Dual-Gender Macrochimerism Microupdate

In a recent post I mentioned that males raised as women from birth (complete with GRS, HRT) transition back to male at a rate several orders of magnitude above the general population rate of transition.

A friend reminded me of a similar case we learned about in AP Psychology. The tragic case of David Reimer. David had a botched circumcision that led to a sex reassignment surgery. His parents took him to see popular psychologist, John Money who believed that babies are born gender neutral and gendered behaviors are socially conditioned. They feared that their son could not lead a satisfactory male life without a penis and intended to seek his counsel about raising him as a girl.

Money convinced the parents and surgical team at John Hopkins that David would be better off if raised as a girl. As it happened, David had a twin brother and so this would be an excellent test of Money’s theory. David also had developmentally typical anatomy, unlike most of the ambiguous genitals that lead to ablations in previous studies that could confound the results.

The entire ordeal reads like a trans person’s worst nightmare. Your parents, your psychologist, your physician are all telling you that you’re supposed to be a girl. Putting you through bizarre and degrading scenarios in an effort to convince you to get additional GRS and continue HRT. The entire time you feel like you must be the crazy one, yet you’re also pretty sure you don’t want to feminize further and don’t understand why everyone is so interested that you do.

David expressed it best:

Doctor … said, it’s gonna be tough, you’re going to be picked on, you’re gonna be very alone, you’re not gonna find anybody unless you have vaginal surgery and live as a female. And I thought to myself, you know I wasn’t very old at the time but it dawned on me that these people gotta be pretty shallow if that’s the only thing they think I’ve got going for me; that the only reason why people get married and have children and have a productive life is because of what they have between their legs.

If that’s all they think of me, that they justify my worth by what I have between my legs, then I gotta be a complete loser.

I’d like to note that this case is similar to the other ones mentioned in that resistance to their assigned gender identity increased as puberty approached and progressed. It’s also a half point for chromosomal organization of gender identity, instead of hormonal because it doesn’t rule out the effect of prenatal hormonal exposure.

Dual-Gender Macrochimerism

I stumbled across this paper:

The title is certainly interesting, even it if it’s watered down by the “predicted to be” meaning it’s mostly well grounded speculation. It’s doubly interesting if you’re a narcissistic trans woman on the search for the underlying biological mechanism responsible for making your life more annoying than necessary.

So what is it all about, and how is it connected to gender dysphoria? To understand the paper we have to understand genetic chimerism. Chimerism is when an organism is composed of cells with two or more distinct genotypes. Microchimerism is when small amounts of cells in an organism have different genotypes from the host. The most common occurrence of microchimerism is fetomaternal microchimerism. Fetomaternal microchimerism occurs during pregnancy, when small amounts of the baby’s cells will cross the placenta and take residence in the mother’s body (and vice versa). Prevalence of these cells decrease with age, but have been found even 27 years postpartum.

Macrochimerism is a whole other ball game. The most common cause of macrochimerism is when a two zygotes merge. This can result in entire organs being of a different genotype from each other. This can occur with different zygotes with differently sexed chromosomes as well. One of the most interesting cases of this is hermaphroditism (intersex), where an individual has both sets of genitalia and/or reproductive organs. Most cases of macrochimerism are not so obvious. Typically they are subtle, harmless, and go unnoticed unless the person has their DNA tested. This makes it difficult to determine the true rate of macrochimerism.

This brings us back to Brian Hanley’s paper. He correctly points out that dual-gender macrochimerism exists, and other forms of non-visible macrochimerism exist. Therefore it is likely there are non-obvious dual-gender macrochimeras, in which other, non sexual, tissues are affected. In Brian’s words:

…the existence of human macrochimeras in which large proportions of cells are male and female is predicted to have a correlation with homosexuality and transgender self-identification because in many such cases, the central nervous system, or crucial parts of it, will be of one sex and the gonads and body form will be of the opposite sex.

So far so good, but the paper is mostly speculation. Brian hazards a guess at the true rate of macrochimerism but admits he is probably off by “orders of magnitude.” He provides a framework for the sort of longitudinal study that would be necessary to properly study the prevalence of macrochimeras, but I don’t see them happening anytime soon I won’t hold my breath.

Genotype vs. Hormones

The most interesting part of Brian’s paper was the assertion that the sex of the nervous system is as important, if not more important contributor to gendered behavior than the hormonal environment the system developed in.

This surprised me because I have first hand experience that hormones change the way one thinks and feels. I would have guessed that brain development was guided by the hormonal environment it was soaking in, which in turn was dictated by the chromosomes of the gonads. This is not without scientific support. For example, gendered personality traits seems to be effected by pre-natal exposure to androgens, and I believe there are some studies on homosexuality and transsexuality that find correlations as well.

Brian references three studies in support of this assertion:

Bilateral Brained Finches

This paper discusses a species of finch with gender differentiable brains. One difference is that the males have a stronger “song circuit” in their brains that causes them, but not the females, to sing a courtship song. There is some evidence that hormonal environment affects brain development in these finches. Female finches exposed to estradiol develop a song circuit similar to males and sing the courtship song. However these finches did not exhibit completely sex reversed behavior, and males with testicular hormonal blockers still develop the song circuit. This suggests that both hormones and sex chromosomes are important for gendered neural development.

Conveniently, a rare gynandromorphic bilateral brained finch was found, with a nearly symmetric split between male and female. You can see the bilateral split in the plumage.

Bilateral Gynandromorphic Finch

One side (B) has male plumage, the other side (C) female plumage. The researchers found the finch had a masculinized right hemisphere and much less masculinized, and partially feminized left hemisphere. This provides evidence that the effect chromosomes of nervous tissue are not over powered by the developmental or current hormonal environment.

To be honest, and this is definitely talking out of my depth, the experiment didn’t seem as conclusive on the brain differences as the other anatomical differences. Although the “song circuit” was larger on the right (male) side of the brain, there were issues comparing the size to the controls, which would have proved insightful.

Quail

In contrast to the finches, these quail brain chimeras had to be built, not found. Japanese quails have a male organized brain by default that is thought to be de-masculinized by estrogen, transforming it into a female organized brain. Fortunately, this differentiation happens after the brain starts to appear during gestation. This allows crazy people researchers to graft cross-sex forebrain primordium, causing the birds to develop cross-sexed brains.

Male-forebrained, female host quails showed typical female quail behaviors, including sexual behavior. This is congruent with the idea that estrogen (prevalent in female quails) demasculinizes the transplanted forebrain, reorganizing it to be more feminine. A point for the hormonal basis for gendered brain differences.

Female-forebrained, male host quails are a different case. They exhibited reduced male behaviors, and reduced to non-existant male sexual behaviors. In addition, sexually dimorphic brain features such as the medial preoptic nucleus were found to be feminized despite being raised in a male hormonal environment. A point for the genotype basis for gendered brain differences.

I would be interested to know if gay Japanese quails exist, and if they do, what their typical behaviors are so they can be compared to the cross-sexed quails. I know it’s a faux pas to conflate sex with sexuality, but given their ontological proximity and extremely high rates of correlation I would be surprised if the biological mechanisms weren’t intertwined in some fashion.

People

Birds are great (#bavi) but what about people? Do we have any questionably ethical studies where we manipulate the hormonal, anatomical or genetic components of humans that might give us some insight?

Yes, yes we do!

In 1975 there was a study that followed the development of males born with abnormally small, or missing penises. Since they were too small to function, doctors removed them, essentially performing infant GRS. The “men” were raised as girls from birth, complete with HRT and raised as girls since birth.

From the abstract:

Forty-five cases of genetic males were assigned and habilitated as females, 43 because of a congenitally defective penis (micropenis with or without hypo- spadias], and two because of infantile ablatio penis. One of the latter has an identical twin brother as a control. Now 9 years old, she has differentiated a female gender identity in marked contrast to the male gender identity of her brother. Some of the other patients are now adolescent or adult in age. They demonstrate that the twin can expect to be feminine in erotic expression and sexual life. Maintained on estrogen therapy, she will have normal feminine physique and a sexually attractive appearance. She will be able to establish motherhood by adoption.

I guess that settles the debate, hormonal and social environment trump genetics.

Now, if you’re like me, you might notice that 9 is a bit young to be drawing conclusions. Pre-pubescent humans still have some significant phase of development from which the brain is not exempt. For instance, gendered personality differences don’t manifest until after puberty, indicating that there is significant differentiation that takes place during puberty.

Fortunately someone did a follow up study  and found that the child in question transitioned to male after puberty and has been comfortably living as one since. A similar study found that 8 out of 14 males assigned girls at birth (for similar reasons) ended up identifying as males by puberty and 6/14 even transitioned physically. The 2 other males with the same condition were raised as males and decided to remain as males. Although the sample size is smöl, gender dysphoria and transition are sufficiently rare that this high rate of transition is shocking and convincing.

Conclusion

So what did we learn? I learned that performing infant GRS should probably be halted until we have more research. I also learned that human brain development is not what that I thought is was.

My new model of gendered brain differences:

  1. Gonads develop according to gonadal chromosomes
  2. Different gonads produce different sex hormones
  3. This hormonal environment informs the organization of tissue, including the brain
  4. Brains that develop in a male hormonal environment are organizationally male and vice versa.
  5. Brains are organized, and thus gendered differentiated, due to genotypical and hormonal factors.

A lot more (expensive, time consuming) research needs to be done. I am convinced that the “sex” of human nervous tissue is a significant determinant in human gendered behavior and identification and that dual-gender macrochimerism is a plausible biological mechanism behind the transgender phenomenon.

An Awkward Game of Baseball


NSFW

This post is personal and sexual; if that’s not your cup of tea then it’s time to leave. Apologies to my boyfriend who’s privacy I am implicating in this post.


I have a problem penis. It’s kind of both. My penis poses several problems for me: dysphoria, can’t have kids, accidentally outing me etc. These things considered, my complaint today is relatively minor in magnitude, but makes up for it in frequency. Like an awkward game of baseball, my sex life is missing third base.

For the uninitiated, the baseball metaphor of sex is as follows:

  1. First Base: Kissing, making out
  2. Second Base: Shirts off, touched her boobs
  3. Third Base: Hand in the pants, touching someone’s junk
  4. Home Plate: Handholding

This is accurate to the best of my middle school knowledge.

My frustration stems from the interruption of natural sexual progression. Fantastic foreplay foments a deep and instinctive feeling in my body about where to go next – but I can’t go there and I don’t know what to do. I get a weird feeling in my perineum, where the base of my bulbospongiosus muscle is, but I can’t really indulge it.

The best analogy I can give is preparing food, sitting down to eat, raising the fork to your mouth, opening wide only to find you cannot chew. It’s still possible to eat, but you feel deep down that there is something you’d like to be doing, but for some reason you physiology won’t permit it.

This post is mostly a dressed up complaint; I find that writing about my problems helps uncover solutions, or at least lay them to rest in my mind. I suppose the only thing to do it wait for surgery. If anyone has found a workaround I’m all ears.

A Letter to Dr. Peterson

Tonight I have the pleasure of attending a talk in San Francisco featuring Jordan Peterson. As an avid fan girl of Dr. Peterson, I am very excited to meet him in person and deliver a letter of thanks.

If you ever doubt Peterson’s claims about the letters he receives, then you can know that at least one is true.


Dear Professor Peterson,

I am so happy to meet you in person and wanted to express my sincere gratitude for your works. My life is orders of magnitude better and I now have the tools to move forward.

I had been suicidally depressed for two years before coming out as transgender. While this provided temporary relief; I had spent two years building up the most vicious, overly rational and nihilistic arguments against existence, hoping to convince myself into suicide. I was afraid that during difficult times in the future, these demons would come back to lecture me on the irredeemable corruption of being and, lacking a counter argument, I would be equally vulnerable.

Synchronous, perhaps, that I was introduced to your works through your criticism of Bill C-16. I found your assessment apt and your University of Toronto free speech oration unforgettable. Intrigued, it lead me to your lecture series and I can honestly say I have watched every video on your YouTube channel. You are the first person in my life to adequately acknowledge the suffering of being while providing a theory for transcending it.

Tangentially related, I think your assessment of trans activists is correct. They do not represent me and often work against my interests by undermining the biological basis of gender. The idea that trans people cannot exist in a system with free expression is infantilizing and laughable. Given the nature of dysphoria, I think that trans people in particular could benefit from your lectures.

Thank you,
-Amy Jie

Figuring Out I Was Transgender

I am often asked “Did you have bottom surgery yet?” and regrettably inform them that no, I still have a penis.

Something that I also get asked a lot is, “How did you figure out you were transgender?” or it’s cousin, “When did you know you were transgender?”

📅 When

I knew I was transgender when I was 24. I know that this answer disappoints a lot of people, and probably any psychs that had to write me a letter.

Although there are a lot of things that make a lot more sense in retrospect that occurred well before I was 24, I never properly articulated the thought until I was 24.

💁🏼 How

I figured out I was transgender by watching a video series “Are You Transgender.” Specifically the following video series at the 4:08 mark of the second video:

I was working on a mobile app and I usually listen to lectures on YouTube to keep me company and maybe teach me a thing or two. So, like a normal cis-het-boy I queued up the “Are You Transgender” playlist.

I have a distinct memory of when I heard the speaker say:

If you are watching this video for yourself, or researching what transgender is online, then you are likely transgender.

After hearing this improper implication, I alt-tabbed back to YouTube and smugly paused the video. It’s true, just because you’re asking the question “Am I transgender?” definitely doesn’t imply you are transgender.

I resumed the video and the next line hit me like a truck:

Because cis-gender people do not ask this question, “Am I transgender?”

Why was I listening to to this playlist? This wasn’t the first time I had watched a video on this, or taken a stupid quiz about it, or read blog articles similar to the one I’m writing now or asked myself “am I transgender?”

Laughably I recall thinking;

Yeah just because I frequently wish I was a girl doesn’t mean I’m transgender.

It wasn’t as funny of a revelation at the time. I remember my heart stopping, my eyes widening and my blood turning cold as I realized, “Oh shit, that’s exactly what that word means.”

I spent the next six hours recontextualizing my life and eventually pulled myself together enough to walk down the street and come out to my friend.

🤦🏼‍♀️ Confusion

If you read my other post about All These Things That I’ve Done or are familiar with the standard narrative of “I’ve known since I was 3 years old” you might be confused as to why it took me 24 years to figure it out. This is the difference between knowing things and being unable (or unwilling) to articulate things.

If you asked me straight up and pressed me I would have confessed to wanting to be female. I knew that’s what I wanted but I hadn’t yet articulated to myself that meant I should transition and therefore I was transgender. Once I was able to articulate the concept of being transgender I was able to act because I had a framework to work within. Until I did that I just thought I was weird (albeit in specific ways stable across time) and being weird doesn’t explain what you are supposed to do, if anything.

So why was I unable to connect the dots? I think it is mostly from ignorance and a tiny bit from internalized cis-sexism. I sincerely believe had I known a trans person growing up I would have come out much earlier. I would have confided in them some of my thoughts and proclivities, laughed nervously and said something to the effect of “but that’s not like you at all, right?” and gotten hit like a hammer when I learned my experience is fairly typical. I didn’t believe I was”trans enough” to be transgender, I thought everyone knew with certainty since they were small children. Sure I wanted to be female, but I didn’t know if I should transition. To be fair, transition is very intimidating. It is long, painful, expensive, time consuming and the results are not guaranteed. In addition, I knew I wanted to be female, but I wasn’t sure if I wanted to be trans. There was probably a little bit of cis-sexism that held me back from exploring the possibility of living as a trans woman.

🤷🏼‍♀️ Questioning

I think everyone questioning their gender identity should understand that you will never be 100% certain about transition. There is no way to know before you do it that such a radically life altering event will be for the better. It is a supremely non-trivial commitment to transition. It is an act of faith that will require many sacrifices.

While coming out I was complicit in perpetuating the ultra-confident, I’ve always known meme. You sort of have to; there’s no “proof” you’re trans besides your own confidence. It took me 24 years to understand and I lived it, I can’t just hope that other people will “just get it” based on my own new, limited and unconfident expression. I think this narrative is dangerous because I delayed transition because I didn’t think I was “trans enough.” Please don’t make the same mistake I did.

I would like to share a quote from Julia Serano’s book, Whipping Girl that I think explains the feeling  I had pre-transition:

 

Trying to translate these subconscious experiences into conscious thought is a messy business. All of the words available in the English language completely fail to accurately capture or convey my personal understanding of these events. For example, if I were to say that I “saw” myself as female, or “knew” myself to a girl, I would be denying the fact that I was consciously aware of my physical maleness at all times. And saying that I “wished” or “wanted” to be a girl erases how much being female made sense to me, how it felt right on the deepest, most profound level of my being. I could say that I “felt” like a girl, but that give the false impression that I knew how other girls (and other boys) felt. And if I were to say that I was “supposed to be” a girl, or that I “should have been born” female, it would imply that I had some sort of cosmic insight into the grand scheme of the universe, which I most certainly did not.

Julia later elaborates on about “feeling” like a woman:

Speaking for myself, I can honestly say that I have never “felt like a woman” before my transition. Even as a preteen struggling with the inexplicable and persistent desire to be female, I understood how problematic that popular cliché was. After all, how can anyone know what it’s like to “feel like a woman” or “feel like a man” when we can never really know how anybody else feels on the inside?

All emphasis mine.

I definitely fell into the trap that I didn’t feel like a woman, so I wasn’t TruTrans™ (even though I had an “inexplicable and persistent desire” to be female). It was only in self reflection I realized how foolish it was to use this reason to keep myself from transition. If you’re considering transition I sincerely hope this post helps you avoid making the same mistake I did.