Obituary: Ursula Mittwoch – Pioneering geneticist who solved the riddle of sexes

Lane N Annals Human Genet. 86: 153-158

Ursula Mittwoch being presented with the painting Mitochondria in Action by Odra Noel, to celebrate her 90th birthday. With (from left) Profs John Allen, Sue Povey, Dallas Swallow and the author, in the Housman Room at UCL in 2014
Picture a tidy, petite, middle-aged lady in Florence in the 1970s, brandishing callipers and marching insouciantly up to a renaissance sculpture to make her measurements. What on earth did she want to know, you may be wonder- ing. Scrotal asymmetry is the answer. Did the great artists, going back to the ancient Greeks, know that the right testis is slightly larger than the left? They did know some sur- prising things—the right ball is higher than the left, for example—but this particular gem eluded them. It did not elude Professor Ursula Mittwoch. She saw it as the excep- tion that proved the rule—not just any old rule, but one of the deepest and most mysterious rules in all of life, the distinction between the sexes. Male development is deter- mined by a higher metabolic rate, she realized, and the elu- sive role of sex-determining genes was betrayed by inter- sexual states: true hermaphrodites have an ovary and a testis, and in two thirds of cases the testis develops on the right-hand side (in humans, at least). In men generally, the right-hand testis is around 5%−10% larger. What kind of genes would arrange that?

Ursula Mittwoch was an unusual geneticist who forged her reputation working with Lionel Penrose on chromo- somal disorders in the early days of cytogenetics, yet who declared later that she ‘didn’t much like chromosomes’. She became Professor of Genetics at UCL, yet often seemed suspicious of genes. In truth, she blazed her own luminous path through the second half of the 20th century. Her views were at odds with genetic determinism in its widest sense, for she was more interested in the subtle interplay between genes and environment—‘genetic indeterminism’. Despite more than 200 publications, including 14 Nature papers through the 1960s alone, many as a single author, her work perhaps did not receive the recognition it deserved, at least among geneticists; but her bold insights into the sexes were appreciated by the media and she wrote regularly (often with a waspish sense of humour) for magazines like New Scientist. In fact, her thinking was decades ahead of its time, more in tune with the renewed interest in epige- netics of recent years. Today, when so many people rebel against a binary definition of sexes, Ursula’s work shows that sex determination is far from a simple switch governed by Mendelian genes but reflects a ‘threshold dichotomy’—
in effect, a quantitative rather than a qualitative difference. To be sure, our genes stack the quantitative odds towards one sex or another, yet the spectrum in between leaves plenty of scope for intersexuality.

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