Instant Genius - Why the liver is the body’s most misunderstood organ

Episode Date: July 5, 2026

Most of us think about the liver as simply being the body’s filtration system that acts as a sponge that removes toxins from our bloodstreams. But the truth is it performs many more functions that are vital for our health such as acting as the primary organ in regulating our metabolisms, storing essential nutrients our bodies can draw from in times of need, and even producing proteins that help our blood to clot when we’re injured. However, changes in our lifestyles over the past several decades are leading to an alarming rise in the prevalence of damage and disease to this essential organ. In this episode, we’re joined by Dr Quin Wills, a researcher and CEO of the biotech company Ochre Bio, who specialises in developing innovative new treatments to combat liver disease. He talks us through the many functions the liver performs in our bodies, explains some of the most common causes of the rise in chronic liver disease and looks forward to the future to detail some of the cutting-edge treatments that may be on the horizon to combat this growing issue. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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Every Monday and Friday, you'll hear world-leading scientists and experts talking about the most fascinating ideas in science and technology today. I'm Jason Goodyear, commissioning editor at BBC Science Focus. Most of us think about the liver as simply being the body's filtration system that acts as a sponge that removes toxins from our bloodstreams. But the truth is, it performs many more functions. that are vital for our health, such as acting as the primary organ in regulating our metabolisms, storing essential nutrients our bodies can draw from in times of need,

and even producing proteins that help our blood to clot when we're injured. However, changes in our lifestyles over the past several decades are leading to an alarming rise in the prevalence of damage and disease to this essential organ. In this episode, we're joined by Dr Quinn Wiltz, a researcher and CEO of the biotech company OkraBio who specialises in developing innovative new treatments to combat liver disease. He talks us through the many functions the liver performs in our bodies, explains some of the most common causes of the rise in chronic liver disease

and looks forward to the future to detail some of the cutting-edge treatments that may be on the horizon to combat this growing issue. So welcome to the podcast. Thanks so much for joining us. Oh, thank you. It's an absolute pleasure. So today we're talking about liver disease. So I think the best place to start here then is let's talk about the liver. Let's get this out of the way.

What exactly is the liver and what functions does it perform? You know, many functions, does it perform in our bodies? Well, I think it's fair to say that most of us think of the liver as this giant filter. That's, I think, what a lot of us have been taught at school and how we think about it. And I think it does it a bit of a disservice because really they're, There are over 500 known functions that the liver now does. No, there is no organ that comes close, right? You think about other organs, the heart, the heart's a part.

Yeah, great to the heart, but the liver has to do so much more. I've often, I've seen analogies to the liver being like a supercomputer. I just think of it as a multitasking feature. It's absolutely fantastic at what it does. Of course, filtering is a very big part of its core function, but another very big part is it's the central brain of your metabolism. I've often said you have two types of brains, the brain that everyone knows of,

and the other big brain in your body, which governs so much from how your muscles build to how you metabolize. And maybe one easy way just to connect those dots for folks is when you think of capitalism medicine, so you want to lower your blood cholesterol, that's a liver drug. That tells the liver, the pump up to glycone,

less strong in simplistic terms of course. If you want to take a tablet to lower your blood glucose, so you're diabetic, that's a liver drug. So the liver is the big regulator of that. I think the amazing, the absolutely amazing thing for me is how much people, how much we still don't know about liver. It's the only organ in the body that fully regenerates. It's absolutely incredible.

And it does this without any stem cells. It breaks all the rules of all we think we know about how regenerates. works. And I don't know if you spotted this, but just recently, I think we figured out that the liver might be your internal GPS. There was that incredible study that came out recently about homing pigeons, and we finally figured out that it's the mewing cells in the liver with these super paramagnetic beads, communicating binders back to the brain acting as a GPS. Now, of course, we don't know how much of that translates over to other species than ourselves, but it's just incredible. We have so much to learn about the liver. Yeah, so having established that then,

we're talking largely about liver disease today. So this also is really complicated, and there are many different kinds. So could you give us a sort of overview of what can happen when something wrong happens to our livers? If somebody says they have liver disease, when we're talking about liver disease, now if it's not something acute happening to your liver, and if it's not genetic, which is rare but happen. We are inevitably talking about what we call chronic liver disease, and that's just an umbrella term

for many things, but three things really, really dominate what is chronic liver disease. And they are viral diseases, so you're thinking of hepatitis, viral hepatitis A, B, C, and what I'd like to

stress is, I know a lot of people think it's a solved problem, it isn't. There still is no cure for hepatitis, B. And a lot of Asia, a lot of Africa, so a lot of the global population really still live with the ramifications of viral hepatitis. So it's still a big issue. Then, of course, there's alcohol use. And of course, many of us are aware of that. And the ramifications are the third big one that is driving a lot of the rise in liver disease that people may not be aware of it is obesity. And in effect, what happens is, as you build up weight, you build up fat,

you're also building up fat inside your liver. You're basically turning your liver to foie gras. That over the long term is quite damaging. But it actually doesn't matter whether it doesn't matter what the initial insult is, whether it's viral, alcohol or fat. The basic process here that's playing out is you are creating a lot of liver stress, which is causing cells to die inside your liver. And those dying cells are triggering long term.

term chronic inflammation, and that inflammation leads to scarring, and that is that scarring that we ultimately think of as cirrhosis. So these chronic diseases that end up as cirrhosis are what we think about as chronic liver disease. Yeah, so as you mentioned earlier there, though often liver disease is only spotted its late chronic stage, but it actually occurs in several different stages. So first off, what are they? And, you know, what can we do to catch it earlier? Liver disease is a multi-decade process that takes up in your body. It's very silent for the first year, many decades, sometimes, and then only towards the end where you realize you have it. And I think the way to think about this is think about yourself a decade ago, two decades ago.

You weren't the same person as you are now. So the key thing to appreciate is, even though we think of it as this linear trajectory of a disease, in many ways it's different diseases, and it's different diseases, different phases, or different stages of the disease that will require different therapies. In many ways, it's a precision medicine question, it's a personalized medicine question. Many of us all now, where it's of this concept of we're all so different, it's not about one drug for everybody, it's about the right drug, it's for the right patient, or I would say the right combination of drugs for the right patient. What we're finding with chronic diseases, like chronic liver disease,

is it's really about the right combination in the right patient at the right stage of disease. And that's why we say there's still so much work to do. The current excitement around these new therapies, they're really, really good at these early stages, reducing the initial insult, reducing fat, reducing early inflammation. But we need therapies now to think about the later stages. when that fibrosis starts kicking in, when it's scarring kicks in, when you get cirrhosis, when the liver starts failing. So you've mentioned fibrosis. So what exactly is that and how does it occur within the liver? So it doesn't matter, except for all chronic liver diseases, it doesn't matter whether it's viral, alcohol, obesity.

The fundamental stress here is triggering cell death. And when cells die, there are actually many ways for cells to do. die and we can get to this in a little bit about when we get to therapies and new therapies coming out. But fundamentally, when cells die, they trigger inflammation. And that's fine. For the most part, the body can respond well to inflammation. But when that is happening chronically over many, many years, decades, in fact, that chronic information will eventually trigger fibrosis or scarring.

And you would know that from, if you had a long-term saw on your arm, and you would, that you kept scratching, for example, over time that would form a nasty scar. We always told as kids, if we're careful of there, the pimples on your face, don't squeeze them too hard, it will lead to scarring.

That's the thing. You have this chronic inflammation, you mess with it, you keep it inflamed, then it eventually scars. The same thing happens in your liver. And then that scarring builds up over time.

The liver can take a lot, but it will also build up the scarring. And that scarring is fibrosis. It is collagen being deposited in the liver. by certain cells. That fibrosis and that scarring is ultimately what we call cirrhosis. So let's, before we go on to sort of some finer details of what we've just talked about,

what are some of the effects that, you say, like fibrosis or liver damage. What happens to the rest of our bodies when we're suffering from that? So here's the terrifying thing about the symptoms or the effects of chronic liver disease is that once you have the symptoms, it's almost too late. The liver is just this incredible mortar. It can handle so much. We just quickly touched on the fact that it can regenerate. So that gives you some sense for how much of a punch it can take.

And so by the time, you are aware, things start presenting. Like jaunders, we're all aware of jaundice as a symptom of liver failure of liver disease. That is already a very bad sign that things are going on. So liver disease, I think the main thing I'd like folks to sort of understand who want to educate themselves on what is happening at the moment in their bodies is that it's very silent and it can catch a lot of people unaware. So we need to be proactive. I'll give you one example. It actually caught me of God. After all these years of educating folks and putting out the bits on what we need to think about with liver disease, I a couple years ago went to have my gallbladder reams.

I've had cold blood problems for a long time. And these days, yeah, it's just so easy. It's a little snip in your belly button. I stick a scope in there, put a bag around it. I said to the surgeon, I said, you know, I mean, I laugh now, but I said to the surgeon, I'm kind of a liver guy. Even then, would you mind taking a few photos thinking I'm going to get these incredible photos of a liver, you know, and I can use this in presentations.

And what I got back was these horrifying images of me with a very full. fatty liver. I was one of the one in three, one in four people with fatty liver and unaware. So it really can catch anyone. Yeah, so let's have a look at that then, because that's something that more and more people are talking about now is fatty livers. So what are some of the things that can cause that? You mentioned people who are overweight or obese. So we're talking about the factors that affect liver health, so whether it's obesity or otherwise. I think that maybe, before we get into what I would like people to understand,

let me tell you another slightly amusing story. I was asked the same question about liver health a couple months ago by certain UK newspaper. And of course, we know that UK, for those who know you knew UK newspapers, we know they like their headlines. And so I was very careful. The journalist was trying to do the kind of questions I was being asked, it's like, what can I do to reduce the age in my liver by two years? Which, of course, is a very difficult thing to answer,

especially when we know so good about liver. But I thought, you know what? I'll give this journal something, and I said, well, did you know, as much as we can tell, coffee is actually really good for your liver. So there's a lot of new now that I don't have bad coffee is for you. And, of course, it's all observational studies, so we need to be careful.

There does seem to be the evidence that, in terms of chronic inflammation your liver, coffee is generally a good thing. One to two cups a day. Solid. And of course, that's the thing the gym that's hooked on to

and that took over the piece dominated narrative of it. I went to a dinner party that weekend, sat next to somebody and immediately the person began educating me on this piece

that they just read about coffee and how good it is. So I think the reason why I tell you that story is I just think there's a lot out there, but really, at the invalvator, I think there are two key messages I'd love to get across to

if they're just about liver and the health. One is we need to get over this public attitude of liver disease is a disease of personal resolve. It's people who are lazy, it's people who can't control their drinking. It's just simply not true. You know, particularly with, and I'll focus on the obesity thing because that's a big driver of what's going on. For example, the weight loss jabs.

get into that a little bit, is they really have taken this sting of obesity. No longer is it this thing of you just need to stop it lazy and you need to move more and eat less and at a person resolve. We can now effectively treat obesity. We all have very different metabolic baselines. We all reactive. And you now is really look after our liver health controlling weight first and forth. And that's a big thing. The other thing I think I'd like to, It's laugh for people to understand liver disease. And this is true. Any chronic disease, but of course, liver disease

we see the same pattern playing out. It's that all chronic disease is, when you think about factors, it's always biopsychosocial. Of course, a lot of today's discussions about the biology of liver disease. But as a clinician, I always think of those three things. And when we look at this liver disease,

it really disproportionately affects minorities, disproportionately fixed impoverished communities. I began thinking about living disease studying alcoholism and impoverished communities here in South Africa. So when we think about those factors and we can talk about the therapies and all the exciting technologies coming out, we really shouldn't forget about the psychosocial elements of this.

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A lot of people, if they've been unfortunate, to have a family member or something that has had this sort of chronic issue, their only option has been a liver transplant, you know, which can be effective, but it obviously doesn't work long term. So what are some of the new ideas? Let's look at some of the exciting stuff. What's happening now? Well, let's touch on the therapies, and let's touch on, I think, a few key numbers.

You know, because, again, I think it's really important to understand the big challenge ahead of us. In the numbers I like to throw out, you touched on transplant. Here are two very big numbers. I think they make the case for why we need so much more research and new therapies of the space. There are one and a half million liver deaths globally every year. For those patients, really the only effective treatment we've had to date is a liver transplant. A very effective approach. Here's the however.

However, there are only about 40,000 liver transplants done globally every year. 40,000. It's not even healthcare. It's a health lottery at best. And we all know with health lotteries, again, it's going to disproportionately affect minorities and poverty communities, etc. That's the real challenge. So we have had really, in the last two years, particularly for metabolic liver disease, the fatty liver disease that are many of us that are talking. about. We have had a lot of exciting advances. The jabs have definitely helped by controlling weight,

and we've had one, a single therapy in our room called Rasmetorum, which is a direct acting therapy, directly helps burn some of the fat or pulaeus adacts directly in your liver and reduces fat inside your liver. But, bad, bad, bad, these therapies, this is Rizmetam are only good at treating the early stages of the disease. We still don't really see a big impact on the later stage when the scarring really starts kicking it. And we still don't even know how much this will really impact long-term patient outcome. You know, a good analogy here is the cancer space.

So 30 years ago, cancer biology was all about reducing tumor burden. That was the goal. Focus on reducing the size of the tumor and the tumor burden. that's kind of the stage we're at now. Everything for us is about reducing fibrosis. That's all we're measuring. That is the, and there's a good reason for it, because there is a correlation.

But the correlation is not perfect with long-term patient outcome. Just as reducing tumor burden is a very imperfect correlation with patient there's a lot more to it. And that's why these current therapies like Resmetterol only have accelerated a pupil. We still have a 10-year,

journey, possibly even longer to fully appreciate all these therapies or whatever. So, you know, we have a health lottery. We have the beginnings of a great story of new therapies. There's a lot more to come. And in terms of new innovations that you talk about, I think, you know, ask 100 researchers in our space and you'll get 100, 100 billions on what excites them. And I think if I had to point to two things, it's about how are we going to be treating of the disease, the near to medium future,

and how are we going to be studying it to understand how to develop therapies in terms of innovations. And the first is RNA therapies. It's something I'm very passionate about. My team and all the therapies were developing RNA therapies. And it's something we've all come familiar with, thanks to the COVID vaccines. If you're familiar with RNA, it's a messenger in between DNA and proteins. And there's a lot you can do with RNA therapies,

very, very simply, but we still them work by dialing up or dialing down. It's like a rear state. So you can increase a level of a protein or decrease a level of a protein using an RNA therapy. We, for the most part, as a team, we focus on decreasing it.

So I'm very excited and what makes me super excited about this is these RNA therapies are really sophisticated now. They're very long action. With a single dose, a single shot, you can achieve an effect for up to a year. now with these therapies. So it's kind of like getting a vaccine, which is very different from

taking a tablet where you need to be taking a tablet every day, right? So that I think is really exciting. The other thing that I think is super exciting about these RNA therapies is we can make them very liver-specific. If you take a tablet, it goes to every cell in your book. And that's one of the reasons why it's so difficult to control toxicities with therapies and why we need to study so carefully. With these therapies, we add a little ligand on the end, a little messenger that tells it to go straight to the hepatocytes, these are the main cells in your liver, and to go straight into those cells, to go almost nowhere else. So we can create these very precision therapies that go straight to the liver. The other thing, in terms of technologies or innovations to study

disease that are very excited about, is the models we're developing. So one of the big bottlenecks in our space at the moment is animal models are very, very poorly predictive of human liver disease. And without talking for hours and hours on this, a simple explanation is liver disease is a multi-decade disease that plays out of your body. Might live for two years. It's very difficult to recapitulate this. In fact, I'd love to point out to people that the gold standard mouse model that many of us use actually predicts increased fibrosis.

with the current antifibrotic therapies that will be improved. So it's we really get stuck there. And so what's researchers like my team and what we've done is actually figure out how to use human-based technologies. So we have this lab in

Taiwan where we've set up this network in disease liver tissue and each biopsy gets turned into about a 150 little waferthin slices that we can culture like a little mini liver. Then we could study that. has a liver in the lab. And we set out this lab in New York, in the US,

where we take donor livers, a whole human livers that weren't transplanted, didn't make it through to transplant. And we keep them alive on machines for many days at a time. There we were actually able to study how the livers, not only respond to our therapies, but how they behave, sort of directly in a human system. And it's incredible.

In combining these sort of human, tissue technologies with AI. We use a lot of courses. It's very vogue right now, but it's very important. It really helps speed up and make predictions. We use a lot of that trained on this kind of data to make predictions of what our therapies could do. And it's the intersection of this sort of big computation, big data, and human-based models.

I think that it's going to be transformed for where this space goes. Having said that, how about things like lab-grown organs? like you're saying the liver's unique in the sense that it regenerates. So you would think that that would be one of the sort of primary targets for making a lab-grown organ. Yeah. Well, I would challenge you to think one step further. How about getting your own liver to start regenerating again in your own body? That's actually one of the big, and it's a bold question, but it is a question that we are researching together with one of the big pharma companies.

And I'll tell you what the origin of this question is. I mentioned it a few minutes earlier. Many of us are concerned, even though we're very excited about treating scarring, so antiphobiotics. We believe that particularly people with late-stage disease, so serotic, we believe that just reducing the scarring is not going to be enough. And so we're thinking about regenerative therapies, which is a very complex question. and it's very, again, difficult to study in animal models, for example. So we teamed up with one of the big pharma companies to find new targets in the liver

that can safely get cells to start dividing again without triggering cancer. And in fact, we're actually studying this on these human livers on machines. So we're learning how to regenerate human livers on machines so that we can learn how to make these therapies that gets your liver to start regenerating again. So looking forward then, What sort of therapies can we expect to be seeing in the next, say, five, ten years?

We've discussed a lot about the metabolic therapies. As we've discussed, the metabolic therapies are exacting, but they really are only treating the initial insult. And they really are only treating a version of chronic disease, the obesity version. What really excites me, I think, is this push towards antifibrotics that are not metabolic therapies like the weight. lost jabs or the rest metteroms in the world. And we've, as a team, have been putting a lot of research into this.

We've been doing, we've been focusing on two elements of this. We've been looking at how to reduce cell death. Now, if you remember, we said, cell death is fundamentally what triggers the information. And this has been a very difficult one to study because others have tried and failed, even got to clinical trial and failed. And we've realized that the liver, liver cells don't die in the same way that other cells in the body die in the same way that regenerate in the same way using stem cells. And so just, for example, reducing apoptosis for those who are aware of these concepts

of program cell death and the different ways cells can die or not die. And those mechanisms, those canonical, those traditional textbook taught mechanisms, don't really play out. There's a lot more. And so the team and I have put a lot of work to building huge data sets around the globe and building computational models to understand these alternative mechanisms of cell death. And I've been developing therapies to reduce that, and we're going up with these therapies. The other arm is, I think, a regeneration.

How can we move just beyond fibrosis to restoring normal liver function? And for me, for our partners, it's really about thinking about regeneration. And we've just talked a little bit about these therapies that we're thinking about, studying on machines that ultimately one day we can get the liver that's erotic to start restoring its normal regenerative capacity. That's what really excites me about where this could be going. Thank you for listening to Instant Genius brought you from the team behind BBC Science Focus. That was Dr Quinn Wills. If you liked what you just heard then please do consider subscribing to Instant Genius on your preferred podcast platform. If you'd like to see our guests and hosts in person,

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