Maggie: [00:00:07] Welcome to the Hearts and Minds podcast. I'm Maggie O'Neill, head of Marketing and Operations. Thank you for joining us today on the Hearts and Minds podcast. We have a series of interesting and curious conversations with the brilliant minds that are part of hearts and minds. We are lucky enough to work with extraordinary individuals and we want to invite you to join these conversations on impact and investing. Today, I'm joined by Hearts and Minds Chief Executive Officer Paul Rayson for a chat with one of our phenomenal scientists, Professor Sally Dunwoodie, out of the Victor Chang Cardiac Research Institute. Hi, Paul.

Paul: [00:00:38] Hi, Maggie. 

Maggie: [00:00:39] How are you today? 

Paul: [00:00:39] I'm very well and excited to share this episode with Sally. 

Maggie: [00:00:44] Yes, tremendous conversation. And it was a really wonderful opportunity to sort of hear her journey for research. I don't think people quite realise how long it takes to reach discovery and breakthrough.

Paul: [00:00:53] Yeah. Now this is a major breakthrough for Sally in achieving a major breakthrough for science in Australia. You know, Sally's team over a number of years have, you know, achieved a breakthrough and identified a deficiency during the pregnancy and birth process that can lead to birth defects. And at the same time they've discovered the potential solution. So this is a major discovery that will reduce the occurrence of birth defects and lead to better lives for literally thousands.

Maggie: [00:01:20] Not even birth defects, but recurrent miscarriages, too, is what they call a double breakthrough, which is even more outstanding. And it was a great opportunity, I suppose, as well. For me in particular, having known Sally since 2016 when we first started Hearts and Minds. You know, she got up on stage in 2017 to reveal her double breakthrough. And we heard in the conversation that, you know, seven years later, they're still in clinical trials to sort of inform those guidelines and work out what that normal vitamin range should be so that they can then screen for it. It's remarkable the tenacity and grit that it takes to be a researcher and how long it can take for an idea to come to reality. 

Paul: [00:01:55] Sure, it is great resilience, determination over a number of years. But it's bearing fruit now and very close to implementing this breakthrough into clinical guidelines. 

Maggie: [00:02:05] Yeah, very exciting to hear the progress. Alrighty, let's jump into it. Here's Sally Dunwoodie. 

Paul: [00:02:14] Today, I'm joined by Professor Sally Dunwoodie. Sally is an internationally renowned biomedical researcher at the Victor Chang Cardiac Research Institute. Now, it's a little known fact that up to 6% of babies are born with serious birth defects. And Sally has dedicated her life's work to understanding why. In 2017, Professor Dunwoodie's team made a major scientific discovery. A double breakthrough that has the potential to prevent multiple types of birth defects, in some cases of miscarriage. Sally and her team discovered that a deficiency in a certain molecule can prevent a baby from developing correctly in the womb. She also discovered that a common dietary supplement can potentially prevent or treat the deficiency. And after 12 years of research into the area, these discoveries have the potential to greatly reduce the occurrence of birth defects. Professor Dunwoodie's discoveries have changed clinical practices and have led to genetic diagnostic tests being available worldwide. Sally is a professor in the Faculty of Medicine at the University of New South Wales. She received her Bachelor of Science with honours from the University of Sydney before completing her Ph.D. on the genetic control of muscle development at the Children's Medical Research Institute and the University of Sydney. She further trained the National Institute for Medical Research in London before returning home to Australia to become a faculty member at the Victor Chang Cardiac Research Institute. Sally, it's wonderful to have you as a guest of Hearts and Minds. Your achievements are truly significant and will likely lead to the prevention of tens of thousands, if not millions of miscarriages and birth defects globally. So, Sally, welcome. 

Sally: [00:04:00] Thank you. It's lovely. Lovely to be here. 

Paul: [00:04:02] I thought we'd start the conversation with your motivations to become a scientist. Was it something you always wanted to do from childhood? Was there a moment or was it just curiosity over a period of time that led you to science? 

Sally: [00:04:18] I think it was just a general curiosity. But you're right, early high school, I decided I was going to be a research scientist without actually knowing what they did, what career path looked like. But science was the subject that fascinated me most, and pretty much the whole time through high school, it was just going to be science. Except later in high school, I had purchased some shares and for a little while I thought, maybe I'll be a stockbroker. One wonders what would have happened if I'd pursued that.

Paul: [00:04:52] But science is a broad area. So what led you to genetics or, you know, cardiac research specifically? 

Sally: [00:05:00] It is very broad. And biology, which is the area I work in, is just one part of it. Obviously, it's physics and chemistry. So the area of biology is very broad. I think I was most fascinated during my undergraduate degree by genes and molecules. So the things that actually in my mind sort of did the work, the mechanisms that were behind whatever the biological question you were looking at. And so then after getting my science degree, I was looking to do a Ph.D. and I figured that medical research and genetics were probably areas that were going to expand. And so that I should be looking in areas around that. And then during my PhD, the topic wasn't that thrilling, but during that time I was exposed to mouse embryology. Now that might sound a little strange to people who don't think about those things, but the scientists use models to understand what they can about human disease and normal human physiology and function. And so the mouse embryo was beginning to be studied with the addition of genetics and molecules being so technology had advanced enough that you could look at mouse embryos, but with these new technologies. And so I managed to get a spot in one of the best mouse Embryology Labs in the world, and that was in London. And so I was there for seven years studying, identifying genes in the mouse embryo that were required to basically build it from a single fertilised egg into an embryo and then something after birth that has all the things in the right positions all perfectly aligned with each other and functional. 

Paul: [00:06:59] So it's really the study of how life develops from the tiny egg and sperm, I suppose, developing into an embryo and life in its full form. 

Sally: [00:07:09] Absolutely. And it's phenomenal that we actually get here. The number of, you know, chemical reactions and cellular movements that have to all come together at the right time in the right place to produce an embryo that functions is phenomenal. So then I was fortunate enough to I wanted to start my own group in London. I was what's called a postdoc, someone who has a Ph.D. and they're doing post-doctoral study. And so I took up a position at the Victor Chang Cardiac Research Institute, but when I was in London, I had to sort of choose which part of the embryo I thought would be most fascinating to me. And I chose two regions, one with these structures called somites, which are precursors for your vertebral column. Just because it was fascinating how they form. They don't exist in us now, but they turn into your vertebral column and the other was the heart. And so no one was really working on heart development. And I'd had a bit of a focus on on heart in my life. And so I thought, I'm going to work on heart development in the mouse embryo and then move back to Sydney and then looked for a more medical slant on it. So that led me to birth defects. [00:08:33][83.3]

Paul: [00:08:33] Right. So that I suppose the study of life then led you to understand when it doesn't work, which is really birth defects and when doing some research, the statistics were birth defects are quite surprising. So can you give us some general overview of the sets of birth defects here?

Sally: [00:08:51] Yes. Yes. So birth defects are more common than I think many of us imagine. Severe birth defects occur in some 3 to 6% of life born babies. That percentage is greater in embryos that don't make it through to birth. And if you think about that issue globally, that's somewhere between 4 and 8 million babies born. With a severe birth defect globally. So those numbers are huge. 

Paul: [00:09:22] So it's a big problem space. It really goes to the, you know, quality of life around the world is the proportion of successful births and the contrary birth defects. 

Sally: [00:09:32] It does. And I was just just since we were focusing well, since I also focus on the heart and we were focusing on it, heart defects, the most common type of birth defect representing a third of the total.

Paul: [00:09:44] Yeah. So I mentioned there's a range of different types of birth defects from heart and spinal and so on. And the stats, you know, up to 6%, quite surprising. So depending on severity, it must be very devastating for families. The child, of course. What's the typical impact, what sort of hurdles that a family face when a baby is born?

Sally: [00:10:04] As a parent, I can only imagine the stress of having to go through this. I guess there are many levels when you think about the impact. Is the impact on the child and then the impact on the parents and the impact on the broader family. Look, some birth defects are relatively simple and might only require one intervention to rectify them fully. Others, for example, the worst type of heart defect requires three open heart surgeries before that child reaches kindergarten. But it's not all over with some corrective surgery, some children have more than just a heart defect. They have vertebral and kidney as well, cleft palate. So there's a broad spectrum. So for the families, it's not just one operation or intervention, but it is a consistent array of appointments, visits to hospital. And that would be tricky enough if you live near a nice big teaching hospital that does this surgery. But for those who might live in regional remote areas, that adds an extra level of complexity for them.

Paul: [00:11:15] Yeah, so it's a serious impact on families lives. And the interesting thing, which is really the area of your study, is that we know the causes of, you know, about 20% of birth defects, but, but 80% are unknown, which is where you've been dedicating a lot of your work. But before we get to the great unknown of the 80%, what are the sorts of things that lead to or cause, you know, the 20% of birth defects that we do know about. 

Sally: [00:11:42] So. Like all diseases, they are caused by genetics, environmental factors and then what we call gene environment interactions, so a mix of those two. So the 20% that we do know in terms of birth defects, about 5% are understood to be due to or less than 5% due to environmental factors, there'd be less than 5%. An environmental factor can be actually the diabetes. If the mother has diabetes, for example, that is a risk factor for having a child with a birth defect. Then we also know that embryos can have chromosomal abnormalities like trisomy. So for example, Down's syndrome, Trisomy 21. There is also a cause of birth defects. And then in terms of genetics, there are a number of genes that have identified a mutation in one gene that can actually cause that birth defect. But the 20% of resolved cases, this sort of almost there selected group, because you only get put forth for clinical testing if you have birth defects running in your family. Or you have more than one type of defect. So heart plus others. Generally, if you just have an isolated heart defect or a cleft palate or a small or absent kidney, you're not offered any testing. And that only occurs in the research setting. So the numbers are a little rubbery, but let's just say it's 80% easily that are uninvestigated and or unresolved. 

Paul: [00:13:22] So you need to study in mouse models and embryology at that level. But still searching for the 80% of unknown causes is a vast undiscovered space. Where did you start? Where did you begin? 

Sally: [00:13:36] So thinking about genetic environment or genes and environment, the easiest one to tackle is genetic. And so you start by recruiting families who've had a child with a birth defect, and they are always very willing to be involved in research because they just want to know why did it happen, and will it happen again, and did I do something wrong? We recruit patients and their parents and isolate DNA from their blood and then start looking for the mutations. So when I first started this back in about. 2002. I guess, which is when I returned and started at the Victor Chang Cardiac Research Institute, we had to use sort of approximate approaches and what we would call candidate gene sequencing. We'd have to think, hmm, I think I know ten genes that might have caused this birth defect. I'll sequence them and see. And more often than not, you came up with nothing. But then the human genome was sequenced round about 2000, 2001, and that information was slowly being released to researchers. Now, the first human genome took 13 years and I think $8 billion. And now I can sequence the genome for $2,000 and have it back within a couple of weeks. So basically, we had a cohort of patients who had unresolved birth defects from a genetic point of view, and then we started sequencing their entire genome and that's tricky, but it has a much better success rate than just randomly picking ten genes out of a list of 20,000 to see if there's a mutation in them. 

Paul: [00:15:25] Yeah. So the advances in genetic sequence have obviously made it easier to sequence individuals genes, but there's still thousands of genes. How do you possibly narrow down to the likely causes of these defects?

Sally: [00:15:38] Well, it truly is the needle in the haystack. So there are 20,000 genes. There are 6 billion pieces of genetic code. And it's not just that you can find the one mutation that's caused the disease because we all carry about 2 million mutations or variations in our DNA. So I had to find computational biologists, we call them biome for mutations to help us with this problem. They take all this genetic material and start sifting through it, and we apply filters such that we end up with sort of a short list of perhaps ten genes that have what looked like the most damaging mutations in them, and that they're very rare in the general population. And that's our short list to then start finding extra evidence. Finding the evidence to decide which of those actually was the mutation that caused the defect in the baby. 

Paul: [00:16:34] So how many, this is over a number of years, but how many false starts and successful fines or failures did it take to get to really narrow it down to this set of genes most likely to cause?

Sally: [00:16:48] Yeah, well, for the NAD story, we had a list of about ten genes, none of which made sense to us. So up until this point, Mouse embryology the knowledge about how a mouse embryo is put together and it didn't exist for the human, really was that these genes that encoded transcription factors, for example, were all important in embryogenesis, but at least had genes in there that didn't fit that mould and had things in it like enzymes and things that we'd never, not just we but others don't considered to be that important. Probably just because we don't know about them, really. And so what was interesting in the NAD stories, we found mutations in genes that actually did encode some enzymes, so they weren't in the list that everyone looks at. And we had to start finding the evidence to convince ourselves and then others that those genes were necessary. But you do have generally a lot of false starts. I've got a lab full of false starts or or partially done projects where we are trying to work out which of the ten on that priority list we're going to put our time and our funds and our effort into. And that's quite a difficult decision. And you push too many things along and you don't get very far. So you have to make a call and go for things. And we've failed a couple of times. We put a lot of resources into some projects and we haven't haven't got a result. 

Paul: [00:18:28] So let's back up and talk about NAD. NAD is critical to cell development generally, but let's describe what NAD is.

Sally: [00:18:37] So NAD stands for Nicotinamide adenine dinucleotide.

Paul: [00:18:40] I'm glad you said that. 

Sally: [00:18:42] I'm good at saying it now. It didn't roll off the tongue quite as nicely as that some years back. So NAD is vital molecule, it is required in every single cell in our bodies, not just during embryogenesis but in all our, you know, in both our bodies as we sit here today to keep us upright and talking. And it has thousands of roles within ourselves. It's an energy producer, but it also does some other things. So that's NAD and so it's sort of interesting. We identified these mutations in babies that had heart vertebral and kidney defects and cleft palate, and they had mutations that prevented NAD from being generated or very much reduced levels. 

Paul: [00:19:32] So that was the at the end of all this research that then became a likely common factor that these babies that had defects, you found that they had a deficiency in NAD. 

Sally: [00:19:43] Correct. And then we had to do much more work on that because when you find what is considered a new gene that is causing new in the sense that genes always been there, but it's new in the sense of being known to cause birth defects, you have to build the evidence. So there was evidence in the babies that they had NAD levels, but that didn't say that those mutations in low NAD levels had actually disrupted their heart and vertebra and kidney during development. So income models. So what we do in my lab is use mouse as a model for human embryonic development. And you might be surprised they have the same 20,000 genes that genes do as far as we know to date, the same jobs in mice as they do in humans. In fact, it's stunning that in another model, the fly, which is used often, it's called Drosophila melanogaster, the fly, and it is more evolutionarily distant from humans than mice. The genes that dictate the back of your hand versus the front of your hand, and the same genes that dictate the back of a fly wing versus the front of a fly wing. So there's enormous conservation in evolutionary genetics. So anyway, getting back to the mouse, it's a wonderful model for understanding human embryogenesis. So what we did is we took the mutations that we identified in these families that had low NAD levels in the children, and we made those mutations in mice. And we asked the question, are the mouse embryos normal or did they develop the same types of defects in the humans and they developed the same defects as the human. So therefore, that's about as good a proof as you can get to say, yes, the mutations in humans caused NAD deficiency and that combination has caused and those mutations have also caused the same defects in the mice. We then went through and continued with the mice and showed they too were NAD deficient. 

Paul: [00:21:49] Which mutations led you to the discovery of NAD deficiency causing these defects? 

Sally: [00:21:54] The NAD story came about because we identified mutations in two genes, how kind of they encode enzymes in a metabolic pathway that are responsible for generating NAD from tryptophan. Tryptophan is an amino acid that we must eat in our diet. And these mutations blocked that pathway. And so that's why there was not enough NAD present when those embryos were developing both in the humans and in mice. We were led there simply by the fact that these families had these mutations. And we have lots of other stories where we're being led down, other pathways investigating other genes through our sequencing. So essentially it's the mutations we identify in the patients that lead us off into a whole lot of different new areas of discovery and research. 

Paul: [00:22:51] But still an extraordinary discovery to find that this deficiency caused these defects, given the potential number of possibilities. But what has made it even more amazing is that the same time as finding the cause, it led you to then potentially find the solution to the cause. Talk to us about that. 

Sally: [00:23:10] Yes, well, that was pretty amazing. I mean, really, we're very happy if we can just find the cause. The cause as in the genes that were mutated. The next step is to understand the mechanisms. So what those genes do in embryogenesis. And then the next step would be to do something about it. And we managed to do all three steps in that one publication that we had in 2017. And we were able to do it because we had the mouse model. So we had these mice that are modelling the human situation. We know the mice were NAD deficient because that's a block and you can't make NAD from tryptophan. So what I was trying to do was think, well, is there a way this is a metabolic pathway? Is there a way around this block? So if you think you're driving somewhere, you're taking the normal route, but there's a roadblock and you can't get through. What do you do? You sit there and do nothing and get angry or you think, well, perhaps there's another way around this. And that's sort of what we did. We found another way of boosting NAD levels by adding vitamin B3. It was already known in the literature that you could make NAD from tryptophan or vitamin B3. We had to sort of rediscover that in the literature ourselves because it wasn't this wasn't an area that we worked in, and then we realised that maybe in these mice we could make more NAD by providing it with its precursor vitamin B3. So we did exactly that. We took the mice that would normally had the mutations of the humans that would normally have embryos with birth defects or miscarriages. We haven't mentioned miscarriages so much and we gave the mother mouse vitamin B3 in her drinking water while she was pregnant and that allowed her to make enough and the embryo to make enough NAD or allowed there to be enough in ad during embryogenesis such that all these mouse embryos that carried these detrimental mutations were all alive and all completely normal. So that was that was the kicker. And that proved also that it was the NAD deficiency, because when you took away thatNAD deficiency through another means by finding a way around that traffic roadblock, that it was NAD deficiency that was a problem. And so then obviously the next thought is, well, could this work in humans? Could we apply this in humans? 

Paul: [00:25:41] Let's pretty remarkable discovery. So when you got that amazing moment to one confirm that a deficiency in had caused the birth defects but then supplementing that pathway with vitamin B3 on ice. And I think to call could generate enough NAD to prevent the defects. That's pretty much. How did the team I don't know they happened at one moment or how did the team feel over that period of time? 

Sally: [00:26:07] Yeah, it was stunning. I mean, this project took about 12 years and there were some wonderful moments along the way. So one of the first ones was finding mutations in two genes that actually worked in the same pathway. So we knew we thought we're on to something here. Then making the mouse that had the same defects. We've definitely onto something here and then rescuing with the vitamin B3. So that's the project does take a long time, but you get some good successes along the way too, to keep you going. Yes, it was very, very exciting. 

Paul: [00:26:45] I hope the team celebrated those moments of breakthrough and brilliance. So we sort of know the cause and the solution. Now, what are the next steps to make this, you know, available was as common advice to expectant mothers and families. 

Sally: [00:27:03] So if you think about it, all we'd really shown was that rare genetic mutations and therefore they don't occur very often have caused some birth defects and miscarriages in at the time for families. We've now published more papers with the Global Referral Centre for what I term Congenital NAD Deficiency Disorder. So now we've assessed 43 patients. We found extra gene mutations in that pathway and people email all the time asking about supplementation for those families. But still, it's reasonably rare. What I figured was it probably doesn't matter how you get to any deficiency, but that you do. And so if I could show you that NAD deficiency caused by another means might cause the same defects, then that lays the groundwork for thinking on a population wide level rather than just rare genetic mutations. So to do that, we went back to the mouse model, but this time we just took mice that had no mutations and we just threw diet, lowered their NAD levels and they had the same heart vertebral kidney defects. And then when we popped vitamin B3 in the drinking water, all that went away. So able to just manipulate the levels of NAD with diet alone. And so for me, that was strong encouragement to then think about could any deficiency on a normal population level be a cause of miscarriages and birth defects. So what do we know about NAD that pathway and NAD deficiency in pregnancy? Very little. No one has ever measured NAD levels or vitamin B3 levels or other what are called metabolites in that pathway in women and pregnant women. And also what we do know about that pathway in the literature is that some things can impact on NAD levels, such as having diabetes, having a high BMI, not being able to absorb your foods and nutrients properly due to irritable bowel syndrome or other inflammatory bowel diseases. So it seem that there are a number of things that could just, you know, start lowering your level. And what we've also shown in mice was that just being pregnant dropped NAD levels. And that's not so surprising because you are servicing, you are providing nutrients and energy for another individual in your own body. So you've got to find those nutrients and energy for them. So what next? We had to go out and basically set the standards. So I mentioned we don't know what the normal level of NADs in women or pregnant women or those are the metabolites and vitamin B3 in that pathway. So we started a study at the Royal Women's Hospital at Randwick. And we are recruiting non-pregnant women, pregnant women with a normal pregnancy, and also women who are having recurrent miscarriage. Women with diabetes and women who are carrying a child with foetal anomaly. So the first two groups, the non-pregnant and the healthy pregnant are our control groups and they're allowing us to just set the level of what's the median level of NAD in these women and what's the range. And so we're doing that at the moment. We're also recruiting, as I mentioned, the other women who are in sort of adverse pregnancy outcomes group. And so this is the first study of its kind, and we've actually funded it entirely from philanthropic funds, because to get government funding for research, you have to have done a lot of the work already to make sure it's very, very feasible that there will be a result. I don't know what the results going to be. That's that's the point of research here. And so it's exciting because we're going to produce completely new information for the world, but it will also provide us, hopefully with information that will allow us to do the next stage and to increase the numbers and then have bigger impact with our results. 

Paul: [00:31:47] So these clinical studies are to work out what is the normal or desired level of NAD during pregnancy. And therefore, if there's a deficiency that, you know, supplementation is required during that period for, for normal development of NAD. These clinical studies will hopefully lead to understanding the right level of supplementation of B3 to prevent these birth defects. I suppose the analogy is folic acid and spinal bifida a number of decades ago. Is that a sensible analogy?

Sally: [00:32:23] Yes, it is an excellent analogy. Folic acid is a B, vitamin, vitamin B9. So wonderful studies were done study in the UK in the 1980s that showed that the incidence of neural tube defects, spinal bifida were highest in areas where benign ingestion intake levels were lowest, and that clinical trials were done to show that the neural tube defects were reduced with high doses of vitamin B9. So I guess we're using that as our model. We don't suggest that vitamin B3 will be quite of that order just because of some nuances in the studies. But nevertheless, it's important for us to understand when women should perhaps be taking higher levels of vitamin B3 than is in a pregnancy multivitamin, which is actually actually has very low levels. And so that's the point of the study as well for us is to identify what's a low level and then in women work out how much they can take to get the NAD levels back up to what would be the normal, normal range. So there are a number of steps in the study. Some might say it's not necessary to do all these steps and not do all this research and take this time because b-vitamins are water soluble. So that means you actually excrete excess unlike other vitamins that are fat soluble and you might accumulate them. You will not accumulate B vitamins if you take higher levels of those. And therefore, what is the problem with taking high levels of B3? And it's sort of hard to argue against that, although we don't know exactly if a very high amount of B3 might be detrimental during pregnancy. So those sorts of experiments can be done in mice and we've started doing those in mice. But I guess it's to change clinical practice or change advice to the population about anything. You have to have good solid evidence that it is not going to cause harm. 

Paul: [00:34:34] So it's important to do the studies to fine tune it to get the right level of supplementation. But we're well down the pathway. And largely due to your remarkable work in this area, which has led to the discovery and the potential solution. So and you've won numerous awards for this discovery and this work. I'll ask you again your how do you feel about you? You're very understated. How do you feel about achievement? It has the potential to, you know, prevent millions of birth defects around the world once it's rolled out. 

Sally: [00:35:06] It does. I mean, it's fantastic. I'm delighted that we had the opportunity. Probably anyone could have if they'd stumbled on it the same way or had enough money. I don't know. But we did it. Yes. And it was a special set of circumstances that allowed us to get there. I think what I like most about it was that no one's really going to come up with a drug that's going to prevent birth defects. Pharmaceutical companies are not going to invest in it. Women are not going to go in double blind controlled trials when they're pregnant to take a drug that may help. It's just not an area that you, anyone will work in. So the beauty of this is that we're talking about a cheap, simple water soluble vitamin that could prevent cases of miscarriage, birth defects around the world. And if you think of developing countries, they also don't have advanced necessarily ready access to high technology pregnancy care. But a vitamin B3 supplement would probably not be too difficult to get out to people in more remote parts of the world. So the bit that excited me was that it seems like a really simple solution to birth defects and miscarriages. I do want to really emphasise though that we are not suggesting reduced NAD is the cause of the majority of birth defects or miscarriages, but it's a contributor. And how much of a contributor one day we may know. 

Paul: [00:36:41] It's still quite an amazing discovery to potentially, you know, solve and prevent a large category if they spread. And it's a beautiful, elegant, natural solution. So you should feel very, very proud. 

Sally: [00:36:54] Thank you. 

Paul: [00:36:55] And I know you work extremely hard, but besides solving these amazing problems, what other interests do you have outside of medical research?

Sally: [00:37:05] Well. When I was younger, I played about ten different sports over a period of time. And I have to say the last 30 years, I'm not very good at what is it called now, the work life balance. But now my children are older. I'm clawing back some time to exercise because it's obviously very important and I mostly cycle but what I love to do is get back to sailing, which is what I did for many years as a younger me. What else do I do? I guess the more you know about anything, the more you know you don't know. And so I know a tiny bit about oh, I know maybe a lot about a tiny bit in the world, put it that way. But it just reminds you of everything you don't know. So I've got this habit of reading to learn more, and sometimes it's a bit of a dry read. I read that short History of Philosophy earlier this year and managed to learn a few things. But I'm a facts person, so a book just on opinion was a little hard for me, but there are some good lessons in there, so I like to read to learn more. 

Paul: [00:38:23] Well, I'm glad that your curiosity and your dedication has led to this breakthrough. You're incredibly understated, but it's been wonderful having you as a guest of Hearts and Minds and explaining this area of birth defects and the deficiency in the potential solution. So thank you very much for your work and thank you for coming on to our Hearts and Minds podcast. 

Sally: [00:38:44] Well, thanks very much, Paul. It's been lovely speaking with you and thank you to Hearts and Minds. They have the contribution that Hearts and Minds have made to the Victor Chang Cardiac Research Institute and other research groups has been phenomenal. I don't think Hearts and Minds appreciates how important their contributions are and not just as a one off, but ongoing. It's the continuity. Because research projects long and that continuity is crucial. So thank you and thank you to Hearts and Minds. 

Paul: [00:39:23] No, thank you, Sally.

Maggie: [00:39:26] What a conversation. I'm always so impressed when I get to hear from Professor Sally Dunwoodie. She's incredibly humble about her achievements, but it's a very exciting double breakthrough that will save many thousands of babies globally. A massive thank you to Sally for taking time to talk us through her important work and to explain the next stages of translating her discovery. It certainly is a very long journey and a big thank you to you for joining us today and listening to the Hearts and Minds podcast. We'll be back next week with another episode to ensure you never miss a conversation. Please subscribe wherever you are listening to this podcast right now, and better yet, send it on to someone you think will enjoy the discussion. Thank you for your support. Until next time, stay curious.