Hello Bryan,
I will comment on your posting piece by piece.
» I don’t believe he ever states explicitly that full thickness is a
» “necessity” for a viable transplant. For the benefit of the other readers,
» here’s a direct quote from the study: “For alopecia prematura [the
» old-fashioned name for androgenetic alopecia] these studies would seem to
» indicate that the determinants of growth of strong scalp hair or of
» baldness lie within the local skin tissues of a full-thickness graft and
» suggest that the pathogenesis of common male baldness is inherent in each
» individual hair follicle. Probably each individual hair follicle is
» genetically predisposed to respond or not to respond to androgenic and/or
» other influences that inhibit its growth.”
What is your objection here: that I used the word “necessary” to describe a dependency link in the experiment, or that you don’t believe that the necessity of full-thickness grafts is implied in this article?
“Necessary” is the correct way to identify this key component of the experiment which is a dependency link between full thickness grafts and growth of strong scalp hair.
The experiment described in the 1959 Orentreich article was conducted using full-thickness skin grafts. I did not quote him. When I quote text I use quotation marks, just as you do. I rather explained in my own language what Orentriech did and I have tried to evaluate the experiments and summarize and emphasize what I considered important in the study, as his scientific statement in my own words. In the section you quoted from the article there is a clear dependency link between growth of strong scalp hair and full- thickness grafts: ”growth of strong scalp hair or of baldness lie within the local skin tissues of a full-thickness graft”. This means that, for the purpose of this experiment, a full thickness graft was understood as a requirement for the growth of strong scalp hair; this is why it is mentioned repeatedly in the article (read also the Methods section where “full thickness circular incisions were made”). The article is about an experiment with full-thickness grafts and it would not have been done that way if the experimenters have not considered that significant to the success of the experiment. You would be right to say, whatever this article says, that full skin grafts have been shown not to be necessary for a successful implant; that is also what I say, and indeed successful individual follicle transplants prove that. However, Orentrieich’s opinion about the importance of full-thickness grafts was expressed quite explicitly in this 1959 article; indeed in time some statements in the article have been proven somewhat erroneous or at least in need of additional evaluation, but that doesn’t alter the fact of their inclusion in the article.
This study was carried out using full skin grafts and, in any experiment, what is done rules. This means that how the experiment is conducted is more important than how it is phrased in being written up and even how readers interpret it. After an experiment is conducted it is no longer in the experimenters’ domain nor under the authority of the experimenters, and every one else’s understanding of the results is as legitimate as that of the experimenters. It is however, in respect to the experimenters that what they say about their own work is discussed and emphasized. In my opinion this experiment with its use of full size skin grafts never gave any chance for the “recipients’ dominance” theory to even be tested. Full-size skin grafts eliminated much of what the recipient skin could offer for the recovery process, so it was reduced to performing mainly as a blood supply template for an implanted skin section. They only tested donors’ dominance over different blood supply templates. Only the more recent 2003 Krajcik-Orentreich work gave a chance to test recipient dominance and strongly confirmed that it is a valid concept.
My statement about the authors’ distinction between “follicles” and “skin” in the article is also not a quote but in the quotation you brought up you can see that he stated ”growth of strong scalp hair or of baldness lie within the local skin tissues of a full-thickness graft” where he links between growth of strong hairs and the scalp tissue as a whole, versus ”pathogenesis of common male baldness is inherent in each individual hair follicle” where he attributes the bad things specifically to the follicle rather than to the entire tissue, and so he makes a clear distinction between the general scalp tissue (of full thickness) and the follicle itself. I also stated that his assumption that the bad things are in the follicle are not actually suggested by this study and that the most that can be said is that the experiment does not rule this option out.
» When looked at in the light of the other evidence like Nordstrom’s study
» and the fact that “follicular unit” transplantation is now so popular, I
» think it all pretty much proves conclusively that individual hair follicles
» ARE “preset” for balding. Furthermore, without making the assumption that
» hair follicles are individually “programmed” to respond to androgens in the
» way they do, it would be difficult to explain the in vitro
» experiments which have clearly shown such differences.
Are people with high genetic susceptibility to develop cancer from cigarette smoking or people who react severely when they are in contact with peanuts are preset to die young? Well, it depends. If they can avoid cigarette smoking or peanuts respectively, they can live to a very old age. People are different from each other in some details but most people have a similar life-span range (with some exceptions) which becomes more clear if compared to the life span of rats which is 2-3 years. The range within a species also varies but I will not get into the aging issues right now, just to mention it as worthy of consideration in the context of follicles. Follicles are also different from each other, even in the same individual. They have differences in their respective genetic setup, but does it make them preset to shrink and than die when the person is about 25-35 years old? Well, that depends on whether they can avoid certain environmental stress within their immediate environment which is deadly or constricting to them and instead get good nutrients that can sustain them and accommodating space to develop. The bio-environmental aspect is a bit complex. There is a grey area where genetic and environmental factors are intermingled. Cells which have their own genetic limitations (preset) can act as an environmental setting for other cells in their vicinity. For example: cells which create a dense network of fibers may cause mechanical and even chemical suffocation to cells or tiny organs within their vicinity. Bio-environmental studies have not developed to that point of understanding yet, but what is important about any new theory is not only that it is a new, but does it have a new practical value? Can new solutions be sought on this new ground? In other words, can it be applied as a new working model? The 1959 Orentreich article, with its donor-dominance approach and with the author’s own dominance in the early development of the field of hair loss, contributed much to further studies of hairloss on one hand but on the other hand also stalled potential studies which could have be done long ago regarding the recipient’s role in hairloss; having one view so strongly established meant that much other valuable data and understanding about hairloss did not come through. It is therefore very important before a new working theory takes off to ensure that the benefits of focused research will not be over-shadowed by ignoring other aspects which may hold the key for a true breakthrough. When a working theory is established it becomes a “mainstream” endeavor, with the usual money flow and the comfortable aura of respectability which surrounds scientists who undertake significant studies in the mainstream of research. It discourages many scientists who think otherwise to try and explore their own theories because research is very expensive and they may be labeled as “eccentric” or “lunatic fringe” scientists and most people are not comfortable with such titles. It may be an unavoidable circular trend but it should be minimized when possible
» It’s a far cry from simply transplanting hair follicles to a different
» location on the same person’s body, to transplanting them to a severely
» immune-deficient mouse!
It is much more amazing that the hair grows in the mice, which are alien to the donor, than it would be if they grew in another skin area of the donor himself. One possible reason that they did not grow in the same donor skin is the use of large transplant grafts. There may be other problems which can be related to less than adequate recovery-support conditions in the recipient skin area but, as I said before, many experiments which were done may yield different results when repeated with individual follicles instead of large grafts.
» This has been a major source of misunderstanding in the past, so I want to
» be absolutely sure that you understand my position: I’m not saying that
» the surrounding tissue has no influence at all on hair growth, because the
» recent Korean studies have clearly shown that it can influence the length
» of hair growing from transplanted hair follicles. What I’m saying is very
» very specific to ANDROGENETIC ALOPECIA: that specific medical condition
» isn’t affected by the surrounding tissue. Hair follicles clearly display
» donor dominance for androgenetic alopecia, but not necessarily other
» alopecias or other medical conditions.
I already commented on this before but I will just add that differences in sensitivity to androgens (assuming that this is even the real picture) within different follicles are not the same as a preset clock for the demise of that follicle. That is also why I have difficulty with the term “apoptosis” because if there are anti-apoptotic avenues that it is not true apoptosis. The concentration of androgens and other factors can be seen as environmental to the follicle. The demise of the follicle is not preset by some genetic vulnerability alone.
» I don’t see any contradiction between those two articles.
I said “apparent contradiction”: this is a rhetorical device, customarily resolved by clarifying how independently-developed ideas support each other in un-obvious ways. I did resolve it by explaining why, in two systems (same person or immune-deficient mice) with no immune issues in either of them and where same-person implants seem more likely to succeed, they failed while the implants into the mice succeeded. The human implants into human skin were large grafts and failed. The human implants into mice skin were individual follicles and succeeded. In combination, they show that grafts can fail under non-hostile circumstances and follicles can succeed under non-supportive circumstances.
» So how do you explain the success AND donor dominance of modern
» transplanted “follicular units”?
Give me a specific example with a reference so that I can better understand your question.
» Well, I still feel that the 2003 Krajcik-Orentreich study needs to be
» duplicated by other researchers. Furthermore, there still remains the
» issue of exactly WHY they got the results that they did. The lack of a
» functioning immune system in the animals may well have something to do with
» that, and we can’t just assume that something in the “surrounding tissue”
» was what did it.
I have no problem with that but people don’t routinely duplicate published work; it is assumed that scientific work is duplicated and/or triplicated before it is published. In order to give a new study an incentive, it should cover something new that was not done in the original study or was incomplete in the original study. I would suggest doing the same study comparing individual follicle implants versus larger grafts in nude mice. I would add another twist to that by suggesting that the experiment also be conducted on athymic nude mice in which wound healing is reported to produce skin with very different physical strength and elasticity. This can also evaluate the role of physical tensile forces on the well-being of the follicle.
» » In my previous response I posed the question of whether drugs which are
» » meant to attenuate the immune system (like after kidney transplant)
» grow
» There’s an interesting case history reported in a medical journal of a man
» who had been receiving significant amounts of cyclosporine for a long time
» for an unrelated medical condition. He had developed very significant
» hirsutism over his body, but it did NOT alter the course of his
» androgenetic alopecia in any way. He still continued to go bald. The
» authors seemed to think that such immune suppression has no effect on
» common male balding. If you haven’t read that case history, I can provide
» you with the full citation.
Only a certain percentage of people develop this problem and for many it disappears after some time. There is a lot of cumulative knowledge about this and it has been a relatively busy area of research for quite a while.
» Yes. Dr. Proctor stated several years ago on alt.baldspot that
» cyclosporine’s (alleged) favorable effect on balding probably has nothing
» to do with its effect on the immune system. Of course, that also makes
» interpreting the immune-deficient mouse study even more problematical!
More power to him.
Thank you.
Elishalom Yechiel, Ph.D.
President
Elsom Research Co., Inc.
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