The pregnancy sickness protein, and COP controversy
In the news this week, scientists identify the protein responsible for pregnancy sickness, what was settled on in the COP consensus, how honeyguides listen out for local language, and the special chemical which could hold the key to preserving a Rembrandt masterpiece. Plus, how many nukes would it take to destroy Jupiter?
In this episode
00:55 - Scientists make progress towards pregnancy sickness cure
Scientists make progress towards pregnancy sickness cure
Stephen O'Rahilly, University of Cambridge
Scientists at the University of Cambridge say they have discovered a protein which causes many women to experience nausea and vomiting during pregnancy. Some women - including the Duchess of Cambridge - become so unwell when they are expecting that they need to be admitted to hospital. So, what should we know about the protein that is causing it? Chris Smith spoke to Professor Stephen O’Rahilly, director of the Medical Research Council Metabolic Diseases Unit at the University of Cambridge...
Steve - So it's called GDF15. It's a protein and a hormone, and it goes into the bloodstream of the mother and it goes up to a very special part of her brain where it goes into a docking station, which is only present in a tiny bit of the brain. That's classically the bit of the brain that makes you feel sick.
Chris - Why does the placenta make it? Does it have another role? Presumably its job is not to make mum feel sick?
Steve - The first thing I would say is, it's present in non-pregnant people. In non-pregnant people, it probably is the signal that, when you've damaged yourself by taking some toxin or maybe even had a huge amount of alcohol and you've damaged cells, a signal goes up to the brain and says, 'that's horrible. Go and lie in the corner, throw up and never do that again.' So that's the job of this hormone in the non-pregnant state. In the pregnant state - primates, only the apes and ourselves have done this - I think what's happened is, to protect the baby during the first trimester, the first three months of the pregnancy when the organs are all developing... When we were evolving, we were hunting and gathering and eating all sorts of rubbish from the forest floor. This signal came and went to the mother's brain and said, 'I feel very nauseous and not so well. I'm not going to eat anything new or anything rubbish, and I'm going to stay safely in the cave and not go out and be eaten by a sabre tooth tiger.' I think this is the signal that the placenta has sent out, in fact, the baby's bit of the placenta because it's actually the baby that's sending the signal to say, be very careful what you eat. That's the job of this hormone.
Chris - When one looks, then, at people who have very bad sickness in pregnancy, is it that the baby's making more of it or is it that the mum is more sensitive to what the baby's got and all babies make an equal amount?
Steve - That's a great question and the answer is both of what you said. When we look at women who get very sick, the baby makes more, but the other factor is how sensitive the mother is. One of our key discoveries is what determines how sensitive the mother is, is how much of this substance, how much GDF15, she's seen before she was pregnant. And that really is a key determinant of what she will feel like when the foetus comes along and makes a shed load of this stuff and she's exposed to it. Her previous exposure determines how badly she feels.
Chris - When you say previous exposure, do you mean as in, if I took a blood sample from a woman, measured the level and her baseline when she's not pregnant level that's always there, that sort of sets her sensitivity? Or is it that if she spends every day of her life throwing up because she's having too many things she shouldn't... how does it work?
Steve - It works from, we think, relatively recent blood levels. What we have done in some of our experiments is given mice small doses for about three days before we give a big dose. If we give a small dose just of saline, a mock injection, and we give them the big dose, they don't like it, they don't eat, they go into a corner and they feel unwell. If we give them very small doses for three days and then give them the big shot, they ignore it, they feel perfectly fine. Even a few days of high exposure is what is doing it and that probably explains why 80% of people feel sick in the first three months of pregnancy, but it generally fades. We think what's happening is that, as the levels are high, the women get used to it and then, for the second and third parts of the pregnancy, most women get through without many symptoms at all.
Chris - But what about women for whom that doesn't happen? Because some women do complain that it continues all the way through pregnancy and in some women it's, I mean, some of my friends have been so badly affected they've ended up in hospital.
Steve - Yes, it's a very serious condition. It's the commonest condition for women to end up in hospital in the first trimester of pregnancy, and in some women it goes on for the entire duration: they don't desensitise for some reason, and we don't quite understand why they don't. But what is true is that if you have very low levels pre-pregnancy, those women have a 10 times higher chance of that happening to them when pregnancy comes along.
Chris - Does this mean then, now you understand the mechanism of how it's working, you can engineer a way to stop it?
Steve - Yes, I think we have. Normally, I know, scientists often talk that their work will be translated into treatments. I am more confident than I've ever been that something we've done will turn into treatments. So I think two things: one is that our work has really shown how important GDF15 is, how dominant it is. I'm confident that if we gave an antibody, for example, that blocked this substance, that would immediately alleviate their symptoms. And if we engineer it so it doesn't go into the baby, we've got the safety angle covered as well. So treatment I think will happen. Then our attempts to prevent this are going to start with women who have had a previous pregnancy where they were very sick and about a third to a half of those women never ever embark on a second pregnancy because of that: they want to have another baby, but they are too terrified of having the same experience again. So what we'd like to do in those women is expose them to GDF15 gently for a few months before pregnancy to reduce their level of sensitivity to this so that when they do become pregnant, they have a reduced chance of being very unwell.
06:29 - 'Litany of loopholes' in COP28 consensus
'Litany of loopholes' in COP28 consensus
Richard Black
Chris Smith spoke to Richard Black from the Energy and Climate Intelligence Unit at the very start of the COP28 summit in Dubai, and got in touch again to find out how it’s all been going...
Richard - I think the highlight was probably on day one to be honest, Chris, by agreeing to set up this fund for something that's called loss and damage. This is the idea that some countries are already suffering from the impacts of climate change, and usually it's the poorest countries in the world who did nothing really to cause climate change. The idea is that the countries that did the most to cause it should pay money into a fund, which will then go to help some of the most developed countries. This is an issue that's been on the agenda for well over a decade. It was really kicked into the long grass repeatedly until last year's COP actually when, to a load of people's surprise, there was agreement in principle that there should be funding mechanisms set up, including a central fund. And this year they won. They basically said, 'let's do it.' And even more remarkably, a number of countries said, 'and here's some money.' So there's about half a billion dollars in this fund already. That was probably the highlight. And certainly, if you're sitting in a small island developing state, or a South Asian country with a massive coastline or somewhere like this, then you're going to be pretty happy about this, I think.
Chris - So obviously there was that day one highlight for you. What were the low points, though?
Richard - I think the biggest part of this, and the bit that I think most people are interested in, is anything that talks about the future of the energy system and how we build out clean energy capacity and how we stop using fossil fuels. Unsurprisingly, this was the most contentious bit of the whole thing. I have thought for the last couple of years that we're in quite an interesting phase here because it feels like the cards are on the table much more starkly than they used to be. You have a certain group of countries, headed by the OPEC plus countries, who really don't want anything in there about reducing fossil fuel use. And then you have everyone else that does. And so it's really about how is there going to be a landing zone found so that you can actually have something in the text that is meaningful and yet every country is prepared to sign off on. So there was a low point, I would say, between 24 and 36 hours before the end when the presidency released a new draft text which really was extremely weak on a lot of this stuff, but they did actually get it back a little bit in the final text.
Chris - The language, though, many have criticised this because what they've effectively agreed to is a transition away from fossil fuels. It sounds a bit whimsical and also some of the island nations have described this as a litany of loopholes, ways for people to wheedle out of actually having to be committed to this. And that would even include the oil producing countries who are hosting. Has this got real teeth in it, the arguments that have been agreed on, or is it really just empty words?
Richard - It certainly doesn't have teeth, but that's very much in the tradition of these conference declarations, actually. No one will sign up to something that is going to oblige them. Basically what they've done this time is they have agreed that there's a need for deep, rapid and sustained reductions in greenhouse gas emissions. They're really calling on each other to do at least one of a number of things: tripling renewable energy capacity globally by 2030, doubling the rate at which we are improving our efficiency with energy use by the same date, accelerating efforts towards the phase down of unabated coal burning, accelerating the transition towards net zero emission systems, transitioning away from fossil fuels, accelerating renewables, nuclear, carbon capture and storage, and low carbon hydrogen production, cutting back on methane emissions. Basically, it says, 'look, this is the need. As countries we're calling on each other to do at least some of these things.'
Chris - Doesn't sound any different from the song that they've been singing for years?
Richard - You always have to have a consensus in the final agreement. And that means, you are right, that often the tune that's being sung is a bit vanilla, it's a bit lift and elevators, frankly, rather than the Flight of the Valkyries type thing that a lot of climate campaigners would want. But, although you can argue it's a bit of a limp form of words, it is the first time that's been acknowledged in any declaration from any climate convention.
Chris - And, in closing, where does this leave us for next time?
Richard - I think we might have quite an underwhelming COP next year. It's going to be in Azerbaijan, which is a country which is ranked very low in rankings of democracy and so on. There's a massive oil and gas industry. It wasn't anyone's first choice, put it that way. Basically, what happens is there are five different regions of the world and they take turns to decide which country is going to host it from their region. So next year we are talking about Eastern Europe, the former Soviet bloc. Now a number of Eastern European countries did express an interest such as Bulgaria, Czech Republic and so on. Russia and Belarus, which are in the same block, vetoed all of them. Belarus proposed itself. And of course the rest of Eastern Europe vetoed that because of the Russia Ukraine conflict. So we had this complete standoff. But anyway, we're off to Azerbaijan next year and Baku, the capital of Azerbaijan, probably has the claim to be the oldest oil capital in the world. Oil's been the thing there for more than a thousand years. The Venetian explorer Marco Polo 700 years ago noted that oil was being produced there and exported. And in modern day Azerbaijan, tourists can still go and have a health giving bath in crude oil. So it's going to be quite an interesting place to host a COP, I think.
13:51 - How honeyguide birds assist human honey hunters
How honeyguide birds assist human honey hunters
Claire Spottiswoode, University of Cambridge
To explore the relationship between human honey-hunters and honeyguide birds in rural parts of East Africa, Chris Smith spoke with Claire Spottiswoode - an evolutionary biologist at the University of Cambridge’s Department of Zoology and the University of Cape Town - from her research base in Mozambique...
Claire - Cooperation between humans and wild animals is really vanishingly rare. One of the few remaining examples occurs between an African bird species, the greater honeyguide; small, rather unassuming, brown birds that are related to woodpeckers. They all share this really curious trait, which is that they love to eat beeswax, which is really rich in energy if you're able to digest it, which honeyguides have the ability to do. But the snag is that beeswax is defended by thousands of stinging honeybees. So while honeyguides are extremely good at finding bees nests, they have rather more of a problem getting access. So, to solve this, they team up with their own species and approach humans in the bush and give a strident, urgent chattering call, 'chatter, chatter, chatter,' which attracts our attention. And if we choose to follow them, they'll then fly from tree to tree, giving this chattering call as they fly in the direction of a bees nest - anything from a few metres if you happen to be standing under a bees nest without realising it, which is remarkably easy to do, up to a mile or more.
Chris - Do we know how far back in history this relationship goes? Is this a modern thing?
Claire - It's entirely possible that it actually predates our own species. And that's because the two key features that make us such useful partners to a honeyguide are, first, the use of fire to subdue these thousands of stinging honeybees, and the use of tools to chop open their nest. These are skills that humans and our hominin forebears have had for in the order of 1.5 million years in the case of the control of fire and up to 3 million years in the case of tool use. For all that time, honeyguides and honey producing honey bees have also lived in Africa, so it's entirely plausible that this relationship is extremely ancient. But of course this is just a hypothesis and unfortunately it's an unfalsifiable one: we can't test it in a way that would allow us to prove it wrong.
Chris - Do they learn this from their parents or does this appear to be bird innate? They come out of the egg and they can do this?
Claire - We can be pretty sure that the aspects of the relationship that are learned rather than innate are not learned from their parents because honeyguides, like cuckoos, are brood parasitic, meaning they're raised by other bird species and, in fact, one of a honeyguides first acts as a chick in a dark nest hole is to stab its foster siblings to death and it'll thereafter be fed by another species until it fledges. It'll never knowingly meet its own parents because they're raised by species that have had no such interaction with humans. A honeyguide hatches from the egg knowing how to cooperate with humans and we think this because even very young honeyguides would seem to be attracted to humans and attempt to guide them. And, furthermore, in parts of Africa where humans no longer recognise the call of honeyguides and no longer follow them because they have access to alternative sources of sweetness besides wild honey - either beehive honey or or sugar - honeyguides do still attempt to call us.
Chris - The human calls to the bird, the bird calls to the human. Is that the same all over Africa in the territories where these birds are? Or, in the same way that humans speak differently in different bits of the world, do the birds' conversations differ?
Claire - Yes, it's really remarkable. In fact, certain calls are used fairly consistently here in the north of Mozambique.
<Human call>
Claire - Even just a few hundred miles away, completely different sounds are used. And if we look across Africa, we see a mosaic of different human cultures using completely different sounds in exactly the same context. These can vary from beautiful whistle melodies, for example, used by the Hadza honey hunters of Northern Tanzania to various other forms of whistles often made with instruments like snail shells or hollow fruits with holes drilled in them, as well as in some places various words and other forms of trills and grunts. So we have this immense cultural variation among different honey hunting cultures across Africa that honeyguides have to contend with in order to recognise a good partner and cooperate effectively with our own species.
Chris - Do these calls work on the birds wherever you are in Africa or have the birds evolved or learned the specific calls made by the populace in those areas so they'll only respond to humans who respectively speak that language?
Claire - Yes, you've just laid out two very nice alternative hypotheses for why these calls work. And these are two of the alternatives that we considered in our new paper that we're discussing. We also considered a third hypothesis, and that's that these calls are designed to travel well through the particular habitat in which different people are honey hunting. So we know that some verticals are tuned to the specific environment in which the birds exist, they move better through the vegetation type, so it's just possible that this could be true for these human calls too. They might work not because honey guides prefer them, but simply because honey guides can hear them better.
Chris - How did you test this, then? What experiments did you do this time to try to get to the bottom of this?
Claire - We carried out field experiments here in the North of Mozambique and also in Northern Tanzania to test honeyguides' responses to the signals that people used to communicate with them in these different parts of Africa. And in each place, the three experimental treatments that we carried out were either the call given here in the North of Mozambique, the beautiful whistled melody given by Hadza honey hunters in Northern Tanzania, or arbitrary human sounds which were honey hunters shouting out their names.
Chris - And what did you find? Did the birds only respond to the local lingo as it were?
Claire - That's exactly right. So we found that honey guides were two to three times more likely to interact with humans who gave the local honey hunting call compared to the foreign honey hunting call or arbitrary human sounds. So here in Northern Mozambique, the honey guides strongly preferred the local honey hunting call, but largely ignored the Hadza whistle melody. Whereas in Northern Tanzania, the opposite was true - the honey guide strongly preferred the local whistle melody, but were not particularly strongly attracted to the Mozambican sound. So this supports the hypothesis that honey guides have learned what their local partners sound like and are attracted to those calls. We were also able to test the third hypothesis that these sounds simply travel better through the bush by directly quantifying how quickly sound does travel through each environment, and we found that both types of sounds travel equally well through the environments at both sites, suggesting that this isn't a good explanation for why honey guides are differentially attracted to the local sounds. And of course this, like our previous finding, is one that would probably not surprise any honey hunter. They know perfectly well that they use these calls because because honeyguides prefer them.
Chris - In some respects, they're using us as their tool then, aren't they? They're kind of manipulating us to feed them by doing us a favour? We cop all the stings in order to give them dinner?
Claire - That's very well put. We are their tools, but also they are our tools and in fact they're described almost that way in as many words by some of our honey hunter colleagues here in Northern Mozambique. Honeyguides are a kind of living tool to them and, as it happens, we are interested in different parts of the resource. Honeyguides want wax, we want honey, so there's no fighting over the spoils either.
21:51 - Rembrandt the chemist: lead formate found in masterpiece
Rembrandt the chemist: lead formate found in masterpiece
Phillip Broadwith, Chemistry World
An international team has identified lead formate in various areas of one Rembrandt’s best-known paintings, The Night Watch. The discovery - which has been published in Science Advances - provides some clues about the practices used by some of the great artists of the seventeenth-century. Chemistry World’s Phillip Broadwith took a look at the painting and the research paper...
Phillip - This particular paper is about Rembrandt's 'The Night Watch.' It was painted in the mid 17th century and it's now at the Rijksmuseum in Amsterdam. The Rijksmuseum itself is a fantastic museum - they have a great big chemistry department doing lots of conservation and analysis work - and what the scientists at the Rijksmuseum were trying to do in this case was look at how Rembrandt had actually painted 'The Night Watch;' what's the condition of the painting? Is it degrading and how can we preserve it? They did all sorts of analysis using x-ray techniques, and they found a very unusual mineral, lead formate, in the painting, which was a bit of a surprise.
Chris - People of Rembrandt's era were using lead all the time, weren't they? Because lead makes colourful compounds. People even used it in makeup, I think, didn't they? To get nice white skin tones and things?
Phillip - Lead compounds have been used in makeup since the ancient Egyptians. Lead oxide was also used as a hardener. The oil, the linseed oil that was the base of the paint, if you mix that with lead oxide, there are reactions that help the paint to harden and set. So there's all sorts of different kinds of lead compounds, and some of those can react together so it looks like this lead formate, which is strictly a compound of lead and formic acid, which is the acid that ants use in their defence, wouldn't have started out as lead formate: it wouldn't have been added to the paint in that form, but it has later formed by some kind of chemical reaction between the various different lead compounds, maybe the oils, maybe other things that are there at the time.
Chris - Is the purpose of this that - in the same way, as we say in biology, in order to conserve a species, you've got to understand it - are they trying to chemically unpick what Rembrandt did so that they can then understand why the picture looks the way it does, but also how we can sympathetically keep it looking good?
Phillip - Yeah, absolutely. That's exactly it. You know, looking at the composition of the paints gives us some insight into the materials that artists were using at the time. Rembrandt is particularly famous for his use of light and shade and colours to make those kinds of images, and this one is an absolutely spectacular example of that. But also, understanding how those materials change over time gives us an insight into how we can conserve these paintings in the best way for future generations to enjoy.
Chris - I was quite surprised actually when I read a bit more about the history of it. I have seen it, and it is a stunning picture. It's huge - 14 feet by 12. And you think when someone can paint on that sort of scale with the detail that he achieved and bring in, as you mention, that element of shading, light and dark, to emphasise certain bits of the picture, it just shows an incredible talent. But one of the things that someone wrote about this is that although we call it 'The Night Watch,' it's not actually intended to be a nighttime scene and it's years and years of accumulated dirt and other people's not so careful conservation that have made it look dark. So does this understanding of the chemistry that these sorts of analyses are giving us, does that mean we might be able to chemically unpick some of what's been done to it? Or are we kind of stuck with it?
Phillip - Yeah, well that's always a difficult thing in art conservation. There's always a balance between trying to preserve what's there, but not necessarily trying to turn back the clock. That's part of its journey, if you like. But if it's something that conservators have done that can be undone, for example, dirt, or if someone has added a varnish over the top that's damaging the painting, then that's the kind of thing that they will look to try and remove, to bring more of the painting back to reality, if you like, without necessarily interfering with the art itself.
Chris - Apart from being extremely good with a paintbrush, does this suggest that people in this sort of era, like Rembrandt, were also pretty good chemists?
Phillip - It's not entirely clear. You're talking about the mid 17th century, this is almost the birth of modern chemistry, the emergence from an alchemical, artisanal kind of practice into a more scientific way of thinking. It's not clear how much the artists of the time were taking that on. You say this painting is massive, if somebody wanted to have consistent colours over a painting that size, they're going to have to be mixing batches and getting some consistency. So my feeling is that they would've been taking a relatively artisanal but quite systematic approach to mixing those pigments, not necessarily understanding the underlying chemistry, but having a really good knowledge of the materials that they were using and how they interact and mix together to create the effects that they want to do. Other painters over time have been very famous for this kind of thing as well. Van Gogh and the other impressionists and expressionists. Edward Munch used a lot of metal compounds to make really vibrant colours. But one of Van Gogh's problems is that, quite quickly, only 50 to a hundred years later, those colours have changed significantly, and that's partly because of the chemistry of the pigments he was using. Now, whether he was using those pigments because he didn't have very much money and those were what he could afford, or because they gave him the effects that he wanted, we don't really know. And modern artists start to blend some of that chemical knowledge into what they're doing and they can deliberately make colours that will change over time and use that as part of the effect of the art.
28:03 - How many nukes would it take to blow up Jupiter?
How many nukes would it take to blow up Jupiter?
Will Tingle took this question on from listener Sebastian with the help of University of Cambridge Public Astronomer, Matt Bothwell...
Will - How many nuclear bombs would it take to destroy Jupiter? Have you ever woken up and wanted to wreak havoc on a cosmic scale, but realised you didn't know how much of your personal nuclear arsenal to bring with you? Me too. So, fortunately for us, the public astronomer at Cambridge's Institute of Astronomy, Matt Bothwell, is here to take us through the physics and forces required.
Matt - It's harder than you might think. The Earth is a big ball of iron and rock that weighs a billion, trillion tons since the earth formed. It's been hit by billions of asteroids and, not only has the earth not been destroyed, they've barely left a scratch. So what would it take in order to destroy anything? The general rule is you need to put in enough energy to overcome whatever forces are holding that thing together. If you take something held together by pretty weak forces like a cake for example, you don't really need much energy to pull it to pieces. If something's held together more strongly like a rock, then smashing it to bits is going to be hard work. So what about a planet? Well, the force that holds planets together is gravity. And if you want to destroy a planet, you're going to have to put in enough energy to overcome the gravity of a whole planet. Scientists actually have a special term for this. We call it the 'gravitational binding energy.' If you take anything that's held together by gravity, whether it's a planet or a star or a whole galaxy, and you add enough energy to equal the gravitational binding energy, that thing is going to be destroyed. You want to destroy Jupiter, and that's going to be pretty hard work. The gravitational binding energy of Jupiter is about as much as a hundred billion trillion nuclear bombs. That's a one followed by 23 zeros. Earth is smaller and has weaker gravity, so it is going to be easier to destroy. It would only take maybe 10 billion trillion nuclear bombs. So, happily for astronomers and stargazers everywhere, I think the planets are safe from your evil plans for the time being.
Will - We hope that answered your question, Sebastian, thank you very much for sending it in. And thank you very much to Matt Bothwell. His upcoming children's book covering topics like this, and many more, 'Astrophysics for Super Villains' is out July of next year. Keep an eye out for that.
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