Wikipedia. Instead, we the editors of Wikipedia must evaluate whether a given topic has received sufficient treatment in scientific journals and by scientific experts to merit an article. In my opinion, eu-FEDS passes any test of scholarly exposure to merit an article. The article is extensively referenced, as well as many featured articles. Furthermore, the material in the article has been published in reputable journals by Dr. Clark and his collaborators, and has apparently been referenced in numerous contexts. I am no rabid inclusionist but I am absolutely certain that this subject merits an article.

On the subject of linking to this article from others, I may stand alone in this view, but I believe that any article is worthy of a link from any other, so long as the link is relevant. Perhaps, disclaimer-type language is necessary in certain contexts, but what can a link or reference hurt? As for neutral point of view and such, I am much more accustomed to dealing with neutrality issues in the context of typically more contentious fields such as history and politics, so I will yield to the judgement of others more familiar with biology and medicine. In closing, I believe that the entire discussion on this page has become overheated and underly concerned with the actual text of the article (as per Hob above). Consequently, I would like to ask that those concerned about the article make concrete suggestion for improvement, or if they feel so move make a deletion nomination (I feel confident that such a nomination would fail, but I may be wrong). Anyway, I'm rambling so every one have a pleasant evening. Cool3 00:01, 11 November 2006 (UTC)

Well, I certainly agree that notability is the key (and I agree that things have gotten overheated). But I'm not sure I understand why you're so absolutely certain about this case. References in the article don't convey notability, and neither does publication in reputable journals (thousands of peer-reviewed papers are published every year). The issue was whether other sources are referring to this particular subject - I mean, specifically to the "eutherian fetoembryonic defense system" theory, either by that name (which, as far as I can tell, is not used by anyone except Dr. Clark and his co-authors) or in paraphrase. If I understand correctly, the gist of the hypothesis is that (a) particular glycoproteins may function as a sort of white flag to protect a fetus from being attacked by its mother's immune system - and (b) disease-causing organisms could avoid being attacked by mimicking and manipulating human glycoproteins; it's the leap from (a) and (b) that would make the model so significant. But so far I've only seen other sources refer to Clark et al. as a source for either (a) or (b) separately. Say Galileo publishes his finding that there are little lights going back and forth near Jupiter, deduces that they are moons, and goes on to construct a model of the solar system. If Renaissance Scientist X writes "there are little lights near Jupiter, as Galileo observes", does that mean X is discussing Galileo's model of the solar system? It does not.

I originally didn't want to nominate this for deletion because what I really wanted was for Clarkgf, or someone, to clarify the context of all of this and locate these other sources who are discussing it. But now I'm leaning toward the notion of deleting the article and moving the separate components of it into other related articles, such as immune tolerance and the HIV pathogenesis article that doesn't yet exist. It would be fine for those articles to say something like "another theory is that glycoproteins etc. etc. (Clark et al., 1997)". But in order for Wikipedia to recognize the notability of a package deal called eu-FEDS, others would have to be discussing it as a package deal. Based on his comments here and elsewhere (e.g. this blog comment) it seems that Dr. Clark is quite passionate about raising awareness of his work and wants Wikipedia to have a page for that purpose, but that's not necessarily a good reason for it to have its own article. Again, I welcome further evidence to change my impression. ←Hob 18:32, 11 November 2006 (UTC)

I rest my case. I think that this work is notable and getting more so. I believe that it will be a mistake for Wikipedia to delete this article based on this strong interaction with User Hob. After all, the real proof of am model like Eu-FEDS is the direct intervention in pathological states, and those studies are now underway. So go ahead and delete it if you wish.--Clarkgf 14:26, 12 November 2006 (UTC)

I'll admit that my statements above were somewhat excessive, including the statement that I am "absolutely certain" that an article is warranted. However, I do believe that this merits an article. In any case, I'd like to direct everyone's attention to Wikipedia:Notability (science), which is just a proposal but nonetheless could play an important role in this discussion. Examining the criteria there, I find that the eu-FEDS hypothesis satisifies criteria 5 in that it has received NIH funding. It might also meet some other criteria, I'm not quite sure. Once again, I'm very pressed for time right now (which may explain the exaggerated nature of some of my earlier statements), but I think that this discussion will in all likelihood not lead to a satisfactory answer. In many ways, this talk page is becoming an informal AfD discussion. Perhaps, Hob should open one so that what I believe to be underlying issue of whether the topic merits an article can be addressed. Cool3 23:04, 18 November 2006 (UTC)

The abstract of the grant makes no mention of the hypothesis, nor is it mentioned in the keywords, so I'm not sure that it's entirely accurate to say that the hypothesis "has received NIH funding", but clearly the author is funded by NIH, and that grant is associated with work connected to the theory. Pete.Hurd 03:48, 20 November 2006 (UTC)

Additional $0.02 from a fellow user

I am a physician, but not an expert in this subject.. I can see that this is definitely a complex topic. I am still an infant when it comes to writing for this format, and this is not a trivial problem: medical literature vs. Wikipeida. I think after reviewing the above discussion there exists a problem of perspective that might be difficult for someone not familiar with medicine/basic sciences.

We appear to be blessed by having the first author of the journal article willing to author a Wikipedia article on the subject. Similarly we appear to be cursed by the same fact.

I am still struggling with developing these skills here. We know than an encyclopedic treatment of a subject is a poor medical literature review and vice-versa. I just quickly searched this subject using our university databases and included all available Medline databases (here are the databases we have available)

This search reveals a single reference to this theory, published by the author in 2001. Seems to indicate that the evolution of this theory remains in its early infancy, and as such is by definition not a widely accepted theory on the subjet (yet).

The only "assistant editors" I see here have noted wishing they had more experience in basic sciences, medicine, and using medical literature. Finding full text articles from a medical library is sometimes not trivial for someone not employed at a tertiary care center. I am still an amateur at writing in this format, but I am having fun learning and enjoy the challenge.

If the involved parties are willing then I would be willing to volunteer to attempt to edit contents for form without substantially altering the content. I will need a second layer of editing from someone with more experience in this style of writing as well.

I certainly dont wish to step into the middle of a fist fight, but I do have access to less mainstream medical literature and have a decent background in molecular biology, evidence based medicine, judgement and decisionmaking theory, and I understand the basics of glycoprotein signaling (and how mistakes lead to illness) etc.. So, I am willing give it a try if Dr. Clark would agree to the effort as well.

I will keep an eye out for a response. I will be participating in an amateur radio contest this weekend and wont be able to spend any real time with this before then, and I have my own research that is being picked apart by our IRB at the moment so I will be doing "real work" that will probably interfere with the project a bit as well - but it looks as if this is not on any deadline.

Williamwells 05:51, 17 November 2006 (UTC)

You don't have to ask permission! Everyone's contributions are welcome. Questions of style can be hashed out as needed - that's part of what this page is for. And stepping into the middle of a fistfight is often a good idea here; it's much harder for a fight to proceed when there are more than two points of view. ←Hob 19:08, 18 November 2006 (UTC)

I am too busy to continue debating this issue. I will just come by once a week to see what changes are being made.--68.111.90.67 02:49, 20 November 2006 (UTC)

I understand the permission issue, but I also understand that by collaborating more progress can be made. This process can be time consuming and if I were to publish original research, then take the time to try to explain it here, I would be diappointed to see edits without discussion that I perceived were not accurate. I dont want Dr. Clark to perceive this as anything but an attempt to furter "translate" the concepts into an encyclopedic entry instead of a medical journal type format and I will need his help to accomplish this as I will not be sufficiently familiar with all the aspects of this research to do so.

That said - I will attempt the initial outline and start posting issues I encounter here in discussion first. If all goes well these will go to the article soon afterwards.Williamwells 04:43, 23 November 2006 (UTC)