Titans of Science: Marc Abrahams

Intro

0:00This BBC podcast is supported by ads outside the UK.

0:05Catch the NBA playoffs on Sling TV, the most flexible live TV streaming service, putting consumers in control to watch games their way with flexible subscriptions. Want to catch one game or a full series on ESPN? Grab a one, three or seven day pass. If you want to catch as many games as possible, get a monthly subscription with our ABC, NBC and ESPN combo package. Either way, Sling lets you watch the playoffs your way with no long-term contracts. Learn more at sling.com.

0:36This episode sponsored by Evie. Treat it, feel better, then start all over again. That was my pattern for years. I kept dealing with the same symptoms, getting the same treatments and ending up right back where I started. That's when I found Evie. Evie is an at-home vaginal microbiome test that analyzes over 700 bacteria and fungi from a single swab. It goes far beyond traditional testing that only checks a few things. When I used Evie, I finally saw patterns

1:06that had never been explained to me before. Then, a licensed clinician reviewed my results and created a personalized prescription care plan based on my actual microbiome. And for the first time, I wasn't just reacting. I had direction. Evie also isn't just data. It connects you to real clinical next steps based on your results. If you're tired of repeating the same cycle, this is where that changes. Visit evie.com and take the Evie test at home today.

Bird Flu Death

1:40Hello, welcome to this week's 5 Live Science. I'm Chris Smith from The Naked Scientist. Coming up, the US record their first human death from bird flu. So should we be concerned? Also, a new drug to treat drug-resistant prostate cancer. And what have the Romans ever done for us? Well, apparently, widespread lead pollution. Plus, a bit later on... The things that I always liked the best were when there was something that I didn't understand.

2:12I felt really stupid. I don't understand what this thing is. And then somebody would describe it in a different way or I would come at it from a different direction. And very suddenly, there was something that was kind of crazy about it and funny. And I understood it. Master of making science funny Mark Abrahams joins us for the latest instalment of Titans of Science. The Naked Scientists on 5 Live.

H5N1 Virus

2:38Up first this week, the United States have recorded their first human death from bird flu. The patient, who did have underlying health conditions, was taken to a hospital in Louisiana after contracting the H5N1 virus, but they deteriorated. The infection is now spreading in cows and it's even killing domestic and wild cats. So what's the risk for us? To find out more, we put in a call to Ed Hutchinson at the MRC University of Glasgow Centre for Virus Research. We've been concerned about H5N1 bird flu for about 25 years now.

3:12It's a virus which is capable of causing severe disease in humans as well as spreading in birds. But it's become a real issue in recent years where a new strain of H5N1 has started spreading really aggressively around the world through birds starting in Asia and then through into Europe, Africa, North America, South America, Antarctica. So it's everywhere now. It's caused enormous problems for wild birds, but it's also been very good at jumping from those birds into other species, particularly into mammals.

3:42And the most surprising case of that so far has been in the United States where it's not only infected dairy cows, but it's become a dairy cow virus. It's fully adapted to spreading among cattle and there's now this big outbreak of H5N1 in cattle in the US. And when it gets into a cow, does it behave like it does in the bird? Or does it behave more like mammalian flu, the kind of flu that you and I get, runny nose, sore eyes and high temperature? So this was a real surprise to virologists.

4:13The first surprise was that cows got infected at all, because up to this point, we would have said that cattle, for whatever reason, didn't tend to get influenza A infections. But the second surprise was the way it's spread. The main thing it's doing in these dairy cows is it's infecting the udders and it's being shed in the milk and it's being shed in the milk at incredibly high levels. Now, if you pasteurise milk, that kills the virus. So that's good news. But if you don't, the milk remains infectious and that seems to be a good part of how it's spreading among these cattle now. And what are the implications for people then?

4:44Are we worried that the cows might act as an interface, enabling the infection to drop more efficiently to us? Yeah. So against the backdrop of the fact that the virus is still circulating in birds, within cattle, these are animals which are obviously farmed in large numbers. So you have two points of contact. You have people who are working with the cattle, you have dairy workers. And if you can imagine a big dairy, there's lots of opportunities for coming into contact with milk from these cattle there. The other is consumption of unpasteurised dairy products.

5:16There's a subculture of drinking what's called raw milk, so unpasteurised milk. We pasteurise milk for good reasons for killing all sorts of pathogens. And this adds another one to the mix. So we are concerned that both humans and domesticated animals like pets could be exposed to the virus that way. And have there been many human cases via those routes? It's unclear at the moment whether there have been human cases from the consumption of raw milk, but there have definitely been cases from occupational exposure in dairies. So these have generally been conjunctivitis,

5:48so people getting pink eye, probably from the milk coming into the eyes, some also respiratory infections. And there have been cases where farm cats have died almost certainly because they've been lapping up milk around the dairy. What we've also seen in the US and Canada have been two really severe cases of human infection, both of which put people in hospital, one of which sadly recently resulted in the patient dying. But these cases did not come from cattle. These came directly from viruses and birds. And we can tell that because the viruses they got

6:19are much more closely related to the viruses still in birds than to the viruses which are in cows. So this highlights the fact that we've now got two different places to look when we're thinking about risks of H5N1 infection of humans. Does this not nevertheless put us on alert that this particular virus, this particular form of H5, appears to be quite good at getting into a range of mammals, of which we're obviously a member of that group of animals, and this might be the first steps towards a full incursion

6:49of this becoming a human flu? It absolutely does. And there are plenty of reasons to be worried about the animals themselves from an ecological perspective and animal welfare perspective. But if we're just going to look at humans for now, adapting to a new species is a really difficult thing for a virus to do. But flu is unusually good at it. And it's good for two reasons. One is that it can mutate really quickly. And we could see signs of that in those two really severe human cases. But the other thing to be concerned about is that influenza viruses can breed with each other.

7:22They can swap genes back and forth between them if two different viruses infects one at the same time. We're currently in the middle of the winter flu season in the US. There are loads of people being infected with influenza viruses, which are already very good at infecting humans. And there is this risk that you could have an H5N1 virus swapping genes with a virus, which is already good at growing humans and getting a head start to becoming a human virus that way. So you end up with a kind of hybrid virus that looks like H5N1, something we don't recognise as a human population.

7:53We've never seen that before. But it's got the inner workings of a human flu that knows really well how to grow in our cells and to grow really efficiently and spread really well. That's absolutely right. And most of the influenza pandemics we've seen over the last century have occurred that way. Most recently, the 2009 swine flu outbreak occurred by different influenza viruses breeding with each other. What then should public health officials, doctors, etc. be doing to A, keep an eye on that and B, minimise the risk?

8:24The most important thing you can do is to keep an eye on it because at the moment there is not any evidence for human-to-human transmission. So we're not talking about a human outbreak right now. What we're talking about is the need to minimise the risk of the virus figuring out how to do that. So that involves minimising the chances of the virus learning its way around humans. So what does that involve? It involves biosecurity measures. So if you have farmed animals trying to reduce the risk of them getting infected,

8:56if you're working with animals which could be infected, both monitoring and wearing appropriate PPE. And this is legitimately quite a challenging thing to do in big, complex farms, but it's important that this is considered. I'm also very concerned, as lots of people are, by raw milk consumption in areas where H5N1 is spreading. What about vaccines? They're our mainstay for preventing seasonal flu. Have we got vaccines that will combat this form of H5? And have we got them at the sort of scale it would take

9:28if this suddenly does start to take off? So this is a kind of partial good news story. We, obviously, we know how to make influenza vaccines, and we also already have produced H5N1 vaccines. Indeed, the UK government has recently purchased an initial batch of vaccines for exactly that reason. What's also good news is that you don't have to have a precisely matched H5 vaccine to get some protection against the virus. Even if it doesn't give you complete protection, it might reduce the risk of severe symptoms or reduce the risk of you spreading it to other people.

10:00And this is very similar to what happens with seasonal influenza vaccines and why it's always worth getting them, even if they're not going to completely protect you against every risk of infection. Ed Hutchinson there from the MRC, University of Glasgow Centre for Virus Research.

Natural Hydrogen

10:14New model predictions suggest that Earth's subsurface might hold billions of tonnes of natural hydrogen. Hydrogen is one of the most abundant elements in the universe, and it can be a source of carbon-free energy too. Burning it releases mostly water after all. But teasing it apart from natural compounds that contain it, like water or natural gas, can be both expensive and carry a carbon cost, which has been a deterrent to the wide-scale adoption of hydrogen previously. But geoscientists think that there might be

10:45vast reservoirs of the gas trapped literally beneath our feet, and a lot of it within relatively easy reach. If they're right, their findings suggest that geologic hydrogen could produce twice as much energy as all of the proven natural gas reserves we still have on Earth. I've been speaking to Jeff Ellis at the US Geological Survey. So we had generally assumed that natural accumulations of hydrogen just couldn't form because it's a very small molecule and it's very diffusive. It leaks out through rocks in the subsurface,

11:17and it's also readily consumed by microorganisms. But there was an accidental discovery of an accumulation of almost pure hydrogen gas about a dozen years ago in the country of Mali in West Africa. And as I learned about this discovery and I started to question this notion that maybe we could form accumulation of natural hydrogen. And presumably, if we were to go burrowing after hydrogen like that, it's not got the same implications as to dig up fossil fuels, petroleum, coal, gas,

11:48because there isn't a carbon footprint, apart from the extraction process, associated with it. So it would be a clean form of, I suppose, fossil fuel. That's exactly right. And today, the hydrogen that we get is actually predominantly made from fossil fuels. In the process of making a kilogram of hydrogen, we actually release about 10 kilograms of CO2 into the atmosphere. I suppose we should point out that there are, of course, ways of making hydrogen in a non-carbon releasing way.

12:18That is, if you use a sustainable energy source to do it. But that is the drop in the ocean compared to where most comes from, isn't it? That's right. Today, very little of this clean hydrogen is being made. The technologies that we have do exist, but they're quite expensive. It's not really clear how we're going to get all this low-carbon hydrogen that we think we're going to need. How have you turned this into a tractable question slash problem then? We looked at what we do know about natural occurrence of hydrogen on Earth. This is something that has been studied for many, many decades,

12:49mostly by biologists that are interested in the deep biosphere and life on other planets. And we know that there are microorganisms that are living on hydrogen in the subsurface. Then there were some knowledge gaps that we had to fill in. And so we used analogs from other things that have been well-studied, things like petroleum systems. So through studies of petroleum, we know how gases migrate and trap and get accumulated in the subsurface. And so we were able to then borrow knowledge from those fields to fill in gaps, to put together

13:19a global model of just how much hydrogen might actually be trapped in accumulations in the entire Earth's crust.

13:27Before we come to how much, just tell us where then we would anticipate this hydrogen might be. The processes that are thought to be capable of generating the largest amounts of hydrogen tend to be associated with crystalline rock settings. Iron-rich rocks that are associated with the mantle underneath the Earth's crust that have been brought up near the surface and also radioactive rocks. The radioactive decay of radiogenic minerals can actually split water and generate hydrogen.

13:58Actually, at the mid-ocean ridges today, we see seawater being reduced and forming hydrogen. And also in many hydrothermal systems, hot springs and so forth, we find hydrogen gases there. And these are, by the way, very different places from where we explore for oil and gas. So this can explain why we don't find hydrogen associated with petroleum. And they're also, by the sound of it, within reach, some of these sources, potentially. Yes, absolutely. And in fact, this accidental discovery in Mali was only 100 metres below the surface.

14:29So in fact, it's very possible that it could be very accessible. Now, notwithstanding the fact this is a model, therefore, it's got strengths and weaknesses. There are going to be knowns, there are going to be unknowns. How much hydrogen might there therefore be lurking within reach beneath the Earth's surface? The units that we refer to are million metric tonnes or megatons. And so we estimate that there could be anywhere from maybe just a few thousand megatons to potentially billions

15:00of megatons in the Earth's crust. And the median or most likely value is on the order of around 5 million megatons. On the order of millions of megatons seems to be probably most likely. Sometimes we just don't realise what is literally underfoot, do we? That was Jeff Ellis and that study detailing the discovery which just published in Science Advances. This is 5 Live Science with me, Chris Smith. And still to come, what have the Romans ever done for us? Well, they could quite possibly have knocked a few points off our IQ levels. You can hear how a bit later on.

15:31And Titans of Science is back with Mark Abrahams, the man behind the Ig Nobel Prizes. We'll hear how he's carved a career from science that makes us laugh and then think.

Prostate Cancer Treatment

15:42But first, researchers in London have found that prostate cancer that's become resistant to existing hormone therapies could be treated with an experimental new drug. It's called NXP800 at the moment and it's currently in clinical trials for other cancers including ovarian and bile duct tumours. It works by stressing out cancer cells to the point of killing them. Here's Adam Sharp, who's a co-author on the study and leader of the Translational Therapeutics Group at the Institute of Cancer Research in London. Over the past

16:1310 to 15 years, we've developed many treatments that can help control prostate cancer and allow men that have advanced disease, so that's disease that has spread beyond the prostate, live for longer. But the biggest challenge we have is that after time, sadly, those treatments stop working because the cancer becomes resistant to them. What it does is it learns ways to overcome the treatments that we're giving to our patients and it stops working and therefore

16:43the cancer continues to grow. So in this work, we were really trying to develop new treatments that work through new ways that could maybe help patients that other treatments had stopped working for. I suppose it's a bit like when bacteria become resistant to antibiotics, isn't it? It's that they have evolved ways to surmount whatever the blockade imposed by the drug is. So how have you attacked this then? How have you gone after flushing out new avenues that will clog the works up and stop these cancers even though

17:14existing treatments can't? The cancer cells are very stressed and they're stressed because they do grow uncontrollably. So what that means is the cancer cell needs to protect itself and one way that it does that is it uses a particular family of proteins, the chaperones. they just really protect the cell from that induced stress that the cell is undergoing so that it survives rather than dies. And what we did in this study was we actually looked at a drug that had been discovered and developed here that really

17:45tries to stop the chaperones from working and increases the stress that the prostate cancer cell is under. And what we wanted to do was to actually decide if we were to give this drug to our cancer cells would they be under so much stress that they no longer could survive and actually they would either reduce their growth or even die and that's what we really wanted to look at in this study. How did you do it? My colleague Professor De Bono has a huge number of patient samples so we first wanted to ask

18:16the question are these chaperones so these molecules in the cancer cell do they make the cancer cell more happy? So we actually identified that patients that have more of these chaperones in their cancer cells sadly did worse to current treatments and then we wanted to take this drug to see whether or not it worked. It's meant to increase the stress or reduce those chaperone proteins that the cell likes to increase the stress so we treated prostate cancer cells in our labs and we

18:46also treated mini tumours that have come from prostate cancer patient samples and these specific cancer cell samples were resistant to our current treatments and what was exciting to see was that with this drug these actual cancer cells started to die then what we did following that was we then tested it in animal models as well to show similar effects to what we were seeing in the lab cancer cells. Effectively you're robbing the cancer cells of a defence they rely on so they become

19:16stressed to the point of toxicity they just die but what's to stop them just evolving a defence against the drug so they can switch those defences back on as it were and just do what they've already done for the other treatments and we're just kicking the can down the road a bit here. Yeah and I think that's a really important statement the challenge as you've said is the cancer will evolve ways to overcome resistance to the new drugs that we're also developing so alongside developing those drugs in themselves we also now following from

19:47this work is start to look about what drugs could we put the new drug with you to maybe overcome the mechanisms of resistance that occur. How selective is the drug for prostate cancer cells because obviously these proteins that you're robbing the cancer cells of play a really important role in protecting healthy cells as well so are there not potentially really serious side effects from doing this? Yes I think again that's a really important question the way that we would describe it

20:18is actually cancer cells themselves can become more sensitive to these treatments because they have more reliance on those chaperones a normal cell that isn't as stressed doesn't actually require them as much as a cancer cell and what we hope is that that's what can deliver us the therapeutic window. Could this treatment also become a way to make other treatments even more effective because when you're treating prostate cancer with for example radiation that's really stressing

20:48cells so if you give a drug at the same time that makes them even more vulnerable does that make the power of the radiation the killing effect even more potent and therefore you could get away with say lower doses or get an even better response in the cancer so the person has a better outcome? Fantastic question and I think that's what I actually hope more about this paper is not so much our work but also bringing interest to the field and there has been some great work from other labs that have already showed

21:18that targeting increasing the stress response can sensitise to radiotherapy. At the moment you've done this in a dish and you've done it in these experimental animals how close are we now to being able to do clinical trials? Do you foresee this being a relatively easy route into the clinic? This work is done in preclinical models in the lab and is exciting but of course that's still a long way from showing that it works in prostate cancer

21:49patients in the clinic. What's exciting is the drug itself has been developed and it's now being given to patients with advanced ovarian cancer and cancer of the upper GI tract and therefore the clinical trials are already running. What I hope is also exciting enough about this work is that it will make our collaborators in biotech and industry start to think about prostate cancer cancer as a potential another indication for

22:20this drug. Great news. That was Adam Sharp and that study has just been published in the journal Clinical Cancer Research.

Roman Lead Pollution

22:27Now if Monty Python's life of Brian has taught us anything it's that we have the Romans to thank for pretty much everything. But it seems it might not all have been entirely beneficial. Indeed new research suggests that intense lead mining and processing at the height of the Roman Empire may have engulfed Europe in widespread pollution which in turn contributed to the cognitive decline of the population although not to the same extent as lead in petrol in the 1970s. Joe McConnell at the Desert Research

22:57Institute in Reno has been telling me all about his study. I study ice cores. In this study we used three ice cores, two from Greenland, from the Greenland ice sheet and one from the Russian Arctic. And these were collected a long time ago over the last 20 years by many of my European colleagues. And we analyzed these in my laboratory at extremely low levels but we can use those variations of those very, very low levels to look at changes in emissions of pollutants. And how do you know when they relate to in time these ice cores? Yeah, it's a great question.

23:27We count annual layers in the chemistry. It turns out in my lab we measure about 30 different chemical species all at the same time, depth resolution. And so we can count just like tree rings, we can count those annual layers starting at the top and just count them backwards thousands of years. And then we use things like known volcanic eruptions and there happened to have been one in Alaska in the year 43 BCE that we can tie directly to the tree ring series and to all these different ice cores. And what, the ice captures a snapshot of what the air was doing when that bit of ice

23:58got made at that particular point in time? Is that the rationale for doing this? Absolutely. So there are these little things called aerosols or little particles and droplets in the air around us all the time. And they come from things like forest fires or pollution or volcanic eruptions, desert dust, sea spray, things like that. And those impurities are captured by falling snowflakes or by raindrops and deposited in the snow or in this case on the ice sheet. And what does the lead footprint look like? Is it significant? It's easily detectable. And one of the reasons that we

24:28focus on lead besides the health implications is that humans in their early mining and smelting created a lot or emitted a lot of lead. And so the background of lead in the natural environment is quite low. But humans, because of our mining and smelting, really put out a lot of it. And so the signature of human impact is quite clear in these ice cores in terms of lead. And was it chiefly the Romans 2,000 years ago that were playing with lead? So you can say, well, it was them that have made the signature that you can see in these ice cores mapping onto

24:59that time point. Or were other humans around the place, other races, were they also using lead? Historians and archaeologists tell us that the primary sources would have been the Roman Empire. And then there was quite a bit of activity in China. Using atmospheric models and then lead isotopes, the isotopes of the lead itself, we can evaluate where the lead must have been coming from. In this case, where these ice cores are located, the sensitivity of the ice, meaning how sensitive the ice core record is to emissions, is about 10 times greater for

25:30Europe than it is for China. So it's not impossible that we're seeing some lead from China. It's just that the emissions would have to be at least 10 times greater to equal the same amount of emissions from Europe. And then finally we can use these isotopes and what we find is the lead deposited in Greenland has a similar isotopic characteristic as the ore bodies in southern Europe. And how do you then relate what the ice is saying was there to what the concentration for where the people were must have been in the air?

26:01So in other words, if you were a Roman, either living in a town or working in one of these settlements that was producing this, how much lead would you have been exposed to, do you think, based on what the ice is telling you? Somewhat surprising for me at least was how widespread the pollution was. The atmospheric modelling suggests that it was basically extended over the entire Roman Empire. And that goes all the way from North Africa to what is now Germany and all the way over to the Black Sea. How would that relate to if we wound the

26:32clock back just say 100 years? Because we were using a lot of petrol that was all leaded until into the 80s we were all using leaded fuel because it was better for engines. So how would our lead pollution in that era compare with what the Romans were doing? Were we worse than them effectively or not as bad? No, we were definitely worse. The blood lead levels that would have resulted from this air pollution were about three times higher during the late 1970s, at least in the US, than they

27:03were during the Roman period. As you mentioned, lead has really been cleaned up in the last 20, 30 years, 40 years maybe, since passage of things like the Clean Air Act in the US and similar legislation around the world. And the Romans were experiencing about three times the exposure children today are experiencing. But of course,