Genetics in Dogs and People | Elaine A. Ostrander, PhD

>> Dr. Elaine Ostrander: [00:00:00] I often say that the development of dog breeds is the most successful genetics experiment ever done by humankind.

>> Announcer: Welcome to Dog Cancer Answers, where we help you help your dog with cancer.

>> Molly Jacobson: Hello friend, I’m Molly Jacobson. Today we have a really special show for you. It’s a recording of a conversation James Jacobson, who happens to be my husband, also happens to be the founder of Dog Podcast Network, a conversation that James had a few months ago with the amazingly talented, big hearted, incredibly insightful genetics researcher, Elaine Ostrander.

Now, if her name rings a bell for you, let me tell you why. You may have seen that incredible 60 Minutes piece about comparative oncology, about how comparing cancer in dogs and people is leading to enormous insights and medical breakthroughs for both. I think you’ll find Dr. Ostrander’s conversation with James about her work in comparative oncology [00:01:00] easy listening.

She’s a fantastic science communicator. She loves dogs and she’s funny. Here’s James Jacobson and Elaine Ostrander, PhD.

>> James Jacobson: Dr. Elaine Ostrander, thank you so much for being with us today.

>> Dr. Elaine Ostrander: Thank you. It’s a real pleasure to meet with you today.

>> James Jacobson: There’s so many things to talk about here at Dog Podcast Network. We have been touching on a lot of the science that you are involved in all the time between what we do at Dog Cancer Answers and what we do in general on our various shows. I want to first start off with a broad question.

When you decided to go to NIH and to focus on the build this dog genome project, some of your colleagues, your esteemed colleagues, because you have a quite a resume with quite an academic background. They kind of said, you’re going to do what with your career?

>> Dr. Elaine Ostrander: Yeah, so actually I started the Dog Genome Project at the [00:02:00] end of my postdoc at Berkeley together with Jasper Rine and then I moved to Seattle to the Hutchison Cancer Center in the University of Washington and that’s where I really dug in, in earnest. And yeah, there was a lot of skepticism for sure.

And at that point in time, you know, half of my lab worked on human breasts and prostate cancer and the other half worked on The Dog Genome Project. And people would always say to me, Why don’t you forget the dog thing? And you had all the success with breast, prostate cancer, why don’t you, you know, just go with the mainstream? And you know, I always tell students and post docs that whatever you do, you kind of have to follow your heart. Right?

It has to be exciting. It has to keep you awake at night. It has to be that you’re walking and you get a great new idea and you write it down. And so, what I told myself was, well, when the dog stuff peters out, then that’ll be the end of it. And I’ll, you know, join the mainstream a hundred percent.

>> James Jacobson: There’ll always be cancer. I can always go back to the [00:03:00] BRCA and prostate.

>> Dr. Elaine Ostrander: Right. And it never petered out. And now, of course, for the last several years, my lab works exclusively on dogs. And partly it’s because many of the questions I wanted to answer in human genetics, I found I could tackle more easily in dog genetics. So, what’s the nature of genetic susceptibility? How does variation exist, occur, evolve? I mean, why is there so much variation within single species? What’s the genetic basis of behavior?

Um, these were all things that I could tackle with a focus on dogs, in many cases more easily than in humans. And so that’s where I landed and that’s where I’ve stayed and most of my naysayers have come up to me and said, congratulations. So it worked out well.

>> James Jacobson: There was like a Nobel laureate somewhere in that process who said, you’re going to do what, right?

>> Dr. Elaine Ostrander: Yeah, there was, there was someone I respect and admire enormously who said, why would you do this to a perfectly good career? And I said, you’ll see. And it’s been wonderful to [00:04:00] dialogue with that person in the years since.

>> James Jacobson: I bet. So why are dogs so good for this type of research and study?

>> Dr. Elaine Ostrander: You know, domestic dogs have only been around for about 30, 000 years, which evolutionarily is a tiny, tiny drop in the bucket. And most breeds you see running around at the dog park have only been around since Victorian times, a couple hundred years. And yet when we look at dogs as a whole, there’s an extraordinary amount of variation in how they look and how they behave and in what diseases that they’re susceptible to.

And so anything we want to sort of study the genetic basis of, we can do it in dogs because they’re divided into breeds, right? And so there’s 350 breeds of dogs. There are breeds that are big, breeds that are small, breeds that herd, breeds that hunt, breeds that guard. I mean, whatever trade it is that you’re interested [00:05:00] in from the simplest level of curl of the tail right down to something like herding versus non-herding dogs.

And to be a registered member of a breed, both your parents had to be registered members, and their parents have to be registered members. So, every breed is kind of a closed population. And so, within that breed, we’re not expecting there to be thousands of genes accounting for any particular sort of variation, right? We’re going to expect it to be a pretty small number.

Closed population, only been around most of 2,000 years. So, they offer an exciting chance to study anything from disease to morphology to behavior.

>> James Jacobson: So you rely heavily, I guess, on relationships with AKC and, and the RSPCA in the UK.

>> Dr. Elaine Ostrander: Yeah, you know, we’ve been really fortunate to have a great relationship with the American Kennel Club. And it is true that most of the dogs we sample are AKC registered dogs. But having said [00:06:00] that, I have to say, there’s an amazingly important role for mixed breed dogs.

And for what we would call village dogs, so dogs that are not under selection to look like anything, to be anything, to execute any behavior, and we and others, you know, led by Adam Boyko at Cornell really, um, have been collecting these village dogs from all over the world because they’re kind of a, a track of, okay, here’s what happens if you don’t select for being big or being small or this color code or having this behavior or that behavior.

And so they become really important as well. But by and large, we focus on registered dogs, dogs that are members of a breed. And it’s important to remember that every breed, it’s all the same species, Canis lupus familiaris. So you can look at that Great Dane and that Chihuahua and that village dog. All the same species.

>> James Jacobson: And how much variation is there between a Great [00:07:00] Dane and a Chihuahua in terms of the DNA? Like how many things are different between the two?

>> Dr. Elaine Ostrander: You know, not nearly as much as you would expect. It’s actually very little. There are, gosh, it must be close to 4,000 dogs whose genomes have been completely sequenced at this point.

And people have shot for sequencing five or seven of each breed. And so certainly there’s variation within a breed. And then there’s also some variation within, you know, groups of closely related breeds. And then variation between breeds or clades that are really unrelated one to another. But really what we’re finding is that unlike human genetics, where a given trait is accounted for by a large number of variants, a very small effect.

In dogs, most of the important traits are the ones we recognize are accounted for by a small number of genes, a very large effect. And that really speaks to the different [00:08:00] evolutionary time scales, right? I mean, for humans, it’s been much, much, much longer. So, evolution can nickel and dime, and this base pair, that base pair.

You know, if you look at the genetics of height in humans, you’re going to end up with hundreds and hundreds of genes in places in the genome. When you look at, at height and body size in dogs, you know, you end up with just two or three dozen. Not much chance to get that difference, right? So, you have to hit, hit big and hit fast.

>> James Jacobson: How does that accelerate your ability to learn and to analyze what the ramifications are for human medicine, which is obviously what NIH is focused on.

>> Dr. Elaine Ostrander: Right. So it comes in a couple of different ways. When you develop a closed breeding population, inevitably there’s going to be some disease, genetic disease. And so, you know, we are very interested in cancer and so there are breeds that have. [00:09:00] extraordinarily high levels of a particular cancer. So, Scottish Terriers are at a 22 fold increased risk for getting invasive bladder cancer compared to the average mixed breed dog walking down the street.

Black Coated Retrievers, Bernese Mountain Dogs, they’re at a very high risk for getting histiocytic sarcoma, and of those that get it, nearly all will die of the disease. 25 percent, that’s extraordinary. We don’t see that in human genetics. So we study those things, we study the risk, we find the genes that contribute to the risk, and that’s true for lots of cancers.

But because we’re at the National Institutes of Health, it’s also our job to develop resources for everybody else. And so a lot of what my lab does is, you know, we’re doing sequencing, we’re building databases, we’re developing new tools and pushing that out to the companion animal community and saying, here, okay, you don’t have to, to, [00:10:00] you know, rebuild the wheel again, to rediscover the wheel again, go ahead and use this. This is what works. And we take great pride in, in doing that.

But I think the thing that I have found that surprised me the most was the morphology story.

>> James Jacobson: Define morphology.

>> Dr. Elaine Ostrander: Oh, sure. Yeah. So morphology is basically size and shape. And so it can be body size. It can be leg length. It can be length of the fur. It can be the curl of the tail. It can be whether or not the face of the dog is sort of pushed in like a Bulldog or extended like a Borzoi. It’s anything about size and shape. And you can’t look at dogs without saying, Wow, that is so cool. How can they look so different and still all be the same species?

I want to find those genes. And so we started tackling that, you know, we looked for genes for leg length, we looked at genes for body size. One of the first ones we found was the gene [00:11:00] responsible for, if you’re a Schnauzer having the mustache and the eyebrows versus dogs that don’t, you know, this is called furnishings and yeah, it’s a single gene, right?

It’s responsible for hair follicle formation. And so as we started finding these genes, we realized that, you know, breeders have been selecting on them to get. animals of a particular trait, and that’s great. But when they’re really perturbed or messed up in a human genome, they’re often responsible for disease.

And so, a good example are genes that are responsible for whether or not a dog’s ears are prick or whether or not they’re floppy. So, you know.

>> James Jacobson: How many genes are responsible for that?

>> Dr. Elaine Ostrander: So, prick versus floppy is one, but size is another, and you know, these different features of ear morphology are controlled by different genes. But what’s interesting is when those same genes are really screwed up in humans, they’re associated with deafness. When we look for genes for body size, because, you know, some [00:12:00] dogs breeds big, some small. Yeah, we find genes breeders have obviously been selecting on. But when the same genes are really perturbed in humans, they’re associated with obesity.

They’re associated with metabolic syndrome. They’re associated with things we care about for our own health. And that’s, I think, one of the big surprises that’s made this very interesting to human geneticists and to NIH. It’s a, it’s a different way to come at the problem that we, we honestly just can’t do with humans, right?

The biggest to smallest dogs, different size by 40 fold. That doesn’t happen in humans. There are non human populations a different size by 40 fold. No, there, that would not work out well.

>> James Jacobson: Let’s use an example of, of the ear piece where you’re saying that, that difference on the human side, if that DNA is messed up, it can result in deafness. With that observation and that knowledge. How does that apply practically to treating, like, is it early detection of deafness or where might [00:13:00] that lead?

>> Dr. Elaine Ostrander: So I think where these sorts of findings are most useful is they give us information about the gene and the protein. So they, they say, you know, this part, you know, you can tickle it and you’re really not going to get much of a change in this, you know, hearing functionality or diabetes or obesity or metabolic syndrome or whatever it is.

But look, this part of the protein, that’s really important. You cannot mess with that part of the protein. And so as you think about diagnostics and therapies and treatments and drugs, This is the part of the protein you really have to think about. Don’t waste your time thinking about that part of the protein, or don’t waste your time thinking about those little base pair changes because they’re, they’re really not important for this or that particular disease.

>> James Jacobson: So 23andMe is real popular in places like that where you can go and get your own results and then look at the stuff and get endless information back and forth. Like, oh look, you don’t have this or this. And it’s kind of interesting. And they’re starting to do that now for dogs. What are your thoughts about, [00:14:00] you know, getting your dog’s DNA.

>> Dr. Elaine Ostrander: You know what? I think it’s great. So with a couple of caveats, right? So of course, you know, dogs are members of our family. For some people, they’re the most important or the only member of their family. And you want to know about your dog’s history. You want to know about its health and you want to know, you know, what its health in the future might look like.

What should you be vigilant about? Are there changes you should be making in diet? Are there particular medicines you should avoid because your dog’s likely to have a response to them? Of course, you want to do everything you can to ensure the health and the happiness and the longevity of your dog. And companies do the 23andMe thing for dogs, you know, I think is great.

But I do have to say two things. One is that companies like that are built upon having big databases of DNA from lots and lots of dogs and lots and lots of breeds. If your dog happens to be some rare thing that’s not [00:15:00] represented in their databases, you know, that’s going to be a problem, right? And so you, you know, you want to ask those, you know, if you have a really unusual dog and you say, Oh, you know, this is a village dog I picked up when I was in the army and I was stationed in, which, which has happened.

People have come up and said that to us, well, you know, you want to tell them that, right? So you really want to be straightforward about that so they can help you understand how to interpret the results that they get. And I guess the other thing I’d say is, you know, people tend to, you know, look at results.

Let’s say they’re looking at what breeds are in my mixed breed dog? And, you know, something is listed at 3 percent and not significant. And I think people process that as, Oh, my Chihuahua is part Saint Bernard. Well, no, it’s probably not part Saint Bernard.

>> James Jacobson: That, that percent matters.

>> Dr. Elaine Ostrander: It means not significant. Means not significant. It means it came up as part of background. [00:16:00] And there’s no statistical evidence then that your Chihuahua is part Saint Bernard. Right? So that was the closest match, but it wasn’t a match that was significant. And it’s just, it’s just noise. Right? It’s, and so I think, I talk to people all the time who come up to me and, and they say things like, You know, my Saint Bernard, you know, it’s, you know, part Toy Poodle. I’m like, I don’t think, you know.

But the other thing I will say, so paying attention to what’s really statistically significant and what’s not, that part of the output from those reports, that’s really important. And then the other thing that happens a lot, and I actually often show slides of this, is people fixate on a small number of features when they look at their dog and they’re trying to guess what breeds it is.

They look if it has really short legs because then they’re thinking it’s a, it’s a Corgi, it’s a Basset Hound, something like that. They look at the color of its coat. If it’s black, they’re thinking Black Lab or, you know, they probably wouldn’t be thinking Black [00:17:00] Coated Retriever. Even those dogs are, you know, totally black.

They look at the length of the fur. And they, they look at the general shape of the face, right? And that’s probably where most of their energy goes. And so I’ve put up pictures before of a dog and asked a room full of people, you know, what do you think this dog is? And inevitably, they’ll be guessing all sorts of popular breeds and they’ll make assumptions and they’ll forget things like, well, you know what, Poodles can be brown.

Poodles can be apricot. There’s a lovely shade of apricot Poodles, right? Or Scottish Terriers can have this whitish color. But we all assume they’re black, but that’s just not true. And some of these really small dogs above and beyond that have disproportionately short legs, are chondrodysplastic. If you see a dog with really short legs, it doesn’t automatically mean Corgi and Basset Hound and those sorts of things.

So, you’ve kind of got to be open [00:18:00] minded when you look at those results and as always, take everything with a grain of salt. But in terms of health, I think it’s great if they can give you guidance on, you know, what things to look for in your dog’s dog. I mean, if they told me I had a dog that was part Bernese Mountain Dog, boy, I would be, you know, looking for lumps and bumps on that dog all the time, right? I would care enormously about that or a dog that was part Black Coated Retriever, right?

And if they told me I had a dog that was part Scottish Terrier or West Highland White Terrier, yeah, sure. I’d be talking to a urologist and saying, What do I do? Do I bring it in for ultrasounds? Do I have urine checks? I mean, what am I supposed to be doing to be right on top of that? So yeah, I think they have a lot of value.

>> James Jacobson: We’ll talk about health and especially cancer in a moment. But I have heard you say that dog breeders were like the original geneticists. They were like, you were really impressed with how for many years they’ve been figuring this stuff out.

>> Dr. Elaine Ostrander: Yeah, you know, it’s true. I often say that the development [00:19:00] of dog breeds is the most successful genetics experiment ever done by humankind. And I still, I still stick by that. You know, 350 distinct dog breeds and many more populations that aren’t recognized breeds from all over the world. And, you know, with the earliest dogs being so important to our survival, we weren’t going to make it unless somebody guarded our sheep and made sure wolves didn’t get at them.

We needed hunting dogs, we needed herding dogs, we, all these things were so important to our survival. And as, as we changed how we lived, we had to find dogs or select for dogs that, that changed what they did as well. And now, you know, every year the American Kennel Club, by way of an example, admits new breeds. And the criteria are fairly, you know, complicated and they have to breed true in certain pedigrees and all this sort of stuff.

But it’s really surprising that it’s [00:20:00] only a small number of generations and they can get a series of traits to read true, you know, that everyone is born from those dogs are going to look that way or behave that way or have those traits. And I think it just speaks to the observational skill of dog breeders. You know, I go to lots of dog shows and I try and guess who’s going to win. I, that, that one for sure.

All the knowledgeable people look at me like, okay, sure. She knows nothing, but I have people in my lab who have been in that role. Then they’ll sit there and explain to me, no, look at this back line. Look at this, look at this, look at that. And I’m like, but it’s pretty. And they’re like, You don’t know anything. And so I think it does speak to the, the observational skills of readers. And that they have figured out, you know, how to develop effective breeding programs.

You know, what’s the best chance that they will have of getting a dog that looks like [00:21:00] this. And they know their stock. You know, they know their stock. They know what they’ve produced before. They’ve got great guesses. What’s dominant, what’s recessive, what’s partially penetrant? You know, early on, they might not have known all those terms when I first started in the field 30 years ago, but they knew exactly what all of those things meant, and they’ve been spectacularly successful because of it.

>> James Jacobson: It’s sort of like, I think it was like a winemaker. People have been making wine for a long time and figured it out.

>> Dr. Elaine Ostrander: Right, exactly.

>> James Jacobson: They’re looking for a good wine or a good blend. And then similarly with, uh, dog breeders who, you know, were doing this well before genomics was possible.

>> Dr. Elaine Ostrander: Yeah. And they’re very nuanced, right? So these different wines, you just go through the store and you, you read the backs of the labels, right? And, and the aficionados will tell you, yes, this does have more floral than this. And it’s, it’s really the same thing, you know, they’ll say I want something like this, but I want it to be different in these, these and these ways.

And so I need to cross something like this, [00:22:00] something like that. And yeah, boy, they’re mass absolute masters of doing this. I think they’re some of the, you know, best geneticists I’ve ever talked to or worked with.

>> James Jacobson: So, you said you go to a lot of dog shows, and it sounds like, uh, how big is your lab? How many folks work in?

>> Dr. Elaine Ostrander: Ten people.

>> James Jacobson: It’s just ten?

>> Dr. Elaine Ostrander: Yeah, but you know, partly because we’re at the National Institutes of Health. It’s very, very easy for us to collaborate with, you know, anybody and everybody, right? And, and we do. I mean, we have hundreds of collaborators all over the world. And people reach out to us, you know, owners will reach out to us and they’ll tell us a story that breaks your heart and say, can’t you work on this disease?

My dog has it. My breed has it. And sometimes we can say, yes, it overlaps with things where we have expertise on. Often we’ll say no, but you know what, we’ll store samples for you and we have the ability to do that. So, you know, we’ll say send us 10 or 20 representative samples and hundreds [00:23:00] come in, of course, and we isolate DNA and we put them in the freezer and we say, tell us in writing when you have a scientific collaborator and who you want us to send them to and we’ll do that for you.

But other times, you know, we just get contacted from scientists. or from interest groups, really from all over the world who have an interesting population of dogs. And, you know, right now we have a collaborator who’s got connections in the Galapagos, in Fiji. We have other collaborators in Vietnam, we’re working with a set of dogs from Patagonia, and I mean, and the list just goes on and on and on and on and on. And it’s great.

>> James Jacobson: So the dog community worldwide has embraced what you’re doing.

>> Dr. Elaine Ostrander: Yeah, you know, I will say the dog community as a whole is one of the most collaborative and generous scientific communities I’ve certainly ever encountered, and I think when I tell my colleagues in other fields, they’re like, wow, you guys really have your act together, don’t you?

[00:24:00] And I think it’s because when we started out, we understood that dogs represented an amazing opportunity to solve problems in human health and biology, and to understand mammalian development in ways that we never had before. But it wasn’t going to work if each of us went out on our own. We were too small. We were too underfunded. We had to work together. And we got that right away. And the community as a whole does that spectacularly well.

I mean, you go to every two years, there’s a, you know, a dog genetics meeting and it’s, it’s like old home week. It’s like, I haven’t 10 years. What are you doing now? Remember when you were interested in blah? I finally got some samples. Let me send them to you. You’d be more interested in them than I am. It is a very, very collaborative community. And we made a commitment early on to share things before publication. So a lot of stuff gets shared prior to publication.

And that’s different than a lot of communities. And I think that’s one of the [00:25:00] reasons it’s been very successful, given that it’s dogs.

>> James Jacobson: How did you elicit that commitment from people to share before publication?

>> Dr. Elaine Ostrander: You know, I would say it started with making the map to navigate the dog genome which, you know, you start a project like this and you have all these pie in the sky ideas. We’re going to map genes for behavior, and cancer, and epilepsy, and diabetes, and… You know, we’re going to do all these things. And then reality sets in, which is, that’s great, but you don’t even know how many chromosomes the dog has, right?

You have to figure out how to navigate the genome. And those were the first things that we did, but it took a lot of people to make that happen. Different people contributed different things to make a first generation map of the dog genome. And it wasn’t a super refined map. I mean…

>> James Jacobson: That was back in, that was 2005, right?

>> Dr. Elaine Ostrander: So that was actually more like in 2000.

>> James Jacobson: Okay.

>> Dr. Elaine Ostrander: Just to navigate… to I’m in [00:26:00] this part of this chromosome, I think that’s where my gene is. And then we had to have a good enough map that we could then go and say, Hey, NIH, sequence our genome. We know what we’re doing. Here’s lots of examples of success. Here’s lots of examples of where we work and play well together. Now sequence our genome next. We want you to do it before you do cats and cows and pigs or you know, whatever.

I don’t remember what order everything was done in, but we want to be at the top of the list. And, you know, obviously after flies and worms and mice and humans and all those obvious things, right? And so, yeah, our genome was sequenced very early on in 2005. And that was great. And the Broad did it and they have consistently made updates and improvements available.

And now lots of people sequence dog genomes. There’s almost 4, 000 of them out there. And we put them out as we get the data, everybody does, rather than waiting or holding on for two and a half years [00:27:00] or three years, will they write a paper because, you know, it benefits everybody.

>> James Jacobson: And the collaborative nature and the thing that makes dog lovers, dog lovers probably contribute to that. As you said, I understand that, that there was like stuff in freezers for dozens of years that were used in some of the early stages.

>> Dr. Elaine Ostrander: Yeah, that’s absolutely true. I think one of the things that makes This field a little bit unique is. I think nearly every person in my lab is a dog owner and two people in my lab own three dogs, right? Between the two of them, they have six dogs, right? And that’s always been true. I mean, there’s the occasional person that has a cat, but they also own a dog, right?

>> James Jacobson: We have the same thing here at DPN. It’s like, okay, you have to, you have to be a dog lover, yeah.

>> Dr. Elaine Ostrander: Right. Well, I don’t require it, but they’re obviously drawn to the lab. And everyone who’s had a dog has had their heart broken when their dog dies. I know I did when Tess died. I mean, my [00:28:00] heart was just broken. You know, my daughter was like, four at the time, and I just remember her crawling into the dog’s crate and just crying and crying and crying, you know, everyone who’s had a dog’s had their heart broken and that stays in the back of your mind.

It’s on the forefront of your mind when you’re working and you’re analyzing data and you’re at the bench. But it’s back there somewhere all the time. And I think that’s one of the things that motivates us as a community to work and play well together.

>> Molly Jacobson: Let me pause this fascinating conversation just a moment so we can take a break and hear from our sponsors.

We’ll be right back.

Thanks, everybody. We’re back with James Jacobson speaking with Elaine Ostrander.

>> James Jacobson: We will talk about heart dogs because heart dogs are sort of what we’re all about. Everyone has that one dog that they really remember that is special. So let’s talk about Tess now. I normally say that to the end, but tell me about Tess.

>> Dr. Elaine Ostrander: Oh, Tess was, Tess was [00:29:00] great. So Tess was a Border Collie, and I had bought her from a farm out in Oregon, and I had watched her parents herd. So I knew her parents were good herders. And so her parents had a, a litter of three puppies. And, you know, we picked that one there and took her home at the appropriate time.

And, you know, Tess was, she wasn’t a good herder, you know, she wasn’t, I’m, I’m just going to come out and say, you know, my dog wasn’t a super smart dog and it wasn’t a good herder and it took a little longer than the average Border Collie to learn stuff. But the flip side of that was she was a much better family dog than a lot of Border Collies are.

And so, yes, she wanted to go out every morning at 6 a. m. and herd the geese at the park and, and herd tennis balls. But, you know, she also came to work with me and at that time I was at the Hutchinson Cancer Center and there was a [00:30:00] floor of patients and of course she couldn’t go on the floor. These were bone marrow transplant patients, but the families were there for months.

And so, you know, this family would take her out jogging and this family would come by and take her to the grocery store and then, you know, there’d be some graduate student that was struggling with their experiments and they’d come by, can I borrow your dog? Yeah, sure. Go ahead, you know. And so at the end of the day, she was exhausted, but she was exceptionally well socialized.

>> James Jacobson: She had a day at work too.

>> Dr. Elaine Ostrander: Yeah. She was busy all day long. And you could just say to her, you know, you could say, Tess, lab meeting, lab meeting, and she stayed in my office, but this is the one time she could go into the lab and go in and out of the bays and herd everybody up, bring them down the hall for lab meeting.

>> James Jacobson: She, she was good at herding, just people.

>> Dr. Elaine Ostrander: Yeah, my husband also worked in the same building, but on a different floor in a different side of the building. And she could easily just get in the elevator and people would be like, oh, it’s Tess, and they’d push the right button. And off she would go to my husband’s office and, you know, up down the hall and [00:31:00] then, you know, she’d end up in his office, I mean.

So she had her role, she had her job, she had her tasks, she had the things that she had to do. And, you know, it was funny, she always slept under the bed right underneath me. And so if I got up during the night for any reason, she’d crawl right out and follow me and see what I was doing and making sure everything was okay.

And I’d go back to bed and then she’d crawl right under the bed and she had to practically dislocate her arm, you know, her paws to do it and dig in, dig in to get under there. And so, you know, she had all of her quirks like Border Collies had and she died when she was 13 and my oldest daughter was four.

And it was just, yeah, it just, it just broke her heart. I remember when she was close to death, my daughter said, well, we have to make her some food. And I said, well, I don’t think she can eat anything. She’s in liver failure. And she said, well, we should make her some macaroni and cheese. She likes macaroni and cheese.

I’m like, you like macaroni and cheese, [00:32:00] right? And she goes, no, Tess will, Tess will like. Tessa likes it’s okay. Make macaroni and cheese, go to the hospital where Tess is. And at that point she was, had stroked and she was fairly paralyzed, but she could lift her head and you know, she saw my daughter and she just lifted her head and she gave the macaroni just a little bit of lick and my daughter was, See, I told you she needed some macaroni and cheese mom.

You were right. You were right and You know, I have a million stories like that, but I’ll cry if I tell them so. But, yeah, it broke my heart when she died. Really, it really did.

>> James Jacobson: That connection that people have with their dogs is so critical. And it seems like such a fundamental part of the success that you’ve had in terms of enlisting support. I saw a story where you, you know, would basically try to, because part of what you have to do is lobby for support to make this stuff happen. And, and, uh, you’ve been able to persuade some people by talking about their dogs with them.

>> Dr. Elaine Ostrander: Yeah, I mean, everybody likes to talk about their dogs and [00:33:00] their grandchildren. That’s what I’ve discovered, right? And if I had to say on balance, people would rather talk about their dogs than their grandchildren. I’m probably going to get in trouble for saying that, but I’m going to say it out loud anyway.

>> James Jacobson: Not on Dog Podcast Network. People will understand.

>> Dr. Elaine Ostrander: Okay, not on Dog Podcast Network. That’s right. But people do, because, you know, again, they’re part of their family. People less and less say, I own a dog. They say, you know, we have a dog, right? And it’s a very different statement, right? It’s our dog is part of our family and it’s important. And we want it to have a long and happy and productive life and reach its full potential, just like we want for everybody in our family.

And I think listening to dog owners and telling them what you do. And for me, you know, a lot of times I’ve said, I’m actually not the right lab for you to talk to. There’s someone who’s a bigger expert than I am on epilepsy. I don’t know anything about epilepsy. Go talk to them. Or, you know, I really don’t study diabetes. Go talk to them.

And our [00:34:00] community is like that. Because if we start being petty and self centered, and egotistical, the whole thing’s going to fall apart and we’re not so rich that we can afford it as a scientific community. This is the only way we’re going to succeed. And everybody gets that, you know, and everybody realizes that this is, there’s so much to do.

There’s so many diseases to study. There’s so many traits to study. There’s so much behavior to study and, and everybody finds something that’s interesting. You know, have you ever noticed that some dogs, the tail curls twice and other breeds, the tail curls once? What’s going on with those bones and, you know, how is that going to tell us something about human bone, whatever it is, right? Everyone finds something that they’re really interested in. And so there’s enough for everybody.

>> James Jacobson: And now you guys are, you’re looking at behavior. You’re looking at the role of behavior. Talk about that. That’s fascinating.

>> Dr. Elaine Ostrander: Well, you know, to be honest, when Jasper and I started the project, that [00:35:00] really was the original driving force. There had been two papers that had been published nearly back to back that showed how you could now make maps to navigate the genome of any mammal. And before, that was not a reality. You know, making a map of one genome was a long, laborious, many years long process.

These two papers came out and they both said the same thing, that no, no, no. It’s really easy now to be able to make a map that navigates the genome. And so suddenly, you know, the curtains flew open because you thought about all the things in nature that were cool and exciting. I want to know why ground squirrels do this. I want to know why zebras do that. Are they black with white stripes or white with black stripes?

Well, if we had a map of their genome, we could figure it out. And they have since figured it out, right? We want to understand this. We want to understand that. And so, we wanted to understand behavior, honestly, and that was the driving force behind making that first genetic map. [00:36:00] I think we were naive in that we didn’t, at that point in time, have real behavioral scientists working with us.

And so you can watch a herding dog herd, right, and you can watch a non-herding dog look at a group of sheep, walk by and run away in the other direction and hang its head. Please don’t let the sheep get me, right? But, mapping something requires those nuanced observations that those breeders have been making for years and years and years.

And so I think it’s taken a while for us to get to the point where we can call traits precisely enough, accurately enough, that we can feed them into our equations and our maps and our sequences. And be able to say, okay, I think there are genes that might be associated with this trait over here, or some are over here, or some over here, right?

I think now is our moment, finally. After all these years, I [00:37:00] think we are here now and that we’re just starting to see an explosion of being able to map these observations that we’ve looked at for such a long time.

>> James Jacobson: Any new insights that you’ve gleaned so far in that?

>> Dr. Elaine Ostrander: Well, I think there’s an emerging trend, and I have to, you have to pick words so, so, so carefully here. But there have certainly been hints from papers that have come out, that genes that seem to be important in dog behaviors, we’ve already seen them in humans. And they tend to be associated, some of them, not all of them, not all of them, but some of them have tended to be associated with traits like ADHD or like autism or like schizophrenia.

Doesn’t mean they cause schizophrenia in dogs. Doesn’t mean they cause autism in dogs. Doesn’t mean they cause ADHD in dogs. It’s just that [00:38:00] we’ve seen them before. They’re familiar to us when experts in those human conditions have studied them. Those are some of the genes that have popped out of their vocabulary. And they’re kind of popping out now in our vocabulary.

So you know, owners come up to me all the time and say, you know, I think my dog is schizophrenic. Well, no, not saying that. Not at all. Not even remotely. But I think what we are saying is that there’s a way that the brain and the nervous system are put together, and there are going to be overlaps in normal and abnormal behaviors as we start to pull those things together.

And that’s probably not surprising. But honestly, for so long, we just swam around in the deep end of the pool trying to figure out which way to go and how to really start. Do we start with abnormal behaviors? Do we start with normal behaviors? How do you get data? I mean, how do you assay owners for behavioral information about their dogs, right? There’s a [00:39:00] perceived right answer, you know, and a perceived wrong answer. So how do you get that data?

How do you get one behavior is to assay, you know, 500 dogs that you know, 500 different locations I mean, we were just floating around in the deep and trying to figure out the best way to do the experiment I think now that we have it.

>> James Jacobson: So if you polish your crystal ball and look at where this behavior research goes 10 years, you know, in this quantum movement that we’re having, where do you see that just on the behavior side?

>> Dr. Elaine Ostrander: Oh, uh, I just see an explosion of just so much information. I think we’re going to, now that we’re able to, to describe different dog behaviors in much more nuanced ways and, and, you know, line them up with sort of sub, sub, sub behaviors in, in human syndromes, I think we’re going to find new genes that we didn’t know were part of the vocabulary of behavior. They’re going to be great for human geneticists to study.

I think we’re going to find genes associated with [00:40:00] behaviors in dogs that human geneticists knew were important, but didn’t know that they were important in that way. I think we’re going to find parts of genes or proteins that are encoded by genes that are super important in interacting with this, which interacts with that, which interacts with this. And part of that’s going to be new to human geneticists, and part of it we’re going to have already known, and it’s going to help us put together our story.

I mean, I think I would say it’s like a puzzle. And I think the pieces are just going to drop in and some are going to fall in exactly the right place and some we’re going to have to move around and get more information. But I think in 10 years, I’m not going to say everything’s going to be answered because it won’t be, but I think we’ll be able to look down and say, ah, okay, this is the general idea of how things are going to go. This is what’s happening.

And so we recently did publish a paper showing that for herding behaviors or some herding behaviors, [00:41:00] that it’s really gene is important in early brain development that turn out to be the most strongly associated. All right. And it could have been anything, right? I mean, the nervous system and the brain and neurology. I mean, it’s all super, super complex. So to even be able to say, okay. Setting you aside, we’re just going to focus on you here.

So I think it’s really exciting, but I would say the same thing about cancer.

>> James Jacobson: Well, that’s where I wanted to turn next. Let’s talk about cancer. I mean, cancer is something that is near and dear to everything that we do here. And it’s so important. And I, recently, 60 Minutes featured a whole episode on the role of cancer and the role, the work that you’re doing and, you know, the connection between dogs and human cancer, and that has helped create greater awareness of this. What was that like to be? I think you were featured at the top of that episode, right?

>> Dr. Elaine Ostrander: Yeah. Let’s see. So, so many questions to unpack there. So, because I started out at the Hutchinson [00:42:00] Cancer Center in Seattle, that’s always been our go to disease that my lab has worked on. And, you know, one of the first things you learn when you’re surrounded by oncologists everywhere is that, you know, dogs and humans get the same cancers, right?

I mean, they’re going to get melanoma, they’re going to get leukemia, they’re going to get lymphoma, they’re going to get CNS tumors, they’re going to get bladder tumors. It’s, it’s the same story. And the pathology is very often going to look the same. The treatment is often going to be the same. The response to treatment is often going to be the same.

And so, if we could understand susceptibility by studying dogs, Wow, that would be really, really helpful for humans because, you know, in dogs, you take a breed like the Scottish Terrier where you, you know that there’s a super high risk of bladder cancer. Well, you don’t have a population of humans that are at a 22 fold increased risk of bladder cancer, but you know, bladder cancer is a big deal in humans, right? I mean, it’s a bad disease.

And so, [00:43:00] you can study a small number of at risk breeds and compare them to breeds that are not at risk and you can find these genes and you can say, Oh, okay, these are genes that are important in susceptibility. Now human geneticists, people who develop therapies and treatments and and companies, these are things that you should think about and these are things you should focus on. And that’s something dogs offer uniquely.

There’s nowhere else that you can do that. Dogs offer that completely uniquely. When we were first contacted by 60 Minutes, of course, it’s incredibly flattering. And I think 60 Minutes initially was sort of thinking about where they wanted to go with the story. You know, where was it it going to end up? And it was great. I mean, they were phenomenal.

Anderson Cooper came to a dog show with me in the pouring rain and he stood there in the pouring rain and, you know, my hair went like this and his was perfect. You know, that kind of thing. And [00:44:00] so I was so impressed with how knowledgeable they were. They had so done their homework.

And so we were able to have discussions with them about cancer and about behavior and about everything at a really high level and so I thought that the pieces they produced were great because I think people understood them. People understood why they were important, but they didn’t pander to people. They, they really got across a message. You know, they were very sophisticated in their own way of communicating things, which was really very, very precise.

And so since then, you know, I always say that the person who has the samples has the gold because samples are everything, right? You can sit there and say, I want to study disease X. But if you don’t have samples from dogs with a disease X, you’re just wishing on a star. It’s just not going to happen. And the more samples you have, the better. And the better their pathology is described, the better it is for you. [00:45:00] And the more you have controls, you know, older dogs who don’t have that disease, the better things are for you.

And I would say one of the terrific things that the 60 Minutes program did is, you know, owners are always generous. Nobody ever says no to us, but so many people really flooded our emails and our phones and said, Hey, Hey, Hey, you know, we want to be part of this. We want to be part of that.

And, you know, people whose dogs don’t have cancer called us and just said, I have this really weird breed, and I said, well, you need to be part of the NHGRI Dog Genome Project. So, we’re going to send you a kit. We send people a kit. They give it to their vet. The vet collects a sample. We give them a mailer. It comes right back to us. We could not make it easier for them. And then we say, hey, now your dog’s part of the Dog Genome Project, so.

>> James Jacobson: And anyone can get involved in that by getting that?

>> Dr. Elaine Ostrander: Oh, absolutely. Absolutely. Yeah, absolutely. Actually, people I hadn’t heard from in 50 years that I went to junior high with contacted me and said, Hey, [00:46:00] remember me? We went to junior high together. I’ve got a such and such a dog, you know, can you send me one of your sample kits? I want my dog to be part of your project. Sure. Yeah. Hi, and how are you? And, you know.

>> James Jacobson: So if our listeners want to do that, what’s the best way to get that?

>> Dr. Elaine Ostrander: So you can go to our Facebook page, Dog Genome or NHGRI Dog Genome Project. And there’s all kinds of contact information there and breeds we’re currently collecting samples from to just sort of fill out our repertoire of all 350 breeds on the planet. And diseases were focused on copies of some recent papers. And we have one woman in the lab who’s amazing, just amazing. Jess is our samples manager.

And so all samples coming in go through her and all the information. And she sends you a kit and you can talk with her about your dog. And all of her contact information is on that Facebook page.

>> James Jacobson: We’ll put a link to that in the show notes.

>> Dr. Elaine Ostrander: Yep. And if you think, you [00:47:00] know, you, you just have an unusual breed, or you see your breed as one we just need to fill out from the Facebook page, contact us. You know, we’d love to talk with you.

>> James Jacobson: You have been involved in another long term project that we’ve been following, which is the Morris Animal Lifetime Golden Retriever Study. You were on the steering committee, right? Or you’re still on the steering committee for that?

>> Dr. Elaine Ostrander: No, I’m not anymore. It’s kind of been a rotating thing, but yeah, initially I was.

>> James Jacobson: What do you think about that? What is the hope there?

>> Dr. Elaine Ostrander: Oh, well, you know, it’s interesting in my human genetics world, people do prospective studies all the time. So, you know, they’ll define a cohort, a geographic region, you know, based on a particular problem. And they’ll say over time, we’re going to collect everybody who gets disease N that we possibly can from this three county area or who are of, you know, these ages and living in this area or, and we’re going to follow them over time.

We’re going to see [00:48:00] what happens to their disease, or we’re going to see if they get this disease, right? I mean, the Framingham Health Study is a good example of, Heart Studies. One of good example of that where people have been followed for years and years and years and years and years to see what they get and how they’re treated and how they respond to it and so on.

It had never been done in dogs, actually. Nobody had ever said, okay, we want to study, uh, cohort, a group of dogs. We want to get as many as we can, and then we want to follow them for their life. And we’re going to contact their owners every year, and we’re going to get health surveys, and blood samples, and urine samples, and plasma samples, and anything we can.

And owners are going to fill out questionnaires every year, and we’re going to figure out a way to get all that into computers so that lots of scientists can work on different questions they’re interested in. And, you know, it’s now at the point where dogs are old enough that they’re starting to pass on.

And I think that study has just come to fruition. I think [00:49:00] it’s so exciting. No one has ever done one of these cohort studies from, you know, little puppies being born and then following them throughout their lifetime and getting all this critical information at every single solitary step. You know, now I want to see more, right?

So now, now, you know, I’m like, okay, that was great. Golden Retrievers tend to have these traits, tend to have these diseases, tend to die of these things. And those are common, you know, the cancers, the dysplasias, et cetera. Now let’s pick this breed and study these things. And now let’s do that breed and study those things.

But, you know, it took a lot of organization and a lot of cooperation on the part of the owners. Very few have dropped out. You know, very few owners got tired of it or bored with it. Every year, they went, they did their thing, just like they said they were going to do at the beginning. So I think it’s been great that it succeeded because it says we can do it again and address other problems.

>> James Jacobson: And the Morris Animal Foundation, obviously a lot of people are interested [00:50:00] because of the prevalence of cancer in Golden Retrievers.

>> Dr. Elaine Ostrander: Golden Retrievers, yeah.

>> James Jacobson: Seventy five percent die of cancer approximately, which is a lot. You work with veterinary oncologists and you’ve been having a lot of dialogue with them. How closely do you work with vet oncologists and general practice vets?

>> Dr. Elaine Ostrander: Yeah, so we do work closely with a number of veterinary oncologists like, you know, Debbie Knapp at Purdue, who’s the country’s expert on, for instance, bladder cancer. And it’s great because, you know, I’m not a veterinarian and so those are the people that we talk with and we work with, we develop hypotheses with because they know more about the disease than we do.

And they’re interacting with the clients, the dogs, right? And so they’re the ones getting samples. And then those samples come to us and we’ll sequence their genome and we’ll analyze their genomes and, you know, do all of those cool things. Look at what genes are expressed in tumors or not. And so, we couldn’t do it without them, and [00:51:00] obviously they’re not going to be doing it without us.

And so, I think those kinds of partnerships exist everywhere in the dog world, no matter what disease you’re studying, right? There aren’t enough veterinary oncologists who are also lab based people, you know, working in the lab and in labs like mine. There’s such a demand for veterinary oncologists, I think the majority are practicing, and that makes perfect sense because cancer is so common in dogs.

>> James Jacobson: There are only a few hundred in North America.

>> Dr. Elaine Ostrander: Yeah, and they’re practicing and that’s great and that’s where we want them to be. But I think when they are willing to take the time, as everyone I’ve ever asked is, to work with a basic science lab or a basic genetics lab like mine, it’s fantastic. And literally no one’s ever said no, right? They’ve said, I’ve got to figure out how to make this work. It’s going to take a little bit here. But we can make this work because it’s so important to the health of the dogs.

>> James Jacobson: And this is within the realm of comparative oncology.

>> Dr. Elaine Ostrander: It is. You know, when I came to NIH, [00:52:00] I was brought on board because of my interest in comparative oncology because I worked on humans. You know, I worked on hormonal cancers, breast and prostate cancer, and I was heading the Dog Genome Project. So showing how things we were learning from one would move back and forth to the other. That’s always been why my lab worked on multiple different things.

People would say, do you have a problem focusing or something? I say, no, no, no, really, this is how you do science. You don’t silo. You know, the days of doing a siloed approach to science are long gone. Now that we can sequence genomes, now that we can map genomes, everything needs to be integrated. And I think that’s obviously turned out to be true.

>> James Jacobson: Has the current administration’s push on the cancer initiative helped what you’re able to do financially and to grow?

>> Dr. Elaine Ostrander: Oh, absolutely. I think people have seen the success stories coming out of dog genetics and dog genomics. And here at NIH, we’re met with tremendous [00:53:00] enthusiasm, whether we’re talking about our behavior work or our cancer work or just genome architecture and genome structure. So I think that, again, speaks to the way that the community has organized themselves.

And I think, you know, there’s an interest now in longevity in dogs. Small breeds live much longer than large breeds. Why is that happening? And so, you know, we’re collaborating with people at UCLA who study, you know, longevity in humans as well as in other species and do a comparative approach to it. And yeah, so I think there’s endless opportunities for traits of interest in dogs.

>> James Jacobson: This has been delightful. My last question to you, Dr. Ostrander, is tell me about your dog that you have now.

>> Dr. Elaine Ostrander: Oh, this is a heartbreak, but my youngest daughter developed an allergy to dogs. She actually developed an allergy to anything with fur. Dogs, cats, horses, anything but fish. So, unfortunately, I’m without a dog right now.

And it breaks her heart because the only thing she ever wanted to be was a veterinarian. [00:54:00] That’s actually what she wanted to do since she could talk, was be a veterinarian. She said, I like dogs better than I like people, I think, some days, you know. So actually right now I’m without a dog, but I’ll tell you, my lab has everything.

>> James Jacobson: I was going to say, you, you get them at work if you don’t get them at home, you get them at work.

>> Dr. Elaine Ostrander: Yeah. I mean, I’ve got one person with a great Chihuahua mix. I have someone with three Shelties who does all kinds of obedience with them. You know, she’s really fantastic. And then I have someone with three hounds, all of which were rescues. All long limbed, just beautiful, beautiful, beautiful dogs. You know, someone’s got a Lab and, you know, someone does rescues, fosters dogs. So, everything you can imagine.

I had a guy once in the lab who had a Lienberger, one of those giant, you know, giant Lienbergers. And that was really fun. That was really a good time when, when he was in the lab because his dog was just fantastic. So, you know, I have to go and play with everybody else’s dogs or go to the dog shows or, it’s okay. She [00:55:00] still wants to be a vet, you know, that’s what she still wants.

>> James Jacobson: She does, okay.

>> Dr. Elaine Ostrander: Oh yeah.

>> James Jacobson: Okay, so the hypoallergenic dogs don’t work, the Maltese or the Poodles.

>> Dr. Elaine Ostrander: Yeah, you know, those are, I’ll just end by saying hypoallergenic is probably not the right word because there’s no dog that truly no one’s allergic to, right? I mean, they have reduced allergenicity. And so I haven’t explored those very rigorously. But boy, she’s, I mean, birds, you know, my brother had some kind of a bird. She went to his house and she was, she’s so allergenic, so yeah, I don’t, I don’t know. She’s going to have to have fish. That’s it. That’s going to be it for her. I’m afraid.

>> James Jacobson: Oh, well, you get your dogs at work. Thank you so much. Dr. Ostrander. I really appreciate it. This has been awesome.

>> Dr. Elaine Ostrander: Thank you so much for your time.

>> Molly Jacobson: And thank you friend for joining us for that wonderful conversation James had with Elaine Ostrander of the National Institutes of Health. Aren’t we all just so lucky that we have folks like Dr. Ostrander doing such great work to help [00:56:00] other scientists get a head start on understanding and treating cancer. The work that she and others at the NIH do is so very important. The pure search for understanding is foundational to progress.

Thank you to Elaine Ostrander for her work and for taking so much time to share it with James and with us.

And that’s it for today’s show. Don’t forget to follow and like us, subscribe in your favorite podcast app. And of course, tell your friends, and your veterinarian, about our show. Check the show notes for links and visit us at DogCancer.com for more information, articles, and podcasts about the number one killer of dogs, cancer.

I’m Molly Jacobson. And for all of us here at dog podcast network, I’m wishing you and your dog a warm, Aloha.

>> Announcer: Thank you for listening to Dog Cancer Answers. If you’d like to connect, please visit our website at DogCancer.com, or call our listener line at [00:57:00] (808) 868-3200. And here’s a friendly reminder that you probably already know, this podcast is provided for informational and educational purposes only. It’s not meant to take the place of the advice you receive from your dog’s veterinarian.

Only veterinarians who examine your dog can give you veterinary advice or diagnose your dog’s medical condition. Your reliance on the information you hear on this podcast is solely at your own risk. If your dog has a specific health problem, contact your veterinarian. Also, please keep in mind that veterinary information can change rapidly, therefore, some information may be out of date.

Dog Cancer Answers is a presentation of Maui Media in association with Dog Podcast Network.