We’re All In This Together: The Integral Role of Animal Biology and Human Health
Contributed Commentary by Ashley Zehnder
December 10, 2020 | COVID-19 has brought the link between animals and humans to the forefront, but given that we share more than 97% of our DNA with mammals, it’s time that we begin to consider diverse animal models not from a perspective of simply modeling human disease, but from a perspective of novel discovery and leveraging unique biology to find new pathways for therapeutics. From treatment of traumatic brain injury to improving survival from heart attacks and even increasing lifespan, we see even more parallels between human diseases and that which evolution and biology have made possible in animals.
Animal Genomics for Human Health
The CDC estimates that 3 out of every 4 emerging infectious diseases originate in animals, meaning, not only is it important to be aware of diseases circulating within the animal kingdom, but we have many opportunities to study disease variation, different responses to diseases, and differences in immune responses that result in very different outcomes for the affected human or animal. The false separation of “human” and “animal” diseases is an antiquated notion. Outside of basic physiology and genomics, the linkage between animals and humans affects nearly every aspect of our lives, from the environment to antimicrobial resistance to food security to rare disease biology.
More specifically, we can use animal genomics to understand fundamental truths of how mammals (including ourselves) control metabolic rate to reveal treatments for traumatic brain injury, avoid lethal blood clots, and combat lifestyle diseases such as obesity, and much more. Research has shown that cross species conservation is twice as predictive as any other factor in determining if a gene plays a role in disease. It’s important for us to remember that humans are also animals, and by ignoring these key evolutionary relationships, we cannot truly understand ourselves. On the contrary, by studying other animals, we can learn more about disease etiology and find ways to naturally combat and cure disease with animal genomics.
In one dramatic example, the very idea that genes can cause cancer comes not from studying cancer in humans, but from studying cancer in chickens. In 1911 Peyton Rous, an American virologist, expanded his observations of naturally occurring cancers in chickens into two major discoveries: the first being that viruses can cause cancer and the second—and arguably more importantly—later researchers built on his initial findings to demonstrate how viruses can co-opt our own genes to drive cancer. This, the discovery of oncogenes, is one of the core discoveries in cancer biology and genomic medicine. It paved the way for new therapies that target mutated, fused, or overactive cancer genes like Gleevec (approved in 2001) and much more recently Vemurafenib, the first targeted therapy for melanoma.
Examples of Animal Insights:
Hibernating mammals could reveal treatments for traumatic brain injury and the long-lasting effects of traumatic brain injuries suffered before arriving at a hospital. These animals experience long-term suspended animation in torpor and receive cerebral blood flow at only 10% of the normal rate, yet they are able to protect their brains from this ischemia and subsequent reperfusion upon arousal. Because ischemia and traumatic brain injury share common pathologies including inflammation, oxidative stress, excitotoxicity, and perturbation of calcium homeostasis, adaptations in hibernators may also be useful in protection against traumatic brain injury in humans if we can gain a better understanding of the pathways utilized by hibernators to protect brain tissue from injury
Investigators studying 13-lined ground squirrels have already discovered that these animals have developed ways to reduce clotting and resist damage from cardiac infarction. Ground squirrels survive dramatic changes in blood flow during consecutive bouts of torpor and interbout arousals throughout their 6-7-month hibernation season. Ground squirrels, bears, and hamsters have developed antithrombotic adaptations including thrombocytopenia and decreases in vWF, Factor VIII and Factor IX to avoid lethal blood clots during hibernation and resist cardiac damage. By using multiple types of genetic data from 13-lined ground squirrels, we have been able to identify two novel compounds that reduce infarct size by up to 73% in animal models of heart attacks.
Animal Genomics to Fight the Pandemic
While animal genomics can give us insight into how to improve overall human health, we can also utilize animal genomics from the standpoint of preventing disease in the first place. In fact, research suggests one of the closest known ancestors of the virus that causes COVID-19 emerged in bats more than 40 years ago.
It is well-known that while bats are reservoirs for many of our most feared viruses (Rabies, Hendra, Ebola, Marburg and SARS-CoV), they do not actually cause diseases in these hosts. A recent study released by scientists at Girihlet examined immune responses in Egyptian rousette bats to Ebola and Marburg infections and documented key differences not only in the immune response, but also in pathways relating to blood pressure regulation and clotting that allow bats to survive infections that rapidly kill humans. It is not only mammals that we should be looking to for clues to novel viruses.
A few months ago, investigators identified a novel nidovirus in Pacific Salmon causing localized infections of the gills. Nidoviruses are evolutionarily closely related to coronaviruses, and by examining similarities and differences in respiratory disease resulting from this viral family across a range of species, we can start to understand more about how different species respond to infection. The many ways that human and animal data intersect is an emerging field and there are a multitude of avenues to explore—including how to apply these learnings to inform treatment and improve human health. For example, recently, investigators have also used special antibodies from llamas (called nanobodies) to develop a potential new therapy to trap SARS-COV2 particles within human nasal passages and help prevent infections.
It is intuitive that genes and pathways conserved over hundreds of millions of years of evolution are probably doing important things. However, what is missing from this approach is an understanding of how those genes, and subsequently proteins, are changing in animals in conditions that mimic or better model human diseases (and natural resistance to diseases) than the mice, rats, fish, flies and worms we use today. In short, functional genomics. This is the focus of our exploration at Fauna Bio as we seek to uncover more about nature to improve human health.
Ashley Zehnder, DVM, Ph.D., is Founder and CEO, Fauna Bio. Prior to starting Fauna Bio, Ashley’s research focused on translational science and veterinary informatics at Stanford, earning a PhD in Cancer Biology and her work spans >20 peer-reviewed publications, including Cell, Nature and Nature Medicine and several book chapters. She is a boarded avian veterinarian with specialty training in exotic/non-traditional species. She is a co-founder of the Exotic Species Cancer Research Alliance and incoming president of the Association of Avian Veterinarians. She can be reached at firstname.lastname@example.org.