The Mc Ginley Question

About 4 years ago I wrote a very sharp critique of the work of Julienne Imperatio Mc Ginley and possibly made a real dog’s dinner of it. So hey articles I write that are not entirely correct I tend to forget about. However I have recently been forced to reconsider revising this article due in part to the claim that there is a bias towards identifying as male among 5 alpha reductase-2 deficiency patients. I am such a patient and no I do not identify as male. My problem with Mc Ginley was not so much the assertion of universal “Maleness” as where the connection lies between the genetics involved and this “universal maleness” I actually cannot see it. I ended up writing a rather lengthy article trying to figure it out and ended up going round in circles. In my somewhat considerable anger at the time, the molecular biology aspect of it just made no sense (It still doesn’t) My attempts to look at it probably made even less sense.

So I really need to consider Mc Ginley’s work in the spirit it seems to have been written, that is via a fragmentary approach and discuss separately the various issues Raised by Mc Ginley’s work.

These are as follows.

1: The limitations imposed by Mc Ginley on her subjects in terms of who was a subject for study. And who was not.

2: The limitations in terms of sample sizes, most notably studying people from very small (Often familial) gene pools.

3: The utter confusion about the molecular biology involved. Involving a frameshift mutation and a stop codon.

4: The fact that anthropologists pointed out that the cultures local to where she studied these people were very patriarchal.

5: The clinical description she gave of this condition.

Imposed Limitations:

In one paper Mc Ginley states:

"A-IV-3 is a 45-yr-old subject, born with ambiguous genitalia and raised as a female, although known in the community as an affected child. The subject did not change to a male gender role at puberty and remains the only known affected person not to do so in the community. A moderate amount of facial hair was present. Blood and urine samples were provided, but a physical examination was declined."

Well this is not unusual for Mc Ginley if she does aknowlege a subject not identifying as male she seems to have issues with it. More often than not she simply ignored those who did not identify as male, choosing to exclude them from the study. My immediate question is why when she often stated “People with 5 alpha identify as male 100% of the time” she had presented evidence to the contrary, and then so evidently tried to dispel it. However objective or subjective her work may have been this does raise a few questions. In one study she excluded two people because they didn’t go with being “male” she even said so, and yet we read “100% of the time”.

As someone who since she published her work has been questioned about my “Gender” implying “I should identify as male” I am far from impressed about this to put it mildly. I would not mind so much but I do not even have the same alleles that these people under study had. Meaning that this condition has manifested differently in my case.

It should be obvious to the layperson that there is something not quite making sense when Mc Ginley states there are people who do not identify as male, and then goes ahead proclaiming all identify as male. Bringing about arbitrary statements form people like Hughes in his DSD consortium where people with 5 alpha “must” identify as male. (Transitioning from female to male is preferred it would seem in that case, no thanks).

Gene Pool Limitations:

What I find unsettling about Mc Ginley is this idea that double recessive genetic conditions are always familial. This is not strictly true, the rarity of these conditions usually means that we do end up with a higher proportion of people affected from specific families, but in the wider gene pool it is not impossible for two recessive genes to occur, look at eye color. So logically it is not impossible for two different alleles that do not work, that are also recessive to occur in an individual. In Europe and the US this is also more probably what will happen because of the wider mix of people. And yet Mc Ginley argues that the familial model is the defining model. I do not buy it quite frankly.

I ended up asking myself some very unsettling questions from a different perspective when I read all this, Like why go flying off to far flung exotic places to study tiny gene pools to prove some hypothesis. If for example (As again I often hear) 5 alpha is almost unheard of in the west, and only prevalent in ethnic minorities, (Which is not quite true), is there some Racist undertone to all this? People of a slightly dodgy disposition have a tendency to do this, fly off to some exotic location and study the natives to prove some point about ethnic superiority. I do have these mental images of Mc Ginley flying off to study some tribe of natives with a pair of skull measuring calipers and a checklist of markers of racial inferiority.

This is the impression you get when reading Mc Ginley’s work, it may indeed be because I am particularly sensitive to such shenanigans but then again it may not. My problem still seems to boil down to the idea of using familial groups in far off countries to define people in the wider population.

Again none of this makes much sense when you look at it. Whatever the real reason was for the study of limited gene pools it leaves a lot of open ended questions.

Molecular biology:

Last time I made a dog’s dinner of this, why? Well I could not figure out how a frameshift mutation could result in a “male gender identity” I can see how in a coding region it would stop the production of the enzyme 5 alpha reductase, you either get a working enzyme or you do not. The problem I have is that 5 alpha reductase deficiency does not always result in a complete lack of it. It can vary, there are also more than two places where it is coded for, so that makes life more complicated. Either way, what this describes is the potential to metabolize testosterone to dihydrotestosterone, not “Gender identity” in fairness yes androgens are involved in the formation of a “male identity” but people with AIS who are insensitive to DHT seem often to end up identifying as women, even in partial AIS it is more common, not absolute, but more common.

And this is where Mc Ginley stopped making any sense. It became a strange read.

"Using single strand DNA conformational polymorphism analysis and DNA sequencing, a new mutation in exon 5 of SRD5A2 gene was detected in certain male pseudohermaphrodites from this kindred. This single base deletion (adenine) resulted in a frame shift at amino acid position 251 resulting in the addition of 23 amino acids at the carboxyl-terminal of this 254-amino acid isozyme."

Oh I jumped on this myself thinking a lot of nonsense about restriction enzymes in her lab tests and so on. But now I am not in such a bad mood let’s revisit this. I said in the last article that what is being stated is that a "stop" codon is read as a codon that codes for another amino acid due to it being shifted back by one base. (A-T being deleted). So the next stop codon occurs at a further 69 bases along the nucleotide.

Basically we can do a very simple demonstration of this, “AATGA” is interesting to use, TGA is a “Stop codon” that means when you find this, you find the end of the coding region of an exon. Knock out the A at the beginning and you will have ATGA in which an ATG is both a start codon and also codes for methionine.. Well that would result in an enzyme that was an “isozymne” which was different. (Actually longer) because it will keep reading more amino acids into the peptide chain until you reach another stop codon.

What Mc Ginley described was supposed to be this:

“CCATTCATCTTTTAA” (With TAA being the stop codon) turning to this (CCTTCATCTTTTAAA) where the CCA at the beginning of this sample is cut to CC so the TAA reads as AAA basically, (The trailing “A” being the next A in the sequence).

Well CCA is not a stop codon. And what Mc Ginley was saying confused me a little. I was a bit frustrated by this discrepancy and asked myself why are we talking about the carboxyl terminal, if it is two amino acids back from the carboxyl terminal in the peptide to begin with? How then were the additional amino acids "added from" the carboxyl terminal onwards.

My frustration lay in the fact that Mc Ginley was vague about the molecular biology.

My reasoning being that Mc Ginleys description seemed to imply that the additional amino acids started at the end of a “normal”strand when in truth they started a few codons back. In the “normal” sequence from the frameshift onwards we read “Pro-Phe-Ile-Phe-Stop” and in the mutation we read “Pro-Ser-Ser-Phe-Lys”. Call me a pedant but this irked me when reading the description and looking at it myself.

I continued last time by asking If the mutation does actually occur at the portion of the nucleotide that codes for position 251 as opposed to 253. Was there some artifact in terms of the restriction enzymes used to look at all this? Well I have since looked at that possibility and realized that this is where I made a dog’s dinner of my argument, because the nearest cleavage site is way back towards the 3’ and requires Bam H1 to cut it. You see most papers I have read are usually much more clear, Describing in detail the lab methods, the materials and tools used, and something of the sequence data. But I am still asking what this has to do with gender identity. The only thing I can ascertain from Mc Ginley’s comment in her paper is that we have a bit of a mutated enzyme and this in itself tells us nothing about the overall assertion.

Either way I am still not sure what that would have to do with “Gender identity” because this addresses little more that the ability of one resulting enzyme to work or not, the one coded for by the normal gene will have a peptide coded for by exon 5 that will work, in the gene under discussion it will not work, the secondary structure will be different. (By having extra amino acids in the peptide chain).

My lesson? Don’t be hasty and over pedantic because my question ended up having little to do with the question I should have been asking. But there was a genuine problem in the description of this mutation, “The addition of x amount of amino acids and the substitution of 3” would have made more sense. Does Mc Ginley make a dog’s dinner of it in the first place? Well my answer to that would be yes. Because the actual description of the mutation is a bit vague, but the assertion that this somehow “Maketh a male identity” is as absurd my then ranting about cleavage sites at the time. You see other papers made more sense, look at the following:

"A transition at the second nucleotide of codon 85 in exon 1 (GGC --> GAC - Quoted as DNA not mRNA) substituting glycine for aspartic acid, can occur"(Vilchis F, Mendez JP, Canto P, Lieberman E, Chavez B. 2000)

That makes sense to me, none of this vagueness, just “This is a substitution changing this amino acid in that peptide for another”. I have found that other researches describing even frameshifts and so on more readable, and often describing the effect on the enzyme (in this instance).

Anthropologists:

Gilbert Herdt was perhaps a very strong critic of Mc Ginley and stated the following:

"It is hard to see in this forced outcome nearly twenty years after birth strong evidence for a hypothetical effect of male testosterone-exposed brains overcoming gender role socialisation. I am impressed much more by the continuity in gender development that was interrupted only by the ultimate failure of the hermaphrodite's body sexually and reproductively to deliver what was necessary for her to fulfill her social destiny."

Meaning in plain English that there were evidently more social factors involved in any “transition to the male role” than there were genetic factors, for me that makes more sense, My problem with Mc Ginley however seems to be where there is little or no linkage between biology and “Gender identity”. Mc Ginley just makes vague comments about the genetics involved, leaving me a bit confused as to the molecular model she is trying to convey. You see her biological argument does not seem to stand up it merely describes (Badly) the genetic mechanisms involved. And then makes this quantum leap from nucleotide sequence to gender identity, the lack of the sum effect of DHT is telling. There is no evidence from what I know of that the lack of DHT still results in a “male gender identity” And what Herdt is pointing out is that this “male identity” issue seems more to do with social factors. It is as if Mc Ginley walked into the situation, picked out those who had “transitioned” to male and simply re-enforced the local custom of people turning male. By blinding everyone (Even me, the reader) with science.

The way it works seemed like “this aircraft has engines and can fly this aircraft has no engines but still can fly as a glider, and the fact that the engine uses fuel and is either a propeller or a jet proves that the glider can fly”

Herdt picked this illogic up by pointing out in what that can be illustrated by saying “Well the glider can fly because other aircraft pull them along” I am here picking up the illogic by asking what has the engine fuel and what type of engine it is got to do with the glider in the first place?”

Clinical Presentation:

In a way this is a culmination of the previous points. Mc Ginley was at great pains to point out that people with 5 alpha are born “outwardly female” with a vagina and clitoris, And with the onset of puberty they grow a penis and sexual differentiation to male takes place. So in the Mc Ginley scenario the cild is a girl until puberty she then virilizes and becomes a “Fertile and fully functioning male”.

That is not strictly true, I mean often 5 alpha was misdiagnosed as PAIS  in the past, that means that the genitalia would have had some visible ambiguity. Myself I was born with ambiguous genitalia, There would have been no surgery if this was not the case would there?

What Mc Ginley says is that there is a fixed and immutable clinical presentation for 5 alpha reductase deficiency when there clearly was not. It may well have been the case with the people she studied, but then we are talking familial groups in very set societies. Societies as Herdt pointed out that had their own narrative for this situation in any case. The problem is that this goes beyond just the clinical presentation, you see today we often find treatment protocols being drawn up for 5 alpha and this male bias invariably appears. And outside Mc Ginley’s work there is no scientific justification for it.

Most work I encounter that talks of “male identity” seems to quote heavily from Mc Ginley. But here is the problem, when I go into a clinic for the first time, the first thing I am asked is “Why do you not identify as male?”  It was such an incident that caused me to write my rather caustic article about Mc Ginley a few years back.

Well Today it is now “official” Read the writings of one Professor I A Hughes and we read:

“Evidence supports the current recommendation to raise markedly virilised 46,XX infants with CAH as female. Approximately 60% of 5a-reductase (5aRD2) deficient patients assigned female in infancy and virilising at puberty (and all assigned male) live as males.”

Notice the little slip of the tongue employed by Hughes. Where the implication is that all 5aRD2 patients raised as male live as male. Wrong! I do not. And as you have probably gathered by now I resent it, but one must not argue with the decrees of a doddering old fool quoting a New York jet set radfem quack. (Yes the issue still makes me angry).

Hughes has said in front of me that he quotes Mc Ginley when discussing 5 alpha reductase deficiency. And this of course adds “Gender confusion” to myn list of crimes having being born with this condition.

But the real question that has yet to be answered is, Where, in terms of DNA and specific mutations, and specific effects on any protein, and what that protein changes is this mysterious “Male gender identity” supposed to be, so far we have little more than a few disjointed comments on lab results, very selective choices study groups and some New York medic with this passion for identifying everyone as “male” (Which in itself is an interesting subject for study, Do we have a Pathopatholological individual in Mc Ginley we wonder?)

Conclusion.

It is clearly evident that Mc Ginley had a bias towards identifying people with this condition as “unquestionably male” there were those undertones of “radical feminist academic” in her writings as well. You can sense the “they start as little girls but they are sexually predatory men in disguise” from the very first sentence, and what gets to me is the fact that this gibberish has translated into accepted medical practice. And to this day I see no biological evidence to support the notion that people with 5aRD2 deficiency “identify as male 100% of the time” Anecdotally I know 5 other people with this condition besides myself, only one identifies as male. Even now the description Mc Ginley offers as a “genetic model” is both vague and meaningless.

Will what I have written her be read by those who take Mc Ginley’s word to be gospel and then will they challenge Mc Ginley? Probably not. And those nice people at the DSD consortium are basically saying that all the vivisection and violation I endured as a child was justified. Thanks a bunch!  

As the title of this article suggests, how did this stuff get past the peer review process. How did “These people didn’t ft my study so I excluded them” and “This is a gene and this is an enzyme and this is a gender identity, that’s it” get past the peer review process? I would argue that the people who reviewed it were a little biased in her favour perhaps?

As it now stands an entire generation of children will grow up, facing the nightmares I did, with probably even more cliical mismanagement and “Oh we don’t do gender, lets talk gender confusion” style secrecy, shame and mixed messages.

Sophie Siedlberg