THE NEXT WEIRD WAY WE’RE CHANGING CATS

Source: The Atlantic (Extract)
Posted:
November 5, 2021

What if you could make your cat hypoallergenic with biotechnology?

The first thing to know is that truly allergen-free cats are a myth. Sorry.

That’s because all cats—longhair, shorthair, no hair—shed a pernicious little protein called Fel d 1, found in the saliva and oil glands, which causes most cat allergies. Some cats shed 80 times more of it than others of the same breed; no one knows why. Some shed more one month and less the next. Certain breeds may indeed make less Fel d 1 on average, but evidence is sparse. Back in the 2000s, a much-hyped start-up claiming to have bred hypoallergenic cats collapsed in disgrace, leaving some customers with pets that still made them wheeze and others who had shelled out thousands of dollars up front with no cat at all. That’s to say, demand for allergen-free cats is intense. It’s just that no one has managed to breed one.

Where old-fashioned breeding has failed, though, scientists are now turning to biotechnology. In recent years, a suite of sci-fi-esque strategies have been aimed at Fel d 1: a kibble coated in an egg-yolk derivative that neutralizes the allergen, a vaccine that uses cucumber mosaic virus to trick the cat’s immune system, and a gene therapy that deletes the Fel d 1 gene from cat DNA with the CRISPR editing technology. This kibble, in fact, is available on store shelves as Purina’s Pro Plan LiveClear cat food. The vaccine has already been tested on more than 100 cats. And although a viable gene therapy is much further off, scientists have managed to delete Fel d 1 from cat cells in a petri dish.

None of these strategies will eliminate Fel d 1 in a cat completely, but they might reduce allergen levels enough to stave off itchy eyes and sneezing. (Hypoallergenic, by the way, is often used colloquially to mean “allergen-free,” but it technically means only “reducing allergies.”) This reduction may be enough to let allergic owners keep their beloved cats.

Whereas those strategies are largely aimed at the human, more recent biotech ideas are all aimed at molding the cat to the desires of the human. And that is maybe not so novel. These ideas involve newfangled technologies, but they may also just be the logical next step in our millennia-long relationship with cats, during which we have turned a wild killer into Fluffy who meows for kibble at 8 p.m. sharp and snuggles in bed.

Even just a century ago, pet cats spent most of their time outside. The exclusively indoor cat is a fairly modern development—made possible by the invention of litter. And it’s only as cats have physically gotten closer to us that all the little bits of Fel d 1 they shed have turned into a problem.

Ebenezer Satyaraj, the director of molecular nutrition at Purina’s parent company, Nestlé, first began thinking about how to use cat food against Fel d 1 more than a decade ago. A key insight, he told me, was simply that cats spend a lot of time grooming themselves. Normally, this behavior spreads the Fel d 1 in their saliva all over their fur, which in turn gets all over your couch, your sweater, your bed, etc. But what if you could interrupt that process by feeding the cats something that neutralized the Fel d 1 in their mouth?

Satyaraj and his team landed on the idea of using anti–Fel d 1 proteins purified from egg yolk, which are made by injecting a hen with Fel d 1. Her immune system treats this Fel d 1 like a piece of a foreign pathogen, mounting antibodies that bind and neutralize it. These antibodies end up in egg yolks as a way of passing protection onto chicks. But they can also work, remarkably, as a kind of interspecies immunity transfer: In this case, Satyaraj wanted the egg-yolk antibodies to neutralize Fel d 1 on the cats—ultimately, co-opting a chicken’s immune system to protect allergic humans.

It worked. The egg-yolk coating on Purina’s cat food reduces the amount of allergen shed by 47 percent on average. The goal here, Satyaraj says, is to bring Fel d 1 levels down below a threshold to minimize allergy symptoms—it might not be enough for everyone, but it should be enough for some. A study in allergic humans found that using Purina’s cat chow did help decrease congestion and itchy eyes. How well the kibble works will depend on how much Fel d 1 a cat starts with and how sensitive the owner is to even tiny amounts of the allergen. And any effect lasts only as long as you keep feeding them Purina’s food.

A second idea to make cats more hypoallergenic involves harnessing the power of the cat’s own immune system, where the effects might last longer. In 2013, scientists at the University of Zurich founded a company, now called Saiba Animal Health, to make a vaccine for cats that reduces shedding of Fel d 1. They used a multipart strategy originally developed for human vaccines: Hide the Fel d 1 protein inside the shell of a cucumber mosaic virus, which is in turn embedded with a bit of tetanus toxin. This tricks the cat’s immune system into thinking Fel d 1 is part of a virus, says Gary Jennings, the chief operating officer of Saiba. Once immunized, the cat starts making antibodies that neutralize Fel d 1. Their allergen levels indeed dropped over several weeks, and Saiba found that the allergic cat owners were able to spend more time petting their vaccinated cats. The company has since licensed the technology to a large animal-health company—whose name Jennings says he can’t disclose—to gather the data necessary for regulatory approval.

Both the human doctors and the vets I spoke with thought such a vaccine would exist in an interesting liminal space: Was a vaccine given to cats in order to treat humans considered an animal vaccine or a human vaccine? Who would even regulate it? Jennings told me that, based on conversations with the FDA and the European Medicines Agency, both would oversee it as an animal vaccine—but slightly differently. The FDA needs to make sure that the vaccine does not harm cats and works for humans, but the EMA wants to weigh the harm and the benefit to the cat itself.

How do we weigh the risks of a pet’s treatment against the convenience and pleasure of its owner? This question felt very novel for a second, until I realized only the novelty of a cat-allergy vaccine made the question seem so. We used to declaw cats to spare our furniture. (No longer acceptable.) We still remove their testes or ovaries to curb the sexual behaviors that would make them annoying as indoor pets. (Totally acceptable, highly encouraged.) Could you even say that a surgery or vaccine benefits the cat itself, if a pet modified to become a more suitable indoor pet ends up making their owner happier and more doting?

To judge the potential harms of targeting Fel d 1, we also need a better understanding of the protein and exactly what it does in cats. Unfortunately, “nobody really knows the answer,” says Drew Weigner, a veterinarian in Atlanta who specializes in cats. Scientists have hypothesized that Fel d 1 may act like a pheromone for social signaling. That might mean it’s less important for house cats, especially ones that live solo. Male cats also tend to make more Fel d 1, and neutering them actually decreases their levels three- to fivefold – which means we’re already routinely altering cat’s Fel d 1 production. The high variability of allergen levels from cat to cat does suggest that reducing it shouldn’t have massive consequences. And indeed, the studies on cats fed with the anti–Fel d 1 kibble and those given the vaccine haven’t found significant adverse effects associated with reducing levels of the protein.

But what if you went even further, erasing the very gene that encodes Fel d 1 from a cat’s DNA? Nicole Brackett, a researcher at Indoor Biotechnologies, has been using the powerful new gene-editing technology CRISPR to delete the gene from cat cells. And as part of that work, she has been investigating the role of Fel d 1 across all cats, domesticated and wild. She has found that the gene sequence of Fel d 1 varies tremendously from species to species—say, panther to lion—but also from cat to cat. The fact that it’s not being preserved over the course of evolution, Brackett says, suggests that “it may not be functionally essential for the cat.”

Indoor Biotechnologies’ goal is not to genetically engineer a new cat without Fel d 1, as the company isn’t interested in getting into the business of breeding cats. Rather, Brackett and her colleagues are hoping to lay the groundwork for gene therapy in the form of an injection that deletes Fel d 1 from enough cells to depress the cat’s overall production. In the lab, Brackett has been able to knock out Fel d 1 from up to 55 percent of cat cells in a petri dish. That reduction might be enough to make a cat hypoallergenic, she says, if a pet went to the vet for a new injection of the gene therapy every few months or once a year. Many challenges are still ahead though. Brackett tested CRISPR in a type of cell commonly used in labs because it grows well—but they come from cat kidneys and don’t naturally produce Fel d 1. So she still needs to make sure CRISPR works in cells of the saliva and oil gland, and then figure out how to smuggle the CRISPR machinery into those cells inside a live animal—which is still a key conundrum for human CRISPR therapies.

But scientists have also come a long way already. Indoor Biotechnologies’ president and CEO, Martin Chapman, was part of the original team that first isolated the gene for Fel d 1, back in the 1990s. Even then, he says he remembers thinking, Wouldn’t it be great if we could delete these genes? But it wasn’t possible with the technology of the time. All of these new ideas for dealing with cat allergies rely on breakthroughs in other fields: CRISPR, of course, but also the development of egg-yolk antibodies, and the invention of new strategies for making human vaccines. In the 21st century, biotechnology quietly touches on so many aspects of our lives that it’s no surprise it would come for our pets too.

The indoor house cat is already a markedly different creature from the first wild feline that prowled around human settlements hunting rodents. We’ve moulded cats to our lifestyles, and we will keep doing that as long as they are common pets. Eventually, we might even have a truly allergen-free cat.

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