For much of Barbara Natterson-Horowitz’s career, her work revolved around one idea: the field of human medicine has suffered from being too human-centered. Natterson-Horowitz is a cardiologist, psychiatrist, and evolutionary biologist who co-authored the 2012 book “Zoobiquity: the amazing connection between human and animal health.”
When people think about the connection between human and animal health, they often think about zoonotic diseases, preventing the next pandemic, or antimicrobial resistance on farms, Natterson-Horowitz said. They usually don’t think about all the diseases we have in common, like how horses can get melanoma or how killer whales can get Hodgkin’s lymphoma. Or that dolphins can get genital herpes and koalas can get chlamydia.
Zoobiquity focuses on medical issues such as heart disease, cancer and infertility, as well as the psychiatric and behavioral diseases that affect people. And millions of animal species experience the same thing. Natterson-Horowitz argues that by viewing health through an evolutionary lens, we can better understand the causes of disease and accelerate the discovery of new treatments.
“What if we started thinking about animals that might have evolved physiology that solves some of the problems that our human physiology hasn’t yet solved?” said Natterson-Horowitz. “[Evolution] is research and development into the highest dose of steroids ever.”
Natterson-Horowitz is a professor of cardiology at UCLA and teaches human evolutionary biology and global health and social medicine at Harvard. She spoke with STAT’s Nicholas St. Fleur in June Aspen ideas: health about how we can use animal health experts to solve human medical problems. Here are edited excerpts from that panel discussion and a subsequent interview in July.
Tell me about yourself and your work.
I am a cardiologist and evolutionary biologist, and the first twenty years of my career were spent as a professor of medicine in cardiology. But for the past decade I have been studying the links between human and animal health. And I have become convinced that answers to perhaps the most vexing challenges in human health can be found in the natural world, especially in the animal kingdom. What I do is innovate strategies to find those answers and turn them into solutions, which we can then bring back to the human bed. After all, people are animals.
What was that moment that turned the switch for you, when you, as a doctor, realized that you also had to look into the animal kingdom?
Around 2005, the Los Angeles Zoo had some great apes with cardiovascular problems, and they wanted a human cardiologist to work alongside the veterinarians. Every now and then I would get a call to go to the zoo to see a chimpanzee with heart failure or a gorilla that they said had a ruptured aorta.
I graduated from great apes to bears and lions. We had a lion with a collection of fluid in her pericardium. It’s called a cardiac tamponade. It’s a diagnosis that’s not uncommon if you work in a busy city hospital. But on a lion it was incredible to see. And what I started to see was that there were a lot of conditions that I had never really thought about whether other species were also vulnerable to these diseases… Over the years I saw so many similarities. I learned so much from veterinarians, and I was humbled in ways I thought impossible about how little I knew as a doctor and how much I could learn.
Are there any specific stories from your work in animal health that made you think to yourself, “Why hasn’t anyone applied this to humans?”
One of them has to do with maternal health. Breastfeeding. The American Academy of Pediatrics recommends breastfeeding for two years, but less than 20% of American women can breastfeed for a year. Many of them stop because of a painful infection in the breast called mastitis.
That’s why I turned to the dairy industry and to some dairy veterinarians. It appears that about a hundred years of research has been conducted into the prevention of mastitis in dairy animals. They have a non-invasive, surprisingly inexpensive approach to preventing this. I went on rounds with this dairy vet in central California. They take a wooden paddle and there are four petri dishes on it. While the milking process is taking place, they take a few drops of milk and add it to the bowl.
That test has a sensitivity of 90% for detecting what is called subclinical mastitis. In other words, the cow doesn’t even have symptoms; there are only a few inflammatory white blood cells in the milk. Guess how much it costs? There is a one-time upfront cost for the paddle, $5 to $15. And each test costs $0.10 to $0.25. They have an intervention that is also non-invasive… If they find that there is subclinical mastitis, they simply change the milking schedule.
So the question is why on earth hasn’t this been introduced into human medicine?
Why on earth isn’t that the case?
Human exceptionalism! It’s a scientific blindfold. It prevents us from recognizing connections. And I think it’s the tendency to think, “Oh, we’re people, they’re cows.” Instead of: “We are both mammals.” The biology of lactation is highly conserved across mammalian species. We look at differences. We do not look at commonality. And because of that we miss so much.
I want to know exactly what the human version of that knowledge is and pass it on to lactation consultants, pediatricians and gynecologists. A hundred times more scientific studies have been written on the prevention of mastitis in cows than in women. It’s very activating because of how absurd that is.
What else do you think we’re missing because of this blindfold of human exceptionalism?
Where it is a big blindfold is when it comes to mental health. There is still the idea that psychiatric disorders are a human problem and not an animal problem. I think we all know now that if we have dogs and animals in the house, that’s not the case.
If you think of biodiversity not just as pretty colored animals in the rainforest, but as neurodiversity in the entire animal kingdom, then any animal with a brain or a central nervous system of any kind, including invertebrates, including insects – if it can be healthy , it can be unhealthy. We see fear in all species. In vertebrates we see depression. Depression has an evolutionary purpose. It evolved in social fish about 450 million years ago, and we can learn a tremendous amount about it.
What does applying a zoobiquity lens to medicine look like?
A zoobiquitist approach, if I can call it that, is to look at a medical problem in humans that has been very difficult to solve and then ask the question, “Is there a non-human animal whose physiology might have already solved that problem?” Has evolution produced a solution?” Then there’s a whole process of identifying what that species might be. Their genome is then examined and how this resistant physiology arises. CRISPR [genome editing]I think this will be one of many technologies to ideally – once you find the species that has the solution – find ways to modify the human phenotype to confer that kind of protection or resistance to whatever the disease is.
What is an example of this?
I’m a heart doctor and I’m a woman. One of the biggest focuses of the National Institutes of Health right now is a condition called HFpEF [heart failure with preserved ejection fraction]a leading cause of heart failure in women. People with high blood pressure often develop HFpEF where the heart becomes very stiff due to fibrosis. So we thought: can we turn to the animal world to find a solution for HFpEF? We turned to the giraffe.
Why the giraffe?
The hypothesis is that there is something special about the giraffe’s heart that exposes it to a high blood pressure of 280/180 – normal for us is 120/80. Giraffes have somehow evolved the ability not to develop this form of heart failure, even though their blood pressure is so much higher than ours. What is that adjustment then? What is that solution?
We have the giraffe’s genome and can compare it to its closest relative that does not have a long neck, the okapi. The giraffe’s long neck causes high blood pressure. They shared an ancestor about 11.5 million years ago. We can specifically identify what is unique about the giraffe heart from a genomic perspective. A group led by Chang Liu in 2021 in scientific progressWhen they compared these two genomes, they found that there were a number of differences between the giraffe and the okapi. One of these was the FGFRL1 gene, which is involved in high blood pressure and hearts.
They took a group of mice and introduced this giraffe FGFRL1 CRISPR into the mice. They had two populations, the wild-type mice that just had normal mouse FGFRL1, and then they had these mice that had giraffe FGFRL1. They exposed both populations of mice to something called angiotensin II, which actually increases blood pressure. The mice that had the giraffe FGFRL1 did not develop the fibrosis. But as you would expect, the wild color had a lot of fibrosis.
What this tells us is that there may be a way to harness this adaptation, which has taken 11.5 million years of evolution, and bring giraffe FGFRL1 to the bedside for my human patients. Many people are working on this.
What other animals should we look to to potentially solve human health problems?
There are a lot of animals that are cancer-resistant to some degree, such as bowhead whales, some bats, and of course the classic elephant story. African elephants have multiple copies of this cancer-suppressing gene called TP53. And some studies have shown that their lymphocytes are particularly good at stopping abnormal cell division. So it appears that elephants have some resistance to cancer.
Any final thoughts we would like to share about zobiquity or human exceptionalism in medicine?
There is human exceptionalism where we think that our species is superior to other species. We are not uniquely unique and we are not superior. But then there’s this professional bit of it. I think one of the barriers is a lack of humility on the part of doctors and medical institutions that have the power to recognize the value of these insights from the veterinary world, and the value that can be transferred to the human side. What have we learned from twenty years of comparative genomics revolution? We have learned that there are differences, yes, but that there are many similarities. And our human exceptionalism is so deeply entrenched that I think we vastly underestimate the value of those animal insights for primary care, cardiovascular care, cancer care and even psychiatric care for humans.