Science Friday - Body Temperature, COVID Vaccines, Dog Genomics. Nov 13, 2020, Part 2

Episode Date: November 13, 2020

Our Average Body Temperature Is Getting Cooler We’ve all been getting our temperature checked on the regular these days. Most restaurants and businesses have been scanning peoples’ foreheads with thermometer guns to check for signs of fever as a safety precaution for COVID-19. We’ve been told that our temperature should be around 98.6 degrees Fahrenheit (or 37 degrees Celsius), the “normal” human body temperature. The value was set over 150 years ago by the German physician Carl Reinhold August Wunderlich. But 98.6 degrees may no longer be the golden standard.  In several studies, researchers have found that the average human body temperature may be lowering. Producer Alexa Lim talks with infectious disease specialist Julie Parsonnet about what temperature can tell us about our body and overall human health.  Fact Check My Feed: How Excited Should You Be About COVID-19 Vaccines? As COVID-19 cases and hospitalizations set new records, worse than even the initial surge this spring, there was one piece of promising pandemic news this week: a press release from the pharmaceutical company Pfizer, one of several racing toward developing a vaccine. Pfizer, working with German company BioNTech, announced Monday that their vaccine candidate, which uses a new technology involving mRNA, had reached an efficacy of 90 percent based on interim data. Trial participants were either given the vaccine or a placebo. Enough of the participants in the placebo group have since gone on to get COVID-19 to offer clues to its success: These rates suggest that nine out of 10 people who receive the vaccine will be protected from symptoms of disease.  But, as many have pointed out, Pfizer’s optimistic claims did not come with any release of data to back them up—nor an understanding of whether the most vulnerable would receive the same level of protection. Furthermore, this is only an interim analysis, meaning there’s more the company still has to learn before settling on a final efficacy number.  There are many questions yet to answer: For example, the process of understanding a vaccine’s safety takes much longer, and more people, than any trial period can fully assess. And even if Pfizer’s vaccine is approved by the U.S. Food and Drug Administration, how will a vaccine that requires two doses and expensive deep-freeze storage be distributed to all the people who need it?  Other vaccine candidates are also moving quickly. Another mRNA vaccine maker, Moderna, also indicated this week by press release that they will have their own interim analysis ready soon. Ira fact—and reality—checks the latest news on COVID-19 vaccine trials with virologist Angela Rasmussen and biostatistician Natalie Dean. How To Decode Your Dog’s DNA While we have been sitting at home for months, some of you have been spending a lot more time with your pets. You might stare at your dog and wonder: What exactly is your breed? Well, some people have been taking the extra step in finding out more about their furry quarantine companion—by getting a dog DNA test. Producer Katie Feather talks with pet genomics experts (yes, they exist!) about what you can and can’t learn from these direct-to-consumer genetics tests for dogs. They also discuss a citizen science project that studies connections between your pup’s genes and their behavior. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Irafledo. When I say 98.6 degrees Fahrenheit, you know what I'm talking about, right? That's the normal human body temperature. That standard was set over 150 years ago by the German physician Carl Reinhold August Wunderlich. That number may no longer be the average, and the human body temperature might be lowering. Producer Alexa Lim has the story. During the pandemic, you may have been taking your temperature a bit more frequently. Just a quick check-in to see if you're running at the quote-unquote average temperature. Some people might even say they run a little hot or a little cold. But researchers have found that the average human body temperature has actually decreased from that 98.6 degrees Fahrenheit mark. So how does human body temperature work? And what can it tell us about overall human health? My next guest is here to talk about that.

Dr. Julie Parsonette is a professor of medicine in infectious diseases and epidemiology in population health at Stanford University. Welcome. Thank you very much for having me. Let's just talk about what is body temperature. Your temperature is an indicator of what's happening inside your body. So what factors determine our temperature? So your temperature is a indicator of your metabolic rate. How much heat your body is burning to allow the body's functions to actually happen.

to have your heartbeat and to have your brain work and to have your breathing and your kidneys and all these other things actually function. Your metabolic rate goes up with some things when you exercise, when you go outside and run. When you eat, your metabolic rate will go up because you take some energy to digest food. But most of what your body temperature comes from is from your the processes of just keeping your body working to make sure all your proteins and everything else functions, you have to maintain a certain temperature. So you're burning calories to be able to do that. So what's the thermostat in our body? What's kind of regulating that? So there are a lot of things that are regulated, but largely it's from your endocrine system, which is the system in the body that

kind of monitors that all your systems are really going right. I want to play a question from our Vox Pop app. This question is from Caitlin from New York City. If the human body temperature is 98.6 degrees, why are we so uncomfortable when the temperature outside is near 99 as well? Just because outside it's 99 doesn't mean that our human body feels comfortable at that temperature. We actually feel comfortable at what's called the thermoneutral zone, which is around the area between about 65 degrees and 75 degrees. And that area is when our body doesn't have to do much to maintain our temperature, when we don't have to do that extra work.

When you get above that, we have to do extra work to keep our temperature low. We're fighting to keep our temperature from getting too hot. When the temperature is lower than 65 degrees, we have to work harder to keep it at that normal level. And I also point out that when we're in 99 degrees, we're typically not outside naked. We're wearing clothes, and there are other things that are keeping us even warmer. So we do have to prevent ourselves from overheating when we get at those high temperatures. So I want to get to this idea of this 98.6 degrees.

that maybe it's decreasing. I mean, where did we even get this 98.6 degrees as a standard in the first place? There was a guy named Carl Wunderlich back in the middle of the 19th century who was very interested in body temperature, and he took millions of temperatures from tens of thousands of people over time. And he looked at what those temperatures meant. He looked at what time of day they were higher, what they were higher than women than men, what they looked like with people with various diseases, what was abnormal, what was abnormal. And, you know, it was an enormous piece of work. And we think of having computers to look at two million pieces of data,

but he sat down there with his pencil and he looked at all these data. And he worked very hard to do it right. And he's the one who came up with this normal of 986 that's been carried on since the 19th century. Wow. So it's been like 150 years of just going on this one data set, basically. Yes. But in the last 30, 40 years, there have been at least 30 years, there have been a number of people who've said that that number is wrong.

Dr. Phil McHoviac, who's at University of Maryland, did some really nice work back in the 1990s, showing that our body temperature was lower than that. His conclusion was that Wonderlich's thermometers were wrong. And he actually went back and found one of Wonderlick's thermometers and tested it and said, you see, it's not good. It's not a good thermometer. And that's the reason. Wonderlick was very careful about calibrating his thermometers.

And he worked very hard to get them to be accurate at the time. And you can do that because the temperature of boiling water and the temperature of freezing are always the same. They haven't changed over time. So you can calibrate your thermometers pretty well. And I think just the thermometer that Professor McCobiac used was probably just not calibrated anymore. And so you did your own study that looked at body temperature in the United States. And you started with data during the Civil War. What did you find out? So we had three groups that we looked at. We had a cohort of veterans of the Civil War. some of them would have been born as early as the beginning of the 19th century and have been followed

after the Civil War until about the 1920s for pension purposes. And then there was a second cohort that was a group that the N. Haynes, which is a national survey that the NIH runs, that looks at temperatures in a segment of the United States, a healthy group of people in the United States. And then we looked at temperatures at my institution, Stanford, and compared those. So the temperatures from Enhanes were the 1970s and then ours and currently. What we found is that temperatures have been declining pretty consistently since the middle of the 19th century, since the Industrial Revolution essentially, at about 0.03 degrees centigrade per decade.

So the average temperature is now about 974, somewhere in that range, rather than the 986 that we see now. That sounds like a pretty big decrease in what seemingly is a short amount of time. It is a pretty fast decrease to me, it seems like that. But there's this recent paper that's been published by a group studying native indigenous population in Bolivia, where they found a very similar decline over even a much more rapid period, so just over a couple decades. So what we're basically seeing is that human beings can change with modernization and industrialization. And we don't really know what the factors are that are leading to that.

We're not absolutely certain why that's happening. But as we are getting less likely to get infectious diseases and as we're having better diets and as we are able to control our climate better and sort of control our environment around us a little bit better, we're finding that our temperature doesn't have to be as high as we once thought it had to be. So does that mean that since we're controlling infections better, that our body doesn't have to work as hard as at controlling them? Or what does that mean exactly? Yeah. So I mentioned when we talked about where bodies are, where our body is comfortable.

We are comfortable at a certain outside external temperature. And our bodies are probably also more comfortable at places where we're not fighting infection. There are certain things that turn us on and say, okay, we have to work harder. Our bodies have to work harder to keep our body going in a normal way. And there are threats like infectious diseases, all those vaccine preventable diseases, tuberculosis, all those other things that make us work a lot harder to keep healthy. And then again, there are things like being in cold weather, having no heat in your home that may also make you work a lot harder. And all those things, we've been able to manage pretty well over the last hundred years.

We've gotten rid of a lot of infectious diseases, a lot of chronic infectious diseases, particularly like tuberculosis. And we live in environments that are much easier for us to maintain our weight and our metabolism. I think it is a sign of being healthier. I don't know that we know that for sure, but I do think it is a sign of. sign of being healthier. I think we have, again, over the same 150 year period of time, we've gotten taller, fatter. Our life expectancies have gotten longer, and we've gotten colder. And I think all those four things are intertwined. We are actually seeing a decrease in life expectancy in many parts of the world, including the United States. And I'll be curious to see whether we see

reverses in this temperature changes and what's going to happen with that over time. And like I mentioned, people might be taking their body temperatures more often these days. Is this actually an effective way to monitor our own individual health or at least set a benchmark for ourselves? I think it's a really interesting question. And there are a lot of companies that are very interested, a lot of groups that are developing body monitors that you can wear all the time. They'll look at your curves of your temperature and see what is your normal, your personal normal. We know, for instance, that temperatures are lower in the morning than they are in the evening by a fair amount. They're higher in women who are premenopausal and they're higher during parts of the menstrual cycle.

And we all know that because we use that for looking for fertility, work on fertility. So each person is going to have differences based on who they are by their height, their weight, women, men, time of day. So taking your temperature at any point of the day without knowing how all those factors are coming together may make that number really hard to interpret. it. So it is pretty important to kind of get a sense of who this person is and what is a normal in that particular person to be able to at least look at small variations and have an understanding of what they mean. And I'll also point out that there's a lot of errors in thermometers. And some of the errors in thermometers can be much higher than the variation in a person. So if you take two different thermometers and you use them or you've been wearing a

hat or you just had a cup of coffee or whatever, your temperature may vary a fair amount that has nothing to do with your body's physiology. These small changes in temperature that people are looking at, or whether it's 991 or not, those are pretty inaccurate. We're still very good when you're 104. Nobody's going to say, okay, that's not a temperature. When your temperature is 104, 104, 102, even 101,

everybody's going to say, well, that's not normal. That's off normal. But these little small variations that people are finding in their daily temperatures are kind of hard to interpret, at least right now. What's the most interesting thing you ran across in this Civil War data study? For me? Well, so there are a couple things that I found out that were really interesting to me, which is that platypuses have really low temperatures. That was very interesting to me on hippos. I kind of thought, wow, that's kind of cool that they have such low temperatures.

But it made me think that we can actually function, proteins and mammalian proteins can function at much lower levels than I would normally have thought they could. But with respect to the Civil War data, what I thought was most interesting is, first of all, that we have those data. And Professor Fogel was at the University of Chicago, an economist, won the Nobel Prize, actually, in part for putting together all these data from these veterans of the Civil War, which I thought was really interesting. And those are all available online. So anybody who's interested in history can kind of go back and see who these people were back in the Civil War, because you can find out what their illnesses were and what jobs they did,

which to me, as somebody who loves history, is just fantastic to have these data available. And the other thing that was striking to me is the different names of all the medical conditions back there. It was really hard to figure out what they were talking about with all these flux and all sorts of things that we don't use in medicine anymore and to look back and see how much we've advanced and how we understand disease. Thanks for joining us, Dr. Parsonette. It's pleasure. Thank you so much. Dr. Julie Parsonette is a professor of medicine in infectious diseases and epidemiology and population health at Stanford University. For Science Friday, I'm Alexa Lim. We're going to take a break, and when we come back, you know COVID-19 vaccine candidates have been in the news this week,

but how much of the news is as good as it sounds? We'll fact-check your vaccine news. Stay with us. This is Science Friday. I'm Ira Flato. As the pandemic continues to set new records and stress overburdened hospital systems, one piece of hopeful news surfaced this week. Pfizer, in partnership with the Germany, company Bioentech had an announcement that sounded almost too good to be true. It said their data so far indicate that their vaccine, which uses a new technique called MRI, has an efficacy rate of 90%. That means out of 10 people who take it, nine will be protected from symptoms of COVID-19. But as is often the case, drug company news announcements don't necessarily paint the whole picture.

And as other vaccine makers race to gather the same data, there still remains much to understand about how effective any approved vaccines might be and how many lives they might save. So here to help fact-check our vaccine news are my guests. Dr. Angela Rasmussen, Associate Research Scientist at Columbia's Mailman School of Public Health. Welcome back, Angela. Thanks, Ira. Thanks for having me. And Dr. Natalie Dean, Assistant Professor of Biostatistics University of Florida, welcome Natalie.

Hi, thanks, Ira. Thanks for having me. Dr. Dean, let me begin with you with the claim Pfizer made on Monday. What is 90% efficacy, and how did they get to that number from their current clinical trial setup? Vaccine trials, these phase three efficacy trials involve tens of thousands of participants, but we expect relatively few of them to ever be exposed to infection and to develop disease. And so what the trial has done is, so it's run for a few months, and 94 individuals have gotten sick with COVID-19, so they have symptoms and their laboratory confirmed by PCR. And what we do is we look at how those cases split across the vaccine and placebo arm,

and there are 90% fewer cases in the vaccine arm than the placebo arm, and that's how we estimate efficacy and see that the vaccine is protecting. Now, I understand that the FDA was prepared to authorize a vaccine with as low as 50% efficacy. 90% feels like an extremely nice surprise. It's exciting. We really didn't know, you know, how efficacious these vaccines were going to be. It's a new virus. It's a new vaccines. And 50% was set as a lower, bound, sort of when a vaccine starts to be worthwhile enough to have that public health impact. We really didn't know what to expect, so this is exciting, and it probably bodes well for other vaccines targeting the same virus as well. Can we tell if this is correct based on what they've

told us? There are a lot of details missing, of course. What we do have is the protocol, so that had been published in advance, and we know some details about the trial population. And so we know what the primary endpoint they're looking at, the symptomatic disease, how it's defined. We know their analysis plan. And those things are quite rigorous and robust. Things that we don't know, we don't know how these cases are splitting across the trial population. We don't know if they're primarily in the younger population. It's possible, you know, you could imagine that all of the older adults who are participating in the trial, maybe they were all staying home. And so none of them got infected or exposed. And in that case, we wouldn't really know how well the vaccine works in that

population. So we still want to see some of that subgroup data. We also want to see how well the vaccine is preventing severe disease. We want to see the data on infection. So that's distinguished from symptomatic disease. So there's still a lot of details out there, but the top line number is very encouraging. As I noted before, this is an interim data analysis. Pfizer has to get, I understand, another 70 or so symptomatic cases among their participants before they can conclude this trial. How much of this good news is likely to change between now and that final analysis? In trials, we have this concept of interim analyses where we can take early looks at the data. And, you know, if something is working really well, we can have sufficient data to demonstrate that before the trial concludes.

So the evidence that, you know, that they're likely to have so far based on what we've seen is very strong and would be sufficient to totally stop the trial if they wanted to. but they're continuing because they want to accrue more information, the subgroup data, more data on severe cases. One question we're interested in is how durable is the vaccine effect. So, you know, these people were only vaccinated, you know, relatively recently a few months ago. And so one thing we'll want to see is does that effect persist over time? And so it is possible that that effect could wane and that would reduce the final efficacy estimate at the end of the trial. That brings me to the next question I was going to ask. Is efficacy the same thing as effective? We have different names for these concepts. So efficacy refers to sort of the idealized biological effect. It's sort of when all of the conditions are correct. And this is what we have from a well-controlled clinical trial where everyone's receiving the doses per protocol at the correct timing. The cold chain has been maintained. So efficacy, we can kind of think of as our idealize, our upper limit when everything's working perfectly. Effectiveness is what we, you know, what happens when we

we actually go out into the real world and things may not be quite as perfect. And so we can see the effectiveness tend to decrease a little bit relative to that idealized estimate. Angela, let me bring you into this real world picture as we keep hearing any vaccine is still months away from being available to you or to me. What are the types of conditions that you see affecting how many people can access to this vaccine? I'm talking about the Pfizer one and how well it works for them? Well, as Dr. Dean said, you know, there are many challenges to distributing this vaccine. This vaccine is also a two-dose regimen. Secretary Alex Azar said that by the end of the year, there should be 20 million doses of the Pfizer vaccine available. In practice, that means that there's

only actually 10 million doses because people in order to be protected with this vaccine have to receive two shots 21 days apart. And then they really aren't considered to develop full immunity until a week after that. So there will be a limited number of doses available initially that should expand, but there is going to be a real challenge in distributing this vaccine in the real world because these mRNA vaccines require ultra-cold storage. And MRNA itself is a very unstable molecule, so we have to keep it at very cold temperatures when we work with it in the lab, usually at least minus 80 degrees Celsius. Most of those ultra-cold freezers that are capable of storing vaccine doses at those temperatures are located in hospitals or major medical centers,

and there are not necessarily going to be a lot of these freezers in certain parts of the country. So Pfizer has been working on this. They have a delivery system that allows them to maintain the vaccine in bulk at these cold temperatures, but it is really going to be a serious challenge for many people in order to get enough of the vaccine doses when it's being stored in the proper way so that it's a when it's finally administered to those people. So to those people, anybody getting that vaccine, they would almost have to go to the hospital instead of bringing the vaccine out into the community.

That's right. So your local Walgreens is not likely to have a minus 80 degree freezer. So you will have to go to some place that does have that cold storage capability in order to get the vaccine. Is this going to be a stopgap, perhaps, do you think, until we get something better? because we know about other vaccines being tested, correct? We do. And Moderna, which also is making an MRNA vaccine, has announced that they are about to start conducting their own interim data analysis.

So we may very well be looking at a situation where there are multiple vaccines available to people, which I think is really a good thing, especially if some other vaccines that are in late stage development, such as the viral vector vaccines, are also meeting these same endpoints. That means that people will have a choice of different vaccines that may be easier to distribute in certain places. As Dr. Dean was also saying, you know, we need to see the breakdown of the cases that were in this interim analysis and the FDA will need to see that when approval packages are submitted to them for consideration. There may be some of these vaccine candidates that work better in certain people than in others. For example, we know that flu shots don't work as well

in older people. So there's a different formulation of that shot. We may well be looking at a situation where there are multiple vaccines that are indicated for one group or another differentially. And I think overall that's a good thing because we need vaccines as soon as possible. We need as many vaccines as soon as possible. We need as many people to get vaccinated as soon as possible. So if there's a wide range of options to choose from and more doses of them, I think overall that's a net win. We've heard about Johnson and Johnson and Astros Zeneca working on vaccines that don't need to be stored at over 100 degrees below zero Fahrenheit. Do you have any idea what the situation with those vaccines are?

Yeah, so those vaccines also started phase three clinical trials around the same time. Johnson and Johnson was a little bit later. Those are the viral vector vaccines that I was referring to earlier. And what they are are ad no viruses, which are viruses that typically cause the common cold that have been genetically modified so that they express the spike protein from SARS-Coronavirus 2. When you get one of these, they're replication incompetence, so they don't replicate and cause a full-blown viral infection the way they normally might. But when you get those, there is some limited viral replication, and that's what your body is responding to, except it thinks that that virus that's

replicating is actually SARS-Coronavirus-2. Those vaccines don't need to be stored at ultra-cold temperatures. So they may be much more easily distributable in the population. So we should be getting data from those trials as well. I would imagine as soon as possible when they meet their trigger points for an interim data analysis. Natalie, if Pfizer gets its vaccine out the door first, let's say, could this affect trials for these other vaccines? This is a big point of discussion. How do we proceed in this setting where we may have one vaccine that may not be fully approved, it may have an EUA, may just be appropriate for certain populations, may be in limited supply. It's a very real question about whether those other trials that are ongoing will need to discontinue the placebo arm.

Certainly, they'll need to inform participants of what's going on and give them the option to discontinue the trial and seek alternative vaccination elsewhere. But yeah, it's a very open question because it becomes much more challenging to evaluate a vaccine when you don't have that placebo arm anymore. The alternative is we can do something called a non-inferiority trial where we're comparing a new vaccine against an existing vaccine that we have some good data on. But when we're trying to show that two vaccines are quite similar, certainly to show that something is sort of similar to 90% efficacy or even exceeds 90% efficacy, that will be very difficult. Those require much larger numbers. So it's a challenge. I think another source of data will be if we have some immune response data, we can start

to see from the Pfizer data if there's sort of a level of immune response that is predictive of actual protection. And that can be another source of evidence that can be used to approve other subsequent products. If we have multiple vaccines out in public at the same time, could one vaccine affect the effectiveness of another vaccine in one person and another? person? We really don't know what would happen if people mix vaccines. Certainly the only people participating in these trials are only participating in one trial. They're not receiving more than one vaccine. So, you know, it's an open question. Angela, would you agree that could be something

that should be looked at? I think it should be looked at in the future. And we certainly have precedent for switching vaccine formulations going back decades. Initially, when the polio vaccine was developed, It was an inactivated vaccine, the Salk vaccine, and that was used to immunize kids in the U.S. for several years until Albert Sabin completed his vaccine trials in the Soviet Union, and then the U.S. switched over to using the Sabin oral polio vaccine. And now actually we've switched back to using the Salkin-activated vaccine. So there is precedent for switching back and forth between two different vaccine platforms, but I don't think that's something we're going to be able to do in the short term.

I don't think if you get your first shot of a Pfizer vaccine, you should go in and get the second shot of the Moderna vaccine or the Johnson and Johnson vaccine. I think that that's something that we're going to have to look at over years to see how these vaccines might interact with each other. And if there's any harmful effects by combining two different vaccine strategies. I'm Ira Plato, and this is Science Friday from WNYC Studios. Let's talk about safety for a moment because some of the things we've been hearing from the public is that they, don't want to take a vaccine, whether it's the flu vaccine, which I think is only 50% of the population is taking it and now any potential COVID-19 vaccine, they're worried about the safety of the vaccine. How long will it take before we know if any vaccine is truly unsafe or not?

I think that's a tough question because normally the phase three clinical trial is not the end of the study of the vaccine. Vaccine side effects are studied once they're also. put out onto the market. And that's because even in a trial with tens of thousands of people, you aren't going to be able to detect those really, really rare adverse events, the one in a million type events. That has to happen once the vaccine is rolled out into the population. So there's always a risk from taking one of these vaccines, from taking any vaccine, but it's probably very rare. I mean, the clinical trials are designed to detect common adverse effects, at least in the short term. So I think that we will be able to conclude that these vaccines are

safe based on these trials in the short term, but we will have to continue to monitor this. Natalie, do you think enough people will get vaccinated to help us get to herd immunity? It's hard to know. I mean, at first, definitely we're going to have limited supply. So it will be challenging. I mean, we'll just be limited by how much is available and who we're targeting. what we don't know is whether that the vaccine is able to prevent infection and to reduce infectiousness. So it is possible for people to receive a vaccine, that vaccine to work at preventing disease, preventing the symptoms of disease, but that person could still be infected and could still pose a risk to others. So that has huge bearing on herd immunity and how far

we are towards herd immunity. So I'm very interested to see the results that come out of these trials when we take a closer look, to see whether there's any evidence, maybe among the people who become sick, maybe they have less viral shedding. There are a lot of interesting questions that will tell us how much the vaccine will contribute to the population level control. Angela, as we see progress toward these other approved available vaccines, how skeptical should the public be in weighing the major headlines we keep seeing when a new vaccine possibility comes out. The most pressing challenges with these vaccines with all of them is the communication aspect of it. So I think it's really important that one of the things we are communicating is that people

really do need to manage their expectations. And people who are skeptical of the vaccines also should know that they will have plenty of time before these vaccines are widely available to judge how the rollout of these vaccines to the population is going. I think that people do need to realize that even when a vaccine is approved, there's still going to be a months-long process of actually distributing that vaccine, making sure that everybody who needs the vaccine is able to get it. So there are some real challenges still in front of us, and many of them are logistical challenges. But the bottom line is that people should be cautiously optimistic, that they should manage their expectations about when they're going to actually be able to get the vaccine for themselves. Good place to end. I want to thank you

both for taking time to be with us today. Dr. Angela Rasmussen, Associate Research Scientist at Columbia's Mailman School of Public Health in New York, Dr. Natalie Dean, assistant professor of biostatistics at the University of Florida in Gainesville. Thank you both for taking time to be with us today. Thanks for having me, Ira. Thank you. After the break, DNA testing has become accessible in ways unheard of 20 years ago. One new frontier, your dog.

Why many pet owners are trying to find out what's in Fido's genome. coming up after the break. Stay with us. Hey there, folks. It goes without saying this has been a challenging year, no. And if there's one thing we know for sure, it's that the need for fact-based journalism and the need for science are stronger than ever. At a time when science is continually called into question, Science Friday remains committed to filtering out the noise and discussing the evidence, supporting the science that you need, to make informed decisions. You know that demand for Science Friday this year was higher than ever, but you may not know that your donations are what's keeping us running. And right now, Science Friday has a dollar-for-dollar donation match, which means that any donations will be

doubled. So, if you have a few dollars to spare and agree that this world could use more science, please support Science Friday with a donation. Any amount. makes a difference. Go to sciencefriday.com slash give. That's science friday.com slash give. Thank you and stay safe. This is Science Friday. I'm Ira Plato. While we sit at home for months trying to entertain or improve ourselves, some people have been investing in finding out more about their furry quarantine friend by getting a doggie DNA test. Science Friday producer Katie Feather looked into the new trend. The first time I heard about consumer DNA tests for dogs, it was from my sister, who got one for her dog, Appa. Then my other sister found out about it and got both her dogs tested.

A week later, I overheard my two neighbors discussing their dog DNA tests. Sitting at home during the pandemic, staring at their pet's faces, people had suddenly gotten very interested in doggy ancestry. Now, I'm a cat person, so I was tempted to just roll my eyes and say, this is just something dog people do. But as a science journalist, I was also curious. What can these tests tell you about your dog's genetic history? Are they the key to unlocking your pup's behavior? Well, it turns out there are some experts in pet genomics, a term I didn't realize existed until very recently,

who can help me answer these questions, and they join me now. Dr. Eleanor Carlson is an associate professor at the University of Massachusetts Medical School and the Broad Institute of MIT and Harvard. And Dr. Lisa Moses is a veterinarian and research fellow and instructor for Harvard Medical Schools Center for Bioethics. Welcome both of you to Science Friday. Hello. Hi, thank you.

So how did you guys become the experts in these direct-to-consumer dog DNA tests? Because wherever I see them mentioned online, you two are some of the people who are most quoted. So I've been working in dog genomics since I was doing my PhD, but it was many years later, and I met Lisa, and I can't remember exactly where we were. but we got into a discussion about dog genetics and her perspective on it, which was very different from the perspective that I had as a scientist. Part of the story of us getting interested in this is a realization that there was a big gulf between the science end of it and the clinical application of it. And I think we were both pretty surprised when we realized the ways in which these tests were

being used and the way that they were being done. Lisa, can you tell me how are these? these dog DNA tests different in the clinical setting and the, you know, these consumer directed tests, which are the tests that my friends and family are getting? Well, there is definitely a big difference. And I think a lot of people who are doing the direct-to-consumer tests are getting back results with pages of information about potentially their dog's future health. And part of the reason that Eleanor and I started talking about this is because we realized that people were getting.

lots and lots of information and really didn't know what to do with it. And I, as a practicing veterinarian, also didn't know what to do with it. And as it turns out, once I started talking to Eleanor, there was good reason for me to not know what to do with it. A lot of people think that we understand genetics a lot better than we do. And so when we do a scientific study, like the ones I was talking about, we tend to do a study where we get a bunch of dogs and we look for differences between the ones that have, for example, white coat color and the ones who don't have white coat color, and find things in their DNA that correlate with that trait. And it's really interesting scientifically when what you want to answer is, where does coat color come from?

What could change in a gene that would make an individual have white fur as opposed to not have white fur? But that's a very different kind of question than what a lot of people think we can answer with DNA, which is making a prediction about what's going to happen with an individual dog. And the problem is that an individual dog has that gene, but they also have, you know, 20,000 other genes. And all of those genes interact with one another to create this very unique individual dog. And we know from, you know, previous reporting about, even on our show, about these 23ME tests, that there are some ethical considerations. And Lisa, I imagine that that's your role here is to kind of bring up some of the ethical considerations with this, with these dog DNA tests. Are they the same types of considerations?

What are you concerned about? There are some considerations that are very much the same as they are for people, but some of them are different. And the ones that are different that we're particularly worried about is, first of all, because this kind of testing is really unregulated, we don't know anything we're not allowed to know unless the company chooses to tell us how the tests are performed, what kind of technology they're using. and most importantly, we don't really know what the results mean.

So when I say that, what I'm talking about is me as a veterinarian, if you come to me with your pet DNA test results that say that your dog might have an increased risk of having a particular kind of kidney disease, let's say. We don't have the kind of research to tell us how likely it is that that test means that your individual dog is going to get sick, how sick, how likely is that overall? We really don't know any of that information. In people, before you can say that a particular change in the genes leads for sure to a disease, there's a very high bar of information that has to be collected through lots and lots of

statistically significant testing before you can make that claim. We don't have that information in dogs. So it's really impossible for a veterinarian to look at those results and say, yes, this is something you need to worry about. We need to do lots more testing. Or no, you don't need to worry at all. A person might make a decision about their health based on their genetic test that would be concerning. Like if they had an increased likelihood of having breast cancer,

they might get a preventative mastectomy that may or may not be actually needed if they didn't consult with a doctor first. And you mentioned that these same kinds of decisions could be being made by a pet owner, although there's the added concern of whether a pet owner would want to put down their animal based on these tests. For sure, and obviously that's the scariest part about this. And one of the things that I think people really don't understand,

the difference between a genetic test and a regular test that gets done at your veterinarian's office is a genetic test doesn't necessarily tell you that you have a disease or you don't have a disease. There's a lot more to it than that. So it's not like finding the parasite in the blood. So unfortunately, this makes it really tricky because I'm worried that people will interpret the results in ways that they're not meant to be used. I'm worried that people don't understand, that we don't have all the follow-up research that needs to be done to tell us whether individual diseases that are really connected to the DNA changes that are in the tests.

So we've kind of covered what these tests don't show you genetically about your dog. But let's talk about what they are purporting to tell you. So Eleanor, when a test comes back from one of these companies, typically it's going to report back what it says your dog's breed is, right? So how accurate is that information? Can you really feel good about the results that come back, that that is accurate? On a scientific level, this is something that we can definitely answer. So if a dog has ancestry from particular breeds, then we can compare their DNA to DNA from dogs from that breed and figure out how close a match we have there. I don't know for sure how well the tests from the various companies work because as far as I know,

they've never kind of published in peer-reviewed journals reporting on the accuracy of what their predictions are, which is a scientist is what I would like to see. But we do have algorithms that we use in our lab for figuring out what breeds a dog has ancestry from. And I can tell you that they work pretty well, as long as that dog actually is a mix of breeds, and we have information about those breeds in our database. Yeah, tell me more about these breed mixes, because you were saying that most dogs are actually not any type of breed.

Clarify what actually a breed is and how we use them. Yeah, so this is actually a really interesting idea that I've really just started thinking about a lot myself over the last few years. In the United States, as far as we know, most dogs are either pure bread dogs or their mixes of birds. breeds. And so that's kind of the assumption that I made. And a lot of the very early genetic studies were all done with purebred dogs because of certain features of their genetics that made them easier to study. But I was talking to somebody that studied dog behavior, a woman in my

research group called Catherine Lord. And she said that actually most of the dogs on this planet don't have any breed ancestry. And I went, wait a minute, what are you talking about? And then I thought about it a bit more. And I, you know, one of the things we'd figured out in our genetic studies was that most of the modern breeds are probably not more than a few hundred years old. And so if you kind of think about it, you're like, how would all the dogs on this planet, considering the dogs were probably domesticated like 15,000 years ago, they're not all going to have ancestry from these breeds that are only a few hundred years old and only came from a few places on the planet. And it turns out that most dogs are just dogs. They're not from breeds. They're completely domesticated.

They're not any different from breeds or mixes. They're just dogs. So yeah, I was going to say I think a lot of people's incentive for doing one of these tests is to understand more about why their dog does something peculiar or weird or just to understand more about their behavior so that they can better accommodate them. So can they read something into their dog's behavior when they get their test back? So there are probably behavioral differences between breeds. There's certainly been a lot of differences described, but they're not as big as I was expecting them to be. You know, you kind of think about breeds and people take a breed and they're like golden retrievers, I don't know, like to retrieve balls. And so then they think all golden retrievers are going to retrieve balls. But that's just never true because dogs are complicated individuals.

And so while golden retrievers might be more inclined to retrieve balls, you're going to have a lot of golden retrievers out there that really don't care about balls at all. So there are these direct-to-consumer companies set up to do you test your dogs DNA. but you actually have a citizen science project in the works right now that does essentially the same thing, and it's to help look at these patterns of behavior and genetics in dogs. Yeah, no, exactly. It's a really interesting project. So when people think about genetics,

they always think about the hard part as being this fancy technology to look at the DNA and do all these statistical tests. And it turns out that is not the hard part at all. The hard part is finding out about the individuals. It's finding out not their DNA, because you can get their DNA out of a saliva sample and then you're done. But finding out about a dog's behavior, what they like to eat, you know, all of this kind of stuff is really complicated. And for most animals out there that we want to study, you have to send scientists out into the field to find the animals and watch them and all this stuff.

But the interesting thing with pets, including dogs and cats, is that every single one of them lives with a person, or often multiple people that spend a lot of time watching what they do. And so the way we set up our citizen science project is, is that you go online and you sign up your dog, and then we ask you a bunch of questions about what your dog looks like and how they behave. And then you can sign up to get a DNA kit and we'll sequence your dog.

It costs about $150, and that's done at cost. So it's a nonprofit. So the reason we want to have so much data is because studying the connections between something as complicated as behavior or something as complicated as a disease test or anything like that is that you need really big sample

sizes to actually be able to figure out what's going on, to actually understand how much this change in your DNA is going to affect your health or your behavior. And I have to say that if you are a participant in that study, you get a chance to think about a lot of really fun things about your dog, like whether or not they kick after they poop and run around and those kinds of questions that every dog owner can answer. I'm Katie Feather. This is Science Friday for WNYC Studios. So, Lisa and Eleanor, we were emailing back and forth a little bit about my sister's dog because I brought that up to you during our conversations before this interview. She had done one of these dog DNA tests and her dog came back as 100% American Staffordshire Terrier. And I was just curious how likely this was to be true and how frequently a test would come back 100% of any type of breed.

The percentages you come out with depend on how many different positions in the DNA you're actually testing in the dog, and then also the algorithms that you use to analyze that data. So in the Darwin's Ark project, we're using a huge number of positions in the DNA that we're actually testing, something like 15 million, because our actual goal is to understand the origins of things like behavior and health, and we need a lot of information about each dog to be able to do that. And so early in our study, we decided we needed to make sure we had all the 100 most common breeds in the United States in our reference panel. So this is the panel of dogs that we compare each dog to to figure out what they have ancestry from. So if we don't have a breed in that panel, then we can't detect it. And so we went to a website, found out what the 100 most popular breeds were and made sure we had them all. It turned out that that was a list that had been put together by an organization called the American Kennel Club and the Pit Bull Terrier. The American Pitbull Terrier is not part of the American Kennel Club, so it hadn't been on that list.

Anyway, as a result of all of that, we have dogs that we called before we put the American Pitbull Terrier in there, and then after we put the American Pitbull Terrier in there, and what we discovered was that if we had a dog that had a lot of American Pitbull Terrier, and my sister's dog, BESCO, is actually one of these. And we didn't have that breed in the reference data set. We tended to see that somewhere between like a half and 75 percent of that ancestry would get called a Staffordshire Terrier. And I'm guessing it's because those two breeds share some ancestry. But it could be that if you go to a company, they have a different way of analyzing the data. And so that's why it's coming out 100%.

Yeah, that's just a good piece of information to have. It all depends on your reference genome. The reference said, if there isn't that breed in there, then it has to go to the next best thing, it seems like. What do you want people to know about these direct-to-consumer DNA genetic tests for dogs? and how do you in general feel about them? Well, I will tell you from the veterinary ethics side of it, what I want people to know is, please don't use these tests to make medical decisions for your dogs.

They're just not ready for that yet. My hope is that with data sharing and large amounts of information collected from projects like Eleanor's Darwin's Ark project and hopefully from some of the companies that will share their data, that we can learn a lot in the future about how dogs get sick, what the genetic component of that is, and that we can do something about it in the future. But I don't think we're ready to use the test to help your dog right now.

And I would just add to that. I think it is absolutely fantastic that people are interested in genetics and that they want to find out more about their dog's genetics. Being curious is always a wonderful thing from a scientist's kind of. perspective. You have to remember what it is the tests are telling you. They're telling you that your dog has ancestry from particular breeds, but that doesn't tell you what your dog is like, and it doesn't tell you what your dog's personality is. So as long as people can keep paying attention to the dog that's sitting in front of them and not to what various books and websites are telling

them, I think it can be a lot of fun. I love that. Focus on the pet that's right in front of you. So we've run out of time, but thank you so much to both of you for joining us. Dr. Eleanor Carlson is an associate professor at the University of Massachusetts Medical School and the Broad Institute of MIT and Harvard, and Dr. Lisa Moses is a veterinarian and research fellow and instructor for Harvard Medical Schools Center for Bioethics. For Science Friday, I'm Katie Feather. If you're interested, you can check out that dog DNA citizen science project at Darwin'sark.org.

And that about does it for this. week. If you missed any part of the program or you would like to hear it again, subscribe to our podcasts, or you can ask your smart speaker now to play Science Friday. And if you were following our sci-fri book club conversation about speculative fiction last month, there is more coming from the New Suns collection. We're teaming up with the Brooklyn Public Library for online author conversations with a healthy dose of science starting next Friday. Yes, you can find out more on our website, sciencefriady.com slash new sons. Sciencefriiday.com slash new sons. Have a great weekend. We'll see you next week. I'm Ira Flato.