Let's start this episode with some numbers. The average adult has around 30 trillion cells in their body. Each time a single cell divides, it accumulates around 10 mutations in its DNA. That's trillions of mutations in your body's genetic material every day. So how does our body stay the course amidst this constant genetic change? And more importantly, what's the connection between our genes and our well-being? In today's episode, we're speaking to a researcher who will help answer those questions and explain why genomics, maybe as much a part of your future GP visits as taking your blood pressure or checking your cholesterol. You're listening to Medical Minds, the podcast that takes you inside the labs at the Garvan Institute of Medical Research. I'm your host, Dr Viviane Richter. And with me here is Associate Professor Owen Sigs, head of the Genomic Medicine Lab at Garvan. Welcome, Owen.

Let's start this episode with some numbers. The average adult has around 30 trillion cells in their body. Each time a single cell divides, it accumulates around 10 mutations in its DNA. That's trillions of mutations in your body's genetic material every day. So how does our body stay the course amidst this constant genetic change? And more importantly, what's the connection between our genes and our well-being? In today's episode, we're speaking to a researcher who will help answer those questions and explain why genomics, maybe as much a part of your future GP visits as taking your blood pressure or checking your cholesterol. You're listening to Medical Minds, the podcast that takes you inside the labs at the Garvan Institute of Medical Research. I'm your host, Dr Viviane Richter. And with me here is Associate Professor Owen Sigs, head of the Genomic Medicine Lab at Garvan. Welcome, Owen.

Hi, Viv. Thanks for having me.

Hi, Viv. Thanks for having me.

Owen, we have a lot of researchers coming on the show who talk about how their family connections or their experience at school inspired them to do the work they do today. But you had quite a personal run in with genetic disease. Can you tell us about that?

Owen, we have a lot of researchers coming on the show who talk about how their family connections or their experience at school inspired them to do the work they do today. But you had quite a personal run in with genetic disease. Can you tell us about that?

Sure. I was about 10 years old at the time, playing basketball out in the schoolyard at recess time and got whacked on the back of the head with a basketball. And I reached back and felt the back of my head. And there was a big lump which turned out to be a tumour, which was growing into the bone and turned out it was, uh, a disease known as Langerhans cell histiocytosis, which is a bit of a mouthful. But it turned out that that was actually, we didn't know it at the time, but a genetic disease caused by a genetic mutation that was acquired during my lifetime sometime. And, yeah, a really rare disease, sort of one in a million kind of material.

Sure. I was about 10 years old at the time, playing basketball out in the schoolyard at recess time and got whacked on the back of the head with a basketball. And I reached back and felt the back of my head. And there was a big lump which turned out to be a tumour, which was growing into the bone and turned out it was, uh, a disease known as Langerhans cell histiocytosis, which is a bit of a mouthful. But it turned out that that was actually, we didn't know it at the time, but a genetic disease caused by a genetic mutation that was acquired during my lifetime sometime. And, yeah, a really rare disease, sort of one in a million kind of material.

Wow, that must have been a scary time for you and your family.

Wow, that must have been a scary time for you and your family.

It was, I think, especially for my family. But it was a disease that we could get a handle on pretty quickly. So, you know, an operation got rid of the lump and five years of scans after was given a a clear bill of health and and it hasn't come back since, and the other good thing about it in terms of, you know, genetic diseases is it's not something that I've passed on in my family to my little boy, so pretty happy about that.

It was, I think, especially for my family. But it was a disease that we could get a handle on pretty quickly. So, you know, an operation got rid of the lump and five years of scans after was given a a clear bill of health and and it hasn't come back since, and the other good thing about it in terms of, you know, genetic diseases is it's not something that I've passed on in my family to my little boy, so pretty happy about that.

So glad to hear that. But there are many genetic diseases that are quite rare and not as easily treatable. Can you tell us about some of those?

So glad to hear that. But there are many genetic diseases that are quite rare and not as easily treatable. Can you tell us about some of those?

Sure, yeah. When we typically think about genetic disease, we think about inherited genetic disease and in particular, these rare genetic diseases that are, they might individually be rare, but collectively there's about 7000 of them, so they're actually quite common and affect about 8% of the population. They can have a range of impacts. They can affect any organ in the body. They can have some really devastating impacts on patients. So that's one of the areas that our lab is interested in understanding. What are the genetic changes that cause those diseases and use that information to try and improve how those patients are cared for? So, for example, cystic fibrosis is one of the better known rare genetic diseases. You know, that's a disease that is reasonably well managed today. There are good targeted treatments now for cystic fibrosis based upon, you know, decades of research into the genetic cause of the disease and using that information to then design targeted treatments. Another example that's, you know, really devastating and affects more adults than children is is Huntington's disease. So that's a genetic disease that has onset later in life. So unlike cystic fibrosis, which you know people are born with and symptomatic from an early age, Huntington's is something that happens later in life. And there are more and more examples of these diseases that just turn up later in life.

Sure, yeah. When we typically think about genetic disease, we think about inherited genetic disease and in particular, these rare genetic diseases that are, they might individually be rare, but collectively there's about 7000 of them, so they're actually quite common and affect about 8% of the population. They can have a range of impacts. They can affect any organ in the body. They can have some really devastating impacts on patients. So that's one of the areas that our lab is interested in understanding. What are the genetic changes that cause those diseases and use that information to try and improve how those patients are cared for? So, for example, cystic fibrosis is one of the better known rare genetic diseases. You know, that's a disease that is reasonably well managed today. There are good targeted treatments now for cystic fibrosis based upon, you know, decades of research into the genetic cause of the disease and using that information to then design targeted treatments. Another example that's, you know, really devastating and affects more adults than children is is Huntington's disease. So that's a genetic disease that has onset later in life. So unlike cystic fibrosis, which you know people are born with and symptomatic from an early age, Huntington's is something that happens later in life. And there are more and more examples of these diseases that just turn up later in life.

Owen, I wanted to ask you about how you came to study genetic disease. When did you realise you wanted to be a researcher?

Owen, I wanted to ask you about how you came to study genetic disease. When did you realise you wanted to be a researcher?

The key moment, I think, was probably at university. So I grew up in a family of doctors and always had an interest in science and biology. But the real watershed moment, I think, was my very first lecture at university. Um, it was a couple of days after the first draft of the human genome was announced. Uh, so that was really like a it's like, you know, the the AI moment of 20 years ago. So that was really exciting time and having just been, you know, starting a science degree. I was really fired up about getting into that area and seeing where it was gonna take me. And and here I am.

The key moment, I think, was probably at university. So I grew up in a family of doctors and always had an interest in science and biology. But the real watershed moment, I think, was my very first lecture at university. Um, it was a couple of days after the first draft of the human genome was announced. Uh, so that was really like a it's like, you know, the the AI moment of 20 years ago. So that was really exciting time and having just been, you know, starting a science degree. I was really fired up about getting into that area and seeing where it was gonna take me. And and here I am.

And I heard that you worked with some research superstars quite early on in your career.

And I heard that you worked with some research superstars quite early on in your career.

I sure did. Yeah. Two in particular, One of whom was the a recent Executive Director of the Garvan Institute. Chris Goodnow. He sort of introduced me to research. My first genuine research experience was with Chris. And then he then introduced me to a fellow by the name of Bruce Beutler, who I did a PhD with in California. And he went on to win a Nobel Prize in 2011 while I was in his lab actually.

I sure did. Yeah. Two in particular, One of whom was the a recent Executive Director of the Garvan Institute. Chris Goodnow. He sort of introduced me to research. My first genuine research experience was with Chris. And then he then introduced me to a fellow by the name of Bruce Beutler, who I did a PhD with in California. And he went on to win a Nobel Prize in 2011 while I was in his lab actually.

That's incredible. What was that, like?

That's incredible. What was that, like?

Very exciting. Yeah. So Bruce was awarded a Nobel Prize in 2011 for discovering how our bodies sense infection, which until then was really a bit of a nebulous question. We sort of knew that we we got sick and we had an immune system to fight it off, but nobody really knew what what alerted our bodies to an infection. So he, using genomics, figured out what the key elements of that detection network were. And that's now become really important for the way we think about and design vaccines and other medications to treat infection and also even autoimmune disease.

Very exciting. Yeah. So Bruce was awarded a Nobel Prize in 2011 for discovering how our bodies sense infection, which until then was really a bit of a nebulous question. We sort of knew that we we got sick and we had an immune system to fight it off, but nobody really knew what what alerted our bodies to an infection. So he, using genomics, figured out what the key elements of that detection network were. And that's now become really important for the way we think about and design vaccines and other medications to treat infection and also even autoimmune disease.

So that's the work that you embarked on during your PhD.

So that's the work that you embarked on during your PhD.

That's right. So the same method that Bruce used to make his Nobel Prize winning discovery, we then applied to a range of other important questions like, how does our immune system develop, or how do we fight other types of infections? So it was a really it was using that same approach but applying it to different important questions.

That's right. So the same method that Bruce used to make his Nobel Prize winning discovery, we then applied to a range of other important questions like, how does our immune system develop, or how do we fight other types of infections? So it was a really it was using that same approach but applying it to different important questions.

And where did you go from there?

And where did you go from there?

From there, I moved to the UK. I went to Oxford and Cambridge and worked in some fantastic genetic research labs, in particular in in Cambridge, in the UK at the Sanger Institute, which was where a lot of the initial draft human genome sequence was was generated. So that was a really exciting time and and surrounded by a lot of great clinician scientists, so really good clinicians who saw patients but then also took samples from interesting patients and brought them into the lab, used these new genomic technologies that were just coming onto the scene to help understand the causes of their diseases.

From there, I moved to the UK. I went to Oxford and Cambridge and worked in some fantastic genetic research labs, in particular in in Cambridge, in the UK at the Sanger Institute, which was where a lot of the initial draft human genome sequence was was generated. So that was a really exciting time and and surrounded by a lot of great clinician scientists, so really good clinicians who saw patients but then also took samples from interesting patients and brought them into the lab, used these new genomic technologies that were just coming onto the scene to help understand the causes of their diseases.

And that's the path that you decided to embark on

And that's the path that you decided to embark on

Exactly. Yeah, I saw that and I said, I want to be like them. So then I went back, came back to Australia, and I did my clinical training in my medical degree. And since then I've really focused on being a clinician scientist. I'm particularly focused on diseases that affect the eyes and the immune system and that have a genetic explanation, understanding what the genetic causes of those diseases are.

Exactly. Yeah, I saw that and I said, I want to be like them. So then I went back, came back to Australia, and I did my clinical training in my medical degree. And since then I've really focused on being a clinician scientist. I'm particularly focused on diseases that affect the eyes and the immune system and that have a genetic explanation, understanding what the genetic causes of those diseases are.

Oh, and how do you now integrate your clinical work and your research? What does that look like?

Oh, and how do you now integrate your clinical work and your research? What does that look like?

So all the research I do now starts with patients so usually an interesting patient or group of patients where we're scratching our heads about something, we don't know what's what's going on or we're having trouble treating it just an unmet need, and typically what we do is we collect samples from those patients. It might be as simple as a blood sample or a saliva sample so we can sequence their genome and understand their genetic profile. Or we might collect a particular tissue sample from a particular part of the body that's especially affected. So a bit of eye tissue if they're having surgery or a bit of joint tissue if they've got arthritis. We generate a lot of genetic information from those samples, and that's that's a real big data challenge. We've got tonnes and tonnes of data from tonnes and tonnes of patients, so we spend a lot of time analysing genomic data from blood cells. But sometimes you know these tissue samples as well. They're really interesting. We don't get as many of them, but they can be really illuminating in terms of what's actually going on at ground zero. In terms of as the disease is progressing, you know, which cells are interacting with, which, who's causing all the damage and what's happening at a real cellular level rather than a genetic level.

So all the research I do now starts with patients so usually an interesting patient or group of patients where we're scratching our heads about something, we don't know what's what's going on or we're having trouble treating it just an unmet need, and typically what we do is we collect samples from those patients. It might be as simple as a blood sample or a saliva sample so we can sequence their genome and understand their genetic profile. Or we might collect a particular tissue sample from a particular part of the body that's especially affected. So a bit of eye tissue if they're having surgery or a bit of joint tissue if they've got arthritis. We generate a lot of genetic information from those samples, and that's that's a real big data challenge. We've got tonnes and tonnes of data from tonnes and tonnes of patients, so we spend a lot of time analysing genomic data from blood cells. But sometimes you know these tissue samples as well. They're really interesting. We don't get as many of them, but they can be really illuminating in terms of what's actually going on at ground zero. In terms of as the disease is progressing, you know, which cells are interacting with, which, who's causing all the damage and what's happening at a real cellular level rather than a genetic level.

And how does that work impact patients?

And how does that work impact patients?

Yeah, we can have really exciting immediate impacts, so the the genomic analyses are the ones I really get excited about, you know, finding a new genetic diagnosis for a patient. It can be really thrilling and and really transform their lives. So I'll give you a case study. So we had an example of a young girl. She was three years old at the time. She was referred to us from one of our genetic research studies. She had really bad arthritis. It was so bad that, you know, her doctors couldn't treat it, no matter what they tried. Nothing worked. She had such severe joint pain in her hands and her feet. Mostly it prevented her from, you know, doing things that a three year old would otherwise do. She couldn't bounce on a trampoline or ride a bike. Things like that. Spent a lot of time in hospital trying out different treatments. So she was referred to us as a real tough nut to crack. And so we sequenced her genome, and pretty quickly we found what we thought was a great explanation for her disease, and it was a single change in a single gene. But the most exciting part about it is that it pointed directly to a targeted treatment or a drug that we thought would be a perfect match for her because it replaced exactly the protein that her body couldn't make. So we managed, together with her rheumatologist, we managed to get approval for her to start that drug and within two months of starting the drug: complete remission. A real demonstration of what's possible with genomics in in medicine. It doesn't happen for every patient, but when it does happen, it can be really life-changing.

Yeah, we can have really exciting immediate impacts, so the the genomic analyses are the ones I really get excited about, you know, finding a new genetic diagnosis for a patient. It can be really thrilling and and really transform their lives. So I'll give you a case study. So we had an example of a young girl. She was three years old at the time. She was referred to us from one of our genetic research studies. She had really bad arthritis. It was so bad that, you know, her doctors couldn't treat it, no matter what they tried. Nothing worked. She had such severe joint pain in her hands and her feet. Mostly it prevented her from, you know, doing things that a three year old would otherwise do. She couldn't bounce on a trampoline or ride a bike. Things like that. Spent a lot of time in hospital trying out different treatments. So she was referred to us as a real tough nut to crack. And so we sequenced her genome, and pretty quickly we found what we thought was a great explanation for her disease, and it was a single change in a single gene. But the most exciting part about it is that it pointed directly to a targeted treatment or a drug that we thought would be a perfect match for her because it replaced exactly the protein that her body couldn't make. So we managed, together with her rheumatologist, we managed to get approval for her to start that drug and within two months of starting the drug: complete remission. A real demonstration of what's possible with genomics in in medicine. It doesn't happen for every patient, but when it does happen, it can be really life-changing.

These genetic changes that you're investigating. How do we get them in the first place?

These genetic changes that you're investigating. How do we get them in the first place?

So there's two main classes of genetic variation. There's there's ones which we inherit from our parents, and those are probably the types that most people are familiar with. So we get part of our DNA from Mum, part from Dad, and on average, we get about 2 million genetic changes from each parent. The other major class, which is the class of variation that I had when I was a little boy, are these acquired genetic variants. So these are ones that we're not born with, but we accumulate throughout our lifetimes, so we're quite interested in that group of genetic changes as well for example, as you alluded to in the introduction. You know, every time a cell divides, we get 10 extra genetic mutations, and over the course of a lifetime, our body undergoes 10 to the power of 16 cell divisions, which is hard to comprehend. But it's a lot of mutations. A great example of an acquired genetic disease is cancer. So it's not something that we're born with, but as we age as we accumulate these mutations over time, most of them do nothing. But occasionally you get a bad apple, and that causes a cell to grow a little bit more than its neighbours and more and more and more until it turns into a tumour. So that's really what kicks off cancer in the first place is these acquired genetic mutations, but it can also influence the risk of other diseases. So we're learning more and more about that every day.

So there's two main classes of genetic variation. There's there's ones which we inherit from our parents, and those are probably the types that most people are familiar with. So we get part of our DNA from Mum, part from Dad, and on average, we get about 2 million genetic changes from each parent. The other major class, which is the class of variation that I had when I was a little boy, are these acquired genetic variants. So these are ones that we're not born with, but we accumulate throughout our lifetimes, so we're quite interested in that group of genetic changes as well for example, as you alluded to in the introduction. You know, every time a cell divides, we get 10 extra genetic mutations, and over the course of a lifetime, our body undergoes 10 to the power of 16 cell divisions, which is hard to comprehend. But it's a lot of mutations. A great example of an acquired genetic disease is cancer. So it's not something that we're born with, but as we age as we accumulate these mutations over time, most of them do nothing. But occasionally you get a bad apple, and that causes a cell to grow a little bit more than its neighbours and more and more and more until it turns into a tumour. So that's really what kicks off cancer in the first place is these acquired genetic mutations, but it can also influence the risk of other diseases. So we're learning more and more about that every day.

Owen, you mentioned 10 to the power of 16. That's an almost inconceivable number. Now I've actually looked this up that is 10 quadrillion, and to give our audience a reference, the number of ants on our entire planet has been estimated at about 20 quadrillion. So that's half of the number of ants on our entire planet. That is a lot of mutations.

Owen, you mentioned 10 to the power of 16. That's an almost inconceivable number. Now I've actually looked this up that is 10 quadrillion, and to give our audience a reference, the number of ants on our entire planet has been estimated at about 20 quadrillion. So that's half of the number of ants on our entire planet. That is a lot of mutations.

And a lot of ants. And it's important to point out, though, but most of those changes are insignificant, so they don't have an impact on our on our health or our body, although some of them inevitably are. And you know they can cause diseases like cancer and diseases like it.

And a lot of ants. And it's important to point out, though, but most of those changes are insignificant, so they don't have an impact on our on our health or our body, although some of them inevitably are. And you know they can cause diseases like cancer and diseases like it.

It's crazy to think that in your body, in my body there are mutations basically happening all the time.

It's crazy to think that in your body, in my body there are mutations basically happening all the time.

Yeah, that's right. And yeah, I know firsthand what that can do. And we're seeing more and more examples of this in patients coming through now. So we're working on an interesting case at the moment. A young girl, she was diagnosed when she was five with inflammatory bowel disease and it's associated with a genetic change. But we were able to sort of go back in time with her. We went all the way back to her heel prick blood spot test, which every baby gets in Australia when they're born and and screened for a bunch of diseases. But that was still sitting in the cupboard for 16 years. We went back to the hospital, said, can we borrow that for a second? Got some DNA out of that, sequenced it and we found that the mutation wasn't there in her blood spot test. So it's something that she picked up between the age of zero and five and is now sort of wreaking havoc in her body and causing all sorts of inflammation. But it that discovery will be useful for her. It's already sort of changing how she's managed, uh, and treated in the clinic.

Yeah, that's right. And yeah, I know firsthand what that can do. And we're seeing more and more examples of this in patients coming through now. So we're working on an interesting case at the moment. A young girl, she was diagnosed when she was five with inflammatory bowel disease and it's associated with a genetic change. But we were able to sort of go back in time with her. We went all the way back to her heel prick blood spot test, which every baby gets in Australia when they're born and and screened for a bunch of diseases. But that was still sitting in the cupboard for 16 years. We went back to the hospital, said, can we borrow that for a second? Got some DNA out of that, sequenced it and we found that the mutation wasn't there in her blood spot test. So it's something that she picked up between the age of zero and five and is now sort of wreaking havoc in her body and causing all sorts of inflammation. But it that discovery will be useful for her. It's already sort of changing how she's managed, uh, and treated in the clinic.

Owen, you're the Co-Director of the Genomics and Inherited Disease Program at Garvan. Can you tell us what you're primarily trying to achieve?

Owen, you're the Co-Director of the Genomics and Inherited Disease Program at Garvan. Can you tell us what you're primarily trying to achieve?

Yeah, this is a really exciting new Garvan venture. It's a group of around half a dozen research teams similar to mine, who all have an interest in rare genetic disease. There's two things that we're focused on, so one of the big challenges in this area is genetic diagnosis. So about half of people with a rare genetic disease don't have a genetic diagnosis, and that's really important information for them. Our primary focus is to use the latest hardware and software and genomic tools to find a genetic diagnosis for those undiagnosed patients. The second major focus is then on making sure those patients can get good treatments. So at the moment, only about 5% of people, even when they're diagnosed, have access to a good targeted treatment. Like that example I used earlier the patient with arthritis. So that's a really urgent, unmet need. We've got all of these people. We know what the genetic mutation is that's causing their disease, but we don't have a targeted treatment. So those two challenges, improving diagnosis and improving treatment for rare diseases. We're applying that to a whole range of different disease areas, so we're good at eye disease and immune disease in my lab. Other labs that look at heart disease, kidney disease, brain disease, so a range of different diseases, and one of the key vehicles that we're we've created to help support our collective research is this rare disease registry. So it's a national registry Australia-wide that we've set up to bring in patients who have a rare genetic disease. Whether they have a diagnosis or not, we don't mind and the main aim of this registry is to find diagnoses for those who don't already have them, and for the ones who do, get them in touch with the right researchers. The right pharmaceutical companies to get either develop new treatments or test new treatments. Get them connected to one another to you know, support networks get them connected to the very best clinicians in the country to look after them. So we're really excited that that's just been approved very recently. So we're open for business.

Yeah, this is a really exciting new Garvan venture. It's a group of around half a dozen research teams similar to mine, who all have an interest in rare genetic disease. There's two things that we're focused on, so one of the big challenges in this area is genetic diagnosis. So about half of people with a rare genetic disease don't have a genetic diagnosis, and that's really important information for them. Our primary focus is to use the latest hardware and software and genomic tools to find a genetic diagnosis for those undiagnosed patients. The second major focus is then on making sure those patients can get good treatments. So at the moment, only about 5% of people, even when they're diagnosed, have access to a good targeted treatment. Like that example I used earlier the patient with arthritis. So that's a really urgent, unmet need. We've got all of these people. We know what the genetic mutation is that's causing their disease, but we don't have a targeted treatment. So those two challenges, improving diagnosis and improving treatment for rare diseases. We're applying that to a whole range of different disease areas, so we're good at eye disease and immune disease in my lab. Other labs that look at heart disease, kidney disease, brain disease, so a range of different diseases, and one of the key vehicles that we're we've created to help support our collective research is this rare disease registry. So it's a national registry Australia-wide that we've set up to bring in patients who have a rare genetic disease. Whether they have a diagnosis or not, we don't mind and the main aim of this registry is to find diagnoses for those who don't already have them, and for the ones who do, get them in touch with the right researchers. The right pharmaceutical companies to get either develop new treatments or test new treatments. Get them connected to one another to you know, support networks get them connected to the very best clinicians in the country to look after them. So we're really excited that that's just been approved very recently. So we're open for business.

But you're not just looking at rare disease. You're looking at how genomics contributes to more common conditions as well, right?

But you're not just looking at rare disease. You're looking at how genomics contributes to more common conditions as well, right?

Exactly. So pretty much any disease has a genetic contribution, so sometimes that might be in the case of rare genetic diseases, it might just be as simple as one genetic change, causing a really bad disease. But some of the more common diseases think about, you know, heart disease, diabetes, glaucoma, macular degeneration. Those are more common diseases that are the genetic contribution there is more hundreds or thousands of quite subtle genetic changes. They're all working together to increase risk of disease. So we study both ends of that spectrum, and our lab in particular, has an interest in blinding eye diseases. So glaucoma is a disease that we study a lot, which is very genetic. It has a big genetic contribution, but the genetic contribution is lots and lots of little subtle changes. So we're spending quite a lot of time understanding what those changes are and how they work together to increase risk of disease. And we're working on developing tests, which can, you know, they're not diagnostic tests, but they're more sort of predictive tests so they can look at a group of people in the population and say, you're at really high risk of getting this disease. You should think about getting screened sooner or starting treatment sooner.

Exactly. So pretty much any disease has a genetic contribution, so sometimes that might be in the case of rare genetic diseases, it might just be as simple as one genetic change, causing a really bad disease. But some of the more common diseases think about, you know, heart disease, diabetes, glaucoma, macular degeneration. Those are more common diseases that are the genetic contribution there is more hundreds or thousands of quite subtle genetic changes. They're all working together to increase risk of disease. So we study both ends of that spectrum, and our lab in particular, has an interest in blinding eye diseases. So glaucoma is a disease that we study a lot, which is very genetic. It has a big genetic contribution, but the genetic contribution is lots and lots of little subtle changes. So we're spending quite a lot of time understanding what those changes are and how they work together to increase risk of disease. And we're working on developing tests, which can, you know, they're not diagnostic tests, but they're more sort of predictive tests so they can look at a group of people in the population and say, you're at really high risk of getting this disease. You should think about getting screened sooner or starting treatment sooner.

So paint us a picture. What will the future of healthcare look like with genomics integrated as a key diagnostic tool?

So paint us a picture. What will the future of healthcare look like with genomics integrated as a key diagnostic tool?

So we're only gonna see it more and more. It's already part of health care at the moment, particularly in diagnosing rare genetic diseases, in cancer. We're seeing it more and more, but I think one of the key driving factors for the integration of genomics into healthcare has been the price. So when I got into this field about 20 years ago, it cost $100 million to sequence a human genome. Today, it costs less than $1000. And it's gonna keep coming down and down and down. So that has really transformed how we use genomics. So if we carry that projection forward, you know, in the next decade, it's gonna be even cheaper. We're gonna have even more research showing how useful this information is, and it's gonna be just everywhere I think. It's gonna be something that's as routine to order as a blood test or a cholesterol test. Potentially even gonna be part of our medical record. And you just keep all that information on file. When someone has an interesting question or is about to make a decision about treatment or diagnosis or risk prediction, they can just dip into your genetic information and and the answer will be there.

So we're only gonna see it more and more. It's already part of health care at the moment, particularly in diagnosing rare genetic diseases, in cancer. We're seeing it more and more, but I think one of the key driving factors for the integration of genomics into healthcare has been the price. So when I got into this field about 20 years ago, it cost $100 million to sequence a human genome. Today, it costs less than $1000. And it's gonna keep coming down and down and down. So that has really transformed how we use genomics. So if we carry that projection forward, you know, in the next decade, it's gonna be even cheaper. We're gonna have even more research showing how useful this information is, and it's gonna be just everywhere I think. It's gonna be something that's as routine to order as a blood test or a cholesterol test. Potentially even gonna be part of our medical record. And you just keep all that information on file. When someone has an interesting question or is about to make a decision about treatment or diagnosis or risk prediction, they can just dip into your genetic information and and the answer will be there.

Owen, do we know what a healthy genome looks like?

Owen, do we know what a healthy genome looks like?

So we do have a reasonably good sense of what a healthy genome looks like. And the way we've got that sense is by sequencing hundreds of thousands of people without disease, and that gives us a good reference data set to compare sick people to and and their genetic information. The problem, though, with these data sets at the moment, is that they're overwhelmingly from people of European ancestry. So that gives us a bit of a skewed picture when it comes to interpreting this genetic information. And it makes it much, much, much harder for somebody who comes into the clinic who's of African ancestry or Middle Eastern ancestry to get a genetic diagnosis. So we need to do much better at generating more diversity in those those reference databases and one of the big key initiatives that Garvan is leading in collaboration with the MCRI in Melbourne and led by Daniel MacArthur actually, who you've had previously on the podcast, is to create a much more diverse and representative reference database. So going out around Australia, finding communities culturally and linguistically diverse communities who are really underrepresented in these reference databases and getting samples from them, consenting them appropriately and improving the value of these reference databases for all Australians.

So we do have a reasonably good sense of what a healthy genome looks like. And the way we've got that sense is by sequencing hundreds of thousands of people without disease, and that gives us a good reference data set to compare sick people to and and their genetic information. The problem, though, with these data sets at the moment, is that they're overwhelmingly from people of European ancestry. So that gives us a bit of a skewed picture when it comes to interpreting this genetic information. And it makes it much, much, much harder for somebody who comes into the clinic who's of African ancestry or Middle Eastern ancestry to get a genetic diagnosis. So we need to do much better at generating more diversity in those those reference databases and one of the big key initiatives that Garvan is leading in collaboration with the MCRI in Melbourne and led by Daniel MacArthur actually, who you've had previously on the podcast, is to create a much more diverse and representative reference database. So going out around Australia, finding communities culturally and linguistically diverse communities who are really underrepresented in these reference databases and getting samples from them, consenting them appropriately and improving the value of these reference databases for all Australians.

So what's your next big thing, Owen?

So what's your next big thing, Owen?

One of the things I'm really excited about at the moment is translating this research into the clinic. So we've got all this amazing research. We know what genetic changes cause disease, what collections of subtle changes we can use to predict risk into the future. And one of the big challenges and most exciting challenges, actually is bringing that information into clinical practice so I can use it for my patients. We can get real tangible benefits to patients in the community. So a few years ago, a group of us started a company. We set it up to develop a genetic risk prediction test initially for for glaucoma, which is a disease that can turn up later in life, affects, you know, about 3% of people over the age of 50. That's been a really exciting ride. So we've, as of, you know, a few months ago we've now got full clinical accreditation. So we've gone through all of the rigorous checks and balances to make sure that it's a safe and effective test. Patients are using it in the clinic already, so that's gonna be a really exciting time to see over the next 5, 10 years how tests like that are used in clinical practice and how they can change patient outcomes. So yeah, so not just doing the research, but making sure that it it gets to the people who need it most.

One of the things I'm really excited about at the moment is translating this research into the clinic. So we've got all this amazing research. We know what genetic changes cause disease, what collections of subtle changes we can use to predict risk into the future. And one of the big challenges and most exciting challenges, actually is bringing that information into clinical practice so I can use it for my patients. We can get real tangible benefits to patients in the community. So a few years ago, a group of us started a company. We set it up to develop a genetic risk prediction test initially for for glaucoma, which is a disease that can turn up later in life, affects, you know, about 3% of people over the age of 50. That's been a really exciting ride. So we've, as of, you know, a few months ago we've now got full clinical accreditation. So we've gone through all of the rigorous checks and balances to make sure that it's a safe and effective test. Patients are using it in the clinic already, so that's gonna be a really exciting time to see over the next 5, 10 years how tests like that are used in clinical practice and how they can change patient outcomes. So yeah, so not just doing the research, but making sure that it it gets to the people who need it most.

How have people traditionally been tested for glaucoma? And how does your test work?

How have people traditionally been tested for glaucoma? And how does your test work?

So, yeah, it's an it's an interesting disease in in that it's asymptomatic in the early stages, so people don't even know that they have it. And actually, half of people with the disease don't know they have it. So we need much better tools to pick this up earlier before people lose vision and it's once you lose it, it's gone. It's irreversible. So that was one of the driving forces for developing better tools to diagnose this disease earlier. And the great thing about this test is that you can do it at any time of your life. I've done it, and actually I'm in the, you know, the highest risk category, which was a bit of a surprise, and my my grandmother had it, so it was a bit of it in the family, but so I'm very high risk. So in someone like me, the recommendation would be. Go to your optometrist earlier. Get a checkup. You're at high risk of getting this disease. Get it checked out and pick it up as soon as possible and start to treat it sooner. So the general use of the test it's kind of like a cholesterol test, right? So it doesn't guarantee that you'll get a disease. And it's more about, you know, changing the conversation from diagnosing disease after it happens to predicting it and preventing it before it happens.

So, yeah, it's an it's an interesting disease in in that it's asymptomatic in the early stages, so people don't even know that they have it. And actually, half of people with the disease don't know they have it. So we need much better tools to pick this up earlier before people lose vision and it's once you lose it, it's gone. It's irreversible. So that was one of the driving forces for developing better tools to diagnose this disease earlier. And the great thing about this test is that you can do it at any time of your life. I've done it, and actually I'm in the, you know, the highest risk category, which was a bit of a surprise, and my my grandmother had it, so it was a bit of it in the family, but so I'm very high risk. So in someone like me, the recommendation would be. Go to your optometrist earlier. Get a checkup. You're at high risk of getting this disease. Get it checked out and pick it up as soon as possible and start to treat it sooner. So the general use of the test it's kind of like a cholesterol test, right? So it doesn't guarantee that you'll get a disease. And it's more about, you know, changing the conversation from diagnosing disease after it happens to predicting it and preventing it before it happens.

Sounds like an incredible time to be in genomics.

Sounds like an incredible time to be in genomics.

Absolutely. Yeah, it's taken a long time to get there from, you know, 20 years ago when, you know, in the lecture theatre we were thinking this was gonna happen in a in a matter of, you know, months or years, it's taken a bit longer, but the rubber really is hitting the road now.

Absolutely. Yeah, it's taken a long time to get there from, you know, 20 years ago when, you know, in the lecture theatre we were thinking this was gonna happen in a in a matter of, you know, months or years, it's taken a bit longer, but the rubber really is hitting the road now.

Now, before we let you get back to the world of genomics, Owen, it's time for the fast five. What do you do in your downtime?

Now, before we let you get back to the world of genomics, Owen, it's time for the fast five. What do you do in your downtime?

I like to swim, so yeah. Swimming pools, open water. Yeah. There's nothing better than you know. At the end of a hard day of research to just decompress and meditative swim. Few laps. Love it.

I like to swim, so yeah. Swimming pools, open water. Yeah. There's nothing better than you know. At the end of a hard day of research to just decompress and meditative swim. Few laps. Love it.

Favourite movie?

Favourite movie?

Would be The Big Lebowski. Coen brothers movie from From the nineties set in Southern California. In fact, I first saw it when I was living in Southern California.

Would be The Big Lebowski. Coen brothers movie from From the nineties set in Southern California. In fact, I first saw it when I was living in Southern California.

What's the most challenging thing you've ever had to do?

What's the most challenging thing you've ever had to do?

I think physically it was probably doing the Rottnest Island Swim a few years ago. So swimming from Fremantle to Rottnest Island with a bunch of friends, it was a 20 kilometre open water swim. A lot of preparation, a lot of training, but it was great fun.

I think physically it was probably doing the Rottnest Island Swim a few years ago. So swimming from Fremantle to Rottnest Island with a bunch of friends, it was a 20 kilometre open water swim. A lot of preparation, a lot of training, but it was great fun.

What's been your best holiday?

What's been your best holiday?

Tanna Island in Vanuatu, which is famous for an active volcano. So we spent a few nights there, you know, living with a local family at the base of a volcano, hiking up. Yeah, it was really, really spectacular.

Tanna Island in Vanuatu, which is famous for an active volcano. So we spent a few nights there, you know, living with a local family at the base of a volcano, hiking up. Yeah, it was really, really spectacular.

Current book you're reading?

Current book you're reading?

A great nonfiction piece. That's actually my student's thesis, So yeah, not something you'd find on most coffee tables, but I still love doing it.

A great nonfiction piece. That's actually my student's thesis, So yeah, not something you'd find on most coffee tables, but I still love doing it.

Associate Professor Owen Siggs. Thank you so much for joining us on Medical Minds.

Associate Professor Owen Siggs. Thank you so much for joining us on Medical Minds.

It's been an absolute pleasure. Thanks, Viv.

It's been an absolute pleasure. Thanks, Viv.

If you'd like to know more about Owen's research or donate to the work we do at Garvan, head to garvan.org.au. And if you've enjoyed this podcast, please leave a review and share with other podcast lovers. I'm Dr Viviane Richter. Thanks for listening.

If you'd like to know more about Owen's research or donate to the work we do at Garvan, head to garvan.org.au. And if you've enjoyed this podcast, please leave a review and share with other podcast lovers. I'm Dr Viviane Richter. Thanks for listening.

This podcast was recorded on the traditional country of the Gadigal people of the Eora Nation. We recognise their continuing connection to land, waters and community. We pay our respects to Aboriginal and Torres Strait Islander cultures and Elders past, present and emerging.

This podcast was recorded on the traditional country of the Gadigal people of the Eora Nation. We recognise their continuing connection to land, waters and community. We pay our respects to Aboriginal and Torres Strait Islander cultures and Elders past, present and emerging.