Malaria fight in jeopardy, and bone collecting caterpillars
In this edition of The Naked Scientists: World Malaria Day, and why overseas aid cuts in the US are threatening to cause a crisis; the carnivorous caterpillar dubbed the “bone collector” that steals from spiders; and the biotechnologist attempting to feed astronauts better in space...
In this episode
01:01 - Foreign aid cuts threaten global fight against malaria
Foreign aid cuts threaten global fight against malaria
Jane Carlton, Johns Hopkins Bloomberg School of Public Health
The 25th of April is World Malaria Day. It’s an opportunity to examine a devastating disease that still claims over half a million lives each year, most of them young children in Africa. It comes as the World Health Organisation warns that huge funding cuts threaten to derail hard-won gains in the global fight against the disease, pointing out that, since the year 2000, these investments have helped to prevent 2 billion malaria cases and 12 million deaths. I’ve been speaking with Jane Carlton, director of the Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health. I put it to her that these are very big numbers, so malaria must account for a significant disease burden internationally…
Jane - Oh, absolutely it does. Over 260 million cases in 2023 is what the World Health Organization annual report came up with. And in fact, this is an increase over the cases from 2022 and about half a million deaths too, mainly in Africa. So approximately 40% of the world's countries have malaria and many of those are in the poorest regions of developing countries where access to healthcare is limited. It's quite a debilitating disease. So it really does have an impact on the economies of those countries. In fact, it's been estimated that about $12 billion is lost in Africa each year due to malaria.
Chris - It's spread by Anopheles mosquitoes. So is the disease everywhere where those mosquitoes are or are there areas where the mosquitoes are but the disease isn't yet and therefore those could be getting it soon?
Jane - That's one way of putting it. Another way of putting it is that there are the mosquitoes, Anopheles mosquitoes species present. For example, in the United States, we have the species which can transmit malaria parasites but we are not endemic for malaria. We used to be all the way up until about the 1950s when malaria was finally eliminated from our shores. And that's not to say that we don't continue to have some cases. In particular, we have malaria cases brought back in travelers and we get about 2000 cases of those in the US each year but we also occasionally get what's called locally transmitted malaria which is where the, because we have the Anopheles mosquitoes that can transmit parasites, people who've never left the country may come down with malaria and that's because there's been this local transmission of malaria. So I like to think of it more that we do still have those Anopheles mosquitoes but we can mitigate the effect of those by global health means to eliminate the malaria parasite from those areas.
Chris - Are there new areas opening up though with things like climate change? Will this make areas of the world more hospitable to the right source of mosquitoes so we could see countries that thought they're off the hook, malaria is not a problem and it becomes a problem?
Jane - The interesting thing about the malaria parasite is that she only develops within quite a narrow temperature range within the Anopheles mosquito. If it gets too hot, the parasite won't develop. So you may see a shift with areas in terms of their mosquito populations so that the range of malaria changes. So that's certainly possible. But actually the plasmodium parasite is quite finicky and as I say, it can only develop in a certain temperature range. So if it gets too hot, then it won't develop.
Chris - You mentioned there'd been an uptick compared to last year in terms of cases. Now, is that a sustained change or was it a one-off and actually the general direction of travel is that it's staying the same or shrinking?
Jane - Yes, that's a very good point actually. Malaria map as we know it is shrinking. So over the past 20 or 30 years, we have seen real gains in the number of malaria-free countries. For example, Egypt was announced as malaria-free under the terms of the World Health Organization last year. It's been malaria-free, no malaria cases for the past three years. So we are decreasing from year to year. There are upticks in particular when there are wars, for example, or ecological disasters. But overall, I think we are gradually managing to shrink the malaria map.
Chris - So why is the World Health Organization worried?
Jane - Because of the cuts in global health funding that the new administration in the United States have made. So the USAID, which funds the president's malaria initiative is one such organization which has really been decimated over the past several months. PMI was started in 2005 and its efforts have been focused in about 30 countries which account for 90% of the world's malaria cases. And PMI has been instrumental in reducing the burden of malaria in those African countries. For example, last year it delivered 37 million bed nets, 15 million preventive malaria treatments, 103 million rapid tests for the detection of malaria parasites. So having PMI no longer exist is something that the World Health Organization is very worried about.
Chris - WHO is a pretty powerful organisation though. And if it's just money, and I don't mean that in a belittling way, if it's just money, that is a relatively simple problem to solve, isn't it? Because couldn't other countries, given the enormous burden, be encouraged to step up and fill the void?
Jane - Well, we do know that some countries in Africa have stepped up. Nigeria, for example, has proposed to put forward $200 million in addition to its current malaria surveillance pot of money. But the problem is, as a colleague said to me, I think a lot of Western countries feel that because malaria is not endemic to their countries, why should they necessarily be providing funds for something that happens so far away?
Chris - What do you think is the solution then? Are there some other sort of things on the horizon if we put the bad news to one side? Where might we be making inroads, perhaps in novel ways, that might bear huge fruit?
Jane - There are definitely some really good initiatives which have been rolled out over the past year or so. Dual action bed nets to make sure that mosquitoes, which have become insecticide resistant, now will be caught by these double action bed nets. There are two new vaccines which the World Health Organization also just approved, RTSS and R21. And those are starting to be rolled out. I think 19 countries in December last year had already started those vaccination programs. So that's very good. And then other initiatives such as seasonal malaria chemoprophylaxis. So treating all of the children during the malaria season. And then in terms of some of the research that's ongoing, there are improved vaccines which are being looked into and researched. The development of genetically modified mosquitoes as well, especially those which then would not transmit malaria parasites. And repurposing anti-malarial drugs as well. These are all areas which are just ripe, I think, for malaria control.
Chris - Presumably your hope is that one day we're not going to need a World Malaria Day.
Jane - Absolutely. I hope that I'm going to be out of a job actually, maybe about the time that I retire, not sooner than that.
Chris - You don't want it to go any sooner than that, Jane.
Jane - So I really hope that that will be the case.
09:26 - Carnivorous "bone collector" caterpillar found in Hawaii
Carnivorous "bone collector" caterpillar found in Hawaii
Daniel Rubinoff, University of Hawaii at Manoa
Researchers in Hawaii have discovered an extraordinary carnivorous caterpillar, previously unknown to science. The insect - which has been dubbed the “bone collector” - lives exclusively in spiderwebs, where it scavenges for food whilst dressed in the remains of the spider’s previous victims. Hence the name. If that isn’t remarkable enough, it’s thought the caterpillar only inhabits a single mountainside on a remote Hawaiian island. Daniel Rubinoff at the University of Hawaii at Manoa made the discovery…
Dan - This is a caterpillar that doesn't look like a caterpillar at all. In fact, the first time we found it, we didn't know what it was that we were looking at. It looks like a broken bag of bug bits, all sort of sewn together onto a tiny little sack. That's, in fact, the idea. It doesn't want to look like what it is, which is a tasty little caterpillar hiding out in a sleeping bag.
Chris - How big is it?
Dan - They're about a half an inch long, which I cannot remember in millimetres.
Chris - Inches is fine. We're very happy with Imperial.
Dan - Yeah, you gave it to us, so it's fair. Exactly.
Chris - But where would I find one of these?
Dan - This entire lineage of caterpillar is only found in 15 square kilometres in the Waianae Mountains on the island of Oahu in the Hawaiian island chain. And in fact, they are the most restricted lineage of their kind in Hawaii. So it's quite concerning how limited their range is, in fact.
Chris - And what do they actually do? What's the biology of these caterpillars?
Dan - There are several layers of craziness that they're involved with. First, they're part of a group, the Hawaiian fancy case caterpillars, that has over 400 species. And all of them spin silk cases that they live in. And there are 18 varieties of silk case that they use. And each one is essentially a team, a lineage that has their own case. A burrito case, a bugle case, a purse case, bowtie with a twist case. And in this case, get the pun, we have the bone collectors. And they make a very particular case and live with spiders. And that's the only situation we're aware of on the planet where you have a caterpillar living with a spider.
Chris - And they decorate themselves with bits of dead insect.
Dan - Yes, they decorate or die. That's basically the motto. They are trying to deceive the spider into thinking they are not edible. And the way to do that is to take bits of the discarded prey that the spiders had. So an ant head, a fly wing, a beetle butt, a leg from something else, and spin them onto their cocoon, such that when the spider does approach them, all it senses is its last few meals and recognises this isn't probably food. And in fact, the caterpillars will also use the shed skin of the spiders as they grow. They leave their shed skins around and the caterpillars will pick those up and chew them into little bits and put them on their case as well to sort of fully convince this spider that there is not a caterpillar inside that case.
Chris - And is the caterpillar therefore stealing the spider's lunch? So living on the spider web, presumably it gets protection from the spider because the spider is going to defend its web and therefore the caterpillar, but does it also steal the spider's lunch?
Dan - So it's not, in my mind, really a freeloader, although I am a bit biased. This is not an orb web spun between two bushes sitting out in open air. These are spiders that make cobwebby webs in closed places where you really wouldn't want to stick your hands, like up in a tree hollow or in a rotting log. And they're catching insects and other things that are sort of running through the open spaces in the log. So the caterpillar is then eating stuff that the spider has caught and already had first dibs on.
Chris - How does it also evade the spider's trap? Because the insects that it's preying on with the spider, they're all blundering into this web and getting entangled. So the spiders know where the webs are sticky and they know where to put their feet. Do the caterpillars also know that? Is that how they don't get snared?
Dan - We think two things are going on. One is that the inside of a log is a very messy place. There's lots of debris and detritus, termite poop floating around, and that often seems to coat the webs. And when that happens, the webs are less sticky, but they act more like tripwires. So if you're a bumbling beetle cruising through a log, you're going to hit a few of these tripwires and that spider is going to run out and catch you. So I think the webs are operating more like that than purely intercepting and tangling things like you would expect with a sheet web. But that fortunately works in favor of these caterpillars because they don't get caught in the webs, in part because the webs aren't super sticky and in part because they move so slowly through them.
Chris - And what do these caterpillars turn into and how do they mate? Because presumably that is risky in itself to get to put the egg that's going to turn into the caterpillar into the right sort of environment so it'll find a spider it can team up with.
Dan - Yeah, so these little caterpillars, when they're done, they've eaten enough protein, they'll crawl probably a little bit away from the spider web and they'll pupate. And then their case essentially doubles as a cocoon. And a few weeks later, a little beige, black and white moth, they're actually quite lovely, but tiny, they're a little bit bigger than a grain of rice. It pops out and they'll crawl up out of the log and fly around looking for mates the same way other moths would do that with pheromones. And then it's only the females that really have to go back in. And we haven't seen that happen in part because these caterpillars are so rare and that's probably happening at night with these moths. But we're pretty sure what they're doing is laying their eggs in what they think are the right environment. So a rotting log that has, you know, signs of spiders. And then the tiny caterpillar is hatching, spitting a tiny case and cruising over to where the spider is. And at that point, you're looking at a caterpillar that's probably the size of a pinhead. And so it's got a little bit of time before it's even going to be on the spider's register in terms of size, where it's going to be able to scavenge little bits of insect jerky that have dried on the inside of the dead insect husks the spider has been eating.
16:45 - Diabetes drug could help tackle rare form of leukaemia
Diabetes drug could help tackle rare form of leukaemia
Brian Huntly, University of Cambridge
Cambridge scientists have found that a common diabetes drug might help prevent the blood cancer called acute myeloid leukaemia or AML. The study - which has been published in Nature - found that metformin slows the growth of cells that carry a key mutation linked to the cancer. This mutation is present in some bone marrow cells for years before the cancer manifests; it seems to confer a growth advantage over healthy cells, meaning affected cells slowly increase in number in the bone marrow before some of them eventually become cancerous and trigger AML. Metformin robs these pre-cancerous cells of their growth advantage, reducing the risk that they’ll turn nasty. Brian Huntly is head of the department of haematology at the University of Cambridge and one of the team behind the study…
Brian - So we've looked at the most common mutation that's associated with this pre-malignant condition. This is a condition called clonal hematopoiesis. It's very prevalent, it increases with age and people are at an increased risk of developing acute myeloid leukaemia. But not all of them develop acute myeloid leukaemia. In fact, the majority do not. The most common mutation in around about half of them is a mutation in a gene which gives cells their identity. We have looked at identifying vulnerabilities that cells that carry this mutation have, which are not present within normal cells, and many of them affect energy production within the cell. And these cells actually have an increased ability versus normal cells, and they increase in number within the bone marrow, which is the factory that produces the blood cells, and they come to be more dominant. And this is the process that leads towards the development of acute myeloid leukaemia. So if we can identify specific vulnerabilities within these cells, we can try and halt this process of expansion, and we can hopefully avert or delay the development of acute myeloid leukaemia.
Chris - And having spotted some of these vulnerabilities, have you got a way to block this?
Brian - Yes, we do. The abnormalities that we found in terms of the genes that cause the vulnerabilities are common in metabolic disorders of humans, things like diabetes mellitus, for example. And we have shown experimentally that we can prevent this expansion process with the use of a drug called metformin, which is the most common drug used for type 2 diabetes, and is probably used in hundreds of millions of patients worldwide with a pretty acceptable safety record. We're now thinking about a step change. We're thinking about treating people before they become patients.
Chris - This is a bit like treating high blood pressure in some respects, isn't it? You're giving people a pill. They haven't got a disease yet. They've just got high blood pressure. It hasn't caused a problem, but we know it will one day. So we give them an antihypertensive, bring down the blood pressure. We know we're reducing the risk of the consequences of high blood pressure. You're saying, I can give you a drug for a disease you haven't got yet, and it will reduce the risk of disease manifesting, and that's what metformin is doing?
Brian - That's what we think. That's what we hope. The experimental evidence shows that. We've backed that up by looking at patient registries where individuals who were taking metformin were at a significantly lower risk of developing this condition. So our experiments and the human evidence suggest that metformin will retard this process.
Chris - How is it working? What's the metformin doing that stops the disease manifesting?
Brian - We think it's targeting the energy production within the cells, and metformin does a number of things, but it targets this protein complex called Complex 1, which is involved in generating energy. But I think it's more complicated than this. Metformin does other things. It causes a lot of intracellular signaling differences, and the suggestion is that this pathway is implicated also.
Chris - Now, obviously, there are limits to what you can learn from mouse experiments, but when you do this in mice, what sort of a difference does the metformin make?
Brian - So basically, in the experiments, we look at the ability of blood stem cells to repopulate the blood system in animals who've been given lethal irradiation. Normally, the cells that carry this mutation have a significant advantage. This is almost completely reversed by the metformin treatment.
Chris - Most patients who come to see you, though, don't come and see you when they've just got some mutations but no disease yet. You pick up most people when they've already got the blood cancer, the AML problem. Does this mean, then, that now we need a screening programme, really, to try and pick this up, or is there a way we can get at the right people soon enough for them to benefit from what you've discovered and be put on metformin early enough to change the course of their disease?
Brian - So you identify a really important problem, and I'll go back to your analogy of high blood pressure. We don't know that people have high blood pressure just by looking at them. It either has to be some sort of test. Now, currently, the way that we test for this mutation is by complicated genetic screening. That is really not cost effective within the population. We often pick these patients up serendipitously. They have blood tests for either another cancer. They have an abnormality of blood counts which is transient. We pick them up. We're trying to develop low-cost screening tools to try and identify patients somewhat earlier. We do know that these disorders are more prevalent in some populations, patients with metabolic disorders, for example, patients with chronic inflammatory disorders. So we may be able to identify some patient populations in which screening would be manageable and likely to give a return on significant amounts of investment. But yes, we do have to come up, I think, with sensible screening strategies to identify the patients.
23:12 - Europe's scientists launch mission to grow food in space
Europe's scientists launch mission to grow food in space
Aqeel Shamsul, Frontier Space
A European Space Agency project is assessing the viability of creating lab-grown food in space. They’re doing it using genetically engineered microbes in bioreactors to produce food from its first principles The project is a collaboration between Bedford-based Frontier Space, Imperial College London and Cranfield University. Frontier Space’s CEO is Aqeel Shamsul…
Aqeel - The daily diet of the astronaut is not as appetising as calling a takeout for your Chinese or your Indian, unfortunately. Because of the constraints that's involved, what we do is we launch the fresh supply of food into the space station, but most of these supplies are often canned food or dehydrated food. You just prolong the shelf life, make it easier to transport, et cetera, et cetera. The problem is twofold. So obviously when you're trying to do this launching, it costs a lot of money and energy to go up there. And the second problem is that because you're eating canned food every day, it's not good for morale and astronauts losing weight, they don't have the appetite to eat. So if you start thinking about how do we support future human exploration, food is a primary and quite critical component.
Chris - One space technologist/food scientist I spoke to also said to me, one other further unappetising element is that you're rehydrating the food with recycled water. And we all know what that means in space. It's basically urine, isn't it?
Aqeel - Yeah, I think you can leave that up to your imagination.
Chris - So how are you trying to solve this then? I mean, there must be sort of short term and long term goals here. The long term is that we won't necessarily have an Indian takeaway on the moon, but we would have more appetising, nicer looking food that's also nutritious. But in the short term, there must be some steps towards getting there that you're trying to realise.
Aqeel - So one of the things that we're working on is the concept called precision fermentation. We use our bioreactor. And what we do is we put the microbes, bacteria and yeast into this bioreactor and grow them up. From the microbes, we can get proteins, carbohydrates, oil and fat. And that is basically the elements to be able to produce the food that you want.
Chris - So the chefs in this case are microorganisms. Will you genetically modify the microorganisms to endow them with the sorts of chemistries that making more nutritious, but also tastier foods in microgravity is going to require? Because they're not going to natively be able to do what you want them to do.
Aqeel - That's exactly right. We genetically modified or engineered the biology to, let's say, produce specific proteins, then get the microbes and then we cultivate them, culture them that we can then use as a feedstock for a 3D bioprinting to print a steak, for example.
Chris - Brilliant. So there'd be a sequence of small bioreactors then that would all produce individual micronutrients or groups of micronutrients or food groups, and they would then feed in almost like the filaments on a 3D printer of different coloured plastics. You would have different nutritional elements that you would print into a foodstuff.
Aqeel - Yes, exactly that. It doesn't even have to be just food, so we can actually engineer them to produce biofuel, biomaterial, so you can actually produce bioplastics. So the opportunity is quite vast.
Chris - This really does sound like rocket science though, and there is a pun intended, but how far along the path are you towards realising this?
Aqeel - Yeah, so I mean, this is kind of an early stage. The ideal precision fermentation has been picked up on Earth drastically for quite a few number of years now, but we're now trying to put that into the space context. As a company, we're raising private capital, obviously, to be able to do this and start building a larger scale system. Providing everything goes well, we can have a system up there and running in the next three to five years.
Chris - That's very near term. What about testing it though? Have you got any ambitions or plans in place to actually do some testing, so you can see if this really will deliver in space?
Aqeel - Yeah, so we actually launched our first mission on Monday. That was on a SpaceX Falcon 9 rocket inside a commercial space capsule. We're planning to do more and more of these tests. For example, we are planning to have another launch by the end of this year. We're planning to have up to three launches next year.
Chris - Have you got some recipes yet? Because it's one thing to be able to genetically engineer organisms to produce what you want. It's a bit like going to that compost heap in Derbyshire, where someone got the fungus that makes marmite.You're kind of at that stage where you can get the microbes, but do you know yet what you're going to cook up with them?
Aqeel - The amazing thing about using microbes is that you can actually get the foundational element or chemistry for any type of food or cuisine. Technically, you can actually produce, let's say, I don't know, Indian takeout, because you can actually get microbes to produce all this different chemistry. So the challenge is, for the time being, obviously start building the reactor and start growing the microbes. But there's maybe one or two steps after that. How do we extract the proteins? How do we then use the proteins to produce the element that we need for the food ingredient?
Chris - And do we know if the microbes are happy in space? Will they behave the way we think they will? And do they actually produce what we think? Or do they change their behaviour? Because some organisms, when you put them in different environments, they completely change what they do. I mean, I'm referring to the fact we spoke to Maggie Koblitz recently, who made miso in space, and she said, her taster team said it tasted totally different.
Aqeel - This is still uncharted territory, right? I think we do need to do a lot of testing to understand the parameters. What we've been working on is really building off 25 years of research in the space station, and using the knowledge that we found from that to kind of predict where we're going. So I mean, in most cases, you're right, there will be some adaptation to the microbes that actually make them resilient. There are also studies showing that you can actually increase the production yield. But this is all kind of hypothesis that we're testing along the way.
Chris - Now, Douglas Adams wrote about the restaurant at the end of the Universe. You're not going quite that far yet, but you're saying restaurant on the moon, possibly in three to five years.
Aqeel - I wouldn't go as far-fetched as a restaurant. But yeah, I think we can definitely produce a certain type of food in three to five years.
29:48 - Could measles help combat autoimmune diseases?
Could measles help combat autoimmune diseases?
Thanks to John Maher for the answer!
James - The measles virus not only invades cells in our respiratory system, which brings on some of the symptoms we associate with the disease, but also the cells of the immune system. This means we're susceptible to diseases we otherwise would have had protection from. Meanwhile, one of the most exciting areas of development in cancer treatment over recent years have been immunotherapies. One of which is CAR-T cell therapy, which could be described as a retraining of the immune system. This has led people to wonder, could we adopt these techniques to fight autoimmune disease as well? To bring all this together and to help us explain is John Maher, a consultant immunologist at King's College London.
John - T-cells are white blood cells, part of our immune system, which protect us from infection. CAR-T cells, on the other hand, involves taking T-cells from the peripheral blood of patients, let's say with cancer, and genetically modifying these cells by introducing a gene that encodes a completely new receptor. This is a designer system to reprogram many, many T-cells so that they can identify the same attribute of a cancer cell, enabling them to recognise and to kill those cancer cells. It has been most successful in certain blood cancers, particularly cancers which arise from another white blood cell called a B-cell. B-cells can become malignant, giving rise to leukemias and lymphomas, for example.
James - This sounds really interesting in relation to Caroline's question, because there are many autoimmune conditions like lupus and MS in which rogue B-cells are attacking the body's healthy cells. So could it be possible to modify CAR-T cell therapy, which is successfully going after cancerous B-cells in leukaemia, to instead go after these rogue B-cells in autoimmune disease?
John - That is a really interesting question, and that is a very hot ticket in the CAR-T cell world, right at this moment, in fact. CAR-T cell therapies have been applied outside of the remit of cancer in the treatment of patients with a range of autoimmune diseases, and the results have been very, very impressive indeed. There was a study in Germany in which I think 15 patients with really bad lupus, refractory to conventional medical therapies, were treated with CAR-T cell therapy directed against their B-cells, and all 15 of these patients achieved complete remission of their disease. And this is not just a one-trick pony, which is restricted to lupus. We are seeing impressive results emerging in a range of other difficult-to-treat autoimmune diseases.
James - Fascinating, and so exciting, because currently we treat many autoimmune conditions with immunosuppressants. They can reduce the symptoms of the disease, but they may come back once patients stop using them. CAR-T cell therapy, on the other hand, is talking about resetting the immune system to be able to fight autoimmunity over the longer term, perhaps.
John - That's exactly right, because these CAR-T cell therapies can deplete B-cells, not just in the peripheral blood, but also in the tissues. So you have a complete, as it were, ablation of the B-cell compartment for a short period of time. And then the bone marrow of these patients begins to produce new, healthy B-cells. So the phrase immune reset is becoming a cliche in trying to explain how these CAR-T cell therapies are working.
James - So Caroline, the way in which measles induces immune amnesia could be viewed as a type of immune resetting. We can achieve something more safe and with more therapeutic potential for all kinds of disease with so-called immunotherapies, and it's showing a lot of promise.
Comments
Add a comment