Christiane Nüsslein-Volhard

On sex, ha ha flies! and the Großmutter of developmental biology

Credit: Marijan Murat/picture alliance, via EMMA magazine.

In 2022, developmental biologist and Nobel Laureate Christiane Nüsslein-Volhard gave an unequivocal interview for EMMA magazine, where she made clear that there are only two sexes, and nobody can change theirs. The interview is scathing about the state of science education on sex and gender, and, on the attempts to deconstruct sex as a material reality, she remarks that, “sex only has female or male” and that, “people have no idea about biology.”

Lots of people are displeased about this interview. You know the ones, the people who have invested large amounts of time trying to convince the rest of the world that sex is really complicated, that scientists have got it all wrong, that the categories are too strict, that it is a social construct. Of course, on Nüsslein-Volhard, there is ageism - at 80 years old, she must be an out of touch dinosaur, right? In a move that will surprise many, we have also been informed that “things have moved on” since Nüsslein-Volhard’s Nobel-worthy research. A 1.2bn year old stable evolutionary function has “moved on” since the late 70s?

But most intriguingly, as a developmental biologist, is the accusation that since she worked on fruit flies—ha ha flies!—she cannot possibly know anything about a basic biological function like sex. The same type of accusation has been repeatedly fired at me when I have argued, just as Nüsslein-Volhard has, on the nature of sex – “ha ha, frogs, who cares? Go do some proper research.” From these kinds of sneers, it is clear that an awful lot of people don’t understand developmental biology (that’s OK, it takes a lot of training) or apparently what animal models are. And they are also presumably blissfully unaware that while Nüsslein-Volhard might (yet) be the only German woman to have won a Nobel in the sciences, flies have won far more. If we add our aquatic friends to the tally, the sneers lose their power as smears.

Much of science occurs in increments, and while no incremental discovery is too small (a scientific discovery may be the most obvious available route to immortality), it is fair to say that some increments are more breathtaking than others. Many will intuit that Nobels are awarded for breathtaking increments, for uncovering a foundational principle, for the technique that revolutionises biology, for an outstanding contribution to public health. Or, off the top of my head, working out how an embryo grows from a single cell to a patterned, complex individual.

What did Nüsslein-Volhard do to win a Nobel Prize? Let’s talk about patterning.

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There is much confusion about concepts of patterning in development, particularly when I and others describe anatomical patterns associated with sex.

In common use, a pattern might be understood in the sense of a repeated motif on a duvet cover, and we see duvet cover patterns in nature, in the stripes of a tiger and the eyes of a fly. These patterns can emerge like a pond rippling after you drop a pebble or by cells jostling for supremacy and forcing their neighbours into subordination. We also understand mathematical patterns, for example, sequences of numbers that are separated by an operation like “add 2”. We see mathematical patterns in nature, in the spiral of a seashell and in the seed heads of flowers, and these emergent patterns tend to represent optimal spacing during growth.

But developmental biologists don’t only use the word “pattern” to describe emerging, repeating or organised units of a stripe or a seed. “Patterning” also describes how a complex, functional system develops.  

In 1995, Nüsslein-Volhard was awarded, alongside Edward Lewis and Eric Wieschaus (we will return to him later), the Nobel Prize in Physiology and Medicine, for her work on embryonic patterning - how does a complex organism grow from a single cell? They used fruit flies, zapping individual genes and working out what effect that had on patterning during the development of fly larvae. From this research, they elucidated the molecular cues within an embryo that say: “Here, see these areas here, this bit is going to be your head and this bit is going be your arse.” (Note: these are, of course, my words, but I might remark on the irony of Nüsslein-Volhard’s detractors not knowing their head from their arse.) Further, they found out how some of these molecular cues work – not only how they “zone” an area, but how they coordinate the process of specialisation in that area.

One cannot understate the value of Nüsslein-Volhard’s work. If one were to try and identify a Darwinian figure in the field of developmental biology, she would be shortlisted, although I’d edge towards Hans Spemann myself, who won a Nobel prize in 1935 (ha ha frogs) for discovering that groups of cells can “talk” to and “organise” the development of surrounding cells. It is not in doubt that she and her colleagues have a well-earned place in every developmental biology textbook one might care to examine. She is a “woman who changed science.” And if not quite a Developmental Darwin, she can certainly lay claim to the title of “the Großmutter of developmental biology.”  

From: “The Heidelberg Screen for Pattern Mutants of Drosophila: A Personal Account” by Eric Wieschaus.

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My own PhD research examined how two signalling molecules, distributed in different areas of the frog embryo, intersect in a specific region to generate a specific “zone” that activates specific genes with a specific role in ongoing development. I would love to say I’m Nüsslein-Volhard v2.0, but the reality is almost all developmental biologists are Nüsslein-Volhard v2.0s. Because developmental biology is not simply the study of specific processes in specific species (ha ha flies, ha ha frogs). The field operates on common principles (like those discovered by Nüsslein-Volhard)—concepts of how regions are “zoned,” how cells “talk” to each other, how tissues and organs interact in synergistic or exclusive patterns, and how such interactions proceed—that apply to multiple events in the developing embryo.

A solid understanding of such principles permits a developmental biologist to quickly build a picture of hitherto unfamiliar developmental events on which one has never conducted original research, like, for example, the patterning of the reproductive system. With a decent level of training, I would expect any developmental biologist to quickly and easily grasp the minutiae of the process of sex development, comprising, as it does, many of the foundational principles of our field. Just as it has not been tricky for me to switch my research focus from eyes to nerves, from muscles to skin, it wasn’t tricky for me, having never studied sex development directly, to know before I read a single paper that these tracts and tubes and tissues would be zoned and talking to each other, and which signalling molecules I was going to find. Evolution is thrifty, and development employs common mechanisms to mark regions of an embryo, whether that’s the back of an eye or the top of a uterus. And developmental biologists aren’t simply well-trained at spotting and applying mechanisms that create tissue patterning, we spend a fair and boring amount of time identifying male and female animals, breeding them, dissecting reproductive organs, analysing sex chromosomes - sex is all in a day’s work for the average developmental biologist.

And as for ha ha flies, ha ha frogs. I suggest some might wish to learn what an animal model is. The preserved evolutionary genetics and mechanisms between humans and other animals, even those species apparently-unrelated to humans, gives developmental biology great power as a discipline. The need for developmental biology in clinical settings and other fields of biology is increasingly obvious. For example, cancer studies, stem cell technology (oh look, another froggie Nobel prize), tissue engineering research and regenerative medicine rely on developmental biology; if one wishes to understand how, for example, a lost limb might be regenerated or how to turn stem cells into liver cells, understanding how a limb or liver develops in the first instance is crucial.

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Nüsslein-Volhard is one of the most high-profile scientists to enter the fraught public commentary on the nature of sex. And this is no series of misinterpreted quotes by a journalist wishing to spin a story: she has come prepared. She bats off common arguments about hermaphrodites (“the fact that there are hermaphrodites does not change the fact that these two germ cells exist, eggs and sperm, and thus also two sexes”) and reflects on the pressures young girls face (“I was also unhappy at the age of 14 and wanted to be a boy”). On the case of PhD student Marie-Luise Vollbrecht, whose lecture on the varying modes of reproduction of a sea anemone was cancelled by trans activists, she retorts: “Do they now also want to abolish biology lessons?”

Well yes, yes they do. With your help, Professor Nüsslein-Volhard, we won’t let them.