Genetic Sex Change : Real or hype?

IMO, the public puts too much faith in science, largely due to the way science news is written for the laymen. News that stopping a single gene, Foxl2, from functioning converts adult ovaries into testes, caused much stir and hope in the transgender community.

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http://www.timesonline.co.uk/tol/news/science/genetics/article6952050.ece

“December 11, 2009, by Hannah Devlin

Scientists find single ‘on-off’ gene that can change gender traits –

Scientists have identified the gene (Foxl2)  that keeps females female. An international team found that the action of a single gene is all that stops females from developing male physical traits, including testes and facial hair.

When this gene was artificially “switched off” in adult female mice their ovaries began to turn into testes and they started to produce a level of testosterone found in healthy male mice.

The discovery could eventually revolutionise gender reassignment therapy and improve treatments for babies who are born with a mixed gender.”

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(I have reproduced a more accurate, less-hyped-up news report of the same scientific discovery here http://mathialee.wordpress.com/2009/12/16/genetic-basis-for-sexual-identity-at-the-cellular-level/ )

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Lay readers tend to make 3 common, basic false assumptions when reading science news like this

Assumption 1: All information that is known about the health/biological condition is reported in that one article they are reading

Truth: Science experiments tend to look at one single aspect of one single variable at a time. They then make a single report based on these set of experiments (called 1 publishable unit). To know all that is known, one has to trawl through the ENTIRE database of scientific reports. (my favourite database search engine is www.pubmed.com ; do a ‘ Foxl2 ‘ keyword search to see everything known about Foxl2 )

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Assumption 2: Everything about the health/biological condition or the gene you’re interested in, has already been discovered. We have COMPLETE knowledge.

Truth: Far from it. Science is not something where there are model answers written at the back of your workbook. Biological organisms are not a computer designed by humans where at least the designer knows something. No one knows the boundaries of Biological science, and one needs always to remember that.

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Assumption 3: Observations of mice and other organisms are reflective of human beings.

Truth: SOME observations of mice and other organisms are reflective of human beings. This is the reason why drug and therapy development has to go through Phase 1, 2 and 3 of human trials AFTER successful animal experiments. 9 in 10 successful animal experiments DON”T become successful Phase 3 human trials.

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In this specific case of Foxl2, what scientists discovered in this latest report was this:

When you stop Foxl2 from functioning in mice, “any developed eggs in the ovary DIED. Follicles, which eventually grow into eggs, slowly transformed into cells that LOOKED LIKE Sertoli cells, which produce sperm in the testes.”

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LOOKED LIKE is not equal to ARE.

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The actual report made by the scientists never said that “The discovery could eventually revolutionise gender reassignment therapy and improve treatments for babies who are born with a mixed gender.”

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The scientists SPECULATED from their discovery, “they might also have important medical implications for the understanding and treatment of some disorders of sexual development in children and premature menopause in women.” And “has important implications for reproductive biology, in particular the treatment of sex differentiation disorders in children, as well as premature ovarian failure and female menopause, both of which are associated with declining estrogen levels and occasional signs of masculinization.”

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Now, what are these disorders in women and children the scientists are talking about? Here’s more information on Foxl2 , and the problems Foxl2 malfunctioning is associated with :

-       Decreased Foxl2 is associated with aggressive ovarian cancer in children
http://www.ncbi.nlm.nih.gov/pubmed/17430735
(Sure you want to mess with Foxl2 for gender re-assignment? I’ll stick with hormonal therapy)

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-       Over-active Foxl2 is associated with aggressive testis cancer in children, where the testis cancer cells looks like ovarian cells
http://www.ncbi.nlm.nih.gov/pubmed/18721930
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-       Foxl2 mutations and abnormalities cause a genetic condition called BPES http://www.bpes.org.uk/index_Informationadvice.htm . The symptoms are given on that page. They’re not pleasant. In both humans and mice, Foxl2 abnormality causes facial feature abnormalities.  Another one of the symptoms is that the ovaries malfunction.
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However, it is ONLY when ovaries malfunction due to BPES that Foxl2 is involved. When ovaries malfunction in non-BPES patients, Foxl2 is rarely the reason.
http://www.ncbi.nlm.nih.gov/pubmed/15181179
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-       And because Sox9 was the gene I worked on for 5 long, hard years of PhD, I shall also mention that Foxl2 feminises cells by shutting off Sox9. Sox9 makes the cells males. When you destroy Foxl2, Sox9 is no longer shut off, and the cells turn male. Incidentally, Sox9 abnormalities result in fetuses dying before birth because Sox9 is needed for proper development of the heart, brain, skeleton, etc etc. The rare children who can be born because the Sox9 abnormality is mild, suffer from severe skeletal distortions, breathing problems, sex-reversal, mental retardation etc. They usually die in childhood. Now would I ever want to mess around with a gene that stops Sox9 from functioning!??!

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[Disclaimer:

In my attempt to make technicalities accessible to laymen, I may not have presented info correctly. Please feel free to leave comments to correct errors that you find. Also, if any part is unclear, please let me know, so that i can correct it too. Further questions welcomed too ; i will do my best to address]