CRISPR – Pain In The Bud

After 10,000 Years, Dire Wolves Walk The Earth Again

The surprise announcement came from Colossal Biosciences, a company best known for its project to bring back the woolly mammoth.

A US biotech company shocked the world Monday when it announced the births of three dire wolf puppies, bringing back a species that hasn’t lived for more than ten millennia.

Or a version of that species, at least.

Scientists with Colossal Biosciences extracted DNA “from a 13,000 year old tooth and a 72,000 year old skull and made healthy dire wolf puppies,” Colossal CEO Ben Lamm said in a statement.

Of course, it wasn’t that simple.

The dire wolf, Aenocyon dirus, was heavier, stockier and had thicker fur than modern-day gray wolves. In addition, its bite was incredibly strong, generating more force than any living species of canid.

To create the dire wolf puppies, Colossal used the genomes reconstructed from the tooth and skull, spliced them with gray wolf DNA, and made 20 gene edits in 14 genes. Healthy embryos were implanted in three surrogates — large, mixed-breed dogs — and were successfully delivered.

Romulus, one of two male dire wolf pups born late in 2024. Credit: Colossal Biosciences

Remus, who was born at the same time as Romulus. Credit: Colossal Biosciences

Whether the new puppies are officially dire wolves is up for debate and beyond the scope of this post, but just like humans and chimpanzees share 98.7 percent of their DNA, dire wolves and gray wolves share 99.5 percent of their DNA.

The species also existed concurrently with gray wolves and there was interbreeding between the populations, meaning gray wolves already have dire wolf lineage.

As a result, the puppies may be more dire wolf than some are willing to admit. Just how far a “de-extinction” project has to go for the animals to qualify as their namesakes will be debated for years, and there are innumerable questions for which we won’t have answers until the pups grow and scientists monitor their behavior in addition to their physical health.

They won’t behave precisely the way their ancestors did, since they are growing up in a captive environment with teams of specialists constantly monitoring them. The wolves are “essentially living the Ritz Carlton lifestyle of a wolf. They can’t get a splinter without us knowing about it,” Colossal’s chief science officer, Beth Shapiro, told the New York Times.

Whether bringing back dire wolves is a “good” thing is also a topic for another day, at least as far as this post goes. You may disagree, and feel free to say so in the comments, but this is a subject you could write half a library of books on, encompassing ecological, moral and philosophical questions that don’t have easy answers.

It’s made even more complex by the situation we find ourselves in, with our own behavior and relentless expansion killing off more than 70 percent of the world’s wildlife since 1970, according to the World Wildlife Fund. The company wants to use its technology to help critically endangered species, like the red fox, avoid extinction.

Colossal has partnered with leaders in the fields of genetics and bioethics, as well as organizations that specialize in animal welfare. The puppies are in a sizable, custom-built facility in an undisclosed location, secured by “zoo grade” barriers, and the company enlisted the help of the SPCA to create an environment appropriate for them. Colossal says their care regimen will include socialization and the development of pack dynamics.

A newborn dire wolf pup. Credit: Colossal Biosciences

The company has well-publicized projects to bring back woolly mammoths and the dodo, and ultimately, its founders say they want to restore balance in places where apex predators have been brought to extinction by human activity.

“This project demonstrates the awesome potential for advances in genetic engineering and reproductive technologies to recreate lost diversity,” Andrew Pask, a Colossal board member and professor of biosciences at the University of Melbourne, said in a statement. “Apex predators are critical to stabilizing entire ecosystems and their loss from the landscape can have profound impacts on biodiversity.”

The pups are named Romulus, Remus and Khaleesi. That last name is in homage to the character Daenerys Targaryen (Emilia Clarke) from the book series A Song of Ice and Fire, and Game of Thrones, the television adaptation. Dire wolves play a major part in the narrative, and the series is credited with bringing the long-extinct animals back into the popular imagination.

Jon Snow (Kit Harrington) discovers an orphaned dire wolf pup in the first season of Game of Thrones. The pup, who grows into a fierce and massive adult wolf named Ghost, plays a pivotal role in many major events in the series. Credit: HBO

Khaleesi, a female dire wolf, named after the character Daenerys Targaryen from Game of Thrones. Credit: Colossal Biosciences

The Buddinese Jaguar: A Fitting Feline For The One Percent!

You can’t have a jaguar pet and you can’t have Buddy the Cat, but what if you could have a breed that combines the best features of both? You’d pay a lot for that, wouldn’t you? Good, ’cause they start at $10k!

SATIRE/CAT HUMOR

Inspired by the exclusive Ashera cat, we proudly present to you the Buddinese Jaguar, the pinnacle in feline luxury.

Why settle for a pedestrian Bengal or Savannah when you could own the ultimate in feline status symbols?

Our Buddinese Jaguars feature royal lineage, the finest genetic modifications, and they’re extremely handsome!

– Ultra exclusive luxury cat
– Available in hypoallergenic variants
– Version 2.15 now available!
– Patented SilkySmooth™ technology results in a luxuriously soft coat
– Eye colors available in Neon Emerald, Viridescent Beryl, Azure Sky, Amber Glow, Flecked Gold, Elvis Pink Cadillac, Crystal Cobalt and Electric Sapphire
– Optional moon roof
– Easy to use Quiet Mode™ technology guarantees your Buddinese Jaguar will shut up when you want it to
– Extended 5-year warranty

Each Buddinese Jaguar comes with a rapid USB 3.0 charger, a V8 engine that provides plenty of power for HyperZooms, and an Apple AirTag-enabled collar.

Buddinese Jaguar kitten — From kittenhood until adulthood, Buddinese Jaguars are exemplars of handsomeness.

In addition to guaranteed software updates for at least five years, your Buddinese Jaguar is equipped with onboard analog algorithms ensuring it downloads exclusively in its litter box and nowhere else.

Base models start at only $9,950! Hypoallergenic models with patented Fel-d-1 Guard™ technology available starting at $12,495.

We are an officially authorized retailer accredited by the Buddinese Jaguar Association and the Buddinese Authorized Distributor Association Service Standards (BADASS), awarded only to retailers who maintain the highest breed standards.

About the breed:

The Buddinese Jaguar was developed by Buddesian Labs. Lead scientist Buddy the Cat tirelessly and selflessly engaged in coitus with 217 jaguarundi females, producing the magnificent offspring that would comprise the first generation of these extremely handsome cats. Using pioneering techniques in CRISPR gene-editing, Buddy did the impossible and improved upon perfection by eliminating allergens and adding even more meowscle mass.

Note: Buddy the Cat himself is not available for purchase, although he will entertain offers for his human.

Buddy sleeping — Chief scientist Buddy recovers after selflessly and heroically engaging in coitus with 217 jaguarundi females in the name of science.

The Ashera Cat Scam: How One Man Invented A ‘Luxurious’ Breed And Cashed In

Although the original perpetrator of the scam was exposed, there are still opportunists selling “Ashera cats” to unsuspecting buyers who have their hearts set on hypoallergenic pets.

Pet site listicles name the Ashera cat as “luxurious,” one of the most expensive and rare breeds ever. Videos show surprisingly large, exotic-looking felines with leopard-like rosettes and a calm demeanor.

In media reports a man named Simon Brodie talks the breed up, presenting himself as the CEO of a biotechnology company that “developed” the Ashera through careful genetic manipulation, selecting only the most positive traits. For a few thousand dollars more, Brodie promises, they come in hypoallergenic versions too.

Brodie often sounded like he was describing the newest iteration of a tech product rather than a cat, calling the Ashera “a status symbol” and listing its optional features the way a car salesman talks about leather and heated seats.

“It’s exotic, but under the skin it’s a domestic house cat, very easy to take care of and extremely friendly,” he told Reuters. “Everybody has thought at one time, wouldn’t it be great to have a leopard at home, or a tiger? Obviously, you can’t and this is about the nearest thing to it.”

Brodie conjured images of engineers poring over genetic data and working with gene-editing equipment in a laboratory to create the perfect pet.

“Anybody can throw the ingredients in, but unless you know what ingredients are the best ingredients in the best percentages, you’re not going to produce the same final product,” Brodie told the U.K. wire service.

The problem? The Ashera doesn’t actually exist, and there’s no evidence Brodie has ever been in a lab, let alone spearheaded the creation of a new breed of feline.

Not an Ashera cat — A Savannah cat with clear Serval lineage is shown as an example of an “Ashera cat” on several websites about the fictional breed.

Sadly, people might not realize that right away because of the publish-now, verify-never nature of web publications. Catster maintains a current page for the “breed,” citing its “outstanding lineage” and its supposed status as “one of the rarest and most expensive cats in the world,” potentially setting back its owners $100,000 or more per cat. You have to scroll down before the site warns about the “controversy and skepticism regarding the breed’s origins,” as if there’s still a debate whether the Ashera is a real breed.

Sites I’d rather not link to include the Ashera in their lists of “most exclusive” and “rare” breeds, and recent Reddit threads claim their price owes partly to their rarity because the company “only breeds about 100 cats a year.” When’s the last time you heard cats didn’t breed enough?

There are even “Ashera cat communities” designed to make it look like there are large online groups of happy owners, and Youtube channels featuring videos of Savannahs labeled as Asheras.

A sketchy operation

But dig a little deeper and you’ll find the truth. The Savannah Cat Association calls the Ashera a hoax, says the cats are Savannahs with fancy marketing, and details experiences people have allegedly had with Brodie. His company appeared to be a one-man operation with a voice mailbox, and people who purchased the pets said they were told to wire down payments to an account in the United Arab Emirates.

There are even claims Brodie was drop-shipping the cats, with customers saying they were delivered directly from an Oklahoma breeder of Savannahs.

And the people who saw an opportunity to have a pet cat despite severe allergies? They weren’t happy either, even those who negotiated deep “discounts” with Brodie.

“I don’t think any cat is worth $4,000,” a customer named Mike Sela told Columbia Journalism review, “but this seemed like a magical opportunity, especially with parents trying to get something for kids. You never thought you could get a cat and this is your chance.”

A group of angry customers who were promised hypoallergenic pets contacted ABC News, whose Lookout team enlisted the help of a biotechnology company to test cats purchased from Allerca, Brodie’s company. The tests showed the Ashera cats had the same amount of Fel d 1, the primary allergen in feline saliva, as the typical cat and could find no evidence of Brodie’s claims that he’d engineered an exotic cat sans allergens.

CJR took mainstream and legacy press outlets to task for reporting uncritically on Brodie’s claims despite the lack of any documentation, peer-review studies proving gene-edited hypoallergenic cats are possible, and for a complete lack of due diligence on the man himself. Per CJR:

“What Time, National Geographic, and other major outlets, including The New York Times, missed was that Brodie has no background in genetics—but he does have a well-recorded background in running scams. He was arrested in England, his native country, for selling shares in a non-existent hot-air balloon company. In the United States, he has left a wake of evictions, unpaid loans, and suits by unpaid employees. One judgment against him that stands out is by a company called Felix Pets, founded about a year before Allerca with the same goal of breeding hypoallergenic cats by eliminating the Fel-D-1 gene.”

Indeed, as the complaints piled up and Brodie’s deceptions began to catch up with him, the San Diego Union Tribune reported Allerca had been evicted from its “offices” — Brodie’s home address.

Ashera cats scam — A listing for an Ashera cat and a second listing for Ashera kittens, bottom left.

News stories say Brodie has changed his name numerous times and if he’s still out there, he’s almost certainly not Simon Brodie anymore. But the Ashera cat scam isn’t dead.

We found dozens of sites offering “Ashera kittens,” and online marketplaces for animals still have regularly-updated listings from people claiming they’re selling “genuine” Ashera cats in 2024. There’s also at least one group claiming they’re “officially licensed Ashera cat breeders,” touting a lofty “mission” not only of providing cats for people with allergies, but also “preserving exotic wildlife.”

The myth of hypoallergenic cats

Although there have been recent efforts to neutralize Fel d 1, they come from actual scientists who have published their work for peer review, or from public pet food companies that have paired with scientists to create kibble they claim reduces the Fel d 1 allergen in cats who eat it. They’re also focused on attacking the protein, not breeding or creating cats that lack it in the first place.

People with allergies should understand that despite what they may read online, hypoallergenic cats do not exist. No one has been able to “engineer” a feline without the Fel d 1 protein.

There’s serious debate among geneticists about whether trying it is ethical, as no one knows exactly what function Fel d 1 serves or what the potential consequences may be for editing it out of feline genetic code.

So if you’re looking for a “luxury cat” or you just want a cat that won’t trigger your allergies, beware before you’re separated from your hard-earned cash. As always, if something sounds too good to be true, it probably is.

The People Who Clone Pets Want To Bring Back Extinct Species — And Clone Animals For Their Organs

Genetics, gene-editing and cloning have rapidly matured since the days of Dolly the Sheep, which means we have less time than we think to grapple with some heady moral questions.

Should scientists resurrect long-extinct species? Is it ethical to clone thousands of animals who will not live, but have their organs harvested for human patients?

Those are some of the questions people are asking as the cloning industry — once relegated to producing one-off copies and genetically identical versions of deceased pets for wealthy clients — is expanding with new capabilities.

This story by the BBC’s David Cox provides an informative, brief history of cloning before pivoting to the current state of the industry and how it could continue to evolve.

Two of the most fascinating prospects have to do with conservation. One company, Colossal, is working on bringing back the extinct woolly mammoth, while other scientists are turning to cloning as a way to prevent the extinctions of species like the white rhino, which is functionally extinct without any breeding pairs left living.

Dolly_face_closeup — Scottish scientists shocked the world when they cloned Dolly the Sheep in 1996.

As with anything in science, innovations in cloning unlock new applicative branches, and scientists have partnered with the medical field to address human health concerns. Some, like the practice of editing genes to prevent diseases in newborns, tend to fly under the radar. But others, like the push to adapt organs from animals like pigs so they can be replacements for human organs, are much more controversial and have met opposition from animal welfare groups.

Then there’s the elephant in the room, no pun intended. What about cloning humans?

Right now no one’s gone down that route, at least not publicly, because of the inevitable backlash. What’s happening deep in the bowels of clandestine medical facilities in nations with murky ethics laws is another question entirely.

I am opposed to human cloning, but I don’t believe it will remain the immutable taboo some people think it is. Someone will break the dam, and while that pioneer will likely get raked over the coals, the bell cannot be unrung. Things change so fast these days that what’s shocking one day merits a shrug the next, and it’s possible the world will be introduced to a man or woman one day before it’s revealed the person is, in fact, a clone. (Not unlike the way the world was introduced to Imma, a Japanese influencer and model who exists only digitally.)

Imma has more than 400,000 Instagram followers, she models the latest fashions and she appears in adverts for products like beverages and watches, but she doesn’t exist. She’s a digital creation.

They’ll be the Dolly the Sheep of the human race, and ethicists won’t get a say in whether they should exist because it’s already been done.

“See how normal they are?” people keen on cloning will say. “They’re just regular people. Are you going to tell them they shouldn’t live?”

But before that, it looks like the movie Gattaca will become reality, and people will order up a great baseball player or a child with intuitive musical genius just like they might commission a piece of art or a custom car job. Gene editing with CRISPR is surprisingly trivial.

Of course, it won’t be lost on people that we’re cloning humans when there are millions of unwanted, uncared-for street kids in the third world, not to mention people who live without the consideration of their fellow human beings in every nation. Just like it hasn’t escaped the notice of activists that South Korea and China are leaders in cloning pets, yet dogs and cats are also food in those countries.

What separates the dogs and cats bound for restaurant kitchens from the dogs and cats having their cells preserved for cloning?

Nothing except for their individual value to humans, just like pure luck separates a cat who finds a loving home from a cat who ends up euthanized with a needle. We are a fickle species.

Yet both the beloved pet and the unwanted shelter cat are sentient, experience intense emotions and have their own thoughts. That’s not conjecture, it’s fact as confirmed many times over experimentally, but it shocks a lot of people. Our education system has not done right by the billions of non-human minds we share our planet with.

Cloned monkeys — These rhesus macaque infants were cloned in a lab in China. The remaining barriers to human cloning are ethical, not technological.

I’ve thought about what might have happened if Buddy had been adopted by someone else, and what his fate may have been. I love the little guy, but it’s possible that someone else may have viewed him as an annoyance, a loud and incessantly chatty cat who needs an inordinate amount of attention and affection, sometimes lashes out, and needs to be surrendered.

Likewise, unwanted cats have languished in shelters for months before viral posts spark interest in them, and suddenly offers to adopt come in by the hundreds from across the globe. Nothing about those cats changed, but humans formed an emotional attachment to them after learning their stories.

Of course, the ethics of how we treat and consider animals can change depending on where you’re sitting. If you’re young, healthy and energetic, your view may be radically different than the person sitting on an organ donation waiting list, knowing their time may be up before a new liver or kidney becomes available. Suddenly a seemingly simple moral calculus becomes murky and complex.

There’s strong evidence that people who take the first steps toward cloning their beloved cats and dogs spend time wrestling with the ethics of the decision as well. Texas-based ViaGen, the western leader in commercial cloning, told the BBC that 90 percent of its clients are not people who have gone through with cloning, but have only taken the initial step of preserving their pets’ cells for $1,600.

And what of the mammoths? Bringing them back from extinction isn’t as simple as filling in the gaps in their genome, implanting gene-edited eggs in female elephants and hoping gestation takes care of the rest. Mammoths are social animals. Will an elephant mother raise a mammoth baby? Where does that mammoth baby belong? Without a herd of its own kind, can it be happy?

We can’t ask the mammoths, and even if we could, it might not be up to them anyway. As one paleogeneticist put it to NPR last year: What if the technology isn’t used to resurrect the mammoth, but to save the elephant? Does the end justify the means in the latter situation, but not the former?

Mammoth, Dolly the Sheep and rhesus macaque images credit Wikimedia Commons

Why Creating ‘Hypoallergenic Cats’ With Gene Editing Is A Bad Idea

Looking to break into the profitable hypoallergenic cat market, scientists have turned their efforts to editing cat DNA.

On paper, the promise of “hypoallergenic cats” sounds great.

For the first time, people who love cats but are allergic to the furry little guys would be able to open up their homes to them. More cat lovers and more homes for cats is always a good thing, right?

Maybe not in this case.

The quest to create cats who do not trigger allergies depends on CRISPR gene editing, a method that allows scientists to edit, delete and replace sections of the genome. In this case, Virginia-based biotech company InBio wants to edit the genome of domestic felines to block Fel d 1 (Felis domesticus allergen I), a protein produced in cat saliva and in tiny subdermal exocrine glands, which secrete the protein via the same ducts that allow a cat’s fur to grow out from its skin.

Since cats are fastidious neat freaks and groom themselves constantly, the Fel d 1-carrying saliva is applied to their coats several times a day. When it dries, it contaminates a cat’s living space by flaking off the fur as dander or by shedding.

That’s why people who are allergic to cats can suffer symptoms like sneezing, itching and watery eyes not only from petting them, but also from spending time in homes where cats live.

What does Fel d 1 do, and why do cats need it?

The problem is that no one knows why cats produce Fel d 1 and what purpose it serves. Other proteins, like Fel d 4 found in pheromones and Fel d 2, help cats communicate by scent and prevent certain fluids from leaving the bloodstream, respectively.

Take a look at this quote from Nicole Brackett, a geneticist at InBio: (The emphasis on certain words is ours)

“The gene sequences don’t appear to be that well conserved over the course of evolution, which suggest things about whether or not the gene is essential,” Brackett told BioSpace, a life sciences publication. “An essential gene, one that would be required for survival or viability, generally doesn’t change much over evolution, and we’re seeing change between the exotic and domestic cat that suggests that maybe those sequences are not conserved, and maybe the protein is not essential.”

While we understand scientists have to be circumspect, especially regarding research that breaks new ground, that’s a lot of hedging and a lot of uncertainty. (It’s also not clear if Brackett is comparing domestic feline Fel d 1 levels to wild cats — felis sylvestris and lybica — wild felids in general, or hybrids like Bengals and Savannah cats, which are more commonly called exotics.)

cute cat lying on pillow — Credit: cottonbro/Pexels

The team members developing the allergen gene edit assume Fel d 1 doesn’t have a critical function because individual domestic cats and other species of felids may produce different quantities of the protein.

But that’s a huge assumption, and it’s also presumptuous to assume we humans would know whether the gene edits have a major impact on felines. After all, we still don’t always know when cats are in pain or the reasons for many of their behaviors, and we don’t know what sort of cascade effect can be triggered by shutting down the production of a protein.

The race to make cats hypoallergenic

Companies see a huge opportunity for profit in the cat allergy alleviation market. Last year, Purina announced to much fanfare the availability of a new kind of cat food the company claimed would drastically reduce allergens after about three weeks of putting kitties on the new grub.

The claims haven’t been independently verified, and most press coverage is either credulous or consists of marketing masquerading as news coverage, like this advertisement from Purina that is presented like a news story in USA Today.

Back when a company called HypoCat announced it had conducted successful trials of a “vaccine” that would “neutralize’ Fel d 1, we spoke with immunologist Kamal Tirumalai, who pointed out that humans making such profound changes to companion animals for the sake of human convenience “passes neither the scientific nor the moral smell test.”

Like others, Tirumalai said she worried about unintended consequences.

“A vaccine given to cats to reduce their allergenicity for humans burdens them unnecessarily when human allergy to cats is primarily a human problem and should have a human solution in the form of reducing people’s cat allergies,” Tirumalai told PITB at the time. “Cats are perfect as they are. Why should they be the ones forced to change in order to be accommodated by a human whose immune system happens to have a problem with one of their proteins? This solution just doesn’t pass the moral smell test.”

HypoCat uses an injection to “induce anti-Fel d 1 antibodies in the cat,” while the CRISPR technique would snip the relevant DNA out entirely.

“Come now, let us not be absurd. Do you really think a designer kitten could be as handsome as I am?” Credit: Big Buddy

So far, Brackett and her colleagues have deleted one of two cat cells that produce Fel d 1 in samples in a petri dish, and have not made any changes to live animals. The experiments yielded a “55 percent knockout rate” for the Fel d 1 allergen, Brackett said, “which we were really happy with.”

Designer kittens: Gattaca for cats

If subsequent attempts are successful and the company sees commercial promise in editing feline genes, the process could be used to create “designer kittens” or to alter the genomes of existing cats. Brackett told Smithsonian magazine that the goal is to accomplish the latter.

But if it turns out the edits don’t work for existing cats, or the designer kitten trend becomes a thing, there’s another major moral concern similar to the objections to cat cloning. If people buy designer kittens, they’re not opening their homes to the millions of cats who need them.

Manipulating feline DNA isn’t a novel idea. A decade ago, a research team spliced genes from jellyfish using a different method to create cats who glow in UV light as part of a study into feline immunodeficiency virus (FIV).

Ultimately it comes down to what we’re willing to do for the sake of our own convenience. At a time when declawing has finally been outlawed in two states and dozens of cities, and people are more conscientious than ever with regard to their pets, do we want to risk their health so we don’t have to pop a few Benadryl?