Coming up this week… how bacteria could be supercharging cancer cells, the ghost fishing nets laying waste to our oceans, and could capturing carbon underground hold the key to our net zero ambitions?
In this episode
00:50 - Bacteria make cancers more mobile
Bacteria make cancers more mobile
Scott Verbridge, Virginia Tech
Cancer occurs when DNA is damaged in such a way that cells begin to disregard the normal controls that regulate their behaviour. But in recent years scientists have discovered that tumour cells may have accomplices that make them more malignant, more likely to spread, and possibly even resistant to chemotherapy drugs. These accomplices are bacteria, including ones carried normally in the human mouth. They've been spotted in a range of cancers, but it wasn't clear whether they were there just because cancer cells are abnormal and have grabbed some harmless bacteria, or whether the microbes are actively contributing to the disease process. Now, Scott Verbridge at Virginia Tech has been able to show that, when these bacteria are present, tumour cells behave differently - growing and moving more actively. And not only that, but they can also alter the behaviour of adjacent cancer cells that don't even have any bacteria in them. He spoke with Chris Smith…
Scott - So there's this bug that is in basically everybody's mouth, and it's been known for roughly a decade that this bacterium has been present in colorectal cancer. So in cancers of the gut, they seem to be present in tumours that are worse for patients. More recently, we've started to discover that there are actually bacteria present in all kinds of tumours. So not just in the gut, but outside of the gut as well. So in breast cancers and lung cancers, pancreatic cancers, which is specific for this study, we're finding that these bugs are really present in a lot of different kinds of cancer where we used to think that these tissues should be sterile. And so our goal here was to understand what this particular microbe might be doing, and that's consistent among different tumour types.
Chris - I guess there are two questions here, which is really, is this cause or effect in the sense that, are these bacteria there because there's a cancer there and it's just abnormal so it picks them up? Or are they causing this cancer to behave the way it does? And are they playing a role in the progression of that cancer? Because cancers do that, don't they? They spread, they then progress, they invade other organs, and to what extent the bacteria might or might not be playing a role in that.
Scott -Yeah, that's exactly right and that's a great way of wording the question here. You know, a lot of the early work was just showing that these bacteria are there in tumour tissues and showing a correlation. People that had more of these microbes in their colorectal cancers would tend to have worse prognosis. But like you point out, that doesn't show that the bacteria are driving the aggressiveness of the cancer. It could just be that the more aggressive cancer is a better host to the bacteria, and there are reasons to think that these bacteria actually like to live inside of tumours. So, these bugs are what are referred to as anaerobes. What that means is that they like to live in an environment that doesn't have oxygen, and that tends to be one of the features of cancers as they grow, they become depleted in oxygen and they become anaerobic. So there's some reason to think that these bugs do well in tumours. And so yeah, we were interested in contributing to separating the correlation versus the causation. If we put the bugs in, do they actually make tumours more aggressive?
Chris - Are the bacteria in the cells, on the cells, next to the cells? What's the relationship?
Scott - Probably all of the above. But one of the interesting features of these microbes is that they do get inside the host cells. And that's really interesting because one of the observations that really drove us down this line of questioning was colorectal cancer cells, which are host to intercellular fusobacterium. Those cells were actually found, um, in liver metastases. The bacteria are not only able to get inside of the cancer cells, but they're able to survive inside those cells long enough to spread from a primary tumour in the colon to a distant tumour in the liver. And so that really was the main questions we have. Are those bacteria kind of just along for the ride or are they actually actively driving that migratory process?
Chris - And how did you test that?
Scott - We directly infected tumour cells and then measured their migratory capacity. We can watch, you know, in real time how they move, both with and without the bacteria in them.
Chris - And how does it make a difference?
Scott - So when we infect the cancer cells, they are more migratory. They move around faster, they're just more active in their movement. They're also more proliferative. They tend to divide rapidly, and the speed at which that happens is greater for the pancreatic cancer cells that have these microbes inside of them. Now, beyond that, what we've also shown is that cells that are next to cells that are infected also have that same set of effects. So what we've discovered in this work is that it's actually the cells that are infected are actively spitting out proteins that are accelerating proliferation and migration movement in both the infected cell as well as neighboring cells.
Chris - So one cell picks up some bacterial passengers, some freeloaders, that in some way manipulates the infected cell, but makes it then feed all its neighbors. So they all get a growth boost.
Scott - That's exactly right, yeah. So there's a kind of a built-in amplification there where you might not necessarily need to infect all of the cells in that tumour. You might have kind of an action at a distance where the infected cells are stimulating growth in the adjacent cells
Chris - And if the bacteria can turn this effect on, have you identified what factors are being turned on and therefore if you block those, does the effect go away?
Scott - So what we've done so far in terms of blocking has to do with understanding the physical structures that are in the membrane of the cancer cells that the bacteria seem to be binding to. These bacteria like to stick to a kind of a sugar that tends to be over regulated or upregulated in cancer cells. And the bacteria cells have a molecule in their own membrane that allows them to anchor to the sugars that are in the cancer cell membrane. And when we go ahead and interfere with that anchoring process, we can block the bacteria from invading in the first place. So that's where we've gotten a handle on interfering with this process so far.
Chris - The question that probably is foremost therefore in many people's minds is that we have drugs that kill bacteria. So if we were to give big doses of antibiotics to patients with cancers, would you speculate that that might have an attenuating effect on the rate of progression of a cancer?
Scott - It certainly might, and that's something that we're thinking about. There's some really wonderful animal work and colorectal cancer showing that you can actually improve outcomes for mice that have colorectal cancer by treating them with antibiotics that can destroy these bacteria. The challenge is that there's also a whole field of work looking into how your native microbiome, how that population might affect your response to cancer therapies. Some of that evidence seems to be that some of these microbes actually help the therapeutic response. So, there are some studies showing that broad spectrum antibiotics that just wipe out everything can actually reduce the efficacy of chemotherapies or immunotherapies. So it's not going to be as simple as just, you know, we want to get rid of all the bugs in our body because a lot of those bugs are really helpful. So we're thinking about ways of doing this in a more targeted way. Can we go after just this one species or can we go after treating just the tissue locally. So just get rid of the bugs that are in that pancreatic tissue versus a more systemic dose. Those are all the kinds of important therapeutic questions that we have moving forward.
07:17 - Sequestering CO2 Underground
Sequestering CO2 Underground
Andy Woods, University of Cambridge
While the significance of tackling climate change by reducing the amount of carbon dioxide we’re releasing into the atmosphere in the first place is paramount, capturing the gas and storing it somewhere where it is not heightening the severity of global warming can be an important part of the solution.
You’ll often hear about companies boasting about how many trees they’ve planted to offset their carbon footprint, but another way to remove carbon dioxide from the atmosphere is by storing it deep underground. This week, The Royal Society published a policy briefing on this very field: offshore carbon storage wells. The report, titled Locked Away - Geological Carbon Storage, details the viability of processes to permanently store carbon dioxide into deep saline aquifers or depleted offshore oil and gas reserves. Here to give us the lowdown is Andy Woods from the Department of Earth Sciences at the University of Cambridge, who chaired the report’s working group.
Andy - There are parts of the energy system where it's very hard to decarbonize, particularly in industry. So in cement manufacture, in fertiliser manufacture, and in iron and steel manufacture, there's a lot of carbon emissions as part of the process of making those products. And so one solution is to capture the carbon as you produce those products. And then that carbon can be compressed and pumped and then stored in deep saline aquifers offshore. There's a couple of projects being developed at the moment. In the UK there's the net zero Teesside project, which is planning to capture a whole series of carbon sources and pump them offshore and store them in a reservoir one and a half, two kilometres below the sea floor in the North Sea.
James - Can you go into a bit more detail on that? What does geological carbon storage look like? How does it work?
Andy - These streams of carbon dioxide, they're compressed and it becomes a very dense, high pressure liquid with a density close to, but a bit smaller than the density of water. And that's injected into these sandstone layers about one to two kilometres below the sea bed. Typically, the geologic strata isn't exactly horizontal, but it'll have highs and low points. And if you can find a region where there can be some trapping, if you put the carbon dioxide into that, it'll float on top of the water in this sandstone layer. And you'd be looking for one where there's shale or some other very low permeability, low conductivity rock above, and that'll trap the carbon dioxide in that store. That gives you what's called structural trapping. And then, over time, the carbon dioxide is soluble in the water in this saline aquifer and so it'll gradually dissolve into the water and that'll increase the integrity of that storage.
James - You mentioned before a couple of the projects already underway. What's the aim then with publishing this report? Is the UK going to be able to perhaps position itself as a real player in geological carbon storage?
Andy - So what we wanted to do is actually focus on the storage side of 'carbon capture and storage' and just look at the technical and engineering challenges and the sciences needed to drive this technology forward, but also to identify how big a part of the energy transition this will be. So the IPCC have projected that we'll need to store between about 300 and 1000 gigatons of carbon by the end of the century. And just to put that in scale for reference, if you look at a net zero energy system, the International Energy Agency have a model about what a net zero energy system looks like in 2050. And that will include carbon storage storing about seven or eight gigatons a year. And that's about 20% of the total emissions that we produce today. So it's a very large fraction of the total carbon emissions.
Andy - And that requires a scale up of our carbon storage potential from what we have today, which is about 40 megatons a year up to this seven or eight giga tons a year. So that's scaling it by a factor of 200. And so the purpose of this report was really to highlight, to policy makers, the great potential of this carbon storage as a very important part of the energy transition, but also to alert them to the need really to scale up investment and regulation, and the policy framework to actually accelerate our implementation of carbon storage. And for the UK this could be a major source of growth and a major new industry that we could develop with huge potential to export the technology and the technical solutions, as well as storing lots of our own carbon emissions.
11:49 - How much fishing gear gets lost at sea?
How much fishing gear gets lost at sea?
Denise Hardesty, CSIRO
The planet has an estimated 60 million fishermen. To do their job, they use nets strung between boats and across rivers, long lines armed with thousands of hooks, trawl nets that get dragged across the seafloor, holding pens for aquaculture, and, of course, good old fashioned lobster and crab pots. Together they feed over three billion people. But in the course of doing that, massive amounts of gear goes overboard contributing to huge environmental impacts. The scale of those losses, which Australia's Denise Hardesty has now managed to calculate, will almost certainly make your eyes pop out. Here she is speaking with Chris Smith...
Denise - So we set out to ask how much fishing gear is lost to the world's ocean. So we went out and spoke with fishers in seven countries around the world and used a lot of different types of gear. So we asked fishers, who fish with fishing line, like long lines with different types of trawl nets or fishing nets that are designed to catch your fish in that way. And also with pots and traps. So we really spanned the full breadth and depth of the world's commercial fisheries
Chris - And is the metric. Then you say to them, how much gear do you buy in a year? And you assume that what they are buying is to replace what they've lost.
Denise - It's not about asking the fishers 'how much fishing gear do you buy each year?' and then subtracting out how much has been lost. Because many of the fishers that we interviewed, they're not the ones that own the companies that are making those decisions. What we did instead was ask the fishers, How long do you spend at sea? How much gear gets lost? How often does it get lost? When and why and where? Under what conditions do you lose that fishing gear? And then we coupled that with information about how much fishing effort happens around the year from an independent data set. And that allowed us to match or to marry those two really different types of information together to make that estimate of how much fishing gear is lost to the global ocean
Chris - And how much is?
Denise - So for one single major fishery a year around 740,000 kilometers of fishing line alone is lost. And with that, our 14 billion hooks. If you wanna put that in perspective, that's about circling the earth more than 18 times for that fishing line or going from earth to the moon and back. We also estimate around 3000 square kilometers of gill nets, 75,000 square kilometers of another type of net called Purse Seine nets. And over 25 million pots in traps each and every year.
Chris - Of course, many of these are man made plastics and polymers, aren't they? So they're going to be adding to the global ocean plastic problem, but they're not going to go anywhere. They're just presumably gonna build up in the sea somewhere.
Denise - So they're gonna fish indiscriminately. And we call that ghost nets. When these abandon or lose commercial or other fishing nets are lost at sea because they just continue to fish indiscriminately. And what this means is they're catching fish, they're catching turtles and whales and dolphins and you know, other marine mammals costing lots in terms of biodiversity impact, as well as having quite a substantial potential impact on the global fisheries and on global food security. Because if we capture these fish and they die in the nets, but they aren't making it to people's dinner plates, then we're actually not able to utilize not only the protein benefit, but the economic benefit from fishing.
Chris - My mind is boggling with these numbers that you're coming up with. This is quite terrifying in terms of how much is therefore out there. Do we actually have evidence that this buildup is doing, as you say, and having a knock on effect on species and so on?
Denise - Well, one thing that we know from some previous works on looking at ghost nets in one particular part of Australia was we estimated that around 10,000 turtles a year are killed or captured by nets just in that particular area. So we do have evidence from that study and from other separate bodies of work from other researchers around the world that have highlighted particular problems in particular small areas. What we've done now is really show what that looks like at the global scale in terms of how much is lost. And you know, you said that's really confronting and when we think about it, that's 25 million pots and traps each and every year. 14 billion hooks each and every year. So you know, this is accumulating in the oceans and it's also getting caught up on sensitive coral reef beds. It's getting washed ashore in damaging sensitive marine and coastal ecosystems and habitats such as mangroves. It's smothering our reefs, it's causing quite a lot of damage.
Chris - What can we do about it? When scientists back in the mid 1980s spotted an Australia-sized hole in the ozone layer over Antarctica very promptly, they were able to galvanize action. They got the Montreal protocol together, we banned CFCs as the cause and hopefully have arrested the progression of the ozone hole. What can we do about this?
Denise - Well, that's a really great point. So what can we do? I think the first thing to do is to not only understand how much is lost out there, but to also really unpack why and when it is that fishing gear gets lost. And so that's what we did. And what we find is that smaller vessels on average lose proportionately more gear. We also find that fishers that are fishing on the bottom of the ocean tend to lose more gear than those fishing in the midwater or on the surface of the ocean. And we also understand a bit more now about why and when we're losing gear. So when there's bad weather and fishers aren't getting that much money, they tend to fish in marginal conditions. As we start to see a reduction in the amount of fish in a particular area, we may have more fishers crowding into fishing in a smaller area.
Denise - And that means we can see conflicts between different gears and between different fishers. And when there's conflict, when lines or nets run over one another, they may end up getting caught or tangled and being cut apart. And so some of the things that we can do is to ensure that fishers have the best equipment possible. We can look at potential incentives to reduce fishing gear losses, and so we can provide buyback programs or low cost loans for fishers to replace their gear before they're so close to end of life that they're likely to get lost.
19:37 - Pharmacists to prescribe antibiotics
Pharmacists to prescribe antibiotics
Nick Brown, Antimicrobial Chemotherapy Council
A plan to alleviate the log jam in general practice by loosening access to antibiotics so pharmacists can prescribe them has received a febrile reaction from doctors, who describe the plan as “risky”, worded as it was to suggest that it would make it easier to more antibiotics for more ailments. The Department for Health on the other hand estimates that around 1,000 of England’s 27,000 pharmacists have a prescribing licence, and that chemists prescribing antibiotics for urine infections alone could free up 400,000 GP appointments each year. But the message was somewhat tarnished, according to a report in the Times newspaper this week that in proposing the move, Health Secretary Therese Coffey had remarked privately that she had “handed out her own supplies of antibiotics to friends and family who were feeling unwell,” attracting widespread condemnation from the medical profession, who called her “reckless”. So what’s right and what’s wrong with all this? Nick Brown is a consultant microbiologist, an expert in antibiotic resistance, and sits on the British Society for Antimicrobial Chemotherapy Council…
Nick - The recent interest in access to antibiotics has come about because of a statement last weekend that people will be able to go to their local pharmacy and pick up antibiotic prescriptions there without having to go to their gp. And this of course is one initiative that has been proposed to get around the problem of people having to wait a long time to get a a GP appointment.
Chris - But what Therese Coffey also said was 'I dished out some old antibiotics to a mate', which many other doctors have, I think quite rightly, objected to very, very forcefully.
Nick - That is correct. And I think every medical professional would not accept that this was a reasonable thing to do and that people should not share their antibiotics with anybody else. Antibiotics are a very precious resource and we should use them wisely. Part of that means that you should not give them to people who have not been prescribed them. These are prescription only medicines that are a legal requirement. Therefore, you should only access antibiotics by getting them prescribed by a licensed medical practitioner.
Chris - The legal side of it aside, why is that bad practice with respect specifically to antibiotics?
Nick - Antibiotics are absolutely fundamental to the practice of modern healthcare. Without antibiotics, you could not have a hip replacement, you could not have cancer chemotherapy, you could not have an organ transplant. The problem with antibiotics is that the more you use them, the more likely it is that the bacteria will become more resistant to them. And that means that the more you are exposed to an antibiotic, the less effective it becomes. That is unlike any other medicine. Paracetamol is always paracetamol and the drug for high blood pressure is always a drug for high blood pressure. But the more you use an antibiotic, the less effective it becomes. And that means only using them, or accessing them, when there is an absolute need to have them.
Chris - Why did she start talking about this in the first place though? What was the general direction of travel that this became an unfortunate diversion for?
Nick - The statement last weekend was prompted by the national issue with GP capacity at the moment that many people are having to wait for several days or even longer to get a GP appointment. And by increasing use of local community pharmacy capacity, potentially people will be able to get a much more prompt prescription of an antibiotic should it be required.
Chris - Is that altogether safe though? I mean, are we comfortable that people would effectively be bypassing the doctor to get antibiotics? Because at the end of the day, a doctor's a doctor and they know what to treat with what. It just seems a little bit of a short change mechanism, corner cutting.
Nick - Yes. Now the important bit is that there need to be appropriate safeguards around that prescription and there are already a lot, lot of examples of where this is being done very successfully. For example many minor injury units, senior trained nurses can prescribe antibiotics for some conditions. And in Scotland there is an initiative called Pharmacy First, which has been going for some years, where pharmacies already can prescribe antibiotics for some limited number of conditions with appropriate safeguards being put in place. The statement from last weekend seemed to imply that this was about increasing access to antibiotics, which it should certainly not be. In the situations in, say, minor injury units or in the Pharmacy First initiative in Scotland. The number of indications whereby a pharmacist or a senior nurse can prescribe an antibiotic are actually pretty limited and the detail of the patient group direction, which allows them to prescribe, has numerous exclusions on it, which adds another layer of safety. People should only be prescribed an antibiotic in a pharmacy or in another setting if they have a simple infection that is not complicated and therefore can be managed appropriately in that setting.
25:04 - DNA Insights into Neanderthal Society
DNA Insights into Neanderthal Society
Lara Cassidy, Trinity College Dublin
These days, the human race comprises a single species - Homo sapiens. But until about 40,000 years ago, we shared the planet with a related but distinct group called the Neanderthals. They were so similar to us that the two groups periodically interbred, which is reflected in the fact that two or three per cent of the DNA in the average person today is Neanderthal. The reason we know this is that scientists can read and rebuild the genetic code present in ancient remains. And now there’s been an incredible discovery. The remains of a Neanderthal community in two caves in Siberia has opened a window into this world for the first time. Chris Smith asked Trinity College Dublin’s Lara Cassidy, who specialises in reading ancient genomes and wrote a commentary on the new discovery, to explain what’s been found…
Lara - This is really big news because we've never had data like this before. The authors have sequenced ancient genomes from Neanderthal remains in Siberia. Neanderthals are a sister species to our own species. Homo sapiens, they were living in Europe and surrounding areas around 40,000 years ago. They have managed to sequence 13 Neanderthal genomes. What's really special about this is that they're all coming from in and around the same time and the same place. And that allows us to explore relationships between these individuals.
Chris - Where did they study these ancient peoples then? When you say there's lots of them together, it does add a huge amount of data - it nearly doubles the number of specimens we've now got genomes on, doesn't it? But where did they all come from?
Lara - These individuals are coming from archaeological excavations in the Altai foothills in Siberia, where we have two nearby caves, Chagyrskya cave and Okladnikov. What they think is that at least some of the individuals they sequenced were contemporary, so they lived at the same time really incredibly. They found a father and daughter pair and they also found second degree relatives like an aunt and a nephew or a grandchild and a grandparent.
Chris - Were these individuals buried there then? Is that why they happen to have this grouping and they're closely related both in space and time or were they wiped out by something? Do we know?
Lara - We don't quite understand why their remains ended up in this cave. The cave itself was a campsite. They were processing bison. They'd go down, hunt bison and bring the remains back to a cave. They were also making tools to do that work.
Chris - And have we got dates from the local stratigraphy, the layers, to tell us roughly when those people were doing this?
Lara - The layers of activity are dated to between 59 and 51,000 years ago.
Chris - What does this enable us to infer about Neanderthal society, then? Because this is a special case. We've got a large group who are closely related. they're all living together. This is almost like a community. So what can we infer about the community and society in Neanderthal times from these DNA codes?
Lara - I suppose there's two conclusions this study drew. The first one was that all of the individuals they could test, they had high levels of background inbreeding. Quite extreme. I think the closest modern day comparison would be what we see for mountain gorillas. Mountain gorillas are an endangered species. Historically there's been fewer than a thousand individuals in the wild and they live in quite small community groups. Maybe 20 or so individuals are Chagyrskya Neanderthals. They're looking like there's similar demographic dynamics going on. They're living in in fairly small communities. So that's very interesting because I suppose we compare that then to our own species, homo sapiens. One of the things we're very interested in is how we differ from Neanderthals because those differences might tell us something about our own species evolution, why our own societies were so successful in terms of dispersing across the globe. Well, the Neanderthals fizzled out. They don't maybe seem as well connected to one another as modern day hunter gatherer societies that we have now
Chris - It won't have escaped the attention of listeners that that time that you're talking about is not far upstream of when this particular lineage went extinct. Neanderthals disappeared about 10,000 years after this. So could it be this is already them in decline or could it be that they disappeared because of this sort of thing - this inbreeding?
Lara - Neanderthals lineage first starts to emerge about 400,000 years ago. So they were survivors in that way. They were in Europe for a long time and they went through a lot of harsh climactic downturns and then re-expanded again. So I would say there isn't a reason to think that this type of population size is a sign of their imminent demise. This is a very debated thing about why Neanderthals disappeared. But I think the most popular theories at the moment are more of a demographic one. That they were just simply swamped by homo sapiens.
Chris - And what was the other point? Because you said there were two key learning points in this. One was this small population size. What was the other?
Lara - It also seems there is a migration between communities, but the authors proposed that this is primarily females dispersing. So leaving the group from which they were born and moving to a new community.
Chris - Is that because the males are going off and getting wives? Or is it that the women are on the move and joining other communities? Is there anything that we can learn from modern anatomically modern human societies where there are similar practices?
Lara - Yep. We can't say the exact dynamics. We don't know how similar Neanderthal social organisation was to our own. So we wouldn't want to project too much from what we see today in modern hunter gatherer societies onto a different species of human. Another thing we can look towards is our closest living relatives, which are the African apes. African apes do show female bias in dispersal. Females move between groups more than men. Some people have used that to argue that this female bias dispersal was the ancestral state. That's why actually trying to jump back in time with ancient genomes and understand what was happening in other species of humans is so important. We still don't know how flexible Neanderthals were. Maybe if we sampled another community from a different time, from a different place, they'd show male biased dispersal.
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