One Health

Welcome to the first edition of Notes on Animal Health brought to you by Digitalis Ventures.

Through our Companion Funds, Digitalis Ventures invests in solutions across the pet health ecosystem. In doing so, we aspire to framing and tackling the most important open problems and opportunities in providing for the health and welfare of our pets. This newsletter will periodically provide notes on our efforts in an attempt to “show our work.” We invite you to be in touch with your ideas about important petcare problems and potential solutions. And we look forward to working with you to develop the best solutions at scale to deliver better health to all.

– Geoffrey W. Smith

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It is particularly easy these days to find ourselves focusing on our differences as humans—different political beliefs, cultures, religions, and diets, to name just a few. However, one thing almost all of us share across the globe is interaction with animals.

We may hunt them for food or consume meat from animals that others have raised. We may adopt and care for them, or we may simply share our environment with them. This cohabitation with animals, in one form or another, is certainly nothing new. In many ways, animals have been essential in the development of human civilization.

While which exact traits separate us from animals is constantly debated, certainly our domestication of plants and animals is unique. It eventually allowed us to form permanent camps, moving away from our ancestor’s traditional nomadic lifestyle, following herds of animals for hunting and foraging edible plants. As those camps turned into villages, cities and eventually the metropolises of today, the types of interactions we have with animals came to vary a great deal depending on our local environment. For the farming family in sub-Saharan Africa, their goats and cattle provide not only sustenance but are also an inheritable form of wealth. They may also keep dogs to safeguard the family and livestock and to help hunt wild game. By contrast, the apartment dweller in the city may have very limited interactions with animals, their own or a friend’s cat or dog, or perhaps just the birds and squirrels in the park.

Despite these tremendous variations in the level and frequency of our interactions with animals, it has become increasingly apparent in recent years that we all must share one ecosystem. Our health and welfare, and indeed even our lives, are intimately entwined. Many of the pioneers of modern medicine, such as Louis Pasteur, Rudolf Virchow, and William Osler, recognized the connection between man and animals, but the formal articulation of the concept of the health and welfare of man and animals being intimately interconnected is fairly recent. Public health veterinarian Calvin Schwabe, known as the father of veterinary epidemiology, coined the term “One Medicine” in 1976. Eventually the term morphed into “One Medicine, One Health,” and finally “One Health” was adopted in the early 2000’s.  As a concept, One Health was first embraced by the public health sector in the United States after a series of zoonotic outbreaks from 2002-2016, including Severe Acute Respiratory Syndrome (SARS), Ebola, and H1N1 influenza or Swine flu. However, the current definition stresses an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, and ecosystems.

While the traditional focus for One Health has been to reduce the risk of the transmission of zoonotic diseases from wild animal populations to humans, one of the best examples of the success of the One Health approach involves wild and domestic species. Rabies kills an estimated 59,000 people annually across the globe and the vast majority of human cases are acquired from domestic dogs. However, in the US, which has a robust vaccination program for companion animals, there are typically fewer than three deaths per year. Underscoring the need for continued diligence, though, in 2021 there were five rabies-related deaths in the U.S. which was the highest number in a decade. Expanding the success of US rabies-control to developing countries is the focus of the Global Alliance for Rabies Control which aims to end human deaths from rabies by 2030.

Beyond infectious diseases, One Health approaches have numerous applications involving companion animals. For example, biomedical research has traditionally used rodents and non-human primates as models for human diseases. However, dogs and cats share not only our environment but suffer from many of the same diseases as we do. It is hoped that mechanistic and therapeutics discoveries in dogs and cats will benefit not only those species but also humans.

The dog has garnered the lion's share of attention as a model for human health and disease. In fact, the National Institute on Aging’s Division of Aging Biology funded a five-year, $23 million grant for the Dog Aging Project which is a nationwide, long-term longitudinal study of aging in tens of thousands of companion dogs. The goal of the project is to better define aging in dogs, uncover genetic and environmental factors that influence aging, and test interventions that may positively impact lifespan and health span in companion dogs. The dog has also been proposed to be an excellent model for cancer, osteoarthritis, and epilepsy, among other diseases.

There are some reasons to question the value of the dog as a model for human disease, however. For example, in terms of cancer, while lymphoma is one of the most common cancers in dogs and humans, mast cells and hemangiosarcoma also occur commonly in dogs but rarely in humans. In a similar manner, while both dogs and humans share some cardiac diseases, such as dilated cardiomyopathy and mitral valve regurgitation, the most common condition in humans, coronary artery disease (CAD), is virtually nonexistent in dogs. One could argue though that understanding the differences in the metabolic processes between the two species may provide us with better insights into the pathophysiology of CAD because common risk factors in humans (obesity, poor diet, lack of exercise, etc.) are not associated with an increased risk of developing the disease in dogs.

While much of the focus has been on the dog, almost as many people in the U.S. share their households with cats. And for a number of conditions cats may be better models for human disease than dogs. For example, cats are one of the few non-primate species that spontaneously develop Type-2 diabetes and the pathophysiology of the disease in cats is similar to that observed in humans. Cats have also proven to be excellent models for a number of inherited ophthalmological diseases, including primary congenital glaucoma and retinal degeneration. In addition, compared to mice,  which are the species traditionally used to study eye diseases, cats have a larger size, longer life, and a genetically more heterogenous background, as well as sharing a number of anatomic and physiological similarities with humans, such as binocular vision and a dual retina, with rod photoreceptors greatly outnumbering cones.

We have shared our world with animals for thousands of years and benefited in a myriad of ways. Now we are recognizing that beyond sustenance, companionship, and protection animals can also provide important insights into shared disease processes. These insights may lead us to discover new prevention strategies and treatment modalities that will benefit both humans and pets.

– Cindy Cole, DVM, PhD, DACVCP



First Five

1/ A purrfect mystery?
One of the great mysteries of the animal world has now been solved. Scientists have struggled to understand how cats produce a low-pitched rumbling sound when they purr, but a new study sheds some light on the mystery. The purring sound that domestic cats make, along with some wild species such as cheetahs and lynxes, is lower in frequency than is typically produced by mammals with small larynxes. It turns out that cats have connective tissue embedded in their vocal folds that can lower the frequency of the sounds they produce.

2/ Good works with AI
In a recent study a deep learning-based algorithm was evaluated for its ability to detect common quality issues in the chest radiographs of dogs. The algorithm had high accuracy in detecting limb mispositioning, as well as blurred images, foreign objects, underexposure, overexposure, rotation, and neck mispositioning. The algorithm had fair accuracy in classifying normal radiographs. The current program can alert veterinarians and technicians when there are issues with the quality of a chest radiograph, so that it can be quickly retaken, saving time and assisting with a prompt diagnosis. Eventually, it is hoped AI may be better than humans at detecting subtle abnormalities in radiographic images which may allow for earlier detection of disease, which may correlate with better treatment outcomes.

3/ The “flat-faced paradox”
This past year the French Bulldog over took the Labrador Retriever as the most popular breed in America after 31 years. In fact, short-headed, flat-faced, dog breeds, referred to as brachycephalic breeds, are increasing in popularity despite the fact that brachycephalism is associated with a range of serious health issues which has been described as the “Flat-Faced Paradox”. In a recent study investigators compared the problem-solving ability of two brachycephalic breeds (English and French bulldogs) to that of a breed with a normal shaped head the Mudi breed. The Mudi’s were much better at solving the problem while the brachycephalic breeds were more focused on the humans present. The researchers speculate that owners might interpret these behaviors as “helplessness” supporting the hypothesis that infant-like traits may be present not only in appearance, but also in behaviors, in brachycephalic breeds, eliciting caring behaviors in owners.

4/ Vaccination hesitancy in pets?
The results of a nationally representative survey of over 2000 adults in the US found some disturbing trends around vaccine hesitancy in dogs. For example, a large minority of dog owners consider vaccines administered to dogs to be unsafe (37%), ineffective (22%), and/or unnecessary (30%). Almost half of those surveyed were opposed to mandatory vaccination requirements for diseases such as rabies, even though unvaccinated dogs are the most common source of human rabies infections in other parts of the world.

5/ Are we shortening our dogs’ lifespans?
Several recent studies have demonstrated the negative effects of inbreeding in purebred dogs. As discussed in a recent article published in Slate, Golden Years, the selection for specific breed characteristics may inadvertently bring along deleterious mutations that may be decreasing the life span of some breeds, such as Golden Retrievers, or increasing the incidence of specific cancers in others, such as Bernese Mountain Dogs.

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