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My contribution this time is a video about a science paper — a case study of an XY woman who gave birth to a child.
You can read the original paper right here, or a transcript of my remarks below the fold.
This video is part of a fundraiser for the freethoughtblogs blog network. As the name suggests, we’re a group of freethinking agnostics, atheists, and humanists who have joined forces to write about social justice issues. We’re currently under a burden of legal debt, a consequence of having to fight off a SLAPP suit, which we won resoundingly, but came out of it owing a lot of money to our lawyer. If you’d like to support us, you can make a one-time donation to PayPal.me/freethoughtblogs, or you can sign up to be a patron at patreon.com/pzmyers. Every penny of these donations is currently being whisked away to erase our debt.
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Now on with the video.
A while back, a commenter on my blog — they’re a smart bunch — pointed me at this 2008 paper published in the Journal of Clinical Endocrinology and Metabolism. I can assume that a lot of people just stopped watching at the mention of a technical journal, and that I’m about to tell you what was in this one scientific journal, but hang tight, it’s actually fascinating stuff.
It’s about a mother and her daughter who both have an XY chromosome set.
As a biologist, I’m constantly exasperated by people who declare that chromosomes determine who you are, or spout that “biological human female” nonsense, by which they intend to claim scientific authority for their tired old bigotry about sex and gender. This paper is a case study of a family where the reductionist views of what a “biological human female” is are denied.
Let’s start with the story of Patient 1.
This 17-yr-old woman from Croatia was the product of a 39-wk gestation, delivered by cesarean section due to a maternal hip fracture. Birth weight was 3.8 kg, and length was 52 cm. She was breastfed for 1 yr. She sought medical attention at age 17 yr because of lack of breast development and primary amenorrhea. Intelligence was normal, determined by her standing as a top student in her class.
On exam, she was an articulate, tall, thin woman. The height was 187 cm (>95th percentile) with a mid-parental target height of 181 cm. Her weight was 68 kg. She had a normal frontal hairline. There was mild facial acne but no facial hair. She had Tanner stage I breasts and Tanner stage IV pubic hair. External female genitalia were normal, without clitoromegaly or labial fusion.
This is a fairly common story for intersex people. They are normal, healthy, functioning children who first detect a difference from their peers at puberty: they don’t undergo the usual transformation of developing primary and secondary sexual characteristics. She wanted to find out why she wasn’t experiencing breast development or menstruation, so she sought out a medical consultation. The simple physical examination revealed that she was a normal girl with normal genitalia, but that her breasts hadn’t developed at all. The Tanner stages are a set of standard criteria for the development of sexual characteristics, and those numbers are saying she had development of pubic hair normal for her age, but that she had the breasts of a young child.
The real surprise came when they karyotyped her blood, and found that her chromosomes were 46,XY — that is, she had the chromosomes characteristic of a normal male. They took a family history and found that there were multiple family members on the mother’s side with ambiguous genitalia, infertility, or problems with sexual identity.
So we come to patient 2, the girl’s mother.
This 52-yr-old phenotypically normal woman underwent normal pubertal development and reached spontaneous menarche at age 11 yr. She had a history of two pregnancies, the first of which resulted in a spontaneous miscarriage. Her second pregnancy was uneventful, except that her daughter was delivered by cesarean section due to a recent hip fracture in the mother from a motor vehicle accident. She breastfed the daughter for 1 yr. She continued to have regular menses until menopause at age 49, after which time she received hormone replacement therapy for 2 yr.
Physical examination revealed a feminine-appearing woman with a normal body habitus (Fig. 1). The height was 177 cm. There was no receding hairline or balding of the scalp and no acne or facial hair. Breasts and pubic hair were Tanner stage V, although pubic hair was sparse. The external genitalia were normal with no clitoromegaly or labial fusion. The vaginal introitus was normal.
A perfectly normal, ordinary woman, in other words. They went ahead and karyotyped her blood, and found … she was also 46,XY. By chromosomal criteria, she was a “man” — a man who had developed as a woman, menstruated, and born a child who she breastfed. The lesson you should immediately take from this is that chromosomes are not sufficient to define sex or gender.
The doctors were a bit surprised, too, and did a lot more tests. They did a maternity test, and yes, Patient 2 was definitely Patient 1’s mother. They also determined that Patient 1’s Y chromosome came from the man who was her father. They did more tissue tests beyond blood, and both patients were XY in skin and gonads, although the mother exhibited some mosaicism. That is, some of her tissues contained some XO cells in addition to XY; her gonads were roughly 6% XO, and her skin sample roughly 20%. 45,XO is the characteristic chromosome complement of Turner’s syndrome, people with a single X chromosome who present as female but are only rarely capable of becoming pregnant.
The mystery deepens. Both patients were subject to a remarkable degree of probing. They got pelvic ultrasound and MRIs. Patient 1 had a laparoscopic investigation of her gonads, and patient 2 had a gonadectomy. Genes were sequenced. SRY, the sex determining region of the Y chromosome was normal for a male in both, no surprise for the daughter since she’d inherited it from her father. They dug deeper into downstream genes involved in sexual development, sequencing SOX9, SF1, DMRT1, DMRT3, TSPYL, BPESC1, DHH, WNT4, SRY, and DAX1, all genes associated with disorders of sexual development — they all matched normal reference sequences.
If all you had to go on were the karyotypes and the detailed sequence data for these genes involved in sex determination, you’d say that both of these patients were men. They most definitely are not. Again, I have to emphasise that sexual development is complicated, and it is a mistake to try to reduce complex phenomena like sex and gender to a single definitive marker, like a chromosome or a gene. So could everyone please stop doing that?
It’s still valid to wonder, though, how a 46,XY person could develop as a female.
As a scientist, this diagram illustrates how I tend to see it. The diagram is incomplete, focusing mostly on the development of male characteristics, because these two patients experienced disruptions of those processes. So we have a sequence of steps from a sexually indifferent gonad to the production of cells which signal further differentiation of the different components of sexual morphology, physiology, and endocrinology, with lots of genes active at intermediate steps, allowing the individual bits to be dissociated by changes in the genome.
Note that this diagram is further incomplete because it lacks any connection to brain development.
OK, so what’s going on in these patients? The authors suggest two reasonable hypotheses.
One is that there are more genes involved in these processes than are recognised here, and that the women carry novel mutations in uncharacterised genes. That is, the process is even more complicated than we know, and that deeper investigation into this family will reveal new genetic elements behind sexual differentiation.
The second hypothesis is that the mother carries a mutation that causes a greater frequency of mosaicism, in addition to a mutation that disrupts male differentiation, to explain her fertility. The idea is that there was a chance distribution of a small number of XO cells capable of functioning as fertile female tissue embedded in a sea of infertile XY cells, all soaking in an environment of female hormonal signals. Maybe. I see that as a possible part of the story, but it does nothing to explain Patient 1’s condition.
As a biologist, I could dwell on this figure at length. There’s a rich body of context behind it.
As a human being, though, this other figure had greater impact on me. Patient 1 and Patient 2 had a family history with 7 other individuals over 4 generations that exhibited anomalies. This is the family pedigree, and the distribution of affected individuals suggests, weakly, that there may be an X-linked trait responsible for the problem.
But it’s the brief family histories behind the pedigree that are most disturbing.
III-5,6, woman with hirsutism who died around age 60 yr
So there were some individuals with masculinised sexual characteristics, which may fit with the increased mosaicism hypothesis. The variability in phenotype in this family tree is rather suggestive.
II-3, woman with masculine appearance, no breasts, infertile, moved away from hometown because of unacceptable appearance and died during World War II at age of 62 yr
Wait, what? Unacceptable appearance? Compelled to move? This is a person, and not having breasts is cause to ostracise her?
III-10, man with confused gender identity, infertile, committed suicide at age 24 yr
What a tragedy. This is a common trope: someone committed suicide because they’re confused about themselves, as if it’s entirely the fault of the individual. Perhaps instead we should place the blame on a culture that created that confusion by telling people they must be who they are not.
III-9, ambiguous genitalia with hirsutism (beard), raised as female, family was ashamed of her and hid her from public, died at age 55 yr
Jesus Christ. How can you be so ashamed of a child that you lock her away until she dies? We know from Patient 1 that this trait does not damage the intelligence or awareness of those who carry it. This woman was tortured with deprivation from human society because her family was ashamed that she did not conform to their beliefs about what she should look like.
That was a crime.
This is where I get off, where I can no longer simply read a scientific paper clinically and dispassionately. And I don’t think I should.
As a scientist, we are supposed to care deeply about the world; it’s about more than just passive description and pitiless experimentation. We become scientists because we love our field, and because we are prepared to embrace all the beauty and horror of the universe — and both of those responses are feelings, emotions, reflections of our human nature. We can not set aside our humanity to pretend we have some mythical unfeeling objectivity, because doing so denies the reason we do science.
So I read this case study of an intersex woman and her mother, and I can appreciate the intricate interactions of molecules in development.
I can hope that Patient 1 finds joy and satisfaction in her life. She carries an unusual gene or two, but she is a worthy person who deserves a happy future.
I can be in awe of Patient 2, who made such sacrifices in order to allow scientists to investigate her body, in hopes of learning more that might help her daughter and her family to understand this pattern of variation.
I can grieve for those family members who suffered so much because of society’s biases. I hope we can someday end this ignorance and learn to respect the dignity and worth of every human being.
I’ll end with this: biological, human, and female are not simple cartoon concepts that you can abuse to denigrate other people. Chromosomes are only part of who we are, and if you can’t reach out and love the wholeness of who people are, you are part of the problem.
I’d like to thank all these names scrolling by — these are my supporters on Patreon who have been helping me out all this time. You can join them, too, if you sign up at patreon.com/pzmyers.
To give you a brief picture of what I do: I’m a biologist, specifically a developmental biologist, but with a growing interest in environmental effects on the organism…and vice versa. I consider reductionism to be a useful tool in doing science, but it is not sufficient to do good science. Science is a human and social enterprise, and don’t you forget it. To paraphrase another cliche, if all you’re doing is gathering data, you’re just another kind of stamp collector.
If you follow this channel, you might find that I’m fascinated by spiders right now. They have their own terrible beauty, and that’s what attracted me to them, but also they are a diverse and important part of our environment, with their own non-human behaviours and perspectives. Don’t be frightened, be open to new ideas, and learn to love everything in the universe, that’s a scientist’s credo.
I’ve been neglecting YouTube, and many other things, for a while now, as I’ve been overwhelmed with teaching obligations during a pandemic. I’m looking forward to trying some new things over the summer, though, so stay tuned to this channel!