Retinas reveal future health, and the first cells on Earth
PodcastsThe Naked ScientistsRetinas reveal future health, and the first cells on EarthPlus, how do pond skaters avoid raindrops?26 January 2024In this episode of The Naked Scientists: what the structure of. . .
PodcastsThe Naked ScientistsRetinas reveal future health, and the first cells on EarthPlus, how do pond skaters avoid raindrops?26 January 2024In this episode of The Naked Scientists: what the structure of your retina reveals about your risk of developing a range of diseases; have we finally cracked how the first biological cells appeared 4 billion years ago; and how pond skater insects survive potentially lethal run-ins with large raindrops. Retina scans reveal your future healthMaryam Zekavat and Nazlee Zebardast, Mass Eye and EarA new study has found that the structure of the retina in the back of the eye can reveal a host of diseases that a person is at risk from developing. By using machine learning to marry up changes seen in retinal images with health and genetic data from tens of thousands of people who participated in the UK’s Biobank study, Mass Eye and Ear hospital ophthalmologists Maryam Zekavat and Nazlee Zebardast think they have a way of using the retina to see what a person’s future health looks like…Nazlee - In recent years, we have come to realise that we can find out a lot more information from images of the eye than we ever thought was possible. And it's opened up this really exciting area of research. And we were fortunate enough to have access to an incredible resource, specifically a large, large study of about half a million people from the UK called the UK Biobank. And we had images of people's eyes and we were wondering, is there a link between images of the eyes? And Maryam will talk a little bit more about how those were obtained and ocular and systemic disease. Chris - Maryam, what are these pictures you've got of people's eyes? Are you looking at the outside or are you talking about what's going on inside the eye?Maryam - It's inside the eyes. The human retina is a multi-layered tissue, which offers a really unique window into systemic health. So here we're looking specifically at that retina, which is composed of nine different layers using OCT imaging, optical coherence tomography imaging, and that's a non-invasive imaging that uses light waves to take a cross-section picture of your retina. And so we had this OCT imaging available across 50,000 individuals in this biobankChris - And Nazlee, why should looking at the different layers of the retina give us an insight into a person's overall health or disease risk?Nazlee - Some of it is actually really surprising. So for example, we didn't know before the machine learning models came out that we could tell someone's age just by looking inside their eyes, or their sex even. But the retina is a very intricate tissue. It's an extension of your brain essentially. And so it's constructed of all these different cell layers that are connected to our brain and our systemic health, or essentially your overall health. So you can look at people's eyes and when they say the eye is a window into your soul, they're not really kidding because you're seeing what is going on with someone's heart, someone's blood pressure, potentially even how they're breathing or their risk of having certain neurologic problems. Chris - And Maryam, when you did this study, what did you actually measure and what did you marry up with what?Maryam - So what we measured was the thickness of each of these nine layers of the retina. And we used this measurement to then look at connections to systemic health to disease and also to genetics. Chris - Nazlee, one of the key things about any kind of disease, we always say prevention is better than cure. So the critical question I can ask you is if you do this, does it give you a window into the early stages of a disease at a time when you might be able to intervene meaningfully in a person before they actually get sick from something?Nazlee - It's interesting that you ask that. One of the key pieces of analysis that we did in this manuscript was looking at future risk of disease. So looking at someone's retinal thickness and determining if that was linked to future disease diagnosis. And in fact, the layer thicknesses of the retina are predictive of future diseases of the heart, of the brain, of the kidneys, of the lungs, including eye diseases as well. So even though this needs to be confirmed, our study does point to the fact that we can use retinal thicknesses or retinal phenotypes to be able to predict disease before it happens and intervene. Chris - So would the approach be then that rather than subjecting a person to a whole raft of different tests and blood samples and genetic analyses, you could plunk them down in front of you, use this technique to look at their retinal structure and then based on what you've learned about the associations between the different shapes and structures of the retina and different disease outcomes, you could make predictions about what a person might be about to develop or indeed is developing right now and then you can make obviously interventions as necessary. Nazlee - Precisely. I think that is exactly how we envision results like this being used. As Maryam previously mentioned. Also, the OCT or these light pictures of the eye are routinely used in clinical practice in ophthalmology. And so you can imagine if someone comes in for their eye exam, then you can use this information to tell them you seem to have a high risk of MS or you have a high risk of high blood pressure, or you might have a high risk of developing diabetes, so you should go see your primary care doctor. The other way you can think about this is exactly as you said is what if we just had this as a screening tool where people would come in, get images of their retina noninvasively without having to do all these extra tests and they could know that they have risk for certain diseases that they need to get checked for or even treated for potentially. Hydrothermal vents source of first cell membrane materialJon Telling, Newcastle UniversityThe origin of life on Earth - and beyond - is a mystery, and, arguably, one of the most important questions to answer. We know that life started simply, probably with self-replicating chemical reactions most likely based around something similar to the DNA molecules we rely on to carry our genetic code today. But, pretty quickly, those reactions found a way to wrap themselves up inside oily membranes that could protect them from the surroundings and make the process more reliable and efficient. Hey presto, the cell was born. But where did those membranes, made of fatty acids, come from in the first place? That question has bothered biologists for decades. Now, though, researchers at Newcastle University have recreated in the lab the conditions around hydrothermal vents, also known as underwater black smokers. These conditions, Jon Telling has found, can spontaneously generate the very molecules that scientists have been searching for…Jon - There's a few lines of evidence that point towards these hydrothermal vents, these hot springs, as a likely place for where life originated. People have tried to find out what the earliest cell that everything originates from was like, and what they've deduced from looking at the genes is that the first cell - known as the 'last universal common ancestor' - liked it hot, it probably lived off hydrogen gas, and it would've used carbon dioxide as well to build itself. So those lines of evidence all point towards these hot springs as a possible place for the origin of life. Chris - It sounds like we actually know quite a bit in terms of what we expect that ancestor to have been like. But what was the outstanding question you were trying to crack with relation to it, then?Jon - Previous people have tried running different experiments to try and mimic some of the conditions that these hydrothermal vents would've had. People had either tried to recreate, say, the high temperatures or the high pressure, or the kind of continuous flow where you're mixing seawater with this hotter fluid, but nobody had really gone on trying to combine all of those at once. That's what we wanted to do. We built some new apparatus in our lab to try and get that; the high pressure, get the high temperature, and get the continuous flow all in one experiment and try and react this hydrogen gas and this carbon dioxide over these metals to see if we could generate organic molecules. Chris - What source of molecules were you looking for?Jon - Ones we were particularly interested in were these molecules known as fatty acids. They have a fatty end and a water loving end. The interesting thing about them is, if you get enough of them in that water, then they can form what are known as these membrane structures, vesicles or liposome sometimes they're known as, but they basically form these little round balls surrounded by a membrane which separates what's in them from what's outside. So it is acting in a way as a sort of first cell membrane, potentially, which could separate the external environment from the internal and let different chemistry happen. Chris - I understand where you're going with that because obviously that was the big question, wasn't it? If life gets started as a series of chemical reactions, where did cells come from? So if you've got a reaction that can produce the oily bags that surround all our cells, that is 90% of the equation. Jon - Well, it's certainly a good step forward. It's the first step to creating a self, something different from what's outside. The ability to do that and then concentrate chemicals differently to outside, generate different reactions, would've been I think an essential step for how life started. Chris - What are the raw materials that you are feeding into your pretend hydrothermal vent and what chemicals did you see coming out at the end in these conditions that lead you to think that is possibly how some primitive cell like structures could have formed?Jon - What we fed in, the basis of it was hydrogen gas which we added under pressure. Then, we combined that with dissolved carbon dioxide. We're reacting them over a mineral, in this case an iron rich mineral known as magnetite, to form hydrocarbons: organic molecules. In particular we were looking for these fatty acid molecules, which are a type of hydrocarbon. Chris - And do you get many and how quickly?Jon - The experiments we've run so far, we only ran for 16 hours and in that time, yeah, we generated enough to find them. If we run it for longer, we might find that we generate even more of them, but there are certainly enough of these organic molecules for us to analyse. Chris - Do they start to self assemble? Because the point you're making is that the fatty bits love other fatty bits, so they tend to get together. So do you start to see that happening?Jon - As yet, no, because when they form they actually form on the mineral surface. The next stage of experiments that we want to do is to try and do this: to actually change the chemical conditions. We think there may be, if we make the environment more alkaline, we can get some of these molecules, particularly these fatty acids, to lift off and hopefully we could then see them self-assemble. Chris - If we bring what you found to the party that already people had envisaged as to how life could have got started, how do you bring and unite your discovery of how these fatty acids begin to form with what people thought might also be going on around the same time, about 4 billion years ago, that was the start of life?Jon - People have found these reactions going on at higher temperatures, for example, before. What we've done is do these experiments under more realistic conditions as to what the conditions may have been like on the early Earth. And it just gives that greater likelihood, I think, that these really important organic molecules may well have been formed within these sub ocean hydrothermal vents. And it might also increase our understanding as well, I think, about how life may have originated in other places in our solar system, or whether a similar chemistry might be going on. Chris - I was going to ask you about that because of course we've got missions that are going to be looking at Europa, which is one of Jupiter's moons. People have also considered Enceladus, one of Saturn's moons, which appear to have warm liquid oceans beneath the surface of ice. So it's possible the conditions there might be similar to the conditions you are mimicking in your laboratory?Jon - Exactly. I think the best characterised ocean so far is actually Saturn's moon Enceladus. There's actually a spacecraft which has travelled around, known as Cassini, and it's actually sampled these plumes which people think are emanating from beneath the icy layer of Enceladus into this ocean. So you've got part of this ocean actually being blasted out into space and been analysed, and when they've analysed the vapours and particles that are in this plume, they found hydrogen gas, they found carbonates - so signs that carbon dioxide there as well. And they've also analysed different organic molecules. It seems that all the ingredients, potentially, for an origin of life might be there, but it's going to take a fair few more experiments to try and narrow that down further.