Contagious Cancers

Our preference for smell feels personal. We have our favourite colognes, soaps, and food scents. But do we like certain smells because everyone around us likes them and so that’s the way we’ve grown up. The answer’s no! It’s apparently not a cultural thing; people the world over like - and loathe - the same sorts of smells, as Julia Ravey heard from Asifa Majid from the University of Oxford…

Asifa - Smell studies like most psychology studies, or medical studies more broadly, typically focus on Western participants, usually living in big cities, usually near universities, usually in the middle classes. When we're making theories about how things work, we hope to be making claims about the whole of the human population. So, you really want to be testing people from diverse backgrounds, especially if we want to try and untangle whether it's culture that, for example, causes our preferences for smells, or just individual preferences, or biology.

Julia - Which communities did you study?

Asifa - We tried to get people with very different lifestyles. So, we tested different hunter gatherer communities. And then we had some small scale farmers in Ecuador, for example, and then people that live in big cities in Mexico and Thailand. So, we're trying to take people with very different sorts of experiences.

Julia - When ranking these different smells, what came out on top and what was the least liked smell?

Asifa - In our study, people across the world all really liked the smell of vanilla and they least liked the smell of isovaleric acid, which smells a little bit like sweaty feet. It didn't matter what culture people were in or what kind of environment they lived in, everybody generally preferred vanilla and they all thought that the isovaleric, sweaty feet smell was really bad.

Julia - How much influence did culture actually have in these preferences?

Asifa - A really small amount. Only 6% of the data could be explained by culture. Most of it seemed to be shared, and then there were some individual differences too, but culture plays a very small role.

Julia - How much of the proportion of what people preferred in terms of smell came down to the molecular structure of the odour molecule?

Asifa - Anything that we smell is basically a molecule, and any molecule has thousands of different features. We can look at those features and see if we can predict how pleasant something is, and, when we do that, it turns out we can predict, just from the molecule itself, which ones people are going find nice and which ones they're going to find stinky.

Julia - If we're genetically built to prefer certain smells over others, why do you think that is?

Asifa- Some smells are probably telling us that something's dangerous, so our sense of smell is very sensitive to things that could be going wrong. We can smell, for example, a gas leak before we can see anything going wrong, we can smell fire from a distance, or the fact that the milk is going off. Our noses are very sensitive to signals of danger and it's likely that what we're finding is the same sensitivity to things that could be potentially toxic for us. I think COVID has taught us that the sense of smell is really important. One of the symptoms that we know that COVID has is a loss of the sense of smell, but luckily the sense of smell is really malleable and flexible, so people do have their sense of smell returning.

Julia - Yeah, I think we take our sense of smell for granted. When I had COVID and lost mine, it was so acute. You don't realise how much pleasure and joy smell brings into your life until it's taken away from you.

Asifa - Absolutely, yeah. So everybody should go out there and sniff something and enjoy it.

4月4日,政府间此种te Change, or IPCC, published the third part of its comprehensive review of climate science. Inside, it argues that stabilising the climate will require fast action and emissions must peak by 2025 for the world to have a chance of meeting the goals agreed in Paris. Here to tell us more is environmental scientist Jo House, from the University of Bristol...

Jo - This report looks specifically at climate action, what we can do and in fact what needs to happen in order for us to limit the worst of climate change. It finds that we really need to much more rapidly look at bringing down greenhouse gas emissions. They need to peak by 2025 and to be reduced by about half by 2030 if we are going to keep warming to less than 1.5 degrees and definitely within 2 degrees.

Chris - This sounds like we are running over the same old ground again, though.

乔-人一直是气候科学家for 30 years, we've been saying this for a long time, but what we are seeing now with this series of reports that have come out is that the science is really clear. Climate change is anthropogenic. The report that came out about a month ago was about the severe impacts that are already being experienced throughout the world, and that will only get worse. This one is making it clear that the window is now very limited to be able to take the action we need to limit to 1.5 or 2 degrees.

Chris - Is it going to basically take the crisis happening for people to take note? We just seem to have been receiving these warnings year after year that this is going to happen, and it's a bit like speed cameras on the motorway, people disregard the speed limit until they get a ticket. At what point are we going to give the world a ticket and finally something's going to change because we seem to pretty much be going business as usual? I haven't noticed my lifestyle change.

Jo - It is really, incredibly frustrating, but there are some things in the report that give me hope, which is there's about 18 countries in the world that have actually already peaked their emissions and have managed to keep reducing year on year. It hasn't cost them a lot in terms of GDP; they have been able to do it in an affordable way.

Chris - It is easier for some countries to do this. If you live in a country where the sun shines 24/7 - I'm being facetious of course - but take California: every day, it's a sunny day. Putting solar panels over enormous amounts of space you have at your disposal means you have enormous opportunities to produce a lot of guaranteed energy. If you live in the UK, the sun doesn't shine half the time, the wind doesn't blow half the time. It's a very different problem that you are grappling with, isn't it?

Jo - Well, actually, in the UK, we have managed to reduce our emissions a lot by switching from burning coal to burning gas. That's been a big move for us. And there's plenty of countries that have a lot of wind energy, as well as solar, and the cost of the renewable technologies has dropped massively - solar energy costs have dropped by 85%. And now, we are getting more technology with batteries moving forward, so we can store some of that renewable energy. Surprisingly, it's actually sometimes some of the poorer countries that are actually doing the most because they are feeling the impact and they know how important this is.

One animal that's experiencing a rare cancer outbreak are Australia's Tasmanian devils. This disease, which only appeared for the first time in recent decades, has pushed the species to the brink of extinction. Threatened species keeper Ben from the Healesville sanctuary at Zoos Victoria in Australia explains how they're helping to save the Tasmanian devil to Julia Ravey, and Hannah Siddle from the University of Southampton talks through what has led to the devils decline in numbers…

Chris - Cancers are made from a person's own cells going rogue. If a cell acquires the right combinations of mutations or changes in its genetic code, it can divide uncontrollably and lead to the formation of a tumour. As these cells contain a unique individual's DNA, if they end up in another individual's body, it should sound the immune alarm, just like an Incompatible organ transplant. They should be recognised as foreign and destroyed. Now some viruses, which are of course also infectious, like the human papilloma virus or HPV, can also cause cancer. But this is because they can trigger changes in a cells genetic code that leads to tumour formation. And in these sorts of cases, the virus is infectious rather than the cancer itself. In the very rare instances of contagious cancers, though, it's the cancer cells themselves that are passing from one individual to another. And that's exactly what we're gonna be exploring this week. To emphasise, these cancers haven't been observed naturally yet in humans, but they have been spotted in other animals and one animal that's experiencing a rare cancer outbreak are Australia's Tasmanian devils. This disease, which only appeared for the first time in recent decades, has pushed the species to the brink of extinction. Threatened species keeper Ben from the Healesville sanctuary at Zoos Victoria in Australia explains how they're helping to save the Tasmanian devil to Julia Ravey during, well, feeding time at the zoo...

本,所以今天我们要养活我们的一些小胡子zy devils. All our food is labeled with little tags so we know whose food is whos because everyone has different weights. So again, we're doing a scatter feed here -we throw foods throughout their habitat. We spread it around so that they have to go forage for it. Some of the devils over here are pretty shy. Tasmanian devils don't really, truly follow their name and they're actually very timid by nature. Tazzy devils are threatened species. So with some of our breeding females that we're hoping to breed this season, we've got camera footage monitoring them feeding. So we just make sure that's turned on every night. And we check that every day just to see if the females have eaten overnight. The main reason we need to check this is because if they're going through oestrus, they don't eat their food as often, or as frequently as normal. And that way we can tell that they are going through their oestrus, and we can start to prepare for breeding.

茱莉亚-避难所"招风的圣所supported by Zoos Victoria in Australia are playing a vital role in helping the Tasmanian devil avoid extinction through their breeding programs. These animals are also being released into the wild on islands and mainland Australia to up their numbers. This is because their numbered sightings have dropped by 80% in the last two decades and as Ben said, they are officially an endangered species. Hannah Siddle, an assistant professor in molecular immunology from the University of Southampton, explains what has caused this drastic decline...

Hannah - The majority of the decline has been caused by what we call DFT1 which is devil facial tumour disease. And that is the tumor that emerged sometime just before 1995. We do now have a second contagious cancer in the Tasmanian devil population termed DFT2. And it is now responsible for some declines, but in a very limited geographic area where it's still located.

Julia - And you say this is a contagious cancer. So how does it spread from one animal to another?

Hannah - It's a little bit like for us a virus or bacteria, because it can pass when the devils contact each other. Rather than being a virally induced tumour, this is actually the cancer cells themselves that are able to pass between individuals. And we think in the case of the Tasmanian devils, that this is primarily occurring when they bite each other, which unfortunately they do tend to do when they're fighting and in the mating season as well. Our best evidence at the moment is that these cells are actually grafting into the next devil when this biting behaviour occurs. And once these tumour cells then seed into the next individual, they grow and establish and make a new tumour, which can then be passed on to the next individual.

Julia - That's rare, isn't it? Because cancer is made up of a unique individual cells that have gone rogue in a way. So what is it you think that makes this cancer able to transmit in a population?

Hannah - We think that these tumours are taking advantage of the fact that although genetic diversity is not so low that these animals are clonal or exactly the same, they do have a lower level of genetic diversity than in populations that have more healthy numbers. We do think that these tumours may be taking advantage of this fact, and that may be allowing them to initially start to spread between a few individuals. After that though, the idea that there is not enough genetic diversity in the population and so this is allowing the tumour to take hold, that idea breaks down a little bit because we do have some genetic diversity, and enough genetic diversity in the population to stop the tumour spreading. But tumours are very good at acquiring new mutations and they adapt to their environment. And so they will acquire adaptations that are then helping them to then passage between individuals. And we have found that one of the adaptations that they have made, these tumours, is to lose some of the proteins or what we call antigens on the cell surface of the tumours, that are usually a flag for the immune system and would stop the tumour from transferring between individuals. This adaptation then allows the tumors to essentially become silent, or invisible in the population.

Julia - Are the cells in this tumour the same in every individual infected?

Hannah - Essentially, yes. So when we say they're the same, they all have derived from a single ancestral tumour cell, which is a cell in a Tasmanian devil that became malignant a long time ago. The tumours that are currently circulating in the Tasmanian devil will be slightly different to what they were when that tumour first arose and started transferring because they've acquired new genetic mutations, new adaptations to their environment.

Julia - You mentioned that there are two of these contagious cancers in Tasmanian devils. So what's happened there? Is this the same disease, but it's just a really mutated version, or is it something new entirely?

Hannah - It is something new entirely. It arose in a completely independent manner from a different individual, this second tumour. Really, really unusual to have that occur. And actually this is the only mammalian species where we know that that's occurred. We think that the second tumour arose sometime around 2014. And interestingly, we think we've been tracing this from nearly the beginning of its genesis. There is a lot of effort going into trapping Tasmanian devils in the geographic location of DFT2, which is in the Southeast of Tasmania and it's quite confined at the moment. Although recent efforts have shown that it is moving northwards, and so it is starting to spread, unfortunately, and become more prevalent.

Julia - It seems like an unusual phenomena for this to happen twice in one species. Is this a case of lightning striking twice in the same place or are these animals, do you think just susceptible to these types of conditions?

汉娜,我认为它可能是闪电引人注目twice, as you say, but I think we need to probably be more aware in wildlife generally. Possibly these tumours are arising at different times, but that they don't have the success that DFT1and DFT2 have had in the population. So I think it's probably likely that these tumours do arise sometimes.

Julia - With communicable diseases in humans, we aim to treat them, we aim to develop vaccinations or other medical treatments. It's anything in the line like that for Tasmanian devils? Will there be a vaccine for these tumours, do you think?

Hannah - Transmissible tumours should be, not easy to vaccinate against, but they should present some sort of routes for vaccination. And certainly we've been able to show that if we can restore some of these antigens that I was talking about before that usually coat the tumour cells, then if you put those into a Tasmanian devil or in a co-culture situation, which is what we call this, then we can actually see an immune response against these antigens on the tumour cells. So that tells us that the Tasmanian devil immune system is capable of responding. But it does seem as if this type of vaccine with these antigens on the surface of the tumour cells, it does work in some animals, but it doesn't seem to work in 100% of animals and we're not quite sure what the efficacy of that is and why it doesn't work in some instances. So I think we need to do just a bit more work to understand what it is that the immune system responds to and whether then we could make a more targeted vaccine based on that information.

Leaving the world of mammals behind, we are now diving into another instance of these rare contagious cancers. This transfer happens in bivalves like mussels, clams, and cockles.但在我们谈论癌症,罗布·埃利斯researcher in Ecophysiology and Sustainable Aquaculture at the University of Exeter, has gone down to his local estuary to “shellebrate” the wonders of these organisms and Alicia Bruzos from the Francis Crick Institute explains to Julia Ravey what is putting this animals at risk…

Rob - I'm out on the estuary in East Devon and in this estuary, bivalves play a critical role for biodiversity. We have a number of different bivalve populations; probably most visibly noticeable are those of the mussels and the oysters. These two species are classed as ecosystem engineers. The two organisms, when they settle, create a natural reef. In doing so, they create a novel habitat that's able to support a range of other species. If we think about a region, for example the Southwest of England, the number of species supported by bivalve reefs can go up by around 750. As well as improving biodiversity, bivalves obviously play a really important role as a food source for things like crabs, starfish and other predators. They are really important in terms of a food source for humans. Around three miles off the coast of east Devon, it's a bit of a cloudy day today so I can't quite see it, but we've got the largest mussel farm in the UK, Offshore Shellfish Ltd. Mussels are readily filter feeding. The population of mussels or a mussel bed can actually improve water clarity, and therefore really benefit adjacent habitats, such as seagrass beds and associated species like that. They can be a really powerful tool that we can employ to therefore improve those coastal environments and reduce human impact. If we were to lose bivalves, this would be a really important problem in terms of impacting coastal biodiversity, impacting coastal function, ecosystem function, and also in terms of impacting our ability to utilize those resources as a source of human food.

Julia - Based on those insights from Rob, losing bivalves would be pretty disastrous, but these animals are also impacted by contagious cancers. These diseases have only recently been found in bivalves, but could have driven past declines in numbers. Alicia Bruzos, cancer researcher at the Francis Crick Institute who studies these rare conditions in bivalves explains...

Alicia - These cancers, which is a leukaemia-like cancer, in bivalves where reported in the late 60's and in the 70's and 80's of last century. But it was not until 2015 when they discovered that they were contagious. Because we needed to analyse the DNA to know that that cancer cell did not originate in that individual and came from a different individual.

Julia - And do we have any idea about how it spreads from one organism to the next?

Alicia - The hypothesis is that somehow the cell is released to the environment. We don't know if it is an active release, or if it is when he's dying passively, the cells are released to the environment. Then the cells float in the sea water and they survive in that sea water, so maybe the temperature and the salinity and all these conditions might have an impact. Finally what these viruses usually do in nature is that they filter water. By filtering water, they take some cancer cells that were floating in the water, and those cancer cells go inside, and then they start to develop.

Julia - Mammals immune systems have evolved in a way to detect things that are foreign and get rid of them. But I'm guessing the immune system of bivalves is quite different to immune systems like ours. Is there a flaw in their immune system that allows this type of contagious cancer?

Alicia - We do know they have defence, but they don't have the same immune system as us. A lot of research has to be done to actually understand why they are not as successful as our immune system to defend themselves from a contagious cancer. There are many parasites that are affecting these kinds of animals; the bivalves. A lot of research is being done to try to understand 'Why is this happening?' 'Why is the immune system of these animals not fighting against all these parasites?' And of course, the contagious cancers.

Julia - You said that these cells appear to float in the water, passing from one organism into the other. How far do we think these cells can travel?

Alicia - Earlier this year, it was published that the same cancer was found in some clams in the Atlantic coast of Spain and also in the Mediterranean coast of Spain. Those two places are located more than 1,000 miles away. How is this possible? Was the cancer cell able to float and travel that far? We are not sure. We also have to consider that maybe human activity played a role in moving that cancer from the Atlantic coast to the Mediterranean coast. But for instance, in mussels, there's another type of contagious cancer that has been found in Chile, South America, North America, Europe, and even in Russia. But in the case of mussels, mussels attach to boats and boats travel long distances. By moving the mussels from one area to another, that is probably how this contagious cancer was arriving to so many places in the world. In the case of the clams, they usually live buried in the sand, so they don't attach to the boats, it's a very interesting question as well.

Julia - And with these cancers, are they restricted to an individual species in the sense of, if a cancer arises in one species, does it stay within that species because they're genetically similar? Or can it jump the species barrier and move into another?

Alicia - For most of them, it is how you describe it. The cancer arrives in an animal and it spreads to other individuals of the same species. But surprisingly, there are several cases in bivalves where the cancer arose in one bivalve species, and nowadays it is found in other species. By reading the DNA, you are able to study the history of that cancer. We found a cancer in the warty venus clam, which is a clam that lives in both the Mediterranean and the Atlantic coast of Spain. By studying the DNA we found out that the cancer cell did not arise in the warty venus clam but arose in a different species, which was called the striped venus clam. Another case of cancer that crossed that species barrier is the mussels. This one is very interesting because it has gone not only from mytilus trossulus, it is also infecting three extra additional species. That is like the master of cancer.

茱莉亚——好像我们这些癌症,can not only spread from organism to organism, but they can spread potentially from species to maybe different species and then also can potentially travel in some way we don't know and spread from population to population. What would this mean if these types of cancers impacted lots of bivalve populations? What would be the impact of that?

Alicia - We should be very careful with our economic activities when moving animals from one place to another and not only animals. Even with the sea water. We should now think of cancer, like a parasite. In the case of continuous cancer, it does behave as a parasite. And try to track at least these movements, so we don't put the disease into a disease-free area, because imagine that these cancers become very aggressive and they potentially reduce the number of individuals and they drive it to extinction; that will be an ecological problem. But if we keep the disease-free areas disease-free, so no cancer goes into there, at least not by our activities, in a scenario where this happens, that all the population reduces, we can repopulate with the ones that didn't have the disease.