Glen Paul: G’day, and welcome to CSIROpod, I’m Glen Paul. Avian influenza, commonly known as Bird Flu, is an infectious viral disease of birds, particularly wild water fowl such as ducks and geese, which can sometimes spread to domestic poultry and cross the species barrier to humans and other mammals.
Protecting poultry and humans from dangerous strains of avian influenza may one day be possible through CSIRO research that aims to switch on natural immunity processes and produce flu resistant chickens.
CSIRO research leader, Doctor Tim Doran, has been looking at ways of enhancing the process of natural immunity in chickens from earlier CSIRO discoveries in plant diseases in the 1990s, and the role of naturally occurring gene silencing mechanisms in plants and animals.
Firstly, Tim, as you’re no doubt aware, when any sort of genetic work is mentioned people’s ears do tend to pop up, so what is gene silencing?
Dr. Tim Doran: Well, gene silencing is a way of switching off the activity of any gene in a plant or animal. As you mentioned, it was discovered in the 1990s by some research that was being undertaking in CSIRO Plant Industries, and it was discovered that it’s a naturally occurring mechanism that’s evolved in plants and animals over millions of years as an immune defence against viruses, and with the research that was done at Plant Industry we’ve been able to, I guess tap into that understanding and now use it as a way to specifically switch off any gene we want in a plant or animal cell, including invading viruses, and that’s the mechanism that we’re using to develop our avian influenza resistant birds.
Glen Paul: So what triggers this process when it’s in a natural situation?
Dr. Tim Doran: Viral nucleic acid. So viruses encode genes, and those genes make proteins, and the nucleic acids are the molecules that viruses use to encode genes, and that triggers the RNA interference response in a cell to specifically switch off the gene so the virus can’t make more of itself and replicate.
Glen Paul: So then how do you know which are the right genes to silence?
Dr. Tim Doran: Well we can target any of the viral genes. So influenza virus is obviously our target; it’s made up of eight genes, and some of those genes vary a little bit between virus to virus, and others are very conserved. And we target the genes that are highly conserved and are very important for the virus to replicate, and we choose regions that we know don’t change from virus to virus, and they’re the targets that we select.
Glen Paul: So once the chickens effectively become immune, would they then breed transferring the resistance to their offspring?
Dr. Tim Doran: They do, Glen. So the mechanism we use to trigger our RNA interference is to generate transgenic chickens, so we insert a copy of our RNA interference molecules into the DNA of the chicken, so that we can breed in resistance from generation to generation, and so that every cell has a way of being able to respond to viral infection.
One of the difficulties with RNA interference research for human applications over the years has been how do you deliver an RNA interference molecule to a cell? Our approach in chickens, also with other livestock species that we have interest in, is to engineer the birds and livestock species so that every cell has a copy of these natural RNAi interference molecules.
Glen Paul: So how long would it take then for chickens to become eventually immune to avian influenza, if just left to their own devices?
Dr. Tim Doran: It wouldn’t happen. You can use selective breeding process, which is a commonly used method to engineer traits for improved productivity in poultry, but disease resistance has been a trait that’s been very difficult to use that method for, and it would be impossible to use conventional breeding methods to develop an avian influenza resistant bird without having to use the technology that we’ve developed.
Glen Paul: OK. The point of all the research then is by giving these domestic chickens natural immunity, then that greatly reduces the chance of the bird flu crossing into humans?
Dr. Tim Doran: Absolutely. And that’s one of the real drivers behind this project as well, is that bird flu is obviously a devastating disease in poultry flocks worldwide, but the virus can also spread from poultry into humans, particularly very virulent strains of avian influenza. The strain in particular is the H5N1 strain, and when that virus spreads from poultry chickens into humans it has a very high mortality rate.
And I guess at the moment that virus then doesn’t spread very well from humans to humans, but the worry and concern is that the virus will change, and that spread from human to human will be enabled, and then we have a very serious pandemic on our hands, and so one of the major goals of this project to develop birds where the virus can’t spread from the chickens to humans and cause a pandemic.
Glen Paul: And it’s good that the research is taking place at the world’s most biosecure research laboratory, CSIRO’s Australian Animal Health Laboratory in Geelong, a fact I know to be true from firsthand experience, and the CSIROvod video of my visit.
Dr. Tim Doran: Yep.
Glen Paul: But what regulatory processes would have to be met before flu resistant chicken breeds could enter the food chain?
Dr. Tim Doran: Right. So we’re working very closely with regulatory bodies here in Australia, to make sure that the project is on track for eventual commercial outcome. The main regulatory body is the OGTR, the Office of the Gene Technology Regulator, and they are very important to work closely with in terms of being able to get approval to eventually release the genetically modified organism. So they’re the first regulatory body that we work closely with.
The next would then be Food Standards Australia and New Zealand, and that would be for the eventual use of these birds in food production, but that’s some way down the line. And currently we see the project as being a proof of principle project, where we’re showing that we can first develop avian influenza resistant chickens, and then the next step would be to go through the FSANZ’s, Food Safety Australia New Zealand regulatory body, to make sure that these chickens would be safe for food consumption, but that’s some way off.
Glen Paul: Now, not wanting to go too far off the track, but you did touch on this earlier, and the obvious question is do you see a time when this technology could be applied to humans in silencing genes that cause HIV or cancer, for example?
Dr. Tim Doran: Absolutely. And there’s a lot of work going on around developing therapeutics for those types of diseases, using RNA interference. As I said, one of the major hurdles at the moment to overcome is how you deliver an RNA interference molecule into a cell.
CSIRO has a large project working across two divisions to be able to develop a way of being able to tap into some chemistry that’s being done to deliver RNA interference to human cells, and a lot of work worldwide as well. And, yeah, I do see the day that it’ll be possible, and I think that’ll have an amazing impact on medical science and biotechnology once that problem of delivery is overcome.
Glen Paul: Yeah, I think that’s a bit of an understatement. Look, it’s certainly a discussion for another day, and I do thank you very much for talking to me today about your research, Tim.
Dr. Tim Doran: Thanks very much, Glen.
Glen Paul: Doctor Tim Doran. And for more information on this podcast find us online at www.csiro.au. Follow us on LinkedIn and Twitter at CSIROnews, or like us on Facebook.