How dogs' health reflects our own, and what ancient DNA can reveal about human sacrifice

This episode explores the connections between human health and dogs as environmental sentinels, and the revelations about ancient human societies and health through the study of ancient DNA.

1. Dogs are excellent sentinels for human health due to shared environmental exposures.
2. Ancient DNA provides profound insights into past human societies, including practices like child sacrifice.
3. Genetic studies link historical populations to modern inhabitants, offering a continuous narrative of human genetic history.
4. Diseases like malaria have been intertwined with human history far longer than previously understood, traced through ancient DNA.
5. Understanding dogs' exposure to environmental toxins can lead to better health outcomes for both humans and animals.

1. Introduction to Ancient DNA and Human Sacrifice

Sarah Crespi introduces the topics with a focus on the power of ancient DNA in uncovering human history. Sarah Crespi: "Ancient DNA can do amazing things, uncovering stories from our past that were previously unknown."

2. Dogs as Health Sentinels

The discussion shifts to how dogs, sharing our living spaces, mirror the health effects of our environments. Courtney Sexton: "Dogs share our physical and social environments, making them potential indicators of human health outcomes."

3. Ancient Diseases and Modern Insights

A detailed look at how diseases like malaria have been traced through time with ancient DNA. Andrew Curry: "Studying ancient diseases like malaria shows how deeply interwoven they are with human history."

4. The Role of Dogs in Epidemiological Studies

Exploring how studying dogs can inform human health strategies, especially in understanding environmental risks. Sarah Crespi: "By observing diseases and environmental effects in dogs, we can potentially anticipate similar issues in humans."

• Regularly monitor pets for health changes as early indicators of environmental hazards.
• Engage with veterinary studies if your pet is diagnosed with a condition linked to environmental factors.
• Advocate for and support research into the environmental impacts on pet health.
• Reduce the use of household chemicals and pesticides that could affect both pets and humans.
• Support initiatives that aim to integrate pet health data with human health research for comprehensive environmental health strategies.

On this week’s show: Companion animals such as dogs occupy the same environment we do, which can make them good sentinels for human health, and DNA gives clues to ancient Maya rituals and malaria’s global spread

Contributing Correspondent Andrew Curry joins host Sarah Crespi to discuss two very different studies that used DNA to dig into our past. One study reveals details of child sacrifices in an ancient Maya city. The other story is on the surprising historical reach of malaria, from Belgium to the Himalayas to South America.

Next on the show, using our canine companions to track human health. Courtney Sexton, a postdoctoral research fellow in the Department of Population Health Sciences at the Virginia-Maryland College of Veterinary Medicine, talks about what we can learn from these furry friends that tend to be exposed to many of the same things we are such as pesticides and cleaning chemicals.

Finally, in a sponsored segment from the Science/AAAS Custom Publishing Office, Jackie Oberst, associate editor of custom publishing, interviews professors Miriam Merad and Brian Brown about the evolution of immunology in health care. This segment is sponsored by the Icahn School of Medicine at Mount Sinai.

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Sarah Crespi, Andrew Curry, Courtney Sexton

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Sarah Crespi
This podcast is supported by the Icon School of Medicine at Mount Sinai, one of America's leading research medical schools. Icon Mount Sinai is the academic arm of the eight hospital Mount Sinai Health System in New York City. It's consistently among the top recipients of NIH funding. Researchers at Icon Mount Sinai have made breakthrough discoveries in many fields vital to advancing the health of patients, including cancer, Covid and long Covid, cardiology, neuroscience, and artificial intelligence. The Icahn School of Medicine at Mount Sinai we find a way.

This week's episode is brought to you in part by the Eppendorf and Science Prize for Neurobiology.

Are you or one of your colleagues doing great neuroscience?

If so, then we encourage you to apply for the prestigious Eppendorf and Science Prize for Neurobiology, an international prize which honors young scientists for outstanding neurobiological research based on methods of molecular cellular systems or organismic biology.

Submissions are due June 15. Visit science.org eppendorf to apply today.

This is a science podcast for June 14, 2024. I'm Sarah Crespi. First up this week, contributing correspondent Andrew Currie joins me to discuss two very different studies that use ancient DNA to dig into humanitys past. One on archaeological evidence of child sacrifices, the other on the spread of malaria thousands of years ago.

Next, using canine companions to track human health. Researcher Courtney Sexton talks about what we can learn from our furry friends who tend to be exposed to many of the pesticides, cleaning agents, and other potentially harmful chemicals all around us.

Sponsored segment from our Custom Publishing office associate director of Custom Publishing Jackie Oberst interviews professor Marya Merad and Brian D. Brown about the evolution of immunology in healthcare today. We have two stories on ancient DNA and what digging into some very old genomes can tell us about the past. Contributing correspondent Andrew Curry is here with two very different stories. Hi, Andrew.

Andrew Curry
Hi.

Sarah Crespi
Hi. This pairing really shimi shows the power of ancient DNA, that it just can do amazing things, that they're just very different from each other and maybe wouldn't be able to be figured out without this technology.

Let's start in Mexico, in the yucatan peninsula at Chichen Itza. This is a site of an ancient Maya city. I actually visited there once. It is really amazing. They have the observatory, which is a place that people used to use to look at the stars. And they have a lot of carvings, and it's very hot and sunny when you go there.

Andrew Curry
It sounds amazing. I've never met.

Sarah Crespi
It is amazing. But let's go back to the 1960s when this story kind of first started developing sure.

Andrew Curry
So, in the sixties, they were trying to put a Runway in about a kilometer away from this pyramid, and they broke open an underground chamber that was connected to a slightly larger underground cave that was full of children's bones. By looking at the bones, they could tell that these were all children under five, and they were probably connected to some sort of sacrificial ritual. But there wasn't much more people could know based just on that discovery.

Sarah Crespi
What did they think back then, in the sixties, seventies, and eighties? What did they think about the source of these bones?

Andrew Curry
They figured it was probably connected to human sacrifice, which was fairly common in the Maya worlds. There was also this notion that had existed kind of since the time of the first spanish colonists, that the Maya sacrificed girls or sort of children indiscriminately, as kind of a fertility or connected to agriculture or drought. So they figured that was probably what it was and put the bones in storage until 2014.

Sarah Crespi
Right, so let's bring the ancient DNA to bear here. You can get ancient DNA from bones, right. How do they do that? What do they have to do to get the DNA out?

Andrew Curry
Ancient DNA you can get from bones, from teeth. But within the last ten years, researchers have figured out that the best bone in the body is one that most people have never heard of. You have a really dense bone in your inner ear called the petrous bone.

Sarah Crespi
So, yeah, I did not know this bone by name. And it's actually the container. It holds the tiny little pieces of the inner ear, if you think about the stone and those other parts.

Andrew Curry
And it's the densest bone in your body, and it preserves DNA better than any other. Any other bone. And you have two of them, a right and a left. And that comes in handy because in this particular cave, all the bones had fallen apart, even the skulls. So they just had this pile of loose bones.

They wanted to get ancient DNA to see what they could figure out about these children and their connection to the present and whether there was any consistency in the ritual in the past.

So they sampled only the left petrospones, because then they could make sure that they were only taking from one person.

Sarah Crespi
How many children were they able to get DNA from?

Andrew Curry
There were, I think, over 100 in the cave, and they managed to get DNA from 64 of them.

Sarah Crespi
Okay, and what did we learn about them?

Andrew Curry
Really surprising. And one of the researchers I spoke with said that almost never in archaeology do you have something that's so clear a pattern. All of them were boys.

Sarah Crespi
Wow.

Andrew Curry
And not only were all of them boys, many of them were brothers or first cousins, and four of them were twins. They had two sets of identical twins.

Sarah Crespi
And they're all under five.

Andrew Curry
All under five.

Sarah Crespi
What was the timing like? Were they all killed the same time at different times?

Andrew Curry
They did radiocarbon dating. They were killed and then put in this chamber over the course of about 400 years.

It's hard with radiocarbon dating to know exactly the year, but they estimate that it was a 20 year cycle.

Sarah Crespi
This is something that was going on for a really long time in the Maya world.

Andrew Curry
Yes. So they have a very specific connection to a maya myth or maya creation story known as the popol vu. And within it is this tale of hero twins, twin brothers who go into the underworld to resurrect or rescue their father and uncle. The twins themselves are sacrificed and resurrected in this sort of endless cycle that mirrors the agricultural cycle. It really blew the researchers away to find this.

Not only are there boys, not only are they closely related, but they even have identical twins that make this really direct connection with a specific maya tradition.

Sarah Crespi
The other thing thats really cool about this study is that they connected it to modern day occupants of this territory, the people who live on the peninsula today.

And they had commonalities in their genomes, right?

Andrew Curry
Yeah. So I really thought that was amazing. This site and this cave, this was all going on 1200 years ago, 800 CE about.

But the boys in the cave, theyre directly related and in the same genetic continuity as people who are living 40 or 50 km away now, with one exception, which is the people living there now have a strengthened immune response to salmonella, which shows that at some point, probably after Europeans arrived, there was a salmonella outbreak, and only the people who were able to resist it survived to pass their genes on to people in the region today.

Sarah Crespi
Wow. So how do the modern day people that have a connection to these children feel about this?

Andrew Curry
It's a connection to the land that they live on. There were some mayan authors on the paper, and one of them I spoke with said it was really important and emotional to have science confirm this thing that they had known. And when they went back to talk to the mayan community, people were really excited, because a lot of tourists come to see this site and sort of marvel at how amazing the ancient Mayans must have been. But don't necessarily look at the people who live there today as equally amazing. But for the community who's living there today, this is nice proof that it's the same people.

Sarah Crespi
Yeah, absolutely. All right, so we mentioned the immunity part of this, which I think also points out the fact that this is kind of an unusual source of DNA. Like, having this many kids all related to each other over time is a unique situation, and it can help you study at the population level what was going on with the genomes and also with disease, which is my transition to the other story that we're going to talk about. This one is about tracing malaria around the globe and through time using ancient DNA. There's so much surprising stuff in this story as well. I had no idea that humans and malaria may have been tangling with each other for like, 40,000 years. Not only have we been entangled with it for 40,000 years, but it kills about 600,000 people a year, and it's probably been doing that for thousands of years. Some diseases leave marks on the bone, but malaria doesn't do that. I mean, and there are some subtle things in our genomes that suggests our exposure. But in this case, the researchers were able to look at ancient DNA from the malaria parasite. How are they able to find ancient genomes from these tiny little things?

Andrew Curry
So if you have an infection, it's in your blood, and what's in your blood can end up preserved. In this particular case, most of the samples came from the inside of teeth, which have blood vessels. And when people die, whatever is in there gets trapped.

Of the ancient DNA that's recovered from human bones, a tiny, tiny fraction is the infections you might have. Whatever else is in your bloodstream.

Sarah Crespi
Any ride alongs, any hop ons, any ride alongs.

Andrew Curry
Exactly. The really complicated thing is separating it from the human stuff and all the other stuff that seeps in there from the soil after you die.

Sarah Crespi
Yeah, or our mouth bacteria or all kinds of contaminants. Yeah. And so how are they able to pull out the malaria genome?

Andrew Curry
In a way, they went fishing. They used modern malaria to create things that would match up with the DNA of malaria in the past. The Max Planck Institute for Evolutionary Anthropology in Leipzig has now collected, I think they have, a published database of over 10,000 ancient human genomes.

They have many more that are on their way, but they went fishing through that database looking for likely bits of malaria in the 10,000 genomes, and they came up with 30. Some.

Sarah Crespi
Not a lot. Not a lot considering it's a microbe, but it's good.

Andrew Curry
Apparently, the malaria contribution to the overall thing is one in a million. Literally.

Sarah Crespi
How far back in time were they able to find malaria?

Andrew Curry
The malaria stuff goes back about 4000 years to the Stone age in Europe, and the 40,000 years, sort of based on evolutionary biology estimates of how long, how many mutations you get over time.

Sarah Crespi
Okay, so it's a good pull. So when you pull out these sequences and you say, okay, here's some malaria, and it's associated with this ancient genome, suddenly you have a place and a time for the malaria to have been. And even a person, in some cases, you might know who this person was. What leapt out to you when you started reading over this paper? Like, what results were you like, wait, what? This is malaria doing this?

Andrew Curry
I didn't realize until I read this paper and spoke to these folks that malaria was an old world disease that, until fairly recently, as far as they can show from the evidence, this was something that affected Africa, Europe, and Asia, but was not in the Americas until 1492.

Sarah Crespi
So they came over with the colonists and the rats. Don't forget the rats.

Andrew Curry
Yeah. What blew my mind a little bit is there's a specific type of mosquito that's capable of transmitting malaria. Those mosquitoes existed in the Americas, but the malaria had to be brought with Europeans.

The mosquitoes then started spreading it all around, and within 100 years, there was somebody in Peru who died with malaria in their bloodstream.

Sarah Crespi
That's the first evidence. Well, the first advent of malaria in the Americas.

Andrew Curry
Yeah, that's the earliest case anyone's ever found in malaria in the Americas.

Sarah Crespi
One thing I want to call out here is that there are two different kinds of malaria parasites. We have vivax and falciparum. One of them is kind of known as the cold form. Like, it's going to be hanging out in the colder climes. And then falciparum is the hot one that we think came from Africa. So, yeah. Which one was this peruvian. First case in the Americas, malaria.

Andrew Curry
The peruvian one was vivax, which survives winters by hibernating in your liver, essentially, so you can survive with vivax. Lots of people have vivax, and it just keeps returning. George Washington and Abraham Lincoln both had vivax.

Sarah Crespi
Yeah, that was another surprising thing, was how widespread this was in Europe and the Americas once it got here.

Andrew Curry
Yeah, until the beginning of the 20th century. So, yeah, they think the first Europeans who arrived probably were carrying vivax in their blood, and then it spread really quickly through the Americas.

Sarah Crespi
Once it arrived, falciparum came later.

Andrew Curry
Falciparum came shortly thereafter. And they think, based on the data, that it probably came directly from Africa. As part of the transatlantic slave trade.

Sarah Crespi
It came over twice, two different types of colonization, actions happening. The other thing that I thought was really interesting was that it was found in parts of the world that I guess I never expected malaria to be. Right, like the Himalayas.

Andrew Curry
The really cool thing with ancient DNA in both of these studies is the way that researchers are able to really zero in on things in addition to giving a global picture. And they pulled out a couple of case studies where you can really see how mobile people were. One was a guy who died of or with falciparum in Nepal, a really cold, dry part of Nepal. And when they first found this case, they thought this must be a mistake. They went back and looked. They called the archaeologists who had done the original excavation.

It turns out that this guy and the village that he lived in was engaged with trade, going down to the lowlands in South Asia and India. This is an instance where somebody had gone down to the wet, hot areas where falciparum thrives, got bitten by a mosquito, got infected, and went back up into the mountains and died with it.

Sarah Crespi
They learned a lot from 36 cases.

Andrew Curry
Yeah, they really did.

Sarah Crespi
Is there a plan to go back and look for more for other kinds of malarial bits and pieces?

Andrew Curry
They're going to keep looking. The database keeps growing, and as it gets more sophisticated, they can pull edge cases and see if the analysis will work. The other trick with this method is because you're using bait based on the modern stuff, there's sort of a limit to how far back you can go, evolutionarily speaking, because if the variety is significantly different than the bait you're using, it won't bite. But they're just beginning to test this out, and this is kind of a great test case.

Sarah Crespi
Absolutely.

Andrew Curry
So hopefully there will be more soon.

Courtney Sexton
Yeah.

Sarah Crespi
Any other diseases that might be able to show up this way that researchers might be able to look at using this kind of dataset?

Andrew Curry
In theory, anything thats bloodborne and similar methods have been applied to genetic disorders. There was a story from the same institute just a few months ago looking at down syndrome, where they essentially did the same thing. They just looked at 10,000 people for this genetic triasomy, and they found cases in the past, and then they could go and look at how those people lived.

Sarah Crespi
All right, Andrew, thanks so much for talking with me today.

Andrew Curry
Thanks for having me. It was really great.

Sarah Crespi
Sure. Andrew Curry is a contributing correspondent for science. You can find a link to the stories we discussed@science.org. podcast. Stay tuned for my chat with Courtney Sexton about how our dogs can act as indicators of health and well being.

This week's episode is brought to you in part by the Eppendorf and Science Prize for Neurobiology.

Are you or one of your colleagues doing great neuroscience? If so, then we encourage you to apply for the prestigious Eppendorf and Science Prize for Neurobiology, an international prize which honors young scientists for outstanding neurobiological research based on methods of molecular cellular systems or organismic biology.

Submissions are due June 15. Visit science.org eppendorf to apply today. All right, this is a big declarative statement here. Dogs were the first animals to be domesticated. They've been living with humans for a long time, at least 15,000 years, maybe twice that long. This week in science, Courtney Sexton wrote about how living in such close proximity with dogs up till today might make them good sentinels for human health. Hi, Courtney. Welcome to the podcast.

Courtney Sexton
Hey, Sarah, thanks so much for having me.

Sarah Crespi
Sure. So this is an interesting idea, this concept of dogs as health sentinels. What kinds of things could we look for in dogs that could help us track human health or predict human health outcomes?

Courtney Sexton
Yeah. So one of the really interesting and kind of distinct things about companion animals, and dogs in particular, is that they share our physical and social environments. So lots of times when we are using animal models or looking at the way other animals are impacted by the environment or health risks, they don't have a lot in common with people. So that makes things a little harder.

Sarah Crespi
Like cows in a barn or wolves in the woods. They got their own niche, their own ecology that they're dealing with.

Courtney Sexton
That's right. And they may be impacted by some of the same diseases, again, environmental factors, atmospheric issues, but those things are going to interact with different parts of their immediate environment or niche.

Sarah Crespi
But dogs, on the other hand, they're just right here, sitting right next to us, sniffing everything, licking everything, kind of living our lives in parallel, maybe with less stress, unless they're an anxious dog.

Courtney Sexton
You know, we joke a lot that they kind of figured it out, the evolution game, and they're living these very charmed lives.

I will say that is the case in the United States in a lot of places. But there are, I mean, about 80% of the world's population of dogs are free ranging.

Sarah Crespi
Yeah, I live in a town with a lot of free ranging dogs, a lot of dogs at shelters, a lot of dogs running wild. And, yeah, I think they live a real different life than my dog.

Courtney Sexton
Yeah, for sure. But for those who do, you know, live in households, especially with people, they're going to be, as you said, they're sniffing a lot. They're licking a lot. So anything that is in our, what we call expo zone. So that kind of combination of external factors that influence our biology are going to be really noticeable when they impact the dogs. For example, if you use pesticides in your yard, you're wearing shoes when you walk on that grass, but those chemicals are going directly into the foot pods of your dog when they go out.

Sarah Crespi
And their noses, probably.

Courtney Sexton
And their noses. Exactly, exactly.

Sarah Crespi
And then we also talk a lot about the environment of the interior. All the stuff that we have in our houses that's synthetic or paints or carpets or cleanings, all that stuff, we're exposed to it. And our dogs are too.

Courtney Sexton
Yes, they are. There's a lot of research right now into forever chemicals, pfiles, PCB's, bpas, all these things that are in personal vocs products, vocs, all the great acronyms, flame retardants, all of these things within the home can be dangerous.

Sarah Crespi
Are there studies out there already that have shown that some of these things are in our dogs, or that they're having health issues because of different elements of our exposome?

Courtney Sexton
We have kind of just a really great list of emerging work from, I'll say from 2020 to present in a variety of different fields. So we were talking about pesticides, rodenticides, also chemicals and toxicants, those personal care products.

And we have studies from the US, from Europe, from the Netherlands, kind of all around the globe that are showing you do detect these pahs, vocs, all these kinds of chemicals. And we're starting to look also at PFAS, those forever chemicals that are so buzzy right now, but they're being detected in tissues, in dogs. Some of our colleagues at Duke University, Heather Stapleton and Cathy wise, we just teamed up with them to do this study where the dogs wore silicone tags and we captured the presence of 119 different chemicals in their environment.

Sarah Crespi
Oh, wow. Yeah, that's just walking around. They just walking around. Okay.

Courtney Sexton
Where we have the bulk of research to date on dogs as sentinels is on these vector borne diseases. And that goes across the globe. Australia, Namibia, southern France, Turkey, Guam. And these are often related to more localized factors like Q fever in Guam. And that impacts people, their hunting dogs, but also livestock, of course. Here in the United States, we know that Lyme is a really rapidly expanding issue. Again with that climate change and their range extending. There have been some that look at reproductive tissues of dogs. We practice bay and neuter with a lot of dogs, and so there is this ample amount of reproductive tissue to be looked at which is a little bit different in human populations. We don't always have access to those things. The idea of animals, or the dog in particular, is sentinel is not novel, per se. And so there are great examples in the literature already, but we're not necessarily, haven't yet linked them up with the then health or disease outcomes.

Sarah Crespi
Yeah, and there are some things called endocrine disruptors that are found exactly in our water or in other places that, you know, it's going to be hard to necessarily see the effect of those in people, but you might see it if you're taking out ovaries every day at your veterinarian practice.

Courtney Sexton
You can also look at what are the down the road impacts on pups or the next generation who've been nursing. And if there are those endocrine disrupting chemicals, the EDCs in mammary tissue or in the milk, and you can imagine that that would also have similar impacts in humans.

Sarah Crespi
The veterinarian, they can take this tissue out, but they're not testing it for things, logging it in a place that the data is then compiled. Like, that's a whole system that would need to be put in place to kind of make this work for us in a broader way.

Courtney Sexton
And that's something that my colleagues and I are really advocating for. A lot of the data that we work with comes from a longitudinal study of dogs called the dog aging project.

We have thousands of human participants who volunteer to give us information about their dogs, their dog's veterinary information, to fill out surveys. Or when we reach out and say, hey, we would love if you would put this silicone tag on your dog's collar for five days so that we can test it for chemicals in the lab. Will you do that? And they say, yes. And so we have this great bank of data that we need and want to share with other researchers. But in order to do that, that data has to be standardized in some ways that it can cross over fields.

Sarah Crespi
Back to the dog aging project for a little bit. Obviously, dog aging and human aging are different. Their lifespans are shorter. They have different things come up for them. Their biology is different. So do we need to worry that, okay, just because they have a bunch of tick bites or just because they have endocrine disruptors affecting their reproduction, do we know that that's really going to have an effect on people?

Courtney Sexton
No, we can't say that this is going to be the exact outcome that we see in dogs and in people. What they do offer is, as you said, unfortunately, they have a shorter lifespan than we do. They are sharing our environment, and they are sharing some of our risk factors over the entire lifetime of that dog. So if a dog lives for twelve to 14 years, we can actually follow them from puppyhood through their senior years and see how their bodies have changed, look at the responses to their owner's surveys and see what is different, and compare those with some of this environmental and biological data that we receive. We might be able to look at how is cancer progressing in this particular dog, and what are the factors that influence it. That might give us some clues as to where to look in aging humans.

Sarah Crespi
The proposal here could be something like a giant epidemiological study of dogs.

Courtney Sexton
Yes.

Sarah Crespi
All over the country. We're taking samples from them. We look at where they live, we look at what their lifestyle is like, and we know something about their health. If we're incorporating surveys or veterinary data, stuff like that.

Courtney Sexton
Correct. And you actually touched on something that is, to me, one of the most exciting parts of this, those lifestyle factors.

Because if we go back to what we were talking about at the beginning, one of the things that's really distinct about the human dog relationship is that they share our social environment.

There is some, again, emerging research that we are really interested to look more into. Some of my colleagues on dog aging project, Brianna McCoy is the lead author in this paper. But showing that social determinants of health in people actually also impacts aging and health outcomes in dogs.

Sarah Crespi
Could you talk a little bit about what social determinants of health are?

Courtney Sexton
Your financial situation, your access to nutrition, and in their case, veterinary care, but also potentially medical care. Things like walk scores, how walkable is your neighborhood? Are things close by? Do you have companions? Do you have social interactions? Do you have a support network? All of these things, they're part of the exposome in ways that I think are not traditionally thought about.

Sarah Crespi
If we gather all this data, we collect it all together. So we're going to say, oh, there's sentinels. They can tell us where people are maybe likely to have certain health problems or might likely encounter certain vectors for disease. Is that the goal here? Or are we also talking about, we see this in dogs, they tell us it's happening, and then we look to regulators to say, this is bad for dogs and for people. We should take care of it.

Courtney Sexton
We take a multi pronged approach. One is two.

There's this kind of not great analogy of the canary in the coal mine, which I'm sure people are familiar with. They served as early alert signals, but no one really cared about the Canaries was the unfortunate part in our case, we really care about the dogs and the companion animals as well. So in seeking information about how they're being impacted, both for our own edification on human health outcomes, we can totally advance veterinary medicine and clinical awareness and the aging process for these companion animals because they give so much. You know, they play so many important roles in our world. They're detection dogs, they're service dogs, therapy animals. The list goes on and on. And so I think our perspective is that we owe it to them.

Sarah Crespi
So this is a way of tracking exposures and disease and socioeconomics through this dog vector. Right. So, yeah, I should ask you, what about cats? I mean, we haven't been living with them as long, but it is very common for people to live with cats these days.

Courtney Sexton
In some ways, even cats may present or other companion animals may present a better model, depending on the expertise factor that we're looking at.

Sarah Crespi
So in some ways, this kind of seems like if you had a health system where people were regularly tested for.

Courtney Sexton
Things, wouldn't that be nice?

Wouldn't that be nice?

Sarah Crespi
Okay, but, okay, so for real, it kind of almost seems like a workaround if, say, in the US, people were part of a health system where their blood was anonymously screened for certain things that we wouldn't need to test this in dogs.

Courtney Sexton
So I think that's one piece of the puzzle. But one of the advantages that we get in looking for these things in dogs is, again, we don't have to wait 70, 80 years to see what the outcomes are being able to assess rather quickly how these systems may be impacted, and then to catalog that data and have it for the next generation, which is coming again pretty quickly. It's really to our advantage.

Sarah Crespi
That's great. Thanks, Courtney.

Courtney Sexton
Thanks so much, Sarah. It was a pleasure.

Sarah Crespi
Courtney Sexton is a postdoctoral research fellow in the Department of Population Health Sciences at Virginia Maryland College of Veterinary Medicine at Virginia Tech. You can find a link to the commentary piece we discussed@science.org. podcast up next, we have a custom segment sponsored by the Icon School of Medicine at Mount Sinai. Custom Publishing. Associate editor Jackie Oberst chats with researchers Miriam Murad and Brian D. Brown about a new realization in immunology that is revolutionizing medicine.

Jackie Oberst
Hello, podcast listeners, and welcome to this sponsored interview from the science AAA's custom publishing office and brought to you by the Icon School of Medicine at Mount Sinai. My name is Jackie Oberst, and I'm associate editor for Custom Publishing and Science.

Once relegated as a field that simply concerns itself with allergies, infectious diseases, and autoimmune disorders. Immunology has recently expanded its repertoire. It is now clear that a key aspect of our body's immune defenses, known as inflammation, is a major component of aging, as well as many human diseases, including cancer, heart disease, depression, fibrosis, and Alzheimer's disease. Today I'm pleased to welcome to our podcast two leading immunologists from the Icon School of Medicine at Mount Sinai in New York City. Doctor Mary Marad is the school's inaugural dean for translational research and therapeutic innovation. Doctor Brian Brown is director of the Icon Genomics Institute. They've co authored a thought provoking article on how advances in immunology are transforming medical care. The article will appear in a sponsored supplement to Science magazine titled Frontiers of Medical Research Immunology, coming out June 21. Miriam and Brian, thank you so much for taking the time to talk with me today.

Brian D. Brown
Thank you for having us.

Jackie Oberst
Let's get started with what the two of you wrote in your article for the upcoming immunology supplement to science. You quote, a revolution has come to medicine, and it was hiding in our blood, tissues, and organs all along. Science and medicine are now coming to the realization that the immune system is a component and even cause of all major human diseases. And the more we learn about this, the better we could treat or prevent these diseases. Could you please elaborate on that? Miriam, let's start with you.

Marya Merad
The immune system is really an army, a little army that is present everywhere in our body, and it's really here to protect us, protect us against threat. But in doing so, sometimes it harms us. So what we are trying to see is continue to retain the beneficial effects while reducing the damaging effect.

Brian D. Brown
Brian in the modern world, our immune system evolved tens of thousands of years ago, before humans evolved. So when we were rodents scurrying around on the planet, and it was there primarily as a defense system to protect us from pathogens. And as we evolved and now form cities, and instead of living till 25 or 30, we lived till 60 or 70, our immune system now has different roles and it reacts differently. And one of the things that we're finding is that as we age, our immune system starts to get hyperactivated. And many of the diseases associated with aging, like atherosclerosis or like Alzheimer's disease, are a consequence of that hyperactive immune system.

Jackie Oberst
Could you just share specific examples where immunotherapy has led to breakthroughs in treatment?

Brian D. Brown
The one I'll start with, which is maybe the most obvious, and the most impactful has been vaccines, actually. So vaccines are a direct result from our understanding of how the immune system works. This idea that we can educate the immune system and it can have this thing that we call long lived memory.

Marya Merad
I can talk about cancer. The big revolution in cancer now is really immunotherapy. We think that every single cancer patient is going to be treated with something that really harnesses the immune system. So here the immune system recognize that the cell is damaged. Right. The same way that the recognizer said is infected. And the beauty of the immune system is that it will eliminate the cancer cells and recognize that the cells next to it is normal and it will spare that normal cell. So something that traditional therapy like chemotherapy, radiation, doesn't do well. So the really dream of all cancer immunologists is that it will one, eliminate cancer cells, but also always eliminate potential recurrence, which is really what kill a patient.

Jackie Oberst
Yeah. I mean, do you see immunotherapy replacing these three classical pillars of cancer therapy, the, you know, chemotherapy, irradiation, surgery? I mean, do you think that, or do you think that they're going to work in tandem?

Brian D. Brown
I'll give you one example, which may be extreme, but I'll tell you, the human papillomavirus vaccine isn't immunotherapy. It's replacing surgery and chemotherapy in the sense that it's actually preventing those cancers from happening. So. And that is a type of immunotherapy.

Courtney Sexton
Yeah.

Marya Merad
It's important to also talk about immunoprevention. This is a big area of research here at Sinai, a theme that miriam.

Brian D. Brown
And I talk about a lot at the center of immunology as a medicine is really restoring balance. The number one issue is how do you prevent pathological inflammation without being immunosuppressive? Well, you can't take steroids a long time. It has all kinds of side effects. In the molecular era of immunology and of medicine, we're getting to the point where, yes, we can pinpoint the specific molecule you need to target. So we're not going to use broad acting steroids, but can we block the molecule or even just block the pathogenic cell in the exact location it's pathogenic, because we have this tendency to say, well, we're going to, you know, drug tnF, big target tumor necrosis factor. Well, that's not really what we want to do. We want to block TNF in the place that it's causing this inflammation. That will be the next era. And if we can do that, I mean, you know, you wouldn't have to immunosuppress a person, and yet you could still block a, you know, an inflammatory bowel disease lesion, if you can do that. So I think this is where the field will go in the future.

Jackie Oberst
So, no doubt collaboration is important in this field. Could you two please speak to the importance of collaboration among researchers of, as well as between researchers and clinicians in immunotherapy?

Courtney Sexton
Yeah.

Marya Merad
So a good example is Brian and I, right where I am an oncologist, an immunologist, he's a gene therapy experts, right? Studied rna regulation and DNA regulations.

We collaborated to approach this problem of how to develop novel immunotherapy strategies against diseases.

Brian D. Brown
Is there something magical about innovation? There's nothing magical about innovation. It usually comes from, you know, taking two things that are far apart, and you put them together like, you know, you notice someone is using this particular technology or methodology over here. I can apply it to my discipline all of a sudden. That's very innovative for your discipline, because you've introduced it. We think of collaboration a lot between investigators. That's been happening for a long time, but also between clinicians, as Miriam was saying. And where we think about innovation happening a lot is when something fails in the clinic. The natural reaction, especially from the clinicians, around a failure, is this drug doesn't work. That's not our reaction. For us in the lab, our reaction is, wow, this is an opportunity to figure out, why doesn't it work, and how can I make it better? And I think that it's only through our talking and setting this up and figuring out, okay, well, how do they react to that? If, well, they got really inflamed, then we're like, aha, you know, there's something there, right? And when Miriam set up this program, which is called interact, a number of different investigators, from neurologists, rheumatologists, oncologists, and basic scientists coming together and talking about what works and what doesn't work in their patients, and that this is how we sort of move things forward. Something as simple as innovation can come from just changing the dose of something.

Maybe what's on the package doesn't make sense in a particular context, and we sort of figure that out, and that's innovation in itself. And that can be the difference between a medicine working and a medicine not working. That's everyday collaboration that leads to something much bigger, kind of an emergent property of collaboration that leads to advances that can cure patients.

Jackie Oberst
So with the rapid advancements in immunotherapy are there ethical concerns that need to be addressed, particularly regarding patient safety and treatment? Accessibility?

Marya Merad
Well, patient safety is always a priority in any research diver. You always try not to think, making sure you're not hurting the patient so that there's nothing different here. Now, inclusion. So your accessibility is an important question because, in fact, there is two answers to that. First, we have to make sure that there is diversity of accrual diversity of ethnic groups that are going to be tested in their ability to respond to these regimens, because we know that the inflammatory response is very much dependent on your genetics and exposure and the diets and the microbiome. So we have to test, we have to make sure that we test all these novel therapy in different ethnic groups and different socioeconomic conditions. And this is, you know, these novel therapy are extremely expensive. The fear is that you will develop therapies for the riches. These are larger questions that we think about but cannot act upon, and that it's an important debate to have.

Jackie Oberst
Could you talk about where this field is going? Like, where do you see this field going in five years or ten years.

Brian D. Brown
Down the road, beginning, absolute beginning of this. I mean, what we've seen in the last 15 years, if you think of the history of medicine, I mean, it's incredible where we're going. I think within ten years, I'm going to use this expression, total programmable control of the immune system, I think will be possible.

Jackie Oberst
Well, Miriam and Brian, it's been a real pleasure having this opportunity to talk with you. Thank you for joining me.

Marya Merad
Thank you for having us.

Brian D. Brown
Thank you.

Jackie Oberst
And our thanks to the icon School of Medicine at Mount Sinai for sponsoring this interview. I'm Jackie Obers. Thank you for listening.

Sarah Crespi
And that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us@sciencepodcast.org dot to find us on podcasting apps, search for Science magazine, or you can listen on our website, science.org podcast. This show was edited by me, Sarah Crespi, Megan Cantwell, and Kevin McLean. We also had production help from Megan Tuck at Prodigy. Our music is by Jeffrey Cook and Wen Khoi Wen on behalf of Science and its publisher, AAA's. Thanks for joining us.