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Received — 18 August 2026 ⏭ The Conversation

What happens when someone’s chromosomes, sex hormones and body don’t align?

The intersex symbol nito/Shutterstock

I teach a university course called Hormones and Behaviour. What surprises students is that biological sex is not produced by a single switch. What surprises me is that many students have never been taught this before. It is basic biology, but it helps explain life.

Sex emerges through a sequence of events before birth and continues at puberty. Chromosomes help direct the formation of gonads, the body parts that usually become ovaries or testes. Gonads make hormones. The body then has to respond to those hormones. In most people, these steps flow in the same direction. But in rare cases, they do not.

These cases are known as disorders, more recently differences, of sex development (DSDs). They are not new but they provide a useful way to understand how bodies develop. DSDs can affect hormone production. Some affect the body’s response to hormones. Some affect chromosomes or gonad development. Two people can have a DSD, yet have very different bodies, medical needs and life experiences.

Each condition reveals what can happen when one step in the normal sequence is altered. Here are five ways sex development can take a different path.

Congenital adrenal hyperplasia

This DSD affects around one in 16,000 births.

The adrenal glands, which normally produce small amounts of male hormones, even in females, are hyperactive in this condition.

A baby with two X chromosomes and ovaries can therefore be born with external genitals that look male.

Complete androgen insensitivity syndrome

In contrast, a child with complete androgen insensitivity syndrome (CAIS), can have XY chromosomes and internal testes that make testosterone, but their body cannot respond to that testosterone.

This lack of a response to testosterone keeps the developing fetus in its “default” female state, leading to female external genitals at birth.

Someone with CAIS will develop breasts at puberty. Since their external anatomy is typically female, people with CAIS are usually raised as girls and may only be diagnosed later, often when their periods do not start.

CAIS is estimated to affect one to five in 100,000 live born females.

5-alpha-reductase deficiency

Another condition, called 5-alpha-reductase deficiency, shows how sex development does not finish at birth.

The body needs an enzyme called 5-alpha-reductase to turn testosterone into a stronger version of the hormone before birth. When a genetic mutation inactivates this enzyme, an XY baby may be born with genitals that are read as female and may be raised as a girl. At puberty, however, the normal surge of conventional testosterone masculinises the body.

The condition is rare worldwide and its exact incidence is unknown, partly because conditions affecting sex development have often been surrounded by silence.

In parts of the Dominican Republic, where this condition is known as guevedoces, studies have reported surprisingly high local rates. A rare genetic mutation is more common in these isolated populations, about one in 90 males.

More recently, some of these communities have begun to recognise guevedoces at birth and raise them as boys.

Small wooden mannequins with magnifying glass against pink and blue background.
A person’s sex is more complicated than you might think. s880/Shutterstock

Sex chromosomes disorders

Usually, females receive one X chromosome from their father and one X from their mother, and are therefore XX, while males receive one X chromosome from their mother and the Y chromosome from their father. However, a person with Klinefelter syndrome, affecting one in 500-1,000 male births, has XXY chromosomes, causing smaller testes, scant body hair, lower testosterone and reduced fertility. It is often never diagnosed.

On the other hand, Turner syndrome, or the loss, in females, of one of the two X chromosomes, affects one in 2,500 female births and impairs growth, puberty and fertility. It can affect physical appearance, for instance a wide neck and broad chest and often comes with health conditions such as hearing loss and kidney problems.

Swyer syndrome is rarer: a person has XY chromosomes but with a mutation in the Y chromosome that disrupts the signal that normally drives testes formation. The gonads do not develop into testes, testosterone remains low and the external and internal anatomy is typically female.

These are the clearer examples. Milder sex differences can result from mutations that reduce, rather than completely inactivate, an enzyme or hormone response. For example, non-classic congenital adrenal hyperplasia, where some enzyme activity remains. Their effects may be less obvious, and their incidence is often unknown because many cause subtler changes or are never diagnosed.

What this does and does not tell us

None of this is new. These conditions have been known to scientists for decades. But now genetic testing can identify the mutation behind some cases.

Specialist clinics and patient groups have pushed for clearer information for parents, better psychological support for patients and greater caution around irreversible childhood surgery when it is not medically urgent. Recent patient-centred research shows that clear information, good communication and psychological support are central to good care for people with DSDs. It’s unclear whether increased awareness has improved people’s lives, but the direction is clear: better information, specialist care and long-term support matter.

The lesson is not that sex is meaningless or endlessly fluid. These rare conditions do not provide a simple answer to every argument about sex and gender.

However DSDs do show sex is not a single event. Just like the growth of our body, it is a process. When chromosomes, gonads, hormones and the body’s response to them all follow the usual sequence, the result often looks simple. When one link changes, the body may no longer fit the binary pattern many of us were taught at school.

For the people affected, this is not an abstract puzzle. Some need lifelong hormone treatment. Some face infertility. Some discover their condition only as teenagers or adults. Chromosomes or sex designation at birth may explain part of the biology behinds DSDs. It does not explain what it feels like to grow up, go through puberty, seek fertility treatment or decide who needs to know.

The Conversation

Jean-Michel Fustin is a Medical Research Council-funded Senior Research Fellow in the Division of Integrative Physiology at The University of Manchester. He contributes the level-3 course Hormones & Behaviour.

An astronomer on what it’s really like to stargaze for a living

metamorworks/Shutterstocl

Jodie Foster tearing up a dirt road, yelling stellar coordinates into a walkie-talkie à la the 1997 sci-fi film Contact. Control rooms alive with a cacophony of “enhance that signal”. Real-time discovery. That’s what I pictured when my PhD supervisor told me I’d be going observing at a telescope.

Cut to 2am on top of a mountain in La Palma last April, at an altitude that makes you forget you’re in the Canary Islands. It was utterly freezing, and I had dressed for the sunny archipelago in thin layers. I almost dropped my mug trying to close the telescope door against the wind.

Coffee and food waited two minutes away in the service building. In the darkness, the wind caught a loose scrap of fabric and scared the life out of me. I fell over within 30 seconds. Winds of 40km/h aren’t uncommon at the observatory; I was just entirely unprepared.

I sat on the road, mourning my dignity. And I looked up. For the first time in my life, I saw the Milky Way. It painted the sky, reminding me violently of my insignificance. Nothing in my life has ever compared to that. I allowed myself to bask in it for ten minutes. Then the work beckoned me: I needed coffee, and hadn’t told my colleague which star was next on the schedule.

How is an observing night prepared?

A night at a telescope begins in the afternoon. At around 4pm, my colleague, who was training me to use the telescope, and I drove up to the Nordic Optical Telescope. It’s a gorgeous piece of kit, with a diameter of 2.56 metres. It collects enough starlight for exquisitely precise measurements.

Every instrument and filter had to be carefully tested. On my side, this was a few lines of code. The telescope operator ensured everything worked properly and set up the telescope. While calibrations ran, I started scheduling the night’s observations.

Telescope time is limited, so having three nights at the helm meant I had to squeeze out every second I could. Hollywood did not prepare me for how many spreadsheets this involves. This sort of scheduling requires careful balancing of many factors. For example, observing stars close together on the night sky consecutively to avoid spending too much time repointing the telescope.

Once calibration and scheduling were complete, I watched the sun set. It was beautiful, but also a warning – working hours will soon begin. If you catch the right moment, you can see a small fleet of astronomers in cars headed to their respective telescopes.

The mountain came to life with domes opening, catching the first starlight of the night. There’s more than 20 telescopes in the observatory on the mountain, whose specialisms range from observing supernovae to exoplanets (any planet beyond our solar system).

The night itself

Around 8pm, the first light from a star – HD153557 in this case , a dwarf star around 59 light-years away – entered the telescope. This is always a bit special. The whir of the dome moving, the shutters opening, seeing the monitors show the first traces of data. I sipped my coffee, turned up the 80s hits, and was content in the knowledge that I’d still be in that chair in 12 hours.

This night started rather predictably. The weather was perfect, not a cloud in sight, and the telescope behaved beautifully. Before long we had a spreadsheet slowly getting filled in with completed observations. I knew the peace wouldn’t last. I’d done ten observing nights at two different telescopes by that point in my career, and not one of them without something disrupting my colour-coded plans. Typically, a cloud will move right in front of a star I’m trying to observe, or it’ll rain and that means we have to close the dome. But every few nights, there’s something a little more exciting.

An email just before midnight brought with it a Target of Opportunity alert. These are observations that need to be done immediately, a blink-and-you’ll-miss-it moment. This one was a gamma-ray burst. It’s one of the most violent events in the universe, over a trillion times brighter than our Sun. This was picked up by a space-based detector and emailed to us to request the observation.

Gamma-ray bursts aren’t in my area of expertise – I research stars like the Sun and their surrounding planets. Far less explosive. Between switching observing instruments, rotating the dome, checking calibrations, I was also digesting as much information as I could about what a gamma-ray burst is. This was probably the closest I’ll ever get to my Jodie Foster moment, and it was a rather anticlimactic, blurry image loading very slowly on a screen.

After the gamma-ray burst was observed, the control room became quiet again. Back to my spreadsheets and falling over trying to get coffee. To feeling slightly lonely but seeing another dome rotating under the moonlight when I stepped outside, and being reminded of the other tired astronomers all working beneath the same stars.

It was 8:30am when I finally got back to my room. Ready for a shower, and bed, and to wake up in five hours and do it all again.

The scientific end product

The reality is that scientific interpretation rarely happens in real time. The telescope measurements are first cleaned and calibrated by a computer programme, which turns them into usable spectra. I then apply my own analysis code to these spectra. For me, this comes much later, at my desk in Birmingham once my sleep schedule has recovered. These particular observations gave us stellar spectra: when a star’s light splits into a rainbow, imposed with patterns that reveal its temperature and chemical composition.

The most common observing nights involve balancing spreadsheets, a whole lot of coffee, and slowly surrendering to the delirium of sleep deprivation. Some of them have dramatic alerts. Some of them end up entirely clouded out and allow for an early bedtime.

There is no pivotal “enhance that signal” moment, but there is the quiet, consistent sense of joy that I’m cataloguing and understanding the stars that could one day be found to host another Earth. Hollywood didn’t prepare me for the scientific process. But it got the wonder spot on.

The Conversation

Alix Violet Freckelton receives funding from UKRI.

Why snake venom may have evolved to catch dinner, not for defence

In the animal kingdom, any hunt for a meal or encounter with a predator is a matter of life and death. To survive both, animals have evolved a multitude of weapons, of which venoms may be one of the most widespread and effective.

But building a chemical weapon presents an evolutionary dilemma. Should venom be optimised to disarm prey, or to cause rapid pain to deter predators? Our new study suggests that in snakes, a meal comes before self-defence.

Venoms are complex chemical cocktails. Their composition is shaped fundamentally by their intended purpose. Predatory venoms disrupt multiple tissues and organs at once to immobilise prey. On the other hand, defensive venoms have only one job: to cause rapid, intense pain to deter predators. Think of a bee sting, for example.

These differences create a conundrum. What if an animal wants to use its venom for both predation and defence? This is not a trivial question, because the storage capacity of venom glands is limited, and producing venoms is thought to carry an energetic cost. That opens the door to an evolutionary trade-off: investing resources into one function might leave less for the other.

Venomous snakes are probably the best-studied venomous organisms, and for a good reason. Unfortunately, snakebite remains a huge medical issue, especially in tropical countries. More than 100,000 people die yearly and more than 400,000 people suffer lifelong injuries as a consequence of snakebite.

In theory, antivenoms could prevent many of those deaths, but there is another problem. Snake venoms are extremely variable, not just between species but also between different populations of the same species. This means that antivenoms developed for one region can fail to work in another. Understanding what drives this immense venom variation is the first step towards more effective treatments.

Snakes use their venoms both for hunting and self-defence. We have good evidence that diet is the central factor shaping venom composition in many snakes. In contrast, defence against predators has rarely been studied as an important evolutionary driver, and never in comparison with diet.

Based on the results of a previous study, we suspected that species that hunt easy, low-risk prey such as insects might not need a highly lethal predatory venom, freeing up resources to invest in more defensive, pain-inducing compounds instead.

To test this idea, we looked at a group of venomous snakes called meadow vipers (Vipera ursinii and relatives). These curious little snakes live in the lowland steppes and alpine meadows of Eurasia. Their diet is unusual among vipers, as they eat mostly or almost entirely grasshoppers, crickets and locusts.

On the other hand, they also regularly fall prey to predators like birds of prey, badgers and foxes. It’s exactly the kind of pressure that might favour a defensive venom.

For our study, we travelled to where their populations can be found across Europe to obtain venom by “milking” them. It’s a process that causes no harm to the snakes, and they were released back to their habitats afterwards. We also collected venom from other European vipers like the adder (V. berus), asp viper (V. aspis) and nose-horned viper (V. ammodytes), which mostly feed on more dangerous prey, like rodents.

If our trade-off theory held, we would expect these venoms to be more predatory and less pain-inducing than those of meadow vipers.

Putting venom to the test

To measure pain, we tested the venoms on cultures of specialised sensory neuron cells. These are cells responsible for detecting harmful stimuli in the body. If such a cell is activated to produce pain, calcium ions flow into the cell. So, to track whether venom triggered these cells, we treated them with a fluorescent dye that reacts to calcium and measured the emitted fluorescence.

To our surprise, regardless of diet, none of the tested venoms activated these cells, not even that of the insect-feeding meadow vipers. So, it appears that European viper venoms, like in most snakes, probably evolved to overcome prey rather than to fend off predators.

All this does does not mean that viper bites don’t hurt. They do. But it seems that the pain is mostly caused as a side effect of other venom actions, such as inflammation, tissue degradation or muscle spasms.

There are however exceptions elsewhere in the snake world. Some toxins found in lanceheads and coral snakes do directly stimulate pain receptors. However, such toxins have been documented in only a handful of species and their ecological function remains enigmatic.

That means the story of snake venom is far from complete. Rather than revealing a universal rule, our findings suggest that, at least in European vipers, the evolutionary pressure to catch prey has outweighed the need to deter predators. Understanding where that pattern holds – and where it doesn’t – could help explain why snake venoms vary so dramatically, an essential step towards developing better treatments for snakebite around the world.

The Conversation

Bálint Üveges received funding from the Leverhulme Trust, the Bangor Fund / Cronfa Bangor, Bangor University and the Taith research mobility programme of the Welsh Government. He currently receives funding from the National Research, Development and Innovation Office of Hungary.

Wolfgang Wüster receives funding from the Leverhulme Trust, Natural Resources Wales, Natural England and the Amphibian and reptile Conservation Trust

What it’s like to discover an ancient Egyptian tomb – and the race against time to preserve it

The first moment you look inside a newly discovered ancient tomb is at once exciting and terrifying. I was fortunate to experience this recently as director of an international research team carrying out fieldwork in the Theban necropolis, a Unesco world heritage site near the modern Egyptian city of Luxor.

Our project’s primary aim is to implement a conservation and risk management programme for the necropolis (burial ground) of Lower Sheikh ʿAbd el-Qurna. Due to its location at the foothills of the Theban mountain, monuments in this area are extremely vulnerable to flash flooding from intense bursts of rain.

To direct this floodwater away from the tombs, we are systematically removing debris and excavating the area, using archaeological techniques that ensure all historical information is preserved. This is how we came across this previously unknown, roughly 3,000-year-old tomb.

As we prepared to enter it, we had no idea if the ceiling had collapsed, if the tomb had been looted or destroyed, or if it was still well preserved.

Its layout is typical of Theban elite tombs dating to the New Kingdom period (ca. 1550-1069 BC). At this time, Thebes (now Luxor) was Egypt’s capital and main religious and political centre.

The tomb features an outer courtyard, rock-cut chapel and subterranean burial chambers. The well-preserved courtyard area includes a mudbrick platform with a niche for a stela (upright stone grave marker) and staircase with ramps on either side, giving access to the tomb.

Once inside the rock-cut chapel, we noticed its walls are decorated with vivid paintings of the main tomb owner adoring various deities in shrines, and also sitting with his wife in front of an offering table laden with bread, beer, fruits, meat and flowers. Based on the iconography and painting style, we determined that the tomb dates to the Ramesside period (ca. 1292-1069 BC), named after the many pharaohs called Ramesses in that era.

This was a particularly exciting moment. These wall paintings offer invaluable historical details about ancient Egyptian daily life and society. They also shed light on the tomb owner’s position in the Ramesside hierarchy, and on the other family members buried here – plus, potentially, later reusers of the tomb.

Identifying the tomb’s owner

The vast Theban necropolis, comprising an area of around 10km², was Egypt’s main royal and elite cemetery for half a millennium, from ca. 1550 BC onwards.

Situated opposite the city of Thebes on the west bank of the River Nile, it features many world-famous historical sites including the Valley of the Kings (a burial ground for pharaohs including Tutankhamun and Ramesses II) and Valley of the Queens, plus hundreds of private elite tombs, royal memorial temples and remains of royal palaces.

Our team has been carrying out fieldwork here since 2018, in close collaboration with the Egyptian Ministry of Tourism and Antiquities.

Based on a first analysis of the painted decoration inside the tomb, we identified its main owner as a male official named Paser. However, the paintings are covered in a layer of dirt. Once they are cleaned by a conservation specialist, we expect to find out more about the identities and personal narratives of the people buried here.

One of the main research questions associated with our fieldwork focuses on the question of tomb placement and tomb reuse – for which the newly discovered tomb carries important scholarly significance. It will help us explain why in the Ramesside period, officials such as Paser chose to reuse, modify or build tombs adjacent to the monuments of the preceding 18th-dynasty elites.

Specific questions we will try to answer include: how did features of the ancient mortuary landscape (including proximity to processional routes, tombs of relatives, or monuments of special cultic importance) influence the placement of these tombs? And what influenced the decision to reuse them for burial, rather than building new ones?

A race against time

Unfortunately, our work is something of a race against time. As a result of climate change, the frequency and intensity of flash flooding is expected to increase significantly in the coming years here.

This poses a major threat to the tombs in this area. Flooding can lead to immediate, extensive damage such as moisture-activated growth of salt crystals, loss of painted decoration and, potentially, structural collapse. So, one of the most important aims of our project is to implement a preventive conservation and risk management programme that safeguards these monuments for future generations.

At the same time, these activities also allow us to explore this area archaeologically for the very first time, revealing the historical and cultural development of the Lower Sheikh ʿAbd el-Qurna necropolis. Up to now, this area has barely been studied in comparison with famous nearby sites such as the Valley of the Kings and the large temple complexes of Luxor and Karnak.

But our ongoing research shows that Lower Sheikh ʿAbd el-Qurna is rich in archaeological material. This includes exquisitely decorated tombs that offer a unique glimpse into the daily lives, funerary beliefs, artistry and monuments of Egypt’s ordinary people and officials over many centuries.

The Conversation

The project led by Carina van den Hoven is funded by the Gerda Henkel Foundation, and it also receives funding from the Luxor Archaeological Heritage Foundation. A proof of concept study on the digital documentation and material analysis of the ancient wall paintings in Theban Tomb 45 was funded by the Netherlands Institute for the Near East and the Leiden University Centre for Digital Humanities. In 2017 Carina established the Luxor Archaeological Heritage Foundation, a non-profit organisation aimed at providing financial support for the Dutch archaeological expedition to the Theban Necropolis.

How animals prepare for war

Chacma baboons don't hang around in risky areas. Danita Delimont/Shutterstock

Battles between rival groups are a story as old as time. This sounds like a human story, but it is also one that is playing out across nature.

Conflict between groups of animals competing for territory and resources is widespread, and contests between animals can be dangerous. Getting ambushed, especially by a larger or more powerful group, can have disastrous consequences.

However, conflict is sometimes unavoidable.

Emerging research shows war preparations are not a trait unique to humans.

A new article by my colleagues and I highlights how many of the same principles apply to animals too, and not just in our closest relatives like apes. We reviewed the literature and found examples throughout the animal kingdom of animals preparing for future conflicts. This behaviour probably explains how animals persist in the face of often intense conflict.

Animals may sense the recent presence of their rivals. Many species, such as dwarf mongooses, leave scent marks to advertise their presence, and react to those laid down by rival groups. Others animals may rely on their memories of past conflict to change their behaviour in situations they deem risky, such as at territory edges or contested resources.

There can be sex differences in how animals approach conflict. Vervet monkeys are a good example here. Males often stand to lose more from conflict, while females stand to benefit – as it could lead to securing long-term access to high-quality food. Researchers have observed males attempting to defuse conflict yet females try to promote male participation.

When assessing that the risk of conflict, there are many questions for animals to consider. Are rival groups likely to be close by? How powerful are they? Are they restricting access to key resources? Do you have vulnerable offspring to protect?

Animals use many different approaches to reduce the dangers rivals may pose. Here are three main ones:

1. Inform yourself

Information is power. Across group-living species, from mongooses to invertebrates, there is evidence that animals can prioritise gathering information in risky situations. Chimpanzees have been seen to climb to the top of hills and wait quietly, listening out for rivals before making their next move.

Two dwarf mongooses wrestling standing on their hind legs.
Dwarf mongoose are highly territorial. PACO COMO/Shutterstock

Similarly, when groups of dwarf mongooses encounter the scent of rivals, they move less, investigate their surroundings more and post more sentinels to look out for danger. Gathering information comes at a cost, often in the form of lost opportunities to find food and engage in social interactions. But if the risk is high this can be a small price to pay.

2. Strategise

The way animals use space can be crucial. Some species, such as long-tailed tits and chacma baboons, choose to minimise the time they spend in risky areas, such as where territory overlaps. Others animals, such as meerkats, lay down scent marks near their burrows, which are a valuable resource.

Staying within familiar areas and defending them can give groups of animals a home advantage, as groups are more likely to win when they are on familiar ground. Groups can also stay closer to one another, reducing the chances of animals getting isolated should a contest arise suddenly.

Many species, including ants and apes, raid rival groups. These include targeted forays into rival territory with the goal of injuring and even killing rivals to reduce the threat they pose to their own group. Raids in ant species also allow groups to steal the brood of their rivals, bolstering their future fighting force.

3. Stick together

Make sure your groupmates have your back. Although groups often cooperate with one another, animals can be out for themselves, especially those less related to their groupmates or with less to gain from winning.

Group members therefore need to be confident that the others won’t turn tail when the going gets tough. This can be achieved by both carrot and stick. Chimpanzees play and groom more before conflict occurs. These bond-building activities aim to ensure nobody defects if backs are against the wall. It happens more on days when they later engage in conflict, which suggests they know to some degree that an attack will be more likely.

Vervet monkeys, however, take a different approach. Monkeys that failed to participate in previous contests can face aggression from groupmates, coercing them to step up and help next time.

All of this preemptive behaviour can require animals to keep track of who their rivals are, how strong they are and where they might be. Gathering and processing this information can take a lot of effort. But if it allows animal groups to survive, then intergroup conflict may lead to the evolution of cognitive abilities. Indeed, researchers have suggested the need to outmanoeuvre rivals contributed to the intelligence we have as humans today. That is not to say that all anticipation is mentally costly. When rivals are predictable, simple rules can suffice.

Although our work focused on animals in groups, many of the same principles should generalise to solitary and pair-living animals too. Just imagine how many potential cold wars are playing out between rival animals, each trying to preempt the other while going about their daily lives.

The Conversation

Josh Arbon receives funding from the University of Cambridge Herchel Smith Fund. He works for the University of Cambridge and has previously worked for the University of Bristol.

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