Welcome to the infectious Science Podcast. This is not just another Science Podcast Nope. Infectious sciences produced by a team from the University of Texas Medical Branch and the Galveston national lab where we study some of the most dangerous viruses on the planet. Our goal is to inspire future scientists towards a career in science with a focus on one health, one
health one planet. That's right, when other approaches public health threats by examining the connections between people, plants, animals, and the environment we all share. The show will explore how one health is your health. So sit back and learn something infectious science where enthusiasm for science is contagious. Can you imagine that a dogs sense of smell is so powerful that it can distinguish a sick person from a healthy person. It can even tell what kind of
disease you have. Welcome back to the infectious signs podcast. My name is Dennis Benton, and I'm an associate professor in the Microbiology and Immunology department at the University of Texas Medical Branch. Today we will be talking to a veterinarian and neurologists Dr. Holga Falk Dr. Focus currently professor of small animal diseases and head of the department of small animal medicine and surgery at the University of Veterinary
Medicine in Hanover. And he's also the past president of the European College of Veterinary neurology, Dr. False group demonstrated in 2020 that scent dogs can identify SARS COVID, to infections in different body fluids. And they were also able to show that the diagnosis that the dog gives you a specific and sensitive it just so happened that Holga focus for my study colleague of mine and we went to the same vet school together back in the mid 1990s. In the
Hannover. I was recently in Hannover, Germany to visit my alma mater and had the chance to talk to Hall guy about this very exciting project. In my eyes. This is really a poster project of what I want to health project should look like because it combines animal behavior animal physiology, virology immunology, in eventually to protect human health. Dogs have been used in many environments for years as real time detectors of explosives, narcotics, salarians people, animals and other
targets of interests. As we all probably know, dogs possess an extreme sense of smell with a demonstrated lower limit of detection of one part petroleum, so a dog's nose bear 300 million scent receptors compared with the five or 6 million in humans, that enables them to detect tiny concentrations of odor that people can't, which is actually three fold orders of magnitude more sensitive than today's available laboratory instruments, which can reliably identify substances of
concentrations as low as one part per million. To illustrate the tremendous canine olfactory sensitivity dog could detect the equivalent of one drop of liquids in an Olympic sized swimming pool. Sniffer dogs already have familiar sights at airports to detect firearms, explosives, and drugs and so on. So scientists have also trained dogs to detect some cancers and malaria. But the animals are not routinely used for this purpose.
The power of the sensory system allows the dogs to detect diseases, pathogens, cadaverous loss people and other biological targets. Hold on. Welcome to the infectious Science Podcast. Hi, really great to be on the podcast. And I'm more excited to talk about, you know, the little project we did and the whole story how it actually we came about doing it. Yeah, tell us how did this project came about? And what gave you the idea to train dogs to smell it on an infected patient?
Yeah, I mean, to be very blunt and honest, I thought in the beginning, this was a totally crazy idea. So we were working on cognition in our lab, mainly on, you know, dogs with epilepsy changing their cognition, and
same with dementia in dogs. And then COVID obviously came and we had some learning paradigm using sniffer dogs and see how they changed, you know, their learning behavior by different sensors, and if that's affected by disease, and obviously what happens then was the COVID came and we thought, like, is there any chance we could use the knowledge and have a knowledge transfer and see if dogs
actually can smell disease? And to be very honest, you know, then I ask you do you use one of those web search engines and then suddenly, you'll find that there have been some publications about it, like you said in malaria, and so some other cancer and some other infectious diseases, mainly bacterial nature. And what I did then I said I had a call to Professor also house I'm not sure if most people will probably know him who's quite an
expert in it. Coronavirus and I said, What do you think about this? And I still remember it was a Friday evening, very early on in the pandemic, when you look at Europe, and he said, Hold on. That's not possible. So I did send him a couple of papers. And then we had another chat. I think it was like a 10am on a Saturday morning. He said, Yeah, why not? And the reason why I obviously needed him is we needed to have some Top Gun biologists to make it safe,
right. So because we couldn't obviously just transfer the virus somewhere a sample from an infectious person without making it safe also for the dogs to sniff. And then from that, it was a really blast. So we got support from the German armed forces, Dr. Esther shulker. She is a B veterinary behaviors diploma holder, a European specialist, so to speak, and I know from the past, or she was at the to before, and I gave her a call and said, Hey, look, you have a lot of detection dogs.
What about this idea that we use them now to curve down the pandemic and make a difference? I mean, that was the whole reason why we did it. It was mainly to help with a huge crisis, which was coming our way and see if we can actually use the dogs to make a difference. And as you mentioned, it then went very fast. So Marin cooker, sunblock Vader, who's also at the lab, she also helped I think, Claudia Schulz, as well.
And we collaborated with a medical school in Hanover and Hamburg Eppendorf University Hospital, because in the beginning, we needed to get samples. And very early on, obviously, the only songs we could get from people being in a hospital, often intensive care. And I have to say, really, app helped us a lot, because he said, Why don't you use better probably an electrode BPL to inactivate those samples to make
them safe. And that time, you know, people didn't know which cell lines ready to use how to really look for violence, you know, is BPL and activation actually even possible in these? So we had to do all this work, initially, because obviously, what we couldn't do is put the dogs at risk. And if you remember, at that time, we didn't know, is it only a disease for humans, there was even some evidence to know it's obviously in ferrets and hamster potentially cats and dogs
perhaps as well, right. So we didn't know. And obviously, one of the things we didn't want to make sure that the handlers or the dogs are, in fact, it makes sense. So as a virologist, I really share up austere house concerns, especially when I read the first report on this I was a bit skeptical of the material in a very on that so little protein in there was so little genomic material, so that we even have a hard time picking up the proteins or the G and jiomoney material unless you use PCR or
something like that. So compared to bacteria, viruses don't have their own metabolism. So you probably rely on on other things. Can you address the skepticism of the people that think well, can you really smell a virus totally, to be honest, I mean, we were very, very, very skeptical in the beginning. And obviously, the virus doesn't smell, it's obviously the change in the body cells, which then will change the medical light and these volatile organic
compounds, or VOCs. For us, it's not variants of concerns, it's actually organic compounds. So those guys, the dogs will pick up and the interesting thing on our setup, and that's why we were the first to ever published a paper, we had this kind of Nintendo game for dogs. It's a machine, which is really addictive, really rewarding for the dogs, you can train them
very, very quickly. It's randomize, there's an effect of training called the clever hands effect because it's very difficult for handlers not to give some indication with sample might be positive or not. And the dogs actually work on this machine totally by themselves. It's like a sniffing machine where the dog was at a nose. And then as long as it puts the nose as more sensitive it is, and you
train them up. And after four seconds, it's a positive indication, if they're only like a one second in and then they move on to the next sample. It's not a positive indication. And women use this approach. It was literally in a week we had them trained up, I like the comparison off Nintendo for dogs. Can you like describe that again? So the dog you have to send dog and then like certain openings? Or can you explain that? Exactly, exactly. It's a machine
with seven holes. And behind each hole, there are multiple revolvers, where you can actually shift per random samples there. So you don't know which one actually will come. If they indicate the positive, then a treat comes either ball or food. And so they learn very fast the target scent, and you can also have huge repetition rates. So classically, what they would do in a scenario is called a lineup. We actually use that
later for the concert study. But what you do there is you have a one after the other samples often like half a meter 40 centimeters apart, and then they will sniff on each of them. But you can imagine that this takes a long time, you have to make sure that it's randomized and make sure that the dog handler doesn't see which sample you change from a training point of view. There's a lot of flaw and I think that's why we were quite fast in getting our dogs trained
compared to others. But I do also have seen, for example, the medical detection unit in the UK, they take really great care, they always have three people involved. So make sure that the dog handler is blinded, but it's a lot more elaborate. So our training has some advantages. So you talked earlier about the inactivation of the samples? But can you tell us a little bit more about your sample selection and the process? We talked about the dog training, but what
samples did you use? And what were the obstacles for you and the training? To be honest, I mean, one of the biggest challenges in beginning was to get enough samples, because you need to get written consent, we had to get ethics
and so on. And then you have to be really careful because a dog is so sensitive, it could have been that they only picked up that we had the disease person in the intensive care unit in a hospital setting, because they might have not smelled the virus or the products they released by changing the cell metabolism, it could have been also just a
hospital smell, right. So we could have trained them against something totally wrong, or classic example where things can go wrong, that you always handle the one sample, which is the target sent with gloves. And then at the end, they learn that the glove sample is always the one which is the target sample. So you you have to think totally differently, because we are
visual creatures. And I think it's very difficult for us to imagine, you see already said imagine to send what a dog would send right so is to think how a dog would think. So we had to get samples from the same setting control and positive samples. And we started at that time with saliva samples and tracheal bronchial secretion, and then obviously inactivated them and then use them safely. But then we had to kind of come to the other samples, because
this is not very practical. So if you think about it, you would want to have mass screening with dogs, you couldn't do that, right? Because the inactivation process takes a couple of days, and you have to make sure it's safe that it's this is not really practical. That might be just a nice research. But we wanted to have something which we can apply other groups in the world, Dominic Gonzalez from Paris and on for who has done a lot of great work as well, he
used sweat samples. And in the beginning, we were not sure how likely it is that sweat can be also infectious. So we were a bit more hesitant, I think Germans, we are probably taking often a bit more care to make sure no one gets, you know, infected or has any problem with that. But then when we learned that it was relatively safe, we actually looked also using sweat samples. But before we went there, what we did is we had a very special device with a special membrane where only the
scent molecules go through. So it's sealed. And we did it in a high security lab where we once tested can the dogs which were trained for the BPL inactivated samples, can they also test the shout the ones which actually are not inactivated, and they could transfer that sent to that. And even more interestingly, when we use that setup, they could also then send
sweat and urine samples. And it looked like there was a little bit of an indication that urine might be even the best fluid, but it was not significant at the end after correction factors. But I thought that was really interesting from a scientific point of view that obviously, there is a ubiquitous cell metabolism change. And the virus is probably not just in the upper airways. I mean, I'm not a virologist, you know, but I thought who this is really interesting, it's actually quite
everywhere. And that really opened the doors because then using sweat samples, and at that time, we knew the chances of infectiousness from a sweat sample is can be ignored. And that opened a lot of possibilities. And when we talk about sweat, we don't talk about someone who has been running in the gym, sweating, whatever, you know, is actually just in the crook, armpit, you know, just a little rough over. And that's that's enough. It's incredible. You can't even imagine how they
do it. But that was sufficient. So can you talk a little bit more about these scent molecules? So you call them VOCs? Not variants of concern. From a biochemistry perspective, are those more like fatty acids? Or are they glycoproteins or has this been characterized? No, not 100%. Because I guess the challenge what we have is that we will be able to measure certain organic compounds, but what the doc actually will pick
up will be very difficult. So and that's where you know the story starts to become interesting. So they have to be volatile, right? And then some people say could there also be some peptides structures which become airborne, obviously, there are some beliefs that proteins cannot be sniffed, but then there are other people who say dogs might be able to do
that. The dogs you earlier mentioned that they have a really, obviously more cells and a human and a bigger area where they conceptualize in the brain, the sand. However, what is also really interesting is they have the vomeronasal organ, it's more like a tasting which is in your mouth and that's all also used by them for picking up pheromones. And so the question is, probably, it might be a lot more complicated than we thought
initially. And it's probably as I would imagine, as we are looking at a picture, it will probably very similar be for the dog when they sent us. And the really interesting thing, and there's really recent research from this year from Cornell University, they have shown there's a direct connection of the olfactory system to the visual cortex. And I think that is fascinating. So I guess they really see within those, and I guess we will not 100%
comprehend. So we were working on that in another experiment, because one of the critical points was, as you said, earlier, do they actually just smell a person with disease, and then we in the first year of the pandemic, everyone was saying, Oh, you have to differentiate to influenza, but that at that time, you couldn't get influenza
samples, it was impossible. So what we did in the in the year after we got some influenza sample here from the Robert Koch Institute, and we got also some other respiratory virus samples, and the ones we couldn't get, we then use cell culture experiments. So we had, like SASC of one FASTQC have to obviously MERS and so on other respiratory viruses. And the interesting thing there was that the dogs obviously did a lot better on the samples coming
from a human. But then when we gave them the cell culture to smell, the sensitivity dropped. So normally, they have a sensitivity around 85 90%, when you then gave them a cell culture supernatant, then it's suddenly dropped around 65 ish. But then when you train them, again, against the supernatant with Sask of two, then they will pick up very well again. So it's makes kind of sense. Probably cell culture is not a body, right, it's not as complex and even there, they were able to
discriminate. And when you look at sensitivity, in most groups, we have done now a meta analysis, which we have submitted. And actually a couple of things. Also a data pooling exercise, which we are soon to submit from all the groups in the world that we're working on working on it, you can see that most would come out around 85. And then on a specific T level, depending how they use the dogs, you will be 97 to 99%.
So do I understand you correctly, what you're saying is not that a whole body a whole organ? Maybe what you were saying is that it radiates probably a different profile of VOCs compared to a single cell type and Euston and cell line. And I mean, as you know, you know, people have tried and have used newer techniques to look at the volatile organic compounds, and they have fallen acetone and whatever. But question is really is this what the dog smells? Who
knows. And what you have to do is you would have to take each molecule and then probably put them in the same mixture that would be nearly impossible to do. No, you're describing this just always reminds me when I walk my dog, I can see that my dog can smell in the spatial way, right, they can smell 3d, so they know where the scent is coming from.
And this is just always blows me away, we can smell a sentence and they have but we cannot tell if it's coming from the top left or from behind us or something like that. And that's just amazing to me. So you brought up the organ in the upper part of the mouth? Do the dogs have to stick out the tongue and so the tongue back and deliver the molecules that way to the organ? Or how does it work? I mean, that is that is a theory, right? The mouse
obviously has to be opened. But in the past people say yeah, it has to be somehow in a leaking way. But I think this is probably the title of isn't true. But hey, who knows? Because when we started with this idea, why can they be so good in differentiating, there has to be something else than just a normal sensory organ. So what we are thinking about doing is obviously to explore this now functionally, how can we actually look into and see how dogs actually are able to do that, which I think is
absolutely amazing. There have been some experiments also where people have said, Oh, they can smell different DNA is but then when people have purified it that it was not the case. So I mean, I think they're amazing. There's no question, but they have their limitations as well. While ago when we talked earlier, you mentioned that you also wanted to prove not only to do the academic exercise, and train the dogs and show and publish, but also to show the
application of this tool. And you talked about these concerts that you guys organized. Can you talk a lot? Talk about that a little bit? Yeah, so the interesting thing is when we asked the public about which tests they trusted most and then I'm really sorry if which is an interesting
result. Actually, the public trust the dogs more than they trust, handwritten tests, the lateral flow test, and even the PCR which I thought was okay, anyhow, but, you know, I wouldn't go so far but that's what the public perceives when we publish the papers, the media attention was incredible people love the story of dogs being able to do that. Also, when other groups in the world did that, I think I will never get such a high ultrametric score
again in my whole life. It was the first pilot study was a really small study, but it has got a lot a lot of attention, because it was so novel, I guess. But then when it was discussed, and a lot of people obviously contacted us because they wanted to come back to normal life, and they just couldn't see how a PCR testing strategy could help you in like a concert situation or a massive and it was just too cumbersome and too time limiting to actually get all the people
through that system. So we came here with the Lower Saxony and they said, Okay, why don't we do a real life trial where we use concert scenarios. And you see if you actually can use the dog as fast as a normal scanning, you know how it used to be. And that was kind of the aim of our study. So we had four concerts where we tested the dogs and all of the participants in that study, were PCR tested, they were at an antigen test as well. And they had a sniffing doc test
as well. That was obviously the first time something like this was done. Other people have used them in Finland, for example, at the airport and have done some similar exercise, people could go there if they wanted to. And again, has got a lot of media attention for us. We had in total four and a half 1000 people and it really broke our brain, you know all the logistics about it, how you actually get them through, but it was a really, really great
project. And the reason why I thought it was so great, and it's often things where you don't see in the beginning, but the reason why it was so great was because the public was so engaged, they really loved to come there and participate in this study. For today's very minute, we're gonna be talking about murine typhus. Although rare disease murine typhus is more prevalent in the tropical areas of the United States, including Southern California, Hawaii, and
Texas. murine typhus is a disease caused by a bacteria called rickettsia typhi, and is spread to people through contact with infected fleas. Fleas become infected when they bite infected animals, such as rats and cats. Hence, it is really important that we keep fleas off ourselves and our pets. Symptoms usually begin six to 14 days after exposure, and usually include fevers, headaches, chills and body aches. People sometimes even experience a rash in their chest, arms or legs.
murine typhus, is treated with antibiotics, which are mostly effective when given soon after the symptoms begin. And people that are treated early usually recover very, very quickly. This has been your viral minute. So the public was unbelievably engaged. And I didn't realize probably how much we missed a trick. When we were managing the pandemic, we told them all to stay at home. But I think they were all keen to help to make a
difference. And it was a really big thing, because obviously, they had to come on the day hours before to get a PCR test, antigen test and so on. And then also gave a sample for the sniffer dogs. And then in the evenings, they had to come again for the sniff attacks. So there was a lot of activity, but they were really happy to participate. It was such a great atmosphere. And something for me being a small veterinary neurologist was a special thing.
So you did a side by side comparison with the antigen tests and PCR. And obviously, the listeners can find all of this stuff in your publications, which we will put in the show notes. And I was just blown away that the side by side comparison is so good for the dogs. It's just amazing. So hold on, why do you think dogs are not being used more for infectious disease detection?
I actually don't know. I mean, I can see there are some challenges, the best comparison I can make is if you enter a plane, I think you would never be afraid, knowing that a dog sniffed it out for explosives, so you feel safe, because you know, the dog might be better than a human walking around and doing this little thing is what they do at the airport. But then obviously, when it comes to medical detection, people might
be more critical about it. And I do know that the people we worked initially with were always very critical. But then when they worked with it and saw all the dogs were in action, they started to believe that
this is possible. I think where the challenge comes is when you roll it out in the field and then you obviously you need to have the right dog handlers the right dog handler pair so to speak, and you need to somehow certify them and in Europe for detection work for explosive there's a very strict guidelines you have to follow this even the EU law and I think that's something you would always So you have to implement, also for the sniffer dogs where I see a
challenge. And that's depends again on the country, I mean, they use them, for example, in Florida, us and so on is in Germany, you would never use them on a person. So you would always take a sample and then let the dog sniff on the sample. And that's why that's why you can't let them sniff on the person. I think there might people feel there are some ethical concerns, some people might be afraid of dogs, some people say that dogs might be distracted, and so on.
And so you know, there was a dark time in Germany, where dogs were used against people, also at the border control, and so on. So there's a bit of a fear factor as well involved. And then you also have to think about it in a way that when a dog suddenly sits in front of you, how do you react with that? So there are some concerns one has to manage, in other countries in the UK, for example, will not be a problem, right? They will be very open.
If you go to an airport, you fly into New Zealand or so in the US, you know, often you have dogs at the airport, which will sniff and then obviously, they will ask you very gently and say, Can you please come with me, but that's definitely approval. I mean, they were there was a bit of discussion, when we set submitted it to the ethic.
I just read to you an article that says that the TSA and so on the border patrol here is trying to get more scent dogs, more security dogs with floppy ears, because they look sweeter and nicer if they have floppy ears compared to the usual German Shepherds. So the breeds that they normally use, I think that's a funny thing that the appearance of a dog matters as well.
Yeah, little white he tail. But if you think about it, when I could really see, especially in the airports, when they would have just sniff around, it would be such a little invasive test at one stage as well, especially when you're now opening and you are traveling again, it would be a nice, I think security level. And the interesting thing, which we didn't discuss, Dennis is a dogs, at least that's what we have seen can detect the person who's infected before they
shared the virus, right? So because obviously the virus enters the cell changes the medical ism, and then process starts. And that would be looking at what definitely happened when I had COVID. It took the antigen test two and a half days before they become positive. So in the beginning, I was like, oh, it's really like COVID pet all the tests. And I mean, obviously I didn't do a PCR I have to confess, but I did multiple antigen tests from
different companies. So like it has to be coded, and then I was not positive. And then when I became positive, suddenly, I was positive for like 10 days. I mean, I'm sure you know a lot more about why that is. But I was like, wow, and everyone would ask Why have you not asked the dog? Yeah, because at that moment, it was just not the time anymore. Right? When we were handling all this stuff, no one of us have the whole group get COVID. And now the last summer, we all get it now when we are
not using the dogs anymore. So much. I'm just getting into this topic and reading a little bit about it. I just didn't know that there are so many sent dogs, not only in Germany or Europe, but worldwide. Do you have some numbers? Do you know like, how many there are there? Oh, I would I would have to lie. But actually, if the authorities would have wanted to do this,
they could have done it. Yeah. And dogs as a huge business, and they are shipped around all the worlds they're looked after where we will as well, because these are expensive dogs because you have to train them. How much is the training? When you buy a dog like this? Is there a price for dogs like this? Yeah, I probably will say no, something wrong. But normally, if it's six to 10,000 euros, and it can go up if there has been the target sensitivity and so on.
Well, thank you very much Holger that this is such a cool topic, such a cool insight from you and hearing some of the stuff if people have questions, I'm sure you wouldn't mind if they reach out to you or your team. And we're gonna put up the articles. But I want to let you go with one question, kind of like an unplanned question. So I was reading this article the other day, and it was about how dogs can tell time. So how dogs know when the owner returns from work. And they often know when
the owner returns. And somebody proposed that it's actually not by a clock inside of their brain, a feeling of time, but rather how the owner sent in the house degrades over time. And they use that as a benchmark as a yardstick to see how long the owner has gone. What are your thoughts on this? Do you think that's a crazy hypothesis? To be honest, it's first time I hear about it. And you know, I wonder every day how
dogs do this? No. I mean, our dog has definitely a clock in obviously not but feels like she has because she's absolutely amazing. She gets totally crazy when the kids are not up at a certain time. And she's totally crazy, where we're not going to bed at a certain time. But yeah, that would make sense, wouldn't it that it's changing smell.
What I do think is fascinating when you deal with animals and people and I'm obviously a finition at heart is people always say that they find it fascinating because dogs cannot speak to us. But when you go to do human neurology and sitting in and you're amazed how little we can speak our little we can communicate what we're feeling. And we also just have some behavior patterns we do, which is not in a conscious mind, it's
just unconsciously gone. And when you think about our rituals, which we all have our idiosyncrasies in life, yeah, I could see that the dog picks these behavior patterns of us. And probably we leave some scent trails as well. Yeah, you see, got me thinking now. So thank you for that. Put me on your next paper on the Send. Thanks again for inviting me. It was a really great honor. And, actually, excellent. Thank you so much, Olga. Always a
pleasure talking to you. And I hope the listeners enjoy this. And if they have any comments, they can leave some comments on our website, and we might be able to follow up. All right, thank you very much and talk to you soon. Take care. Thanks for listening to the infectious Science Podcast. Be sure to hit subscribe, and visit infectious science.org to join the conversation, access the show notes and to sign up for our newsletter and receive our
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