 I'm now joined at the Royal Society by Laura Holland from the Rosalind Franklin Institute. Laura, tell me, what do llamas have to do with viruses? Well that's an excellent question, not an obvious pairing I think it's fair to say. So we are here talking about a piece of work that has been ongoing since the early days of the pandemic. We're based at the Rosalind Franklin Institute which is a research institute in South Oxfordshire and we're working with colleagues at Reading University. At Reading they have a herd of research llama which again probably isn't a phrase that many people expected to hear and we are really interested in a very specific type of antibody that llama produce. So llama, their cousins alpaca and camels all have this very special quirk of their immune system that some of their antibodies which are the molecules that your body makes in response to seeing a disease or a pathogen or something it isn't expecting to see. Those molecules I'll just show you this. This is a human antibody so you can see that it's quite large, it's got several components to it, it's a big version. The most important thing that your antibodies do is that they stick really specifically like a key in a lock to one particular target. Now this is human, this is llama. So it does the same job, it sticks very specifically but you can see it's missing all of this heavy complicated machinery and it's just doing the sticking bit. So we've known that llama can do this for a long time. It's 1993 I think it was discovered that their immune systems work in a slightly different way but when the pandemic came around we thought okay we know how to work with these, we've been using them for a long time. What could we do against COVID? What would a what would a nanobodyd do against this emerging pandemic threat? So we produced these, we injected llama at Reading and I'll use the virus now. This is COVID, so it's just a friendly COVID. You can ignore the eyes, they don't have eyes in real life. You can see all the spikes, we're familiar with the term spike protein so we exposed the llama to just the spike so we didn't give the virus any live virus to the llama just in the way that the vaccines work. We showed them very specifically the spike protein and that causes the llama to produce antibodies so these emerge and those antibodies stick very specifically to the spike protein and what we discovered is that they stick to it which helps the immune system of the llama recognise that there's a threat. They also kill the virus, they stop it from working because spike is how the llama is how their virus gets into the cells when it's infecting. So by effectively blocking those spike proteins you block an infection and the virus dies. So we had these. What we then did, the llama's immune system does a brilliant job of making quite strong sticking but we thought we could improve that. So by taking it through several rounds of eviteration, looking at the exact sequence of the antibody, we made it stick even more tightly, even more strongly and what we can do at the Roslyn Franklin is we can use very very advanced microscopes to look at the exact atomic structure of the nanobody bound to the spike so that we can really understand, okay it's sticking really well there, what does that mean for the amino acid sequence of the protein, how can we make it stronger, how can we make it better. So we now have a nanobody agent that is curative, so it works beautifully well in animal studies, it completely cures COVID in those animals, they get better in a very short space of time and really excitingly you don't have to give it as an injected therapy, so you don't have to deliver it straight into the bloodstream, you can deliver it as a nasal spray. So a quick sniff, the nanobody goes into the bloodstream, does its job, mops up the virus, kills the virus, so really exciting, obviously you can't overstate these things because it needs to get into humans next and we've got a lot of work to do but in terms of how drugs work it's a good candidate. That's really exciting, so that's the next stage then is it, is human clinical trials and how long would those tend to take, you know, when might we sort of thing on the market? That is a million dollar question isn't it, so as a imaging institute, so we're basic research, our interest in nanobodies has never been in the therapeutic space, we don't make drugs when at a pharmaceutical company, so we're partnering with someone else to do that next phase and we are hopeful that we'll see that move into the next phase in the next few months but need to keep everything crossed. Yeah very exciting, how did we first discover that llamas had this different way of their immune system working? That is the story that I would love to know the answer to, so they have been known about since since 1993 like I said, different camelids have different proportions, so some antibodies in the llama look a bit more like this, others are the tiny nanobodies that we're interested in, they have different percentages so camels have a different percentage of nanobody to large antibody to alpaca, who has a different percentage to llama, we don't actually know what the evolutionary advantage of that is, so we don't know why their immune systems have come up with this solution, it must be a solution to a problem because that's how evolution works, but yeah we're not sure what it is, but we're very glad that they do because they're very useful. Definitely, so there could be lots of other animals out there whose immune systems work in other ways like the llamas that might be out there. That's absolutely more, you also find nanobodies in sharks, but from a husbandry perspective I'd say llama were the better candidate to work with. They were dangerous to keep those in South Oxfordshire for a reason. Absolutely. Fantastic, so for you then in terms of the teams that you work with, you're based working on the sort of molecular side of this, you know the very very zoomed in working out what the atoms are doing inside these materials, what other types of scientists do you work with? So at the Roslyn Franklin Institute we were born as a technology institute so we're there to make the next generation of microscope, the next generation of tools that will help us see further into cells, see life in a new way. The nanobody work actually is part of that so nanobodies are used as a tool to stabilise proteins when we're imaging them to help hold them still or it's a general rule that the more interesting a target the harder it is to look at. So that tends to be because very very interesting proteins doing really important jobs, they're often based in the membrane of the cell which means that they have complicated moving parts so we often just need to hold them still while we image them and nanobodies were used as a tool in that. But we work with all kinds of scientists, we work with physicists and computer specialists to build detectors and build new microscopes, we work with people like clinicians to bring us new interesting research problems to apply to our microscopes and our technologies so it is a very interdisciplinary place to be. Yeah definitely and so let's hope not but maybe one day a similar type virus will come along that's different from covid and we will again science will have to come together and react to that very very quickly. Will your type of work be able to sort of learn from what you've done with this type of disease and in the future produce something maybe quite quickly to be able to tackle that? Yes so that's a really important next step for us so the covid work is incredibly important but it it makes far more sense to pursue that as a as a pipeline that we can apply to new emerging threats to or even to existing viruses because it's really important to know that there's there's hardly any therapies against viral disease so we can vaccinate and that's it we've seen the importance of vaccination as a tool but vaccination isn't for everyone there are there will always be some groups who can't be vaccinated for medical reasons or where vaccines are hard to deliver out into communities in low and middle income countries so having a therapy that works is really important so we're hoping that our nanobody tools will form part of a 100 day challenge so the G7 met after during the the covid pandemic and they set the challenge of okay for the next time this happens and it will happen again 100 days is the target you need to get therapies and vaccines out within the first 100 days to stop pandemic situations occurring and we think tools like this could be really important in that 100 day challenge. Super impressive and very exciting stuff Laura Holland from the Roslyn Frackin Institute, thank you so much for joining me.