Modifying insulin, and the melting Sphinx
In this edition of The Naked Scientists: The new form of insulin that switches itself off before blood sugar falls too low; also, scientists suss out the origins of most of the meteors that fall to Earth; and why the longest lived patch of snow in the Scottish Highlands finally looks set to melt away…
In this episode
00:58 - Modified insulin prevents sudden drops in blood sugar
Modified insulin prevents sudden drops in blood sugar
David Sacks, National Institutes of Health
Scientists have engineered a chemical switch into the insulin used to treat people with diabetes. This enables the hormone to sense the blood sugar level and turn off the insulin signal if blood glucose drops too low. It could work as a way to prevent life-threatening “hypos” that diabetics run the risk of developing if they inject too much insulin or don’t consume enough sugar. To find out more, we put in a call to David Sacks, from the National Institutes of Health. David has just written a news and views piece on this topic for the journal Nature, where the research is also published…
David - People who inject themselves with insulin to treat their diabetes often develop very low glucose called hypoglycaemia. And this is a potentially life-threatening problem. Parents, if you have a child who has Type 1 diabetes and they inject themselves with insulin. Glucose goes too low, the child loses consciousness and has seizures. The parents are devastated and so they tend not to try to get tight glucose control, which is necessary to prevent the long-term complications of diabetes, which include blindness, kidney failure, and heart attacks and strokes. The novelty of this paper is that the authors developed a special insulin molecule that responds to the glucose level in the blood. When the glucose is high, the molecule is switched on and when it is low, the molecule switches itself off because it detects the low glucose in the blood.
Chris - When you say a molecule can turn itself on and off, how on earth does it do that?
David - They took the insulin and they added, stuck onto it, a ring-shaped structure called a macrocycle. And this binds glucose at a different part of the insulin. They stuck on another molecule, which is similar to glucose. And normally when the glucose is low in the blood, this insulin is switched off because the glucose-like molecule called a glucoside is stuck in the ring. When glucose goes high, it replaces the glucoside in the ring shape molecule and the insulin then is switched on.
Chris - So basically the molecule warps the insulin according to how much glucose there is, and that affects whether it can lock onto the cells that would normally see the insulin. And that affects its ability to be an insulin signal or not?
David - That's exactly correct. So what happens normally is that insulin binds to a special molecule inside the lining of the cell, the membrane, and then it signals to the inside of the cell. So the cell then knows that insulin's there and it produces effects inside the cell.
Chris - And I suppose that the benefit here is if you did over inject yourself with this, as soon as your glucose level falls below a limit that we'd define as a safe threshold, that signalling would stop. And so your body would stop lowering your blood sugar and you wouldn't end up going into a coma.
David - That's absolutely correct, because in people without diabetes, when you eat glucose, in your blood goes up, insulin is released, and then it lowers the glucose in your blood and then it stops being released and is eliminated from the body. When you inject normal insulin, which patients do, they've injected under their skin, it can stay in the body for up to 40 hours and it continues working. It doesn't get switched off. So even when the glucose is lowered, the insulin continues lowering it more, causing this dangerous condition of low blood glucose. Now this modified insulin molecule that is described in the paper, when the blood glucose goes low, it stops working, switches itself off.
Chris - How have they tested this? Have they proved it does actually do that?
David - They did studies in rats and pigs to show that the molecule is effective. And in a pig model of diabetes, they demonstrated very clearly and nicely that the glucose does not go very low when they use this modified insulin. And they demonstrated that using standard insulin, human insulin that is injected by people with Type 1 diabetes, the glucose did go low. So it appears to protect against the development of low blood glucose.
Chris - Could it be used then in a sort of depot way where a person could just give themselves a massive injection of this which would last them all week and their sugar would refuse to budge and go too low, but wouldn't go too high either?
David - Most people who inject themselves with insulin do multiple injections every day. They use a long acting insulin and they also use short acting insulins that they inject with meals. You need both of them because they have slightly different effects in the body in terms of controlling your blood glucose concentration. So it could, if effective, replace the current long-acting insulins that most people with diabetes use.
07:02 - Can cancer's development alter our brains?
Can cancer's development alter our brains?
Paola Vermeer, University of South Dakota
People diagnosed with cancer also frequently develop mood disorders like depression, but sometimes before they even know they have the disease, ruling out just having cancer as a cause. But could the reason be that their cancer is in conversation with, and manipulating their nervous system? Paola Vermeer is a researcher at the University of South Dakota. She’s found that developing cancers seem to form associations with nearby nerves, and strike up a relationship. The nerves can grow into the tumour, which can “listen to” and respond to the signals issuing from those nerves; but even more intriguing is that the cancer seems to be sending messages back to the brain via those nerves, altering brain activity and chemistry, and therefore potentially also mood. She’s just published a paper in the journal eLife documenting how this seems to happen. It might, she argues, lead us to new ways to approach the management of cancer…
Paola - So we've known that tumours actually can infiltrate the nerves and that's associated with a poor prognosis for many cancers. But what we're now learning is that it happens the other way around, that the nerves can actually infiltrate the tumours as well. They are two very separate processes. So when the tumour contacts the nervous system, it can utilise that as almost a roadmap to get to different parts of the body and metastasize. So, it's a route for metastasis, but when the nerves infiltrate the tumours, they can actually release factors that further promote increased proliferation of the tumour and allow it to grow.
Chris - So it's almost like in the same way as the nerve would talk to a target organ in the body, like a muscle, it can talk to the tumour and provoke behavioural change on the part of the tumour?
Paola - Oh, absolutely. We've started to define some of these molecules that are used in these conversations. So there's actually talk from the nerves to the tumours and then from the tumours back to the nerves. It's a very active communication where the two entities impact each other.
Chris - And what about higher centres? What about, if you have a sensory nerve contacting a tumour and obviously the job of a sensory nerve would normally be to relay information centrally up to the brain. Does that actually get reflected in a change in behaviour then?
Paola - Yes, absolutely. And we were very intrigued by this because cancer patients really suffer a decline in their mental health. And we can study this by looking at behaviour in mice where we implant tumours. So we saw that the brain was changed and the mouse behaviour was also changed.
Chris - When you say the brain was changed, what did you actually see?
Paola - We saw that the brain regions that were connected to the nerves in the tumour, had a very high activity. They were firing a lot more than the same regions of the brain from a non-tumour bearing animal.
Chris - How was that reflected in behavioural change?
Paola - The behavioural tests that we use were really reflecting the wellbeing of the animal. And so their behaviours for those animals that had tumours went significantly down as the disease progressed. So they wouldn't make a good nest or they wouldn't eat a cookie because they were essentially depressed.
Chris - And this is not just because tumours are painful, because as we know when you have a tumour growing invasively through various tissues, that is extremely uncomfortable. It wasn't just that in these animals, they're in pain, that's why they withdraw socially?
Paola - No. In fact, we tested that, and we had a group of mice that we gave a tumour to, but then we treated them with a medication for their pain and that did not fully restore their normal behaviour. So it's not only pain information that is being relayed to the brain, there's more to it than just that.
Chris - And what about different types of tumour? Because some are more nerve-like in their behaviour and the sorts of tissues of origin and the things they make, the tumours themselves. So would you expect that some tumours are probably going to have these sorts of effects to a greater extent than others?
Paola - Yes. And as you said, the location of the cancer can really dictate not only the extent of how many nerves infiltrated, but also what type of nerves. So, all the tumours that we've looked at so far are innervated, but the types of nerves could be different and therefore the influence of the nerves on the cancer could also be different.
Chris - What do you think this tells us then? Does this sort of show us a way that we should manage cancer differently or does it open up different avenues for management?
Paola - Absolutely, It tells us that so far all the cancer medications that we have completely ignore this nerve component of the tumour. So that isolates the nerves as a therapeutic target. And since we know some of the molecules, we can design drugs to target them. But it also tells us that beyond the local tumour, we need to consider what the connections to the brain are and how we can therapeutically mediate changes in behaviour in cancer patients as well.
Chris - And looking at it the other way around, if you make the person's mood better, does that affect the behaviour of the tumour?
Paola - We haven't tested that directly, but given the bidirectional nature of these communications, I would expect that yes, if you can change the neurons in the brain and the behaviour that should have an impact on the tumour itself.
Chris - Why has no one looked at this before?
Paola - The understanding that nerves are in cancers is relatively new, as surprising as that sounds. So we are just at the early stages of understanding, not only that the nerves are there, how are they getting there? What are they doing? And what other neural components are they connected to? It's a very young field.
13:33 - Where do all the meteors that hit Earth come from?
Where do all the meteors that hit Earth come from?
Matt Bothwell, University of Cambridge
Two new papers in the journal Nature suggest the most common types of meteorites that reach Earth are likely to have come from just a handful of parent asteroids. Commenting on the research, and with news of a new comet you can look out for, here’s public astronomer and space science author Matt Bothwell, from the University of Cambridge’s Institute of Astronomy…
Matt - Essentially they're trying to answer the question, where does all the stuff that lands on Earth come from? The Solar System is actually quite a busy packed place and something like 5,000 tonnes of cosmic material falls on earth every year. Lots of it is very, very small like space dust that slowly wafts down. But lots of it is quite big. It's like chunks of stuff causing fireballs and burning up very dramatically. And it's been a bit of a mystery for a long time. Like where does all this stuff come from? And researchers think they've finally identified a few major breakups of large asteroids that caused all this debris.
Chris - How did they do it?
Matt - So chemical composition, a lot of it. So a lot of the things that fall on earth are what we call chondrites, which means they have these small little kind of like blobby spheroids inside the meteorites. And we chemically analyse the stuff that lands on Earth and we do the same. We chemically analyse these families of asteroids we see out in space using reflection spectroscopy. Essentially we look at the light that reflects off them and infer what we can about their chemical composition and they found a match.
Chris - What's come from what and what does it explain?
Matt - We think that there was one major breakup around 450 million years ago, which resulted in one particular family of asteroids. And we think there was also a series of breakups between 5-7 million years ago that caused the rest. It's something like 80% of all the asteroids hitting Earth just came from a few very big things breaking up in the not too distant past.
Chris - And can we link those to any events that have happened on the Earth? Can we see any consequences?
Matt - We absolutely can. So the really, really big one that smashed up about 450 million years ago, as well as breaking up into chunks which have caused the asteroids that are now hitting Earth, also released a lot of dust. So the solar system would've become a very dusty place around 450 million years ago, and that dust settled on Earth and would've raised the opacity of the atmosphere blocking sunlight from the ground, which would've caused an Ice Age. So we know there was a couple of million years around 450 million years ago where there was a bit of an Ice Age and there was a bit of a die off, and we think now it was all caused by that big cosmic crash.
Chris - Do you know what I find really surprising is that that is the blink of an eye, really, the time you've just mentioned. Given the age of our Solar System, we measure that as close to sort of 5 billion years. And yet relatively recently, we're still seeing these sorts of breakup events. What's, what's actually causing them to still be jockeying for position in the solar system like this?
Matt - I think the answer is that just our solar system on what you might call medium timescales, is just still quite a dynamic place. Even on human timescales, right? I mean, listeners might remember Comet Shoemaker-Levy 9 slamming into Jupiter very dramatically, which I watched as a kid and it was very dramatic. I think just seeing over timescales of tens of millions of years, there's a lot of stuff in our solar system flying around and smashing into each other.
Chris - I think I saw that report. I remember watching Patrick Moore on The Sky At Night reporting on that. And I was also very lucky to see Comet Hale-Bopp when it came past here. That was really bright. That was the first time I'd properly seen a comet. But speaking of comets, it's pertinent that you raised this because if people look in the sky at the moment, they can see another one.
Matt - Yes. So there's a comet called Tsuchinshan, which is very close to the sun right now, which means you have to wait till after sunset. It peaked just a couple of days ago, but over the next week or two, the comet will be getting fainter and fainter and fainter, but also getting further and further away from the Sun. So hopefully those two things should slightly counteract and leave the comet visible till the end of October. So what you want to do, if you want to see it, is look to the west just after sunset and hopefully in the kind of the sunset glow, you should see a nice comet and a nice tail hanging there in the sky.
Chris - And that's true in both the northern and southern hemisphere. Is it?
Matt - Yes, absolutely true. So wherever you are in the world, as long as you have clear skies around sunsets, you have a good shot of seeing this.
17:55 - Scottish Sphinx snow patch reveals warming climate
Scottish Sphinx snow patch reveals warming climate
Iain Cameron
It has been revealed that the Sphinx - which is a patch of snow believed to be the longest-lasting in the UK - has now melted for four years on the trot. Citizen scientist, author, and keen walker Iain Cameron - who incidentally also works in the Scotch Whisky industry, ticking another stereotype box! - has spent decades surveying the patch, which is hidden in one of the most isolated parts of the Scottish Highlands…
Iain - Sphinx is a patch of snow. It got its name from a rock climb. Two climbers in the 1940s were pioneering some climbs in remote parts of the Scottish Highlands. The patch lies directly below it. And so there's no real mystery to the name, there's no esoteric similarity between this patch of snow and this Sphinx in Egypt. It's purely because the climb above it was so-called. But it is the most enduring, if you like, patch of snow in all the British Isles. It has been monitored closely since probably the mid 1800s. But there's good anecdotal evidence going back to the 1700s and even beyond
Chris - How big is it?
Iain - Reasonably. So it depends when you go, because it does all depend on winter snow. So if you go there in a snowy year it can be as much as 30, 40, 50 metres even. But some years you go at the end of September, the start of October, it can be a little larger than a dinner plate. And that was the case this year. So it really depends.
Chris - And what got you interested?
Iain - I've been interested in patches of snow since I was a lad, literally a lad nine years old. When I gazed from the bedroom of my parents house that they still live in to this day, in fact. Through onto Scotland's most southern Munro. A Munro is a hill above 3000 feet. And on the southern flank of this hill, there was a large patch of snow, and this was in May. And I found this very curious because all the snow around had melted ages ago. As far as I was concerned. All the snow that I used to go out and play in as a young lad. Here I was looking at this large patch of snow, it looked like a medallion hanging around the neck of this hill. And it just flipped a switch in me. It just triggered an interest, which is endured to this day.
Chris - And how do we know that this patch that we dubbed the Sphinx is genuinely the longest lasting? And there must be other bits because I remember being at the top of Ben Nevis, I was sort of navigating my way through dense fog <laugh>, and I was looking at bits of snow at the top of Ben Nevis. So presumably this is not an isolated example.
Iain - No, it's not. You're right. Ben Nevis is another hill which contains long lasting patches of snow. And in fact Ben Nevis is probably one of the most reliable places to see long lying snow. However, because Scotland is a reasonably small place and the areas of upland that exceed 4,000 feet or 1,220 metres, there aren't that many. And they're quite busy on these hills and they have been for quite a while. So there are quite a lot of people out there and quite a lot of people observing. And so we know that the Sphinx is the longest lasting just because there are very good records going back, you know, well over a hundred years.
Chris - And what's the problem with it?
Iain - It's melting more often than it used to. So it persisted from the 1700s all the way through unmelted. And in 1933 it melted the first time this was a big deal and members of the Scottish Mountaineer Club thought it needed to be recorded. So they wrote The Times and The Times published a letter from there. It was quite closely observed until it melted again in 1959, so 26 years later. Okay, not a biggie, you might think. 1996 was the next time it melted. So there was a third time now in the 20th century. You couldn't say it was a regular occurrence at melting, but it melted again. But then after 1996, things started to change. And it melted again in 2003, 2006, 2017, 2018, 2021, 22, 23, 24. So it's now melted in four consecutive years. So it used to be an isolated incident of it melting. It is now an isolated incident of it surviving. So there's a complete 180 flip.
Chris - Have we got an explanation as to why it's melting? I'm not being facetious, obviously ice melts when the temperature rises, but can we attach this to any kind of particular change in climatic conditions, winds? Is there any particular factor that's doing this or is it just that we think average temperatures are rising year on year and it's intensified the frequency of melting.
Iain - The most important factor for a patch of snow surviving from one year to the other is not summer temperature, but is in fact the amount of snow that falls in winter. So if for example, you have got 20 metres of depth up in an average season, then it's going to take summer a lot less time to get through 20 metres than it is to get through 30 metres of depth. The reason why not as much snow is falling is because the precipitation that used to fall as snow is now falling as sleet or rain at high level. And even the difference of a degree or so in temperature can affect drastically the amount of snow that falls at these locations.
Chris - Indeed, researchers pointed out, I think just this week, that we assume with climate change we're going to see a warming that's going to be evenly spread across the year and across the seasons. But in fact it's not like that. We don't see warmer summers and warmer winters. We may see an asymmetry with the winters getting a lot warmer, but the summer's not much warmer and that could have quite dramatic shifts in the way the weather works.
Iain - Yeah, that's right. I'm hopeful that this period is anomalous and we will go back to a period where Sphinx and others like it survive from one year to the next. I am fearful, but as long as I'm able to, as long as I've strength in my legs, I will keep going back because for me it's a little pilgrimage going to these places and one which I enjoy thoroughly. Not only to see the snow itself, but just to be in the wildest places that Scotland has to offer is a real joy.
24:15 - How do spiders know how to make webs?
How do spiders know how to make webs?
Thanks to Sara Goodacre for the answer!
James - Spiders make webs for a variety of functions, some to catch prey, to raise their young or even as a mode of transportation with help from the wind. And the short answer to your question is spiders do innately know how to build their webs, but to explain how and to provide some insights into the amazing variation in these silky structures across species, his professor of evolutionary biology and genetics at the University of Nottingham and spider specialist Sara Goodacre.
Sara - Thanks James. Like you say, each web is perfectly formed to fulfil its function. And if you get this wrong and it stops fulfilling the desired function, then the spider doesn't do so well and is much less likely to pass its genes on. I think Darwin would've found this a good example actually of how only the fittest survive. So for example, some spiders need to be able to make sticky silk so they can glue their webs to a branch or to your windowsill, but they might also need stretchy silk that will be able to catch a passing fly. Some spiders back comb their silk as well, using a special comb on their legs. And all of this involves delicate, intricate leg movements whilst they're reeling silks from their spinning glands and they have to do this in the right time using the right combinations and in the right ways.
James - Absolutely remarkable, isn't it? And despite how beautifully intricate they can seem in competitive ecosystems, sometimes less is more when it comes to web design.
Sara - That's right. There's a skill in only using the minimum quantity of silk required as well. So it's not to waste energy. And as an example of good judgement in this way, we know that some spiders alter the composition of their webs when they're in a windy tunnel and they put more resources into those silks that hold the web firm in a windy tunnel so that the threads don't bend in the wind. And molecularly we know how this works, it boils down to differences in the types of amino acids, so building blocks of proteins and particularly one of them called prolene, which changes in the proportions that the spiders are able to use.
James - Are there any exceptions to these rules? Any other factors from the environment that might contribute to a different kind of spider's web?
Sara - One of them that's really conspicuous is the case of the parasitoid wasp that infects a spider and makes it spin a really strange looking web. And this is so that the wasp survives; it really is not for the spider's benefit. And whilst we don't know exactly how the wasp does this, what we think is that chemical cues from the wasp from that species changes what the spider does with its silk. And it's really dramatic if you see it. And given the time of year. And I know some of us on a Saturday evening, myself included, might be watching dancing on the telly. I can say that the change is as if instead of doing an elegant tango across the dance floor, the spider sort of starts doing a frantic breakdance on the spot. And it creates this funny structure inside which the wasp stays safe.
Comments
Add a comment