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Opening quote: When I first started out in this field, this was unimaginable. What we're doing now is absolutely unimaginable. It's science fiction. Really now it's a reality.
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Brian: Hello, and welcome to RSPCA Australia's humane food podcast. My name is Brian Daly. And in this episode I'm envisaging we're going to hear a lot about DNA, RNA, gene editing CRISPR / cas nine technology and how they can help solve a considerable ethical and welfare issue in the egg production industry. Because my guest today is senior scientist and project leader at CSIRO’s Australian Animal Health laboratory, Dr. Mark Tizard. Mark, welcome to the podcast.
Mark: Hi, Brian. And thank you very much for having me on today.
Brian: Mark that terminology merely represents my research for this episode, but for you, it must represent a good portion of your professional career and your involvement in the field of genetics from would I be correct in saying the pioneering days of the 1980s?
Mark: Yes, indeed. You're right. I mean, those are terminologies that are very familiar to me now. But yeah, way back in the 1980s, when I first started out in the field, some of this thing in terms of technology was unimaginable. And we've taken great strides in the last 30 years. So, it's become very exciting and the possibilities are fantastic. I kicked off my career helping identify a gene in malaria that was being proposed as a vaccine. I moved on quite rapidly to working with some human viruses, herpes virus, actually again, looking for cloning technology to help us find a vaccine, and then moved on to another field of bacterial disease, which again was started out as an interest in human disease and Crohn's disease which was linked to something called Johne’s disease in cattle. So, I've built up my skills across a wide range of areas and had the opportunity to try a lot of different things.
Brian: I reckon any of those topics would fill an entire episode any one time. But today I wanted to focus on the work you've done to hopefully eradicate this ongoing issue in the egg production industry. And it's not the battery cage welfare issue for layer hens, which a lot of our listeners will be familiar with. It's the issue of male chick culling. But before we get to your solution, could you give us an idea of the issue?
Mark: Yeah, sure. So just coming out of the research background that I was in, you know, we had the chance to work with viruses and bacteria. And as the technologies got more sophisticated, we've been able to take that right up to the level of working with animals. And we very quickly identified that there were some big needs in animal industries. And one of the highest profile ones, of course, is in the egg production and the fact that it's fairly obvious, but hens lay eggs, roosters don't, and unfortunately, that means that for the egg laying industry, the roosters are actually surplus to requirement. Now, the interesting thing with chickens is that many people don't realize the breeding of great strains that that do really well and produce great meat or great eggs has led to two types of chickens. And it's a little bit like in the beef industry, people know that there's dairy cows and beef cows, and you don't drink milk from a beef cow and you don't eat steaks off a dairy cow. The same thing applies in, in the world of chickens and in poultry. And so the genetics that you find in the egg laying industry and the birds that are great at laying eggs means that when they eat food, their body says, look, we don't need to turn this into muscle, let's turn it into egg, which is great if you're a hen producing eggs, but if you're a rooster, it means that you're eating food and your body is not letting you turn it into muscle, which is what the industry is looking for. So, it's unfortunate, but it's not economic for farmers to grow those roosters out and to put them to the across to the meat industry. And so, as a result, they basically as soon as they can tell that they're a rooster, that they're male and not female. And that's a day, hold They're taken away and humanely euthanised. And that's something that the industry really, really would love to get away from. They looked and they've explored a range of different possibilities, but nothing presents itself as being as being really viable. And so unfortunately, you have to the hatch the birds, and then take a look at these little day old chicks and say, your girl great, off you go, your boy, sorry, you know, you're off for humane euthanasia. And so, they've been calling out for this. And it was something that leapt out at us in the area of the technology that we were developing as a real possibility for us to employ this kind of genetic technology to bring about a solution that would really bring benefits both to the industry but also to the animal.
Brian: Exactly. Yes. It is a huge issue. Obviously with that 6 billion eggs eaten in Australia in a year. That's a large number of birds need to be culled at the moment?
Mark: Yep, that's absolutely right. So, it's actually 23 million hens that are laying eggs for us. Here in Australia every year, which means that every year there's 23 million day old males that have to go for humane culling.
Brian: So, your method can negate this wastage?
Mark: Yes. So the basic idea behind the technology, is one that I think most people will be able to grasp, you and I, as you know, are male, and therefore we have the X and Y chromosomes. For our listeners out there that are female, they know that they have X and X as their chromosome sets. Those are the sex chromosomes, that from that single cell that came from the ovum and the sperm and the fertilisation event, it was those chromosomes that told us whether we were going to become male or female. The same thing applies in chickens. They have two chromosomes, one that defines being male and one that defines being female. And so what we realised was with the advances in technology, and you mentioned one of those before CRISPR and cass nine, the technology that allows us to very precisely find and break DNA, it allows you to place a fragment of DNA very specifically in a location in all of the DNA that makes up the instructions for constructing an animal, in this case the chicken. So, what we've done is we've placed a gene on the chromosome that defines that the animal will be growing up as male. And that gene essentially expresses a little protein. It's a perfectly harmless protein, all it does is glow red when you shine a laser light onto it. Now when an egg is laid, many people know this if they go to two farms out in the country, but you can kind of see it on the eggs you see in the supermarket when you crack an egg, lovely clear white and then a lovely yellow yolk and on top of that yolk, sometimes you'll see a little white spot. That white spot is actually the ovum in the unfertilised eggs that we see in the supermarket but in a fertilized egg, that little white spot is a ball of cells that is the beginnings of the making of the chick There's a little ball of cells with no structure, and as yet, no real activity other than starting to build, what will become the chick, when we put this marker on the chromosome that defines that an animal is going to become male, means that that little ball of cells if it contains that chromosome, and therefore is destined to grow up as a male, will glow. So what we can do is when the egg is laid by the mother hen, we can shine a laser through that egg right at that point of lay, and we can see a little glow come back, that tells us that the chromosome is there, the marker is there, and that it's going to be male. If we shine the laser in, and there's no glow coming back, it means that the chromosomes in that egg in that little embryo are the ones that are going to lead to females, the hen, no glow means no gene. And that means you can take that egg and now put it in the incubator. They get incubated for 22 days at 37 degrees, and when they hatch, all that's going to hatch is females. And the beauty of this system is that you take the egg away before it goes to the incubator before there's any kind of structure. Before, there's all the bits and pieces that we recognise as ultimately the chick that comes out of the egg, it's just a tiny ball. So effectively, it's like an egg that you might get when you're on a farm. And so, it contains the protein and the yolk of the egg white and, and all the nutrients, you can take it out at that point and recover high value material from that. And you also only going to incubate half the number of eggs that are laid, because it's a typical thing with animals where they got the two sex chromosomes 50/50 in the population. So, the males as an egg, never go into the incubator. Now, if you think about that, in Australia, instead of 46 million eggs going into incubators to be grown up and then hatched. Only 23 million go into an incubator. So, at the end of the day, you halve the incubator space, at the end of that what hatches is only females so you don't now have to sort through and look for the males and euthanise those little day old chicks. So, it has potentially big impacts in terms of improvements for industry, not just in terms of removing this ethical dilemma for them, but improving the workflow and the profitability of what they're doing.
Brian: Yeah, that sounds absolutely fascinating. And I guess it's important to emphasize too, that gene editing that you're talking about is quite different from GMO.
Mark: Absolutely right. Gene editing is something that has come through in recent years, and allows us to have this ability to precisely target parts of the DNA, the recipe that leads to the generation of an animal or a plant and make very precise and defined changes. However, the technology that we're talking about here today is actually something that incorporates GMO. So, the mark that we use that is put onto the male chromosome, the red glowing protein is unavoidably a GM issue. So, the mother hen that carries that and passes it to her sons. But not to a daughter's, she is carrying a gene and she is GMO. But what happens during the process is this separation of the male and female chromosomes, male and female defining chromosomes like the x and y. And what happens there is that we're putting a gene into the system. So, there is GM in the system, but we take that GM out, so it is clearly only on the male. And we identify it using laser interrogation of the egg to see the presence of the gene by the red protein. And we remove that. And the female actually doesn't have the gene at all, is a null segregation event. It's recognised by regulators as something that's been used in plant breeding for many years. So, the segregation of the chromosomes leading to the females only getting one and the male getting the other, and that that outcome means that the hens actually are not GMO, and therefore the hens go into the henhouse are the same as the hens that go into the henhouse today, the eggs that they lay are exactly the same eggs as they lay today.
Brian: So it's really fascinating. And some jurisdictions have addressed that situation in different ways?
Mark: Yes, in terms of genome editing that is approached differently in different jurisdictions around the world. In Europe, they say anything that changes DNA is, is genetic modification, and therefore the product is GM. In America, they asked the question, have you deliberately changed the DNA? And that then acquires a certain amount of regulation, in Canada, they asked the question, how do you change the product, which is actually a really good way of coming out the question if you've used technology, doesn't matter what the technology is, have you changed a quality of the product that we need to consider for the consumer? In South America and in Japan, and here in Australia, we've taken a different line, which is what the actual changes to the organism, the regulations as they were originally established, were to determine if they foreign genes introduced into a new animal. And if you haven't introduced foreign genes, then that's considered to be something fairly equivalent to normal breeding practices and therefore have low risk. And so, the approach is to just take a look and ensure that there's no significant concern from that outcome. Of course, in this case, we're dealing with having introduced a gene that creates a GMO the mother hen. And the question is, how does different jurisdictions deal with that? And what we have found is that in outreach to countries around the world, in America, in South America and Japan here in Australia, the outcome the offspring are not considered to be GMO. So, the hens that come through this process are not GMO, and neither are the eggs that they produce as food. The males that we identify clearly are GMO, but we're taking them before they actually grow up into a chick. And so, what you got there is basically just an egg and it contains valuable material. That valuable material can be extracted for various uses. But what you've done in this process is you've used technology, we've added gene technology in, we've identified it and taken it out again, which seems strange, but it's for a purpose. And that purpose is to take out those males, before they have to become a little old chick that then has to be euthanised. And that's the power of this technology to basically address that key concern of industry, something that they haven't yet been able to deal with by other means.
Brian: Yeah. And I was reading that there is another technology involving in Ovo detection of the sex in the egg before it's hatch. Is that another comparable or viable solution? Or does your technology seem to go one step further?
Mark: That's a very good way of describing it. Brian, our technology goes that one step further. So, there are ways of detecting whether your egg contains a male or female chick in development. The problem with those technologies as we see it, is that you have to put the eggs into an incubator. They need to be in an incubator for us a certain period of time for that tiny little ball of cells to start growing form and structure, that then allows differentiation of the growing male and the growing female. Now at that early stage of embryo development, it's very difficult to do but there are some techniques that involve identifying hormones that are beginning to be produced and other structures, but those techniques require incubation of the eggs to a certain period, usually halfway through incubation. So, nine days of incubation, and they require a sample to be taken from inside the egg. And for that sample to be analysed for the egg. The sample came from to be identified and then removed and that normally means taking the eggs out of the incubator, doing the analysis, and then re assaulting the eggs, handling them, and then putting them back into the incubator. Those kinds of techniques are known to reduce the hatchability of the eggs so you mess around with those eggs during that period. Some of them then fail to hatch so you reduce the number of hens that come in at the end of this process. But you also want to identify the male or removing an egg that contains a quite well formed embryo that you then have to euthanise. So, it actually doesn't really remove the issue of euthanasia, it just brings it forward. So that you're not doing it on a cute fluffy, yellow little hatch chick, you're doing it on an embryo within the egg, which, you know, from our point of view, as we're approaching this problem is questionable in terms of the value that presents also, what's in that egg is a pretty well formed embryonic chick. And the material that's in there is now a very low value waste product. Now, that's a very kind of callous economic view of these things. But if you use the technology that we're presenting, you take an egg at point of lay, when there is essentially what we all would recognize as egg white and yolk and a tiny little ball of cells. Now we're actually thinking right now of how can we remove that ball of cells because that's the only GMO material in the egg yolk and the egg white are really good high value materials that can be used for a whole range of things. So, there are other approaches going on to try and remove the need to cull the hatched male chicks. The question is, to what extent those actually address the key issue of euthanasia of an organism? We're trying to get that before it is really even a recognizable organism, just a tiny ball of cells. And that little ball of cells is about a quarter of the size of your little fingernail. When the egg is laid, there's 60,000 cells all clustered together, and they haven't yet decided what they're going to be whether they're going to be the backbone or the legs, the arms or the head or whatever. There's just a little clump of cells.
Brian: And when you talk about this high value material that's left when you remove these male chromosome eggs at such an early stage in the process, what is that useful for?
Mark: One of the things that we can do with the eggs that we identify as male and removed from the system is actually take them across into production of vaccines and many people aren't aware that the flu vaccine is used every year for the seasonal flu is actually grown in eggs. And there has to be a supply of eggs to, to the companies that manufacture that vaccine. This is a way of actually, if you like diverting something that would have been, you know, an unfortunate waste product from the production of eggs for food, and taking that across into something that's really important and valuable for the public, which is the generation of vaccines to protect them from some very nasty viruses.
Brian: I guess that's another added benefit for looking at this system is the industry beating down your door do we implement it?
Mark: Not exactly beating down our door and there's been a lot of effort looking at the other types of technology with the recognition that you have to introduce eggs into an incubator, so you know that's not halving the amount of eggs going into an incubator, its not saving as much money as you could. And it's not entirely addressing the problem. But they're trying to, you know, step away from having to hatch and cull. We've been talking with industry and we work very closely with a range of people in different aspects of the industry from the top end, the genetics companies, right through the breeders and the hatchers, really to say, you know, how would our technology integrate into their current practice, and there are very straightforward ways of introducing it. But the most important thing is that we have to introduce this gene into the male defining chromosome of the chicken. That means we have to work with birds and genetics, and we're changing those genetics ever so slightly. But we are introducing into the system of GMO and of course, the industry is like really keen on how our solution addresses the issue. But they're also concerned, they're concerned that, you know, we're now introducing something new into the system that's never been there before. And that's why it's so important to have opportunities like this, to talk to you, Brian and to the audience, to get a sense of how the public going to respond to this, because we see this as being a great way of dealing with this issue. But at the end of the day, it's the consumer is the public that will decide whether this is a great way or not. And the companies, they're hesitant, they see the value, but they are also concerned as to what will the public make of this, they I think, are pretty confident that this is such a good solution, and is something that the public can understand and not be concerned about, and realize that the eggs they're getting in the supermarket are the same as today. But that still has to happen. So you know, we're part of the work that we're doing now is not just in the lab, but is you know, out there on the streets and trying to reach out to the public and, and start those conversations. It's really important part of what we're doing.
Brian: That's true. And I guess with your background for so long in this area, you would have seen all the discussions about ethical implications genetics and cloning and GMO and so on. So, it's good for you to be, I guess, have all that knowledge and be able to bring it to the table in in this instance?
Mark: Absolutely. I mean, we understand that from a public point of view, they really need to know that what's being presented to them as food products from agriculture, are safe and healthy. And if this kind of technology is being used, then there's been appropriate oversight. And the regulators are there for that. The office of the gene technology regulator who looks at anything that involves this sort of genetic technology, and Food Standards Australia, New Zealand, who looks at what the outcomes are, if they're food, that's a product going to the marketplace, and we've worked with them over many years, to understand what it is that they want to see in a product, that will mean that it is safe. And it's absolutely essential we do that from a point of view of providing something to the marketplace to the consumer. But I think it's something that you know, sometimes people forget, we may be scientists, but we're also mums and dads, we also go to the supermarket and buy food, we bring our friends over and feed them, we have our mums and dads round, our kids at the table, we want to know that food is safe too. And that's the role of the regulator. And that's why we take it very seriously to work with them closely and make sure everything is up to scratch.
Brian: Well, thanks, Mark. I really could talk all day about your work. It's, really fascinating. And, you know, to see how the gene technologies like yours can have this huge positive impact on animal welfare. It's really exciting. It's something couldn't have even contemplated, you know, 20 years ago, really?
Mark: Yeah absolutely. When I first started out in this field, this was unimaginable. What we're doing now is absolutely unimaginable science fiction. Really, and now, it's a reality and it's so powerful. I'm just, I feel privileged to be involved, you know, in this field at this time, it's just like, right place right time. But also, just a quick, you know, thank you to you because I think as I've tried to emphasize in this, the conversation with the public, so important, you know, to actually get those conversations happening, absolutely critical for us as scientists we can't be working in, in ivory towers, and then descending from the ivory towers to the lands below showing the shiny thing that we've developed. It's got to be with the public alongside is all the way in the journey.
Brian: as you said, you're part of the public anyway, you're part of it. It's not like you're removed or anything. It's really exciting. And again, I wish you all the best and thanks for your time today. Really appreciate it talking to you.
Mark: Fantastic. Thanks for hosting Brian.
Brian: We've been talking today with Dr. Mark Tizard senior scientist and project leader at CSIRO’s Australian Animal Health laboratory, and thank you for listening. If you would like any more information on male chick culling visit the RSPCA knowledgebase at kb.rspca.org.au. You can also subscribe to the podcast series at the RSPCA Australia website rspca.org.au or all the usual podcast suspects I'm Brian Daly and I look forward to your company next time on the RSPCA Australia humane food podcast.
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