Science Friday - Fact Check Your Feed, Climate And Fungi, Cells Solve A Maze. September 4, 2020, Part 2

Episode Date: September 4, 2020

Can Fungus Survive Climate Change? One of the most extensive global networks for sharing information and moving around essential nutrients is hidden from us—but it’s right below our feet.  Networks of fungi often connect trees and plants to one another. But scientists are just starting to untangle what these fungal connections look like, and how important they are. Mycologist Christopher Fernandez explains how these fungal systems might be affected by climate change—and what that means for the entire forest ecosystem. A Cellular Race Through A Maze Cells are the basic building blocks of life. Our bodies are made up of trillions and trillions of them, and they all serve a specific purpose. But these tiny workers don’t always stay in the same place. Many move around the body—whether they’re creating a developing embryo, helping the immune system, or, distressingly, spreading cancer.   A team of scientists in the UK recently set up an experiment to learn more about how cells move. They put dirt-dwelling amoebas and mouse cancer cells at the start of a maze, to see how well each would migrate.  While amoebas proved speedier than their cancerous counterparts, Luke Tweedy, a postdoctoral researcher at the Beatson Institute for Cancer Research in Glasgow, Scotland, says the cancer cells were surprisingly mobile.  Tweedy joins Ira to talk about what his team learned about cancer cell movement, and explains why recreating a famous English hedge maze proved to be a little too difficult for his cellular subjects.  Fact Check Your Feed: Are Kids Really COVID-19 ‘Super Spreaders’? Late last month, as parents and teachers were gearing up for an unusual and stressful start to the school year, conflicting media reports of coronavirus transmission among children started populating our news feeds. One headline proclaimed, “New study suggests children may be COVID-19 ‘super spreaders,’” while other articles cited researchers saying the opposite. But the disagreement didn’t stop there. Some outlets reported that very few preschoolers are catching the coronavirus, while others cited a study that suggests children younger than 5 may harbor up to 100 times as much of the virus as adults. Angela Rasmussen, associate professor in the Columbia University Mailman School of Public Health, joins Ira to talk about the data behind these stories in a round of Fact Check Your Feed. She also explains new testing guidelines issued by the CDC, and a misleading report on the coronavirus death rate.  Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Ira Plato. One of the most extensive networks for sharing information and moving around essential goods is hidden from us. Yeah, it's right below our feet. You might have heard of it. It's the wood wide web. See what I did there? I'm talking about the fungal networks that connect trees and plants to one another. Scientists are starting to untangle what these fungal connections look like and how fungi respond and are affected by climate change. and what that means for the entire forest ecosystem.

This is something I really want to talk about with my next guest. He's here to walk us through this mycological maze. Christopher Fernandez is a postdoctoral associate in plant and microbial biology, University of Minnesota and Minneapolis. They call it the you over there, right? Chris. That's right. Welcome to Science Friday. Thanks for having me, Ira.

Even though we can't see it, fungi play an important role, right? when it comes to trees and plant ecosystems. Can you take us through a bit of fungi 101? What a fungi fungi provide for plants? Absolutely, yeah. So the organisms that I study are called mycorrhizal fungi. So these are fungi that are really important for the plant nutrition. Basically, these fungi colonize the finest roots of plants

and provide access to nutrients that would otherwise be unavailable to for direct plant uptake. So plant productivity is directly dependent. dependent on these kinds of associations. And so about 90% we're saying these days of plant species actually have one of these types of microisyl associations. So there are two basic types of microisyl associations are buscular microasal fungi, which are really common in grassland type ecosystems and prairies and tropical forests. And then there are ectomicorazil fungi, which are really important in temperate and

boreal forests, and those are the organisms that I work with. Which ones do we see on our lawns and in the backyards on trees? Yeah, so it would depend. If it's a mushroom-forming fungus, then it is an ectomacorazil fungus, or it could be a satirphic fungus that just is decaying soil organic matter. There are also free-living fungi? Yeah, and they depend on carbon and nitrogen and phosphorus that exists in soil organic matter, and they break down that soil organic matter to obtain those resources.

Whereas microisal fungi, they acquire nitrogen and phosphorus and trade those nutrients to the plant in exchange for carbon. Is it true that the largest organism in the world is a fungus? That is true, yeah. That would be an armillaria species out west in Oregon, I believe. Yeah. And that is supposedly very, very large acres. Which fungi are populating my sourdough bread?

Those would be yeast primarily. So those are free-living single-celled fungi. How many different fungal species does the average tree have, let's say, associated with it? In the systems that I work in, which are temperate and boreal forests, trees can have dozens of different fungal species colonizing their root system. It's quite common to see, you know, 50, 60 different fungal species colonizing a single tree host. Wow. A fungi are like the microbiome of the forest, it sounds like. Yeah, absolutely. Just like you and I have our own microbiomes associated with our bodies. These trees have their own associated microbes, including microasal fungi as well as some other bacteria and other things.

So you're saying that different types of forests have different types of fungal networks there. Depending on which systems you're looking at, they have completely different sets of fungal associates. Yeah. So if you planted a tropical tree in a conifer forest, would it be able to tap in and use this different fungi in the soil? Probably not. So most tropical trees, not all, but most tropical trees are buscular microasol associates. So they tend to form these microisyl associations with a different set of synlion. So these are quite different in terms of their functionality as well as. you know, they're phylogeny.

So they're very different. I didn't know that. So if I dig up the soil in my backyard, am I disturbing a ecosystem that's taken decades, centuries to form? Probably not. So where we dwell, usually those soils are pretty disturbed anyway. Unless you're living in, you know, a forest system, you're probably not causing any more disturbance to those soils or anything that would be dramatic.

Like with most things, climate change is affecting these fungal communities, correct? What changes are you and other scientists observing here? So here in Minnesota, we have a system, an experiment set up by Dr. Peter Reich in 2008, who's also at the University of Minnesota. It's called Be Forewarmed. And basically, the experiment is warming and excluding precipitation in these forest plots that have different boreal and temperate hosts planted together. And there's been a lot of research on above ground responses to climate change,

these climate change treatments. And we are interested in understanding how those changes cascade below ground and influence communities. And what we're finding is that the networks that are formed between these different plant hosts are starting to degrade. So the communities are shifting from those that have species that have extensive long-lived mycelium in the soil to those that are kind of weedy. They don't produce a lot of mycelium. They shift a lot of resources to reproduction rather than exploration structures.

Basically, we're hypothesizing that this is going to result in the breakdown of these really important networks. This doesn't sound good. No, no, it does not. You know, these networks are quite important for plant nutrition, right? So we think that this will ultimately affect seedling recruitment. So seedlings are really dependent on kind of these established common microisal networks, we call them, for being connected and tapped into an established network and having access to nutrients provided by those networks. And so we think that this might alter how seeds.

things are recruited in the future. So the trees, the population of trees, may go down because the fungus is doing something different than it used to. Right, exactly. And instead of providing these really important benefits in terms of nutrition, maybe those won't be there in the future. There is research out there that some fungi play a role in drought tolerance in trees. How does that happened? Yeah, so there's a lot of interesting work coming out of Catherine Gering's lab down at Northern Arizona University showing that some of these ectomycorrhizal symbionts that have evolved in these really droughty environments have abilities to basically help the plant tolerate increased drought stress. Those are very different fungi than some of the fungi that we see here in Minnesota

or, you know, in higher latitude system that have not evolved to tolerate those challenges with water stress, but they are out there. If you know that fungi, they're beneficial or do better in the face of climate change. You know there are certain fungi, right, that do better. Can you give a tree a fungal probiotic, an inoculation, so to speak, to help it out? That's certainly a strategy that could be explored. Today, I don't think there's a whole lot of research that would, suggest that can be done immediately, but that is something that can be explored for sure.

You know, Sina cacum, the species of fungi that I'm interested in, actually is known for its ability to tolerate drought stress, but it doesn't really, it's not really abundant in a lot of these communities. So, and we don't really see it go up in abundance with, when we increase warming and drought stress in our system here in Minnesota. So it gets complicated. I know that fungi are also important in carbon sequestration, how will climate change affect this? 20 to 30 percent of net primary productivity, that is the amount of carbon that plants pull down from the atmosphere and fix into biomass is allocated below ground to microasal fungi. So that's a significant flux into the soil.

So the turnover of that microrizo biomass that is produced from carbon allocation, from this plant is important in terms of potential for carbon sequestration. So what we're seeing is that with warming and drought, at least here in our system, the photosynthetic capacity of these hosts are declining significantly. And we think that their ability to allocate carbon

below ground to microasal fungi is also being inhibited. It's kind of like a sinking ship, right? So the fungi are attached to these hosts. and are dependent on that carbon, and those fungi are really thought to be really important in terms of the ability to sequester carbon in soil. So it's quite troubling. Will fungal species that are better adapted to higher temperatures,

are we going to see them start to dominate the forests under climate change and determine which trees grow in an area? Yeah, so perhaps, yeah. We're seeing not so much drought-tolerant species, but drought avoiders. So these are kind of weedy fungi, again, that invest a lot in reproduction rather than biomass in the soil. So instead of producing biomass that can tolerate, you know,

droughtier, warmer soils, they're just avoiding those times of the year, right? And they're growing when there is moisture available and reproducing really quickly and then just kind of dying off. I know we've already certified you as a, fungi geek. And there's probably nothing you don't know about fungi. But what are the big questions?

What more do you want to know about fungi and the role they play in these forest ecosystems? We're just scratching the surface on what we know about these fungi. So we just have the ability for about 10 years to actually observe these fungi in situ with high throughput sequencing. So for the longest time, we couldn't actually study them. very effectively. So we're just now beginning to piece together patterns from these datasets. So what I'm particularly interested in is kind of understanding functional diversity. So what are the traits that these different fungi have? What does their effect on their performance in ecosystem? So are there traits that confer tolerance to certain stressors?

are, you know, what are the traits that are really important for accessing nutrients? And how do those traits then affect these ecosystem level processes? So basically, we're just now being able to actually observe these things in the environment. Well, we've run out of time. It's been quite informative. I want to thank you, Christopher Fernandez, postdoctoral associate in plant and microbial biology. University of Minnesota in Minneapolis, thank you for telling us all about the fungus among us. Thank you, Ira.

We're going to take a break, and when we come back, the media is reporting that kids are super spreaders of COVID-19. Is there science to back this up? We'll fact-check this claim and others in your newsfeed after this. This is Science Friday. I'm Ira Flato, as parents and teachers gear up for an unusual and stressful start to the school year. Conflicting media reports of coronavirus transmission among children have populated our news. News feeds. Here's one headline. News studies suggest children may be COVID-19 super spreaders,

while other articles cite researchers saying just the opposite. These conflicting media reports means it's time for another round of fact-check your news feed. Joining me again to help clarify the studies of kids in coronavirus transmission, as well as a few other misleading claims circulating online right now, is Dr. Angela Rasmussen, Associate Research Scientist and the Columbia University Malman School of Public Health. Welcome back to Science Friday. Thanks for having me back, Ira. So on top of an already confusing start to the school year for many folks, we've been seeing these conflicting news reports about how kids may or may not be spreading the virus. What is the real answer to this question, Dr. Asmuson? Do we know?

Yeah, so this is a tricky one to sort out because oftentimes these reports appear to be conflicting And those differences might just be differences in circumstance of the population of kids that are being studied in any given paper or report. The things that we do know is that children can definitely become infected with coronavirus. And they can spread coronavirus as well, both to people in their households, other adults, as well as to other children. There was a summer camp in Georgia in June in which over 200 kids spread the virus among each other as well as to some adults who are acting as camp counselors and older teenagers who are also running the camp. So we know for sure that kids can definitely become infected. They can definitely spread it. As to whether their viral loads are higher than adults, that was one study that showed that certain kids had higher levels of virus.

RNA than adults. But overall, all the data that we have shows that kids at least have as much virus as adults. And this varies from kid to kid, just like it varies from adult to adult. So overall, the things that we really do know that we have consistent evidence of is that kids can become infected. They can spread it to others. And in some rare cases, they can get very, very sick from it. There was also a report about summer camps in Maine. I think there were four summer camps that showed how effective social distancing and wearing of masks were in preventing the spread from kid to kid and from kid to counselor and vice versa. That's absolutely right. Those summer camps in Maine really show how important these risk reduction measures are to take. Those measures were

not taken at the camp in Georgia, I believe. And it also kind of gives us some insight as to why some of these reports might be conflicting and why it's so important to look at the circumstances that are in each situations. Each study like this is really reporting a different set of circumstances. And just because, you know, there was more spread or less spread or higher viral loads or lower viral loads in one population doesn't mean that these are completely conflicting. Again, there are different circumstances at play and there are different people at play too. So I think that it's it's sort of a mistake to present to studies that have similar situations and say that they're conflicting with each other. It's really just a report of two different situations.

Let me tease this apart a little more because there's this study from JAMA pediatrics that looks at viral loading kids. And some news outlets report that it's as much as adults. Some outlets report that it can be as much as 100 times more than adults. What's going on here? So that study, again, is one slice of a particular population. And it also looks at viral RNA. I don't believe that study actually looked at infectious virus. So you really have to be careful when making conclusions about the viral loads because you're looking at the viral genetic load. You're not necessarily looking at differences in the amount of infectious virus that would

actually be, you know, virus that you could transmit to somebody else. I think that, you know, what we can conclude, we already know that in different people at different points in infection, there will be different viral loads. That can be influenced by a lot of different variables. It could be a person's susceptibility, how good of a host they are effectively for the virus. It could be the dose of virus that they were infected with. That could distinguish viral loads in one person versus another. It could also be the time since they were infected.

They could be in different places in their infection. Their immune system could have different capacities for controlling the infection. So it's important to understand that viral loads and people are going to cover a certain range. I think that with a study of a couple hundred people, it's very difficult to say conclusively that viral loads are, you know, 10, 100, 1,000 times higher in one group than another. I think it's important to say that they are at least within, you know, the same ranges. And that, again, suggests that kids are not somehow more mysteriously resistant to this virus than adults. they can be infected and they can have viral loads that are at least equivalent or an equivalent

range to adults. Would it be fair to say that we don't have as much data on kids and the coronavirus as we do on adults? I think that's fair. I think that one thing we also know about children is that many of them have very mild infections or potentially asymptomatic infections, which means that there are probably a lot of cases in kids that have been undiagnosed. So we just haven't had as much opportunity to study them. A lot of what we know about patients are patients who have become very sick and have been hospitalized.

And obviously, it's easy to find those patients because they're showing up at the hospital. They need care and they're very sick. Not as many kids are doing that because they don't generally get as severe of disease. We're not going to be able to study as many of them. I think one of the confusing issues here seems to be this relationship, how much viral load kids have and how much they're actually spreading the virus. I mean, do we understand that dynamic yet? Not really. Although we do know that kids, there was one study that showed that at least in symptomatic children,

they did detect infectious virus in their nasal passages or their nasal swabs. So some kids, at least, are shedding virus that could be capable of infecting somebody else. I can't personally see any reason why kids would be less transmissible or less contagious than adults. If they have the same viral loads as adults, then presumably they're shedding as much virus. But this is an area that we don't have a ton of data for. Early reports that kids were less capable of transmitting it were based really on epidemiological studies of households in which they deduced that the children were not spreading it to other members of the household. but of course there are exceptions to that. So that data might again appear to be conflicting. I think that it's really hard to make very general conclusions based on sort of circumstantial

epidemiological investigations like that. And so is there anything we can take away from this data and apply it to the start of the new school year? I mean, what should teachers and parents think about all of this? Well, teachers and parents should definitely not think that children are immune or more resistant to the virus. Just because they don't develop a severe of disease, that doesn't mean that they can't be infected, and it doesn't mean that they can't bring the virus home with them to transmit to other people in their household. It also doesn't mean that they would be incapable of transmitting it to faculty and staff and schools. And in general, I think a lot of the discussion about schools has sort of assumed that schools are an isolated bubble that is separate from the rest of the

community, and they're really not. If children are getting infected, whether outside of school or in school, those children are still part of the same community, and they're capable of spreading the virus within that community. So we need to stop thinking of schools as a separate space or children as a special population of people who are less susceptible. We need to take the same precautions with preventing transmission in schools as we do within the rest of the community. You know, we talk a lot about schools, but I know parents, there are parents all over who are

sending their kids back to daycare, their preschool kids. Should we think about the same precautions and the same transmission rates for these younger children? Yeah, and with younger children especially, it's really difficult because oftentimes, you know, try getting a three-year-old to wear a mask the correct way and being in close physical proximity to each other, especially in an indoor environment. We should definitely try to implement some of those protections, but I think another thing that can be done with daycares is to really limit the number of kids that are going there in the first place, maybe having a smaller daycare setting or being lit up groups of daycare kids so that there are not as many people in one given space might help with being able to try to

implement as many measures as possible to reduce transmission in those environments. I want to touch on a news item and get your opinion about a couple of things that have been circulating just this week. pointing to CDC data that reports only 6% of COVID-related deaths are actually from the virus itself. I mean, this statistic is getting a lot of heat and just flies in the face of everything we've been talking about before, doesn't it? It really does, and unfortunately that statistic is sort of cherry-picked from that data set, which was describing the causes of death as reported on death certificates. Death certificates usually have several lines in which a coroner, the person completing the death

certificate, can put causes of death. And in many cases, they will say what the cause of death was, either heart failure or respiratory failure, something like that, due to COVID-19. This has been misinterpreted to suggest that only the first cause of death is the cause of death and that it had nothing to do with COVID-19. The idea that people are sort of incident. incidentally infected, but they're dying from something else that they would have died from anyways. And that's just simply not true. There are a number of diseases in which people might die from a secondary condition that was the direct result of the first disease. HIV is a great example of this. One of my colleagues who studies HIV pointed this out to me that people,

often with AIDS, die of a secondary pneumonia. They die of cancer. But that cancer was the direct result of them being infected with HIV. We would never say that this person didn't have AIDS. They didn't die from HIV infection. They did die from AIDS. They just died specifically from a pneumonia that was caused by the HIV infection. And this is the same case with these COVID deaths. So if somebody dies of respiratory failure due to COVID-19, they weren't going to have that respiratory failure, even if they had other comorbidities if it weren't for them being infected with SARS coronavirus too. The CDC recently issued due guidelines for testing of asymptomatic people were all about data here. So did the CDC cite any studies that would support that change? Tell us what that

change was and why it was motivated. I can't say why it was motivated because the CDC has not disclosed to that. But what the change was was that the CDC is no longer recommending testing of people who believe that they've been exposed to coronavirus or know that they've been exposed to coronavirus. if they are asymptomatic. And there really is no basis and evidence for making this decision. The CDC did say to a reporter at the New York Times that the decision wasn't made to conserve testing resources. So that leads to a lot of questions as to why they made that decision. Because what we do know from the evidence is that there is a substantial amount of transmission from pre-symptomatic people. And those are people who are eventually going to get sick with COVID-19, but don't have any symptoms when they are

producing and shedding the most virus. So it's really dangerous to suggest that people who believe that they've been exposed to coronavirus should not seek testing because if those people are actually infected and they don't know it, they might not take the necessary precautions to avoid transmitting it to people while they're in that pre-symptomatic stage. And it's really, really troubling and that the CDC has released this guidance, because the obvious conclusion that many people have come to is that it's politically motivated rather than motivated based on evidence and good public health practices. I'm Ira Flito.

This is Science Friday from WNYC Studios, talking with Dr. Angela Rasmussen, Associate Research Scientist in the Columbia University Mailman School of Public Health, talking about fact-checking your feed. Speaking of the CDC, do you think the CDC has lost respect as an independent, reliable source of information? I think to some degree it has. I think that it's important that people understand that the CDC does many things. They do scientific research. They collate all this data, like, for example, the death certificate data, and they report that publicly. And then they also make policy. The CDC is still doing their agreement. They're a good. great scientists who work at the CDC. They're great epidemiologists who work at the CDC, who are doing great work. The problem here is in the policy arm of things where they're making

guidance that's more based on political considerations than scientific evidence. It really does undermine their credibility for releasing that guidance. If you can't trust that the CDC is providing guidance on really critical public health issues in a way that's based on the evidence that they gather and analyze that causes you to question what their motives even are. And I think that for many scientists, it's been tremendously disappointing to realize that this, you know, premier agency for dealing with infectious disease threats is, is compromised in this way. Lastly, I want to bring up a New York Times article you were quoted in. that suggested that coronavirus tests could be less sensitive.

Why would we want that? Yeah, so I think that this has been somewhat misinterpreted because the headline of that article said that the coronavirus test may be too sensitive. And this is really referring to the fact that the PCR test, the molecular diagnostics test that is being used, can detect viral RNA even at very low levels. And so people who've recovered from coronavirus will test positive sometimes for many days, sometimes even weeks. And that's residual virus, that low levels of residual virus genetic

material that's being detected and not actual live infectious virus. The idea that tests could be less sensitive is really an intriguing one in terms of increasing our testing capacity and putting testing really into the hands of people themselves, allowing them to make real-time sort of actionable public health decisions. That's the idea that maybe the PCR test, is so sensitive, it's picking up all this non-infectious virus. If you had a test that you could do at home that was less sensitive but would still pick up high enough levels of virus to be transmitted, you could say test yourself in the morning and decide not to go to work because all of a sudden you have high enough viral load that you might be infected, you might be shedding. So time to isolate

yourself and call your medical provider. I think that that would be incredibly useful for not only empowering people to engage with public health and to take their health into their own hands, but also it would really solve a lot of the problems that we've had with testing capacity and turnaround time. It would allow people to really find out on a daily basis or a routine basis anyways, whether or not they might have been infected and might also be contagious. So I think that there really is an important place for some of these rapid sort of do-it-yourself at-home tests. We just need more of them to become available. We need the FDA to consider approving more of these tests.

Dr. Rasmussen, always a pleasure to have you on. Thank you for taking time to be with us today. My pleasure, Ira, it's always great to be here. Dr. Angela Rasmussen, Associate Research Scientist, in the Columbia University Mailman School of Public Health. We're going to take a break, and when we come back, we're going to talk about cells running a maze, a little tiny one, to understand how cancer cells spread throughout the body.

We will be right back after this short break. This is Science Friday. I'm Ira Plato. We all know that cells are the basic building blocks of life. Our bodies are made up of trillions and trillions of them, and they all serve a specific purpose. But did you know that cells don't always stay in the same place? They move around the body. And for a long time now, researchers have been trying to better understand

and how they move and why. One team of scientists in the UK set up an interesting adventure for two kinds of cells. They put them through tiny mazes to see what would happen. Joining me today to talk about this research is my guest, Dr. Luke Tweedy,

a postdoctoral researcher at the Beetson Institute for Cancer Research in Glasgow, Scotland. Welcome to Science Friday. Thank you for having me. You're welcome. It's really interesting research. Let's talk about it. What was the idea here from the beginning? Well, our lab have always been really interested in why cells move and how they move. And we see all sorts of examples in the development of the human body and in disease,

for example, when cancer is particularly dangerous when cells from the original tumor start moving. And we look at this all the time, and the thing that strikes us is that they always seem to know which way to go. I mean, it's a very complex environment, and there isn't necessarily a lot to go on. So where are they getting the information that steers them away from an original tumour or to the right part of the body? And what other cells besides cancer cells? Are there other cells that move around the body? There are lots, particularly in a developing embryo. So obviously there are lots and lots of different types of cells that go in to make your skin and pigment your skin and develop certain organs and there are nerves of various types and huge, huge numbers.

I'm sure your listeners are aware of this. Most of them don't start in the right place. So when the embryo is developing, when a human embryo is developing, or this is true for any animal, really, there is a lot of migration going on. Cells have to get to all sorts of places. But in a healthy adult human, the obvious example is the immune system. I mean, immune cells patrol your body looking for infection, looking for signs of damage. And when they find it, they have to signal to all of the other immune cells in your blood, around the peripheral tissues. Oh, look, here is something that's going wrong. And then you find that quite a lot of other cells will come out from rather disparate regions to cause, say, inflammation in that site. Now, I'm really intrigued that the tact you took

to test these cells, you built mazes for the cells. What's the idea there? Well, we've been doing a lot of very useful research using just ordinary petri dishes, right? But we thought to ourselves a lot of the challenges of navigating in the body are navigating a complex environment. I mean, there isn't just a nice flat surface to go along. They have to get around all sorts of other developing nerves and blood vessels and tissues. And so we thought maybe we could replicate that kind of idea. It's too complicated to always do this kind of research in, say, an animal. So instead, we thought, well, that sounds rather like a maze.

Maybe we could literally just make a maze and see how the cells are. do. And tell me how big these mazes were. Oh, very, very small. With some designs, we were fitting maybe 16 or 24 or 36 mazes in a dish that was the size of a fairly ordinary coin. We were using mazes that were about 900 micrometers across, so less than a millimeter. So these mazes were they like the kinds of a mouse would run, or are they more like the kinds of human would run in a hedgerow? Well, certainly more like the kinds of human would run. One of the mazes we designed was literally a replica of Hampton Court Palace maze. It's a famous garden maze in London.

No kidding. Yeah, absolutely. Whose idea was that? That one was mine, I think. It was a less informative maze than some of the others. We learned an awful lot about how cells make decisions from these mazes because, of course, mazes are all about making a decision. Do I go left or right here? right? Hampton Court was very showy and there's been a very popular maze for images on websites.

It wasn't fundamental to our research, I must admit. Yeah. It's interesting what you just said. They make decisions. Does that mean they have some kind of intelligence within themselves? No. They are very, very kind of programmatic in the way they do things. Obviously, there's a lot of randomness to the environment. But what the cells are doing is trying to, read from the chemicals in the environment about which way they might want to go, what's where, where might they find more nutrients, say. Or in terms of human biology, obviously the nutrition's usually supplied by the bloods. Quite regularly, the dangerous cancers are the ones that start to move toward blood vessels and to enter the blood and drift to another part of the body, where they

can set up disparate tumours. We're interested in these kinds of mechanisms and these kinds of decisions, but they're not intelligent. They're just complex. Let's talk more about the starting line of the maze. Do you put one cell at the starting line of the maze, or do you put a whole group of them together and let's see how well they work as a group? As it turns out, they kind of need to work as a group. So the system we used was not a kind of a path of chemicals through the maze. instead we just put them absolutely everywhere and then put a group of cells in one starting location and we saw

how they made their decisions as they progressed but they absolutely had to work as a group group size varied a bit basically because there's some randomness in how well they're able to metabolize kind of break down these chemicals that are in the environment but yeah absolutely they were working

in groups of four and five up to 30 and 40 and what kinds of cells did you choose And what reason did you have for choosing whatever cells you chose? Well, we used two different cell types, and the one that we used for the majority of our experiments is soil-dwelling amoeba. They're called Dictiostelium, or colloquially Dicti. And the reason we use them is that they're effectively prodigies at guided migration. They're very fast. They are very, very good at reading quite subtle cues, and they've been a go-to kind of, we call it a model.

organism for this particular kind of behaviour in cells for a very, very long time. Also, there's strong evolutionary conservation, the mechanisms that Dictuselium use, with the mechanisms that mammalian cells use. So they are important for understanding kind of broader mechanisms. We also used a pancreatic cancer line, which are obviously much more close to what we are interested in in a medical point of view. But they're a lot slower to grow. they're a lot harder to keep.

And mazes that the Dictia Stelium would solve in an hour and a half, the cancers would take 72 hours to do. So in terms of fitting in enough experiments, we concentrated on DICTI. They're much, much kinder to the researchers. The cancer line did at least demonstrate that they behaved in the same way, and so we could effectively use the DICT as a model for these kinds of questions. So how do you set up the cells for this maze trial?

I'm trying to picture this tiny little dish the size of a coin. I would imagine that there isn't a gun going off and a rush to the finish line like races we might do. No, well, I suspect there'll be a few cells that don't wait and cheat a little bit. But what you will end up looking at

if you were looking at it yourself is there's this dish and there's a big rubber block in it. You can't see the mazes. They're too small. The details are very, very tiny. But there are some whopping great holes in that I sat and painstakingly punched with a biopsy punch.

These holes can fit a pipette tip in, and so I'll just drop a few cells in that way. Now, do they learn, like a mouse does, do they have trial and error? Do they follow along the walls? How do they find their way around? And what influences them to turn right, to turn left? And if they make a mistake, do they try it again?

Well, absolutely not. Unfortunately, I can't get them back out. to try the same cells in the same maze. They can try the same type of cell maybe the next day on a replica, but they're one-use mazes. I mean, they certainly weren't learning in that kind of way. What we were interested in is exactly what kinds of decisions they would make.

And they reliably, one set of cells one day and another set of cells the next day, they would reliably make the same decisions for the same design of maze. So what we actually did was vary the design of maze in order to answer exactly your second question, what makes them turn left, what makes them turn right? And it turns out that when you fill the environment with these attractive chemicals,

they break it down exactly where they are. And a big group of them will break down an awful lot. And then you end up with this sort of gradient of low concentration where the cells are and high concentration elsewhere. And then they just follow that gradient of high concentration, chasing wherever they can find more of the chemical. But down very, very short dead-end branches. You could twist them and turn them, but they were very short dead-end branches.

By the time they arrived to make the decision, all of the chemical had drifted out and been gobbled up by the cells already. So they never even looked at short dead ends. Whereas as we made the dead ends longer and longer, it took longer for this attractive chemical to drift out. And so with those ones, yeah, quite a few cells would often go the wrong way. And how close to what happens in the body when they're out traveling in the bloodstream or finding other cells? How close is your maze to what's going on in the body replicating that? It's a very good question. I would say we are not incredibly close yet,

but what we've done is develop a framework for understanding these sorts of problems. So now we can introduce additional levels of complexity. I still think we're not ready to analyze this directly in the body, but we might start introducing specific cell types that are human cell types or mammalians. So we might look at immune cells. We might look at cancers. And previously we would have questions about why are cancer metastasized to this or that location, or why an immune cell chose to cause inflammation in this particular site.

There are already some things we know about it, but we can start to dissect it a little more, maybe put some into a maze, introduce some of the hormones and the chemicals that we know are involved in these processes, and we'll have a better idea of how they cope with it, because we are now able to do two things, both introduce the chemical environment, which we've been doing for a very long time, and introduce the topological complexity at the same time. So introduce this complex, long branching structure to them as well. If I heard you correctly, you said the cancer cells took, what, 72 hours to go through the maze,

which is not really sprinting, is it? I mean, how does that impact your understanding of them as you are a cancer researcher? I actually started life as a theoretical physicist. Cancer research has been a relatively recent change for me, but I'm honestly still quite terrified by them. The degree to which they can be guided in one direction is extraordinary. But I would say two things to that. First of all, the cancer cells made the same decisions as the DICTI.

They just took a lot longer over it. So they were actually very good at guidance and understanding guidance. They just weren't as quick. And then the second thing I would say is the, three days to travel that kind of distance, I mean, it might seem like it's quite slow, but that might be the distance to a blood vessel. And then you have a tumor that lets out these metastasizing cells and they get to a blood vessel and suddenly you've gone from an operable cancer to something that's going to require radiotherapy and chemotherapy and further analysis.

Honestly, that speed still terrifies me. And I think it's a very important thing to look at further. Quick reminder, I'm Ira Flato, and this is Science Friday from WNYC Studios. In case you're joining us, we are talking to Dr. Luke Tweedy, a postdoctoral researcher at the Beetson Institute for Cancer Research in Glasgow, Scotland, who set up a maze for cells to run through. You mentioned the chemical attractant that you use as sort of the cheese for the rat maze here. Yes. Is that also found in the body? And could we use that to sort of fend off the travels of a cancer cell and to be attracted to another place in the body?

So it's an interesting question. There are two different attractants, of course, that we're using, one for the dictustelium. And though that is naturally occurring in the human body, it's not particularly medically relevant. It has a very different role for us as it does for amoeba. The other one is a signaling lipid called lysophosphatitic acid. acid or LPA. And LPA is very commonly found in healthy skin. And we find actually that where melanomas develop, you end up with a little bit of a dip in the amount of LPA because they start

gobbling it up. We might be able to convince tumours in the very short term to stay put a little longer by adding LPA, but it has important roles in the body. So I'm not sure I would want to dive straight into messing with that. However, where we know that it's being degraded, it might might be nice to add a little bit more. There is one fundamental problem with that, though, and it's that LPA also tells cancer cells to grow and divide. Oh, small detail here. So we're in a dangerous situation where on the one hand, yes, you might convince them to stay put a little bit longer, but on the other hand, it's what's known as a mitogen. It causes further growth. So we probably don't want to encourage that aspect of it. If we could find something that interfered with the receptor

without causing it to signal, without causing the cell to understand that it's getting a kind of growth instruction, then that will be wonderful. So tell me what your next steps from here are that will help you better understand how these cells move. What do you want to know? What do you need to know?

There are a huge variety of ways that we could take this. A lot of what we want to do now is what you term translation. So we take a basic biological finding, and we've tried to keep this general. We've used amoeba as well as mammalian cells. And then we want to find some kind of medical application. My boss at the moment and I are going in slightly different directions with this. I'm interested in the immune and inflammatory implications of it and trying to build devices that analyze the computation of the immune system. So we might better understand what's going wrong if you get arthritis, for example.

My boss remains a very hardened cancer researcher and is looking more at that kind of angle. One last question. You said before that you were terrified by knowing something. What was terrifying you? The rapidity and the certainty with which cancer cells metastasize when you're watching them on a microscope. We choose metastatic lines. We choose lines that are going to give us an idea of what the worst cancers are doing. deliberately select them for worse and worse features in this way. But nonetheless, seeing it

happen, I do find it very intimidating. The very first time my boss saw one of the videos we made, he said that he was going to go and make an immediate appointment to have all of his moles mapped. I think understanding diseases like cancer doesn't make it any more comforting, certainly. Wow, that's a great perspective. I want to thank you for taking time to be with us today, Dr. Tweedy. Absolutely. I'm delighted to have come. Luke Tweedy, a postdoctoral researcher at the Beetson Institute for Cancer Research in Glasgow, Scotland. And if you want to see pictures and videos of the mazes and the cells going through them,

you're in luck because you can head over to our website at ScienceFriday.com slash cell maze. That's about all the time we have for this hour. If you missed any part of the program, you'd like to hear it again. Subscribe to our podcasts. Or ask your smart speaker now to play Science Friday. And on the Science Friday Voxpop app, This week, this is what we want to know. Are you deaf or hard of hearing?

Have you tried any so-called cures to regain your hearing? We want to hear about your experiences. That's on the Science Friday Voxpop app wherever you get your apps. You can also say hi to us on social media, Facebook, Twitter, Instagram, or email us the classic way, SciFri at ScienceFri.com. Send us feedback. Tell us what you'd like us to cover. Have a great weekend.

We'll see you next week. I'm Ira Flato.