Oct 16 2023

Gene Editing Chickens to Resist Bird Flu

There are 33 billion chickens in the world, mostly domestic species raised for egg-laying or meat. They are a high efficiency source of high quality protein. It’s the kind of thing we need to do if we want to feed 8 billion people. Similarly we have planted 4.62 billion acres of cropland. About 75% of the food we consume comes from 12 plant species, and 5 animal species. But there is an unavoidable problem with growing so much biological material – we are not the only things that want to eat them.

This is an – if you build it they will come – scenario. We are creating a food source for other organisms to eat and infect, which creates a lot of evolutionary pressure to do so. We are therefore locked in an evolutionary arms race against anything that would eat our lunch. And there is no easy way out of this. We have already has some epic failures, such as a fungus wiping out the global banana crop – yes, that already happened, a hundred years ago. And now it is happening again with the replacement banana. A virus almost wiped out the Hawaiian papaya industry, and citrus greening is threatening Florida’s citrus industry. The American chestnut essentially disappeared due to a fungus.

And now there is a threat to the world’s chickens. Last year millions were culled or died from the bird flu. As the avian flu virus evolves, it is quite possible that we will have a bird pandemic that could devastate a vital food source. Such viruses are also a potential source of zoonotic crossover to humans. Fighting this evolving threat requires that we use every tool we have. Best practices in terms of hygiene, maintaining biodiversity, and integrated pest management are all necessary. But they only mitigate the problem, not eliminate it. Vaccines are another option, and they will likely play an important role, but vaccines can be expensive and it’s difficult to administer 33 billion doses of chicken vaccines every year.

A recent study is a proof of concept for another approach – using modern gene editing tools to make chickens more resistant to infection. This approach saved the papaya industry, and brought back the American chestnut. It is also the best hope for crop bananas and citrus. Could it also stop the bird flu? H5N1 subtype clade is an avian flu virus that is highly pathogenic, affects domestic and wild birds, and has cause numerous spillovers to mammals, including humans.

What the researchers did was use CRISPR/Cas9 to alter the ANP32A protein in chick embryos. This protein is important to the development of the brain, heart, and bones, but also is used by the avian flu virus to replicate inside avian cells. The viruses RNA polymerase, which is responsible for transcription and replication of the viral genome in the host cell nucleus, is dependent on the ANP32 family of proteins. This protein also has key differences between birds and mammals, likely responsible for the greater infectivity of birds. The researcher used CRISPR to make key amino acid changes to the ANP32A protein. They then tried to infect test chickens and control chickens with a typical dose of avian flu and a 1000 times greater dose.

In the usual dose scenario, 9/10 test chickens resisted the infection completely, and the one that was infected did not pass the virus along to unprotected chickens. In the control chickens, all became infected and passed it on. In the high dose scenario, five of the 10 test chickens became infected, but none passed it on. So the mutation provided partial, but pretty good, protection from being infected and even more protection from being contagious to other chickens. This could go a long way to stopping the spread of the virus.

The authors then tested what would happen if they also used CRISPR to change ANP32B and ANP32E, two other related proteins that the virus seems to be able to use as an alternate to rescue their ability to replicate. They tested these changes in chicken cells (not living chickens) and found the virus was unable to replicate. But they have yet to test what will happen to the chickens if they use CRISPR to alter all three proteins.

More study is needed before this approach can be applied to commercial chickens, but it was a successful proof of concept. Of course, anything we do, the virus can theoretically mutate to get around. They can become overcome resistance from vaccines, and they will likely evolve an alternate pathway to get around CRISPR altered chickens. No solution is ever going to be a permanent victory. We essentially need to stay one step ahead of pests and infecting organisms, and we need the ability to react quickly in the arms race when a new threat emerges. Bioengineering is the best way to keep ahead in this race, because it allows for specific rapid changes. We don’t have to rely on breeding and waiting for fortuitous mutations to spontaneously occur.

Again – its not a panacea, and we still need to explore and use all available methods to limit infections in crops and animals. But we cannot afford to take bioengineering off the table. It’s been difficult recently to get a read on the bioengineering vs anti-GMO battle. The anti-GMO crowd has not given up, but they seem to have lost some steam. The entrance of new bioengineering techniques has rendered a lot of their rhetoric obsolete. Plus, the necessity and advantages of bioengineered crops are simply too great to ignore.

The anti-GMO crowd simply does not talk about how bioengineering was used to save the papaya industry, for example, and even in very anti-GMO Hawaii, they quietly carved out exceptions for GMO papayas. Similarly, the anti-GMO law in Vermont quietly carved out exceptions for the cheese industry, because without GMO yeast there would be almost no cheese industry. I predict the same will happen for the banana and citrus industries. They will not go down because of anti-GMO pseudoscience. Further, bananas are actually a staple crop for billions of people. If faced with the choice of mass starvation vs introducing bioengineered bananas, we know what will happen.

The anti-GMO crowd will only have succeeded in slowing down and hampering a safe and useful – arguably critical – technology. They never had the facts on their side, and now the danger of their bad arguments is becoming much greater.



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