Notes on Animal Health, August 2025: Is Better Breeding Best?

Genomic engineering is not new. Humans have engaged in selective breeding of plants and animals long before the discovery of genes or DNA. Dogs were, for example, initially domesticated from wolves thousands of years ago. Most of today’s 350 plus breeds, however, have appeared in just the last 200 years, when humans created them by cross breeding dogs that possessed desired traits, such as a particular body size, coat color, or temperament. Through this process we have created different breeds of almost every domesticated species from cats to pigs to horses to cattle. The traits that distinguish one breed from another are the results of genes, and therefore, when we subject a species to selective breeding, we are engineering their genome in a fundamental way.

New technologies, however, allow us to engineer or edit the genomes of plants and animals, including humans, with amazing speed and increasing accuracy. Developing a new breed used to take several decades; now, it’s several years, and soon it may be a matter of months. These new tools are also being deployed to correct genetic mutations that cause diseases in plants, animals and humans. The promise of genome editing is enormous, but there are ethical implications to consider, including unintended consequences, animal welfare, and its long-term effects on genetic diversity.

What Exactly is Genome Editing?
We have been able to create novel combinations of DNA sequences, referred to as recombinant DNA, since the 1970’s. A sea change occurred, however, in 2012 when Jennifer Doudna and Emmanuelle Charpentier demonstrated that the bacterial CRISPR-Cas9 enzyme, along with a guide RNA, could be used to precisely target and cut DNA, enabling programmable genome editing. In 2020, the pair won the Nobel Prize in Chemistry for their discovery.

CRISPRs are Clustered Regularly Interspaced Short Palindromic Repeats found within bacterial DNA. Inserted between CRISPR arrays are DNA sequences from viruses and bacteriophages that were copied by the bacteria during previous infections. If the bacteria are infected again by these same viruses or bacteriophages, they can use these copied sequences to guide CRISPR-associated sequence (Cas) proteins to the complementary DNA or RNA of the virus or bacteriophage. The Cas protein then snips the DNA or RNA, like a pair of molecular scissors, preventing the invader from replicating. In this way, the CRISPR-Cas system functions as a defense mechanism for bacteria.

Although the CRISPR-Cas9 system is the most well characterized, there are many other CRISPR based proteins, providing, in essence, a large toolbox of gene editors. These CRISPR-based systems represent a significant advancement in the precision of gene editing, but unintended consequences can still occur. For example, the CRISPR-gene editors can make unintended edits at locations in the genome other than the original target site. These off-target edits can lead to DNA damage, immune responses, cytotoxicity, and disruptions to gene function.

CRISPR-gene editors could also affect genetic diversity within a species. They can be used to increase genomic diversity by introducing specific mutations into a genome, mimicking natural variations or creating novel ones.

The Current State of Genomic Editing
CRISPR- gene editors have been used in a number of species, including horses, pigs, sheep and dogs. Gene editing in animals, however, can raise significant animal welfare concerns due to the possible unintended consequences and invasiveness of the techniques. Results of studies conducted on dogs provide ample illustration. In 2015, investigators used CRISPR-Cas9 to disable the myostatin gene in dog embryos. Myostatin inhibits muscle development, so when the gene is disabled, the animals develop large, hypertrophied muscles. Therefore, simply by looking at the puppies the researchers could determine if the genome editing process was successful. In that study, over 60 canine fertilized eggs were collected and implanted into 16 surrogate females. Ultimately, 27 puppies were born from the eight surrogates that became pregnant, but only two puppies had disabled myostatin genes. Although the study was inefficient, requiring many dogs to produce only two gene edited puppies, disabling the myostatin gene had no obvious negative consequences for the dogs. Unfortunately, that is not always the case.

In a 2018 study CRISPR-Cas9 was used to disable the apolipoprotein E (ApoE) gene in dog embryos. The puppies born with disabled ApoE genes developed severe and widespread atherosclerosis, causing gangrene and ischemic strokes by the time they were 18–24 months of age. The goal of the study was to develop an animal model for atherosclerosis, which is one of the most common causes of morbidity and mortality in humans. Nevertheless, the disease is almost unheard of in normal dogs, and therefore these gene edited dogs experienced significant pain and suffering with no potential benefit to the dog, either individually or as a species.

There have also been studies aimed at creating dog models for human diseases, such as Parkinson’s disease and Duchenne’s muscular dystrophy. On the more positive side, there has been at least one attempt to use genome editing methods to cure a genetically associated disease that does occur naturally in dogs, hip dysplasia (HP). In dogs, HP is a degenerative condition of the hip joints that has a strong, but complex, genetic association. It is common in larger breeds and is characterized by progressive pain, lameness, and reduced mobility. In 2020, researchers found 25 single nucleotide polymorphisms, or genetic markers, that correlated with the development of HP in Labrador retrievers. In 2024, they used CRISPR-Cas9 in dog embryos to correct the mutation with the strongest correlation to HP. The study was successful in the sense that puppies were born with the corrected DNA sequence, but at the time of publication the dogs were too young to determine whether that single change would affect the development of hip dysplasia, which typically develops later in life.

Because of selective breeding, the genomes of purebred dogs are generally less diverse than mixed bred dogs, and as a result they suffer from a higher prevalence of genetically inherited diseases. Unlike HP, many of these diseases are caused by single gene defects, making them better targets for genomic editing. Nevertheless, treating individual dogs using somatic gene editing methods is not currently financially feasible. For example, Casgevy, the world’s first CRISPR-based cell therapy approved for the treatment of sickle-cell disease in humans, costs $2.2 million per patient. Germline editing, which entails making the edits in the DNA of eggs, sperm, or embryos, would be more cost effective and is appealing because the goal would be to “fix” the entire breed, but it would require monies and significant cooperation among breeders. Nevertheless, this approach could also allow new traits, such as decreased shedding or specific coat colors to be introduced in a breed, truly creating “designer dogs”.

This has already been done in the horse. Earlier this year, Argentinian scientists reported that they created the world's first genetically modified polo horses using CRISPR-Cas9. They incorporated specific genes related to muscle development from a renowned polo mare, Polo Pureza, to improve explosive power while keeping the champion horse's other qualities. As the methods of gene editing continue to advance with improved specificity and efficiency, it is likely only a matter of time before we see the commercialization of gene edited dogs.

Genomic editing is already being commercialized in production animals. In April, the FDA approved the use of a gene-editing technology that creates pigs resistant to the porcine reproductive and respiratory syndrome (PRRS). PRRS, which is caused by an arterivirus, is highly contagious and produces pneumonia, immunosuppression and reproductive failures in pigs. It is estimated that between 2016 and 2020 the U.S. pork industry lost $1.2 billion per year due to mortality and morbidity caused by PRRS. Researchers are also trying to create pigs resistant to African swine fever and chickens resistant to avian leukosis virus.

Genomic editing holds great promise to benefit humans and animals. The cost is still exorbitant but as methods improve it will no doubt decrease, and usage will rise. Along the way, we should keep asking and addressing the ethical questions that accompany this innovative engineering.

– Cindy Cole DVM, PhD, DACVCP



First Five
First Five is our curated list of articles, studies, and publications for the month.‍

1/ An Unlikely Friendship
Recently the Western Plains Zoo in Dubo, Australia recruited a puppy to help socialize a precious cheetah cub. The cub, named Rozi, had been delivered by emergency caesarean surgery after her mother, Siri, went into labor early. Because Rozi was sick for the first few weeks of her life and her mother never produced any milk, zookeepers separated the two. When Rozi was about 2 months old she was gradually introduced to Ziggy, a labrador-kelpie-collie mix around the same age. The two have become fast friends, playing and napping together. At some point, the zoo will separate the two, and reintroduce Rozi to other cheetahs, but for the time being they are keeping each other happy and zoo visitors entertained.

2/ Octopus Are Even More Like Us
We instinctively know our hands and legs belong to us when we see them. This perception, known as the sense of body ownership, is a fundamental aspect of self-consciousness. Although studies show that this sense exists in some mammals, such as humans, monkeys, and rodents, research on its existence in non-mammalian animals is still lacking. In humans, this illusion involves covering a person’s hand so they can no longer see it, then placing a realistic-looking rubber hand next to it. When both are touched simultaneously, many individuals begin to “feel” the sensations in the fake hand—and feel like the alien appendage is their own. In a recent study, researchers used a rubber tentacle and conducted a similar experiment in an octopus, an invertebrate (cephalopod mollusk), which also demonstrated an awareness of body ownership of its arms.

3/ Have Dire Wolves Been Brought Back From Extinction
Colossal Biosciences claims three pups born recently are dire wolves, but according to an article in the New Scientist, they are actually grey wolves with genetic edits intended to make them resemble the lost species. Dire wolves are large, extinct canines (Aenocyon dirus) that lived in the Americas until around 10,000 years ago. Colossal claims that the grey wolf and dire wolf share 99.5 per cent of their DNA. Since the grey wolf genome is around 2.4 billion base pairs long, that still leaves room for millions of base-pairs of differences. Colossal indicated it made 20 gene edits to the grey wolf genome: five of those mutations were known to produce light coats in grey wolves, and the other 15, based on the dire wolf genome, were intended to alter the animals’ size, musculature and ear shape. It will be a year or so before it’s clear if those changes have had the intended effects on the genetically modified animals. So, although they may look like dire wolves, it is difficult to conclude that they are actually the revived species.

4/ Some Dogs Prefer Yellow
A recent study investigated the importance of color to untrained Indian free-ranging dogs (FRDs). Using one-time multi-option choice tests for color preference in 134 adult dogs, the study found the dogs preferred yellow objects over blue or gray, with little to no preference between blue and gray. Next, a yellow object was tested against a gray object containing food. Surprisingly the dogs ignored the food and approached the yellow object first indicating the color preference to be quite strong. Color preference has previously been investigated in many other animals and has implications for behaviors like mate choice and foraging. There are plans to study companion dogs in other parts of the world to determine if this is a common trait or one specific to the dogs in India.

5/ More Bad News For The Planet
Several of the world’s most extraordinary fish could be in danger of extinction due to a massive bloom of toxic algae engulfing parts of the southern coast of Australia. In March, a massive algal bloom of the species Karenia mikimotoi broke out in Gulf St Vincent near Adelaide, South Australia. This has resulted in mass deaths of fish and other marine life, with dolphins, sea lions and even great white sharks washing up on beaches. Thousands of dead leafy seadragons (phycodurus eques) and common weedy seadragons (phyllopteryx taeniolatus), are being found along hundreds of kilometers of the South Australian coast. As these species were already vulnerable, this event may have implications for their long-term survival.

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