Thursday, January 04, 2007

Male & Female & Somewhere In Between

Today, Sauntering Resident Scientist Garfield reports from the field about males, females, and the space between the two:

Unless you have been living in a cave, you’ve almost certainly been involved in a water-cooler discussion this past month about the Indian runner, Santhi Soundarajan, who was stripped of her silver medal in the Asian Games after failing a gender test.

I was told about this story during the Department Christmas Party about 45 minutes after I decided that the free bar was not receiving enough attention from the invertebrate zoology wing and that I was the only one capable of remedying this situation. For those dissatisfied with my treatment of this issue in the next few paragraphs, I refer you to the preceding sentence.

My first thoughts upon hearing this story were:
  1. How hard can it be to determine gender? Did this really require a team of specialists?
  2. What in the world did they mean when they said she had “abnormal chromosomes” and “more Y chromosomes than allowed?”
The plant people, who decidedly were making good use of the free bar, and I came up with the following observations which, fortunately for this blog, were recorded on a cocktail napkin because I thought it would make for an interesting letter to our irritatingly conservative student paper.

Topic One: Gender is a complicated issue.

Actually, complicated doesn’t cut it. Gender is a mind-boggling complex set of issues that are often related to, but can be analyzed quite independently of, what sorts of gametes you produce and your sexual orientation. The best treatment of this topic, from a biological perspective, that I am aware of is Joan Roughgarden’s Evolution’s Rainbow, which is nicely reviewed here.

In her book, Roughgarden, who in addition to being a transgendered individual is one of Biology’s great synthesizers of theoretical and empirical approaches to evolution and ecology, catalogs the vast array of gender roles that occur in natural populations. While gametes tend to come in two flavors (Big/Egg and Little/Sperm), individuals can change sex during the course of their lifetimes and, even in cases in which sex remains constant over time, can play many, many more roles in the production of offspring than the binary distinctions “male” and “female” can effectively capture. If I’m ever invited back to post again, I’ll rant about the many sad ways in which failing to understand that gender is anything but a binary classifier have ruined lives. In the mean time, I invite you to read about the Bonobos, our sex-crazed relatives whose embrace of complicated gender roles have lead to a vastly more peaceful existence than that experienced by rest of the Chimpanzee world, in which the usual mode of conflict resolution involves beating your neighbor to death if he looks askance at your favorite female. If I die and get to come back as anything interesting, I’m coming back as a Bonobo. No pun intended.

As fascinating and complicated as the topic of gender is, it is presumably not what the officials were concerned with when they decided that Soundarajan was too man to be woman. What they were concerned with is the observation that while gender and sexuality come in many flavors, a great deal of the variation between humans can be effectively captured by two labels, “male” and “female,” and that individuals to whom these labels apply tend to perform differently in sporting events.

The primary culprit for this dimorphism of concern to sports enthusiasts is Testosterone, that most wonderful of hormones that builds larger muscles and bones, produces less hair on your head and more everywhere else, poisons the minds of 15-24 year-old males the world over, and would presumably give an unfair advantage to any female athlete producing (or injecting) unnatural levels of this hormone. This brings us to topic two.

Topic Two: There’s more to a being a man than a Y chromosome.

From my perspective, the line “The official also said the test revealed more Y chromosomes than allowed” sums up the most interesting aspect of the case. If having a Y chromosome is the biological definition of male-ness, as it was for many years for the International Olympic Committee, how can one have more Y-chromosomes than allowed? Isn’t one enough? The process of sex determination is, like gender, a complicated thing. While the end result of the process is usually binary, there’s a lot of ways to get intermediate results.

Human embryos default female. That’s right, each XY male out there started out on the road to being female but was halted in the process by an influx of testosterone released when genes encoded by the SRY region of the Y chromosome cued your nascent gonads to start pumping the stuff out. Of course hormones other than testosterone play a causal role in the development of sexual traits. But baring the activity of testosterone, your developing body would default to produce the hormones that trigger cells to build female structures, not male.
At each step along this process of differentiation, processes can go awry, and cells can fail to respond appropriately to the hormones all around them, resulting in a developing embryo with sexual characteristics both male and female. At the department Christmas party, we came up with the following list of common ways of generating intersex individuals. I list them here with the caveat that none of us are human endocrinologists and that its not a complete list. Furthermore, it doesn’t acknowledge the fact that even when nothing “goes wrong” with the sex determination system, there’s more of a gradient between male and female structures than is generally acknowledged.

Androgen insensitivity: The Jamie Lee Curtis Syndrome
I don’t know if its true or not, but I grew up with the rumor that Jamie Lee Curtis is, in fact, biologically male, but has a mutation in the receptor for testosterone that made her developing body insensitive to the effects of testosterone and other androgens. I don’t know if this is true or not for Curtis, but the phenomenon is well documented and has effects ranging from male sterility to the production of females normal in almost every regard, but lacking a uterus and, obviously, the ability to bear children. If I had to guess, I’d put my money on some variation of this.

Klinefelter Syndrome
In something 1 in 500 male babies, an early nondisjunction event leads to cells containing XXY instead of the usual XY or XX. This is probably not viable contender here, because Kleinfelter’s individuals are pretty obviously male. But people keep asking me about this, so I put it in. Related is Turner Syndrome, in which females have only a single X chromosome (XO rather than XX or XY). While these individuals have reduced female sex characteristics, they are pretty clearly female, and are unlikely to be running track given the other symptoms that come along with having only a single sex chromosome.

Other types of chromosomal mosaicism
It does happen. Every so often you get individuals containing both XY and XX containing cells, but the relevance of this to the case in question is far from clear. In most cases, humans with unusual chromosome counts are fairly abnormal, and would probably not be winning silver medals in track events. Furthermore, humans, unlike butterflies, show secondary sexual characteristics as a result of hormonal influences. Even if some cells were XY, in a body with female gonads and sex hormones, they’d act female, and vice versa.

Swyer Sundrome
This label applies to a suit of genetic abnormalities, usually involving mutations to the SRY region of the Y-chromosome, and often resulting in an inability to synthesize testosterone, that affect the process of differentiation from female to male

What strikes me is that in each of the above cases, having a Y-chromosome in a woman has little effect on a woman’s physiology other than adversely affecting her ability to have children. That’s because in most cases, biological females with Y-chromosomes are either unable to produce or are unable to respond to male sex hormones, and as a result do not “enjoy” the athletic enhancements associated with having high levels of testosterone. For individuals with ambiguous genitalia, this may not apply. The effects of androgens may be in full effect. But in these cases, I’d argue it doesn’t matter as much to which gender individuals have been assigned or adopted. What matters is the extent to which androgens like testosterone have affected muscle production and physiology, and suggests to me that if the world’s sports authorities were really concerned with equity in sports, they’d do better paying attention to Chinese women swimmers with 5 o’clock shadows than bothering this poor woman.
Garfield really is a scientist and reports to you occasionally from the Biology Department of a fine research institution dedicated to the discovery and creation of sanctified knowledge.


Andy said...

Any possibility that Santhi is a chimera or exhibits microchimerism?

Anonymous said...

Correction to your assumptions: I have a child with turner syndrome. Your assumption that other symptoms of turner syndrome would likely keep that individual from running track is inaccurate. There are some individuals with turner syndrome impacted by certain learning disabilities that could possibly impact their athletic skills. However, girls and women with TS are generally capable of all athletic pursuits, and like the rest of the population, ability varies widely. Additionally, children with one x chromosome are not "pretty clearly female", they are female.

Ralph said...

"a fine research institution dedicated to the discovery and creation of sanctified knowledge"

Oh is that what this place is? I was wondering...

It sounds like you had more fun at the party than I did (although the desserts were quite good).

Anonymous said...

I rather like what this post has done to your google ads.

Andy said...

I think my favorite one uses the tagline: Your clone search is over.

I'm so glad my arduous clone search is finally complete.

Anonymous said...

If Jamie Lee Curtis was androgen insensitive then she would be very curvaceous, and have absolutely no male characteristics (thin build, tall, thick body hair). Without any effective testosterone she would be "more female" than regular XX, testosterone responding females. I think this is highly unlikely given her morphology. I've also seen suggested that she is Turner's syndrome or XO, but usually they are short stature.

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