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Come and unleash your potential as a customer support expert at Sage. This is a CBC Podcast. Hi, I'm Bob McDonald. Welcome to Quirks and Quarks. On this week's show, some like it hot. A NASA probe will be diving into the sun's atmosphere. It actually goes into the corona, and so we are directly sampling.
And gathering information from that part that, you know, that inside that wispy outer super hot atmosphere. And brains in pain. How understanding pain response in crustaceans is complicated by their multiple brains. We had to record from two different areas from the frontal brain. And then when we wanted to look at the legs, we went to another part of the central nervous system. Plus.
Researchers figure out how and when humans hooked up with Neanderthals, understanding the song of the reindeer, and navigating our bodies with the human cell atlas. All this today on Quirks and Quarks. Well, it's almost officially winter, and I don't know about you, but a vacation in some sunny spot is definitely something I'm really thinking about.
And while I sometimes wish I could reach out and touch the sun, I don't think I'd try to get as close as the Parker Solar Probe. On Christmas Eve, the NASA spacecraft will be making an historic approach to the sun, swooping down just 6.5 million kilometers from the solar surface, deeper than we've ever probed into a star's atmosphere. To put that in perspective, that's 22 times closer to the sun than we are.
It's the final objective for a spacecraft that was launched in 2018 and dreamt up decades ago. Dr. Alex Young is the Associate Director for Science Communication in the Heliophysics Division at NASA's Goddard Space Flight Center. Hello and welcome back to Quirks and Quarks. Hello, I'm glad to be here. How are you feeling as the Parker Solar Probe makes its final approach to the sun? I am very excited and the anticipation is building.
What are you anticipating this time? So Parker Solar Probe just made its last Venus flyby, which gives it a gravity assist to help it to make its closest approach. And so this December 24th, the spacecraft will make its final closest, make its closest approach. It's already...
touch the sun's corona, and it's going to get as close as it can possibly get right now. Well, this isn't the first time that it's been close to the sun. It's, what, done 21 other approaches? What have you learned so far from the mission at this point? You know, it's exciting. I've been at the American Geophysical Union meeting, and so some of the newest results have come out.
There are several different instruments that are giving us both measuring the particles coming directly from the sun, measuring the electric and magnetic fields, measuring radio waves. And then we have these imagers on the side which actually show us stuff coming away from the sun. And so one of the things that we've seen is dust, the inner dust in the solar system.
which comes from comets, for example, reaching the sun and evaporating. And that's important because it's telling us about the solar system's evolution itself. And then as we've gotten closer, we've passed what we call the boundary between where the solar wind sort of begins and the corona ends. This is a transition between these two regions.
It's not a steady point, but it's very important for understanding where the solar wind is actually being accelerated. And just to set a context here, the corona is the atmosphere of the sun. That's the part we see during a total eclipse. Exactly. That is that sort of ethereal.
piece structure that you see during totality coming out. And that is one of the most exciting areas, especially for those like myself who study solar activity and space weather, because that's really where all the action is happening. That's where solar flares occur, where coronal mass ejections, these big blobs of solar stuff are spit out in space. That's where it's all happening.
And the solar wind, those are the particles that come off the sun that actually go right by the Earth and the other planets. Right. There's this constant flow. You know, there are gusts from it. It goes faster and slower, but it's always flowing out from the sun. And this, in fact, was something that was predicted by Eugene Parker, who, you know, the name Parker Solar Probe is named after him in 1958.
Now, does the Parker Solar Probe actually dip into that corona or does it just skim over the top? It does. How deep into it does it go? Yeah, it actually goes into the corona. And so we are directly sampling and gathering information from that part that, you know, that inside that wispy outer super hot atmosphere.
Now, this approach is happening during a period of heightened solar activity. We've had lots of sightings of aurora, the northern lights here on Earth. What does that allow you to do this time?
You know, one of the things that we want and one of the things that's already happened is we actually want the spacecraft to fly through these solar storms. In particular, these will be called the coronal mass ejections or CMEs. And that is billions of tons of solar material and magnetic field that is blasted away from the sun at, you know, up to.
10 million kilometers an hour so these you know really crazy speeds we want to fly through those and in fact we have already flown through them and so during
high solar activity, we're in a period we call solar maximum right now, you have a lot more of them. You have many of them during any given day. And so that means the chances of us having an encounter with one are much higher. And that just gives us unique information. These CMEs are very difficult to study. They're very complicated. And one of the challenges is both the solar wind and the CMEs as they travel away from the sun,
By the time we measure these CMEs and solar wind close to Earth, a lot of that information is gone. And so we want to fly through them. We want to fly through them at their origin. I understand the probe will be really moving along at this approach. How fast will it be going? Yes.
Now, this is my brain. I'm used to, unfortunately, living in the U.S. where we're still using the imperial system. And so I'm constantly having to shift back and forth. So the number that I have in my head is approximately 500,000 miles per hour.
That's about 800,000 kilometers per hour. Yes, that sounds about right. And that is the fastest human-made object ever. It's already broken the record, but it's going to make an even bigger record and be the fastest probably for a long time. Well, after this close approach to the sun, what happens to the Parker Solar Probe?
The spacecraft, if it just did sort of minor adjustments, it has enough fuel that it could operate for 100 years. But given that it's probably going to have to use slightly more power, we think it has enough fuel to last for at least 10 years. Eventually,
It will run out of fuel. And so what will happen is eventually the spacecraft will no longer be sending back data. It will no longer be working. And it will, after many, many orbits, will just become part of the corona. It will just slowly start to form into smaller and smaller pieces. And it will sort of like a comet. And it will eventually just become part of the sun. Dr. Young, thank you so much for your time. It's a pleasure. Thanks for having me.
Dr. Alex Young is the Associate Director for Science Communication in the Heliophysics Division at NASA's Goddard Space Flight Center. If you've ever done at-home DNA testing, you may have gotten a result suggesting you have a small percentage of Neanderthal DNA in your genome.
Neanderthals are our closest relatives, and for a while, tens of thousands of years ago, both of our species occupied the same parts of the planet at the same time. And we learned some years ago that many modern humans have Neanderthal DNA because they were interbreeding. We know that it happened, but we don't really know when it happened and for how long. But two new studies are narrowing down answers to this question.
offering a clearer picture of when our ancestors and our closest relatives were swapping genetics. Leonardo Yazzi was the lead on one of those studies. He completed his work for his PhD at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Mr. Yazzi, welcome to our program. Hello, thank you for having me. Before your study, what did we know about how humans and Neanderthals mixed? So we know that all...
Present-day individuals outside of Africa have like 1 to 2% of Niantal ancestry in their genomes. And we had a rough idea that it must have happened between 60,000 and, say, 45,000 years ago. Well, how do we know that they interbred at all? So we figured that out.
by actually having a Neanderthal genome. So more than a decade ago, actually, scientists were able to sequence a Neanderthal genome. And by comparing the genome to present-day individuals, they found out that there is sharing with some present-day individuals. Well, take me through your work. What did you do to find out when this happened and narrow down that time period? So what we did in our study is that we examined the genomes of 300 present-day and ancient modern humans.
including 59 individuals who lived between 2,000 and 45,000 years ago. So we set out to determine the timing and the duration of neonatal gene flow and study also the variants that are coming from neonatals into the gene pool. So what we find out by actually taking or integrating so many ancient DNA samples, we could actually find out that the gene flow was...
peaked at 47,000 years ago and was somewhere between 6,000 to 7,000 years long. Wow. They were interbreeding for 7,000 years, 6,000 or 7,000 years? Yes. And when we actually look at archaeology, what we found, at least in Europe,
where Neanderthals and modern humans lived, the picture fits together. So also if you look at caves, you know, where you see Neanderthal stone tools and modern human stone tools, also there archaeologists estimated that the overlap between those two was roughly 6,000 to 7,000 years long. Well, if this interbreeding was happening over a period of 6,000 or 7,000 years, do you have an idea?
like how much this was going on, how often this would be happening? That's a good question. So what we estimated is that the initial interbreeding was like 5%. So initially 5% of the genomes of people leaving Africa was contributed by Neanderthals. So if you have a rough estimate, that would mean like one out of 20 individuals in this joint population of Neanderthals and modern humans was a Neanderthal.
So they were sort of co-living in the same space? Presumably. I mean, they must have met. Obviously. Well, is Neanderthal DNA found in every human? Neanderthal DNA is nowadays found in people living outside of Africa. And it's only in very small quantities in individuals from sub-Saharan Africa.
What we think is that people in sub-Saharan Africa, their ancestors did not leave Africa. And Neanderthals, there are no signs that Neanderthals ever went to Africa. So their ancestors basically never met Neanderthals. So in modern day humans, what do these Neanderthal genes mean for us? Yes, that's an interesting question. So we looked at this and what you can see in some regions.
you have a very high neonatal ancestry, right? If you take 100 present-day individuals, 60 of them would have at a specific region of the genomes neonatal ancestry. So that can hint that there's something that's actually beneficial because that's way more than you would expect by chance. And what we found is that some of these regions and some of these genes in these regions are related to things like metabolism, skin pigmentation,
and most of them actually to immunity. And I think it makes kind of sense when you think of it like this. So you're leaving as a modern human Africa, and you're going into these new habitats, and there's...
New food, new climate, new diseases. So it kind of makes sense that you would take the genes of Neanderthals by interbreeding with them, because they're already adapted to all of that, right? So that gives you a huge advantage in these new continents. On the other hand, in present individuals, you see regions in the genomes where you don't find any Neanderthal ancestry.
And what we found is that even in the earliest individuals, and they're 45,000 years ago, so they're super close to the interbreeding event, even they don't have Neanderthal ancestry in these regions. Oh, I see. So coming out of Africa, you're going from a warmer climate to a more colder, difficult environment. The Neanderthals were already adapted to that. So we picked up the genes that would help us and got rid of the genes that would not help us. Yeah, basically, yes.
Well, what does this change about what we know about what was happening 46,000 years ago between humans and Neanderthals? So, I mean, this time was really a time of complex interactions. Also, you know, in this time, modern humans go out of Africa and they colonize the other parts of the world. So in this time, they're not only meeting Neanderthals, and it seems they met them for a longer time than we thought before.
But also, all of these human groups start to split up, right? In this time, Asia, Europe, and Oceania. People are colonizing these new environments. So it gives us kind of an idea when this must have happened. And it gives a kind of like a lower bound. Since we estimated that...
Kind of the last exchange between Neanderthals and modern humans must have happened 43,000 years ago. So that gives you like a lower cutoff when this out of Africa event must have happened. Does this tell us anything about whether this interbreeding contributed to the extinction of the Neanderthals?
I think from genetic data it's very hard to say what was going on and there's a lot of theories. So by 39,000 years ago, if I'm correct with the dates, you don't find any Neanderthals anymore. It could be that it was simply like they were kind of assimilated into the modern human population and it was just a very uneven mixing, right, that you have like 1 to 20 mixing basically.
So after a couple of generations, you don't find anyone who is like 100% Neanderthal anymore. So in a way, at least in part, Neanderthals didn't go extinct because we still carry their genes around. Exactly. From all these little snippets of Neanderthal ancestry, not everybody has the same segment at the same location.
And we were able actually to puzzle together from our 300 genomes 61% of the neonatal genome. So it kind of lives on in us. Mr. Yazzie, thank you so much for your time. Thank you so much for having me on the show. Mr. Leonardo Yazzie is a PhD student at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.
From the holiday movies and carols that are playing non-stop these days, you might think that reindeer sound like this. But actually, in the wild, reindeer, more commonly called caribou here in Canada, actually sound like this. But we don't know as much about how and why the animals make these noises.
compared to what we know about the calls of reindeer relatives like elk and moose. Which is why biologist Robert Wolaji and master student Laura Posh analyzed the frequencies found in these reindeer vocalizations to figure out if these grunts were actually conveying information to other reindeer, or if they're just noise. Dr. Wolaji is a professor of biology at Concordia University in Montreal. Hello and welcome to our program. My pleasure.
Tell me about these reindeer vocalizations we heard in that recording. What are they actually like to hear in the wild when you're out there? Ranger, as other deer, they use vocalizations during the rotting period. This is the mating season for this species, and this is used for many reasons. It could be to chase off rivals, to secure access to females. It could be to make sure the females are aware of their hierarchy, like this is the big guy here. But they also use them to...
to not allow females to stray away. So when a female is trying to leave, they will grunt, not a harsh grunt, but to get them to come back to what we call a harem, that is a mating group in reindeer. So it's only the males that are making these grunts, is that true? Exactly, only males do the grunt. What's happening in these mating groups of reindeer that they need to communicate so much?
It is the fight for survival and spreading out your genes. So each male wants to secure reproduction. So if you have 5 males and 50 females, well, one of the males will want to have all the 50 females to secure 50 offspring.
So this is about maximizing your fitness. So they grunt a lot when they're fighting. They use the grunt to actually displace other males. So an older male will grunt and a younger male will just run away. He will not go for a fight. But two males that are relatively equal in size will definitely go for a fight. So this will combine body size and the shape and the length and the grunt. And the winner of the fight will keep the female. Well, why were you so interested in these vocalizations?
Reindeer is special in that, first of all, as I said, they vocalize only during the rut. Female do not vocalize. They get together during the rut. So contrary to moose, where you hear a male calling from distance, being alone, so the call will be a signal like, hey, I'm here. If you are looking for a male, move towards me. While reindeer, they will get together. in a large harem where it could be very large.
But because you can only control a certain number, you'll have smaller groups that we call mating groups or harem being formed. And usually you have one or two males. It could go to four males. But when there are more males, you have more fights. And the winner will be the dominant, as we call them. And he will stay around, be alert, keep grunting to make sure the female knows he is at the center. So I was interested in this particular species.
because not only I thought they were understudied in reindeer, but because contrary to other deer, reindeer has a peculiar vocal tract anatomy in that they have a laryngeal air sac. So in the vocal tract, they have an air sac that elk or moose do not have. So we thought, well, if they are vocalized and this species has a specific vocal tract anatomy, is there any reason for that?
So reindeer, with this air sac, they have a unique way of making sound that's different from other members of the deer family. Exactly, exactly. So others do not have the air sacs. So we thought maybe the air sac has a function that may, in a way, filter the...
So that what we hear is convey information to females that we don't know of. So we wanted to look into the acoustic feature and try to see if in those parameters there is some information that will relate to the body condition. Well, take me through your research. What did you see when you analyzed the reindeer sounds? So we were able...
Luckily, to extract from the vocalization two acoustic parameters, the fundamental frequency and the formant frequencies. And from their measure, we tested whether they correlated to the age and the width. So we were trying to see if female can without seeing.
being able to differentiate between males just based on their call. And we found that there is a correlation between age and some of those parameters, meaning that females are able, just by hearing without seeing, to assess the quality of the males. It seems similar to men who have deeper voices if they have larger bodies. It's not always the case, but sometimes you'll see that compared to a slighter build.
Exactly, exactly. These are real similarities. So now we want to, that's the next step actually, we want to see now that we know this, can we then confirm that females are perceiving it that way? So we started first only the male segment to document that yes, vocalization actually has information that could be used by females to judge on the quality of the males.
That's easy to say, but next, is it true? To test this, we have to go out again in the field and do what we call a playback experiment. So what do you think these grunts mean to the females? We are putting this in a sexual selection context, meaning females may be using this information to decide on whether they will choose.
to mate with a male or not. Of course, this is when they have options. In these species, they only go into oestrus twice in a year, and it's only two weeks apart. That means when they go into heat, if they're not fertilized, they re-ovulate after two weeks. If they're not fertilized, that's over for the year. So they want to be fertilized, but they don't want to be fertilized by any...
They have to be choosy, as we say. So we're hoping that the females may be choosy also based on the quality of the car. Just one last thing. Considering the season that we're in right now and how reindeer are popular in movies and stories and fantasies, do you think the reindeer make these grunts when they're flying?
I wish I knew. More scientific research needs to be done into that. Definitely. Definitely. That's a topic of interest. I think I will definitely look into that. That will be exciting. Dr. Walaji, thank you so much for your time. My pleasure. Thank you. Dr. Robert Walaji is a professor of biology at Concordia University. From the Los Angeles Times, this is Boiling Point. I'm Sammy Roth.
I've been reporting on energy and climate change in California and across the American West for a decade. I'll be asking scientists, politicians, activists and journalists the same questions. What are the challenges we face to building a better world? And what are the solutions we need to embrace even when it's hard? Boiling Point will be available everywhere you listen to podcasts starting January 16.
I'm Bob McDonald and you're listening to Quirks and Quarks on CBC Radio 1 and streaming live on the CBC News app. Just go to the local tab and press play wherever you are. Coming up later in the program, Google Maps for your body. The Human Cell Atlas is going to give us a way to navigate our bodies in sickness and in health. If you compare it to a Google Map, in a Google Map you have all of these layers of information.
So you can drill in to very, very high resolution. You can see very individual pieces of information. That's like getting into the level of one cell out of the 37 trillion and seeing the molecules inside it. Many people cook crab or a lobster by placing the live animals into a pot of boiling water. There's always been a bit of an assumption that these animals, with their hard shells, don't feel pain the way we do.
But scientists have started challenging that notion. Observations of the animals have suggested that their behavior can change in response to what we assume would be painful. However, just because they react to what we think would cause pain doesn't mean they actually register pain as a negative experience like we do.
To investigate this further, Dr. Lynn Snadden decided to study how crabs' nervous systems with their decentralized brains respond to pain. She's a professor of aquatic animal biology and welfare at the University of Gothenburg in Sweden. Hello and welcome to our program. Hi Bob, thank you very much for inviting me. Why did you think more research was necessary into this question about whether or not crustaceans like crabs can feel pain?
Well, it's a complete unknown, really. We have some behavioral evidence that shows that crabs and prawns and lobsters are affected by painful events. But this is just behavioral evidence. And, you know, it might be just showing an avoidance response. What we don't have is recordings from the central nervous system or the brain. And that's exactly what we did. We applied.
noxious, potentially painful stimuli to the soft tissues of the crab's claws and legs, antennae and eyes. And then basically we recorded directly from the brain or the ganglion that the crabs have and showed that there is these external painful stimuli are conveyed to the central nervous system of the crab and that activity differs from non-painful stimuli. And these are hallmarks of pain in mammals and humans.
Well, take me through some of the criteria that you use to determine whether or not pain is being detected. Yes, so what we do is we probe the tissues until we get a response in the nearby brain area or ganglia.
And then we record from that. We show it's repeatable. And then we apply different stimuli, mechanical stimulation, and then a noxious chemical, acetic acid, which I'm sure you know is vinegar. And if you get vinegar in a cut, that really hurts. It's a standard pain test in humans and other animals. So we applied these different stimuli and got repeatable responses. But we found that the...
The potentially painful stimulus, the acetic acid, was different from non-painful stimulus. And further, we applied non-painful stimuli such as seawater and food orders, but we didn't see a response. And pain receptors, they're called nociceptors, they preferentially detect potentially painful stimuli. And so here we have in the crab this exact same response.
Now, you mentioned mechanical stimulation. What's that mean? Yeah, so what we do is, of course, the crabs could respond to touch or pressure, just like we do. When you touch your hand, if it's a light touch and it's soft pressure, a feather, for example, that feels very different to cutting and crushing, which is painful to us. And so what we did was we used these little devices. They're called von Frey hairs or filaments. They are little...
filaments of a specific size and diameter that apply a known pressure. And they're used in the electrophysiological studies of humans and other animals. And we know exactly what pressure we're applying to the soft tissues of the crab. Okay. So you're applying these different stimuli, the pressure, the chemical, the electrical. What about their brains, the so-called decentralized brain? What's the nervous system of a crab like?
Yeah, so we have cephalization. We have our big brain in one area at the front of the body, the anterior portion. In many invertebrates, they have a decentralized brain. So the brain is split up into different units within the body. And then the crab, they have two main units. One unit is at the top behind the eyes, which is called the brain. And then the other unit is down below at the abdomen. And they are connected to one another.
that goes in from the eyes at the front goes to that frontal brain area, whereas from the walking legs it goes into the abdominal brain area. Well, how did the fact that the crab has more than one brain affect your research and the response to pain stimuli? Yeah, well, we had to record from two different areas, from the frontal brain where we exposed it. The animal was...
held in place and we used neuromuscular blockers which effectively paralyzed the animal and so we could apply stimuli to the front claws to the antennae to the eyes and then when we wanted to look at the the legs we went to another part of the the central nervous system to record from because we wouldn't get necessarily get responses in the front little ganglia of the brain when we're applying stimuli to the back of the animal
So what were you recording? We were recording the electrical activity that comes in from the external world of the crab. So we applied stimuli. acetic acid, for example, to the antennas or the antennae or to the soft tissues in between the joints of the claws. And then we had electrodes placed in that frontal ganglia in that brain. And we were effectively recording what you might think of as EEG, you know, when you record brain waves.
And what that tells us is that that external information is being sent from the skin, from the eyes, from the antennae, to the brain, and it's being processed there. Well, it's one thing to respond to a stimulus, but do you have any indication that the crab would perceive that as pain like we do? What I can tell you is that...
Crabs do detect these potentially painful stimuli. Their brain can differentiate between different types of stimuli. Their brain can detect how strong the stimulus is. And then if we look at the behavioral studies that other laboratories have done, we know that these animals perform strange behaviors when we apply acetic acid to their antennae. We know that they will avoid a shelter where they receive a painful stimulus. We know that they show a stress response when they...
they receive a painful stimulus. So the evidence is quite strong for the animals to be capable of some form of pain. So given what you've learned so far then, is there a humane way to dispatch these animals if we plan to eat them? Yeah, well, obviously we have this cultural and social aspect of preparing food. And I understand that most people will place crustaceans like crabs into boiling water.
But you wouldn't put a cow or a chicken into boiling water. You would just be horrified by the whole thought of doing that. What we're doing now is experiments where we're trying to find the best way and the most humane, most rapid way of killing these animals. And we've been trialling electric shock, which kills the animals within seconds.
We've also been looking at laboratory methods like overdose with anesthetic. And we've been looking at ice slurry, which is effectively putting the animals in like a slush puppy of ice. And we were investigating freezing as a method that people could use at home. And so far, we haven't completed this study. Electric shock is the most rapid way and we feel the most humane.
But, of course, people at home don't tend to have electric shock equipment. So it seems like placing animals in a freezer for around 45 minutes does result in death. And so then you could put them in the freezer 45 minutes later, take them out and then boil them because then, of course, you're using a second method to kill them. Dr. Sneddon, thank you so much for your time. Thank you. Yeah, that was really interesting.
Dr. Lynn Snodden is a professor of aquatic animal biology and welfare at the University of Gothenburg in Sweden. It's being called Google Maps for the Human Body. The Human Cell Atlas is a mammoth global project to map every cell in our bodies.
Think of it as the ultimate extension of the study of human anatomy that's been going on since the ancient Greeks. First, we figured out the parts of the body, the muscles, tendons, bones, and organs. Then we made progress looking inside the tissues to understand their structure. Then we probed the insides of all those different cells that make up those tissues and even the molecular mechanisms operating within them.
Well, now the Human Cell Atlas Project is starting to bring all of that detail together at an unprecedented resolution and scale. And it's already revolutionizing how scientists can probe the human body with significant implications for future health care, from diagnosing diseases to developing drugs to ushering in a new era of personalized medical treatments.
It even helped scientists when the pandemic hit to quickly identify which of ourselves could get infected with the coronavirus. Dr. Aviv Regev is the co-chair of the Human Cell Atlas Consortium. Last month, she and a huge team of colleagues released some key elements of the atlas. She's also the head of research and early development at the biotech company Genentech. Hello and welcome to our program. Hi, Bob.
First of all, why do we need a human cell atlas? Well, it turns out that we're each made of about 37.2 trillion cells, and they come in many different shapes and sizes and do many different things. And we don't really know our cells. Even though they're the fundamental units of life, there are still different kinds.
types of cells and their characteristics that we do not know. And if we don't know our cells, that we cannot understand how disease happens and how to treat diseases. 37 trillion cells? That's more cells than there are stars in our galaxy. That's unbelievable how many there are. It's a lot of cells. It's a lot of cells. Each of us are made of that many.
And they change all the time. They're not even exactly the same. Like by the end of this interview, my cells are not going to be exactly the same as they were in the beginning.
Well, what kind of information will the human cell atlas contain? So the cell atlas will actually tell us the types and properties of all human cells. And it would do this by characterizing the kinds of molecules that are in them. So all of the cells in the body have the same genome. So all of my cells, say, or yours, have one particular genome, and that's the same. But they don't read the same instructions from the genome. So based on what the cell needs to do, they read different...
portions of the instructions. So the cells in our brain, the neurons are different than the immune cells that we use in order to fight off and defend us from pathogens.
And what the Human Cell Atlas will tell us is what parts of the instructions the cells are actually reading, which genes are being used by them, or as we say, expressed in them. And it will tell us additional things like what do they look like and which proteins do they have inside and where they reside in the body inside our tissues and organs. So in the end, we will have a pretty comprehensive map, a little bit like a Google map of the human body.
Well, it's hard to get my head around how many cells are in the human body, but how many different cell types are in the human body? So the answer is we don't exactly know yet, but we know now that it's a lot more than we knew before. So if you opened up Wikipedia at least a few years ago, it would say that there is a few hundred types that are characterized and that have names. And we definitely know that the number is much bigger than that because just in our brains, we now know that there are thousands of different.
types of neurons. And in our immune system, there are hundreds of different types of immune cells. And we're still figuring out the full number because we haven't finished building the map. Well, you talk about maps. We're all familiar with the geographical maps of the Earth. And you mentioned that this would be like Google Maps. So what kind of detail will we see in the Human Cell Atlas compared to, say, Google Maps?
First of all, you should think about where we started. So we started not really with a Google map. We started with something that looked more like the maps in the atlases of the 15th century, which were very crude. There was some information.
And some pieces were really not characterized. And then in the end, it said terra incognita, meaning we know there's something there, but we don't know what it is. If you compare it to a Google map, in a Google map, you have all of these layers of information. So you can drill in to very, very high resolution. You can see very individual pieces of information. That's like getting into the level of one cell out of the 37 trillion and seeing the molecules inside it. But you can also zoom out in a Google map.
see the big picture and know the general categories that are there and so on. And you can see different kinds of information in a Google map. So you don't just see the street view map, but you can also see a street map. You can also see traffic patterns. You can see topology and topography, just like, you know, the earth is really shaped.
And the same is true for our cells. You would be able to see individual cells based on one kind of molecule and other kinds of molecules and how they're organized in the tissue and how they even develop and change over time. So a dynamic view, not just a static view. Wow, that's amazing. So I'll be able to zoom into the human body and see, say, a white cell destroying a virus that's trying to attack the body and watch that happen? You would be able to reconstruct.
with a machine learning algorithm or AI, even how that happened, the series of steps that it took. The moment we actually measure the cell, we actually ruin it. We have to destroy it in order to see what's inside it. But by looking at a lot of cells, we can actually reconstruct the movie. So what stage are you at now? How far along are you with the Human Cell Atlas?
Yeah, so we started with the fact that there's 37 trillion cells in each human, but we don't really need to look at every single one of them because they do repeat themselves. There's many of one kind that look quite similar. We have more than 100 million cells that have been profiled. And in our map, in the first version of the map, about 60 million of cells will be assembled.
into maps for 18 different organs and systems. Most of these data are already collected and the maps are being assembled. Four of them, for the first maps, for the brain, for the eye, for the lung, and so on, have already a first version been assembled. And the remainder, all the way to 18, are going to be released over the next year, year and a half.
Wow. And is this information already available in 3D? Some information is available in 2D and in 3D. So some information is available just for individual cells. In other cases, we have information from tissue sections. So you can see how the cells are organized next to each other in the tissue. And in some cases, you even have a reconstruction.
of many, many sections, one layer on top of the other, so you can see things in 3D. But much of this level of 3D will really be the second version, not the first version of the atlas. This feels like a turning point in our scientific history, where up until now we've been zooming into the body to go down through tissues, into cells, into genes and molecules, and now...
We're zooming back out again to see how the whole thing works. Yeah, that is very true. And that's why I love the Google Map analogy, because you can zoom in on Google Map, but you go all the way down to somebody's doorknob. And it's nice to know that there's a doorknob there, but it doesn't really mean anything if you don't know that it's attached to the door and the door is part of a house and the house sits in the street and the cars are driving and somebody is coming into that house is going to do something. You need the full picture and you need the detail of the doorknob.
And the Cell Atlas with these technologies and with the AI actually allows us to see both the parts and integrate them back to the whole. And in biology and in medicine, that is critical because there's so many moving pieces. There's so many parts, so many genes and ways in which they can combine and so many cells and so many parts of our body. And in the end, we want to be able to say something like...
But why does this person have Alzheimer's disease? And what can I do about it? And for that, you need to be able to connect the pieces back together. And these technologies will now allow us to do that. And how one system is related to the others and how it all works together. Can you take me through some examples of how this atlas has already been used?
Yeah, absolutely. It's become actually part and parcel of how we do both basic science, just to know the basic facts of life and what we're made of. And also it has real practical applications that are happening now in the effort to understand the causes of disease and develop new therapies. So, for example, we have discovered as part of the human cell atlas, as part of the lung cell atlas, that in fact there is a very rare cell.
we didn't know existed, and that this cell is the one that actually uses and expresses a very famous gene, which is the cystic fibrosis gene. This is the gene that has a mutation that when an individual carries both copies of that mutated copy, they will actually have cystic fibrosis. We have actually known the gene for more than three decades.
But no one actually correctly knew where that gene is being used. We were misled. We thought it was in another cell type. This is really important. We want to understand the disease. But also if you think about an effort, for example, to develop a gene therapy for cystic fibrosis to fix the gene, you need to know where to deliver the fix to. And if you don't know the right cell, you wouldn't be able to do that. How was the cell atlas used to understand the COVID-19 pandemic?
Yeah, it was actually very useful in the time of COVID-19. So when the virus first emerged in COVID-19, we really knew very little about what this virus could cause in the human body. But we did know which protein needed to exist on the cell surface for the virus to infect the cell. And so, in fact, the entire human cell atlas community came together originally.
we thought we would look in the lungs and the airways to see which cells might be susceptible to the virus, because we knew that the virus was causing a disease with respiratory symptoms. But we decided to look actually at the entire map, not just at the lungs. And we discovered very early on in the pandemic, really in the very first few weeks, that it seems like there could be cells in many other organs, in the heart, maybe in parts of the brain, in the olfactory epithelium, in the gut. And in fact,
These were things that emerged from the cell atlas at the time or even before.
Patients were reported with what we know now can be cardiac symptoms, neurological symptoms and gastrointestinal symptoms. So it was enormously helpful at that time. And it was very galvanizing also to see how an international community of scientists that really covers scientists in countries all over the globe, in all inhabited continents, can come together like this and help solve a scientific conundrum that was very crucial and important.
Dr. Regev, thank you so much for your time. Thank you. Dr. Aviv Regev is the co-chair of the Human Cell Atlas Consortium and the head of research and early development at the biotech company Genentech. Now, one of the parts of the Human Cell Atlas that was recently released was a map of one of our most important organ systems, our skin. But it's not a static map. It's a dynamic picture of the development of prenatal skin.
Skin as it's growing and developing to become our first line of defense against the hostile world. And once they'd built this atlas of our skin, the researchers used it as a blueprint to grow a miniature replica called an organoid of fetal skin tissue in a lab. Here's Dr. Elena Vinheim, one of the lead authors of the Skin Map Study. My boss sometimes compares it to Lego, where you have like a Lego house that you're...
dissociating, you're taking the individual pieces, and by taking the pieces and looking at them, you can basically rebuild the whole thing, right? This work is already providing new insights into things like how our hair follicles develop in the skin, how we might avoid scarring, and the unexpected role the immune system plays in all of it. Dr. Vinheim is a postdoctoral research fellow in immunology at the Wellcome-Sanger Institute in Cambridge in the United Kingdom.
Hello and welcome to our program.
Thank you for having me. First of all, what were you trying to figure out with your study? So we were quite interested to study how the prenatal skin develops. Now, currently, there's only limited understanding of the exact processes of normal early human development, which does hold back our ability to understand or correct when things go wrong. And prenatal skin development is especially interesting because it's the only time period where hair follicles are formed. And it also has the...
Interesting ability to heal without scarring. That's amazing that all the hair follicles are formed before we're born. I guess the rest of our lives we just lose them. Yeah, basically, basically. Well, what were you able to learn from the skin map and organoid about what happens during development? One interesting thing during development in prenatal skin that we discovered by looking at it was that we found...
macrophages which is a type of immune cell very early in the prenatal skin so even after one and a half months post-conception macrophages are in the prenatal skin and we were surprised to see them because their role is usually in
immune defense, like defending against pathogens. They also help wound closure. So why are they in the prenatal skin that is in a sterile environment and is usually not wounded? What we found actually is that the macrophages are located close to blood vessels. So blood vessels are super important because they kind of bring nutrients to tissues, they supply oxygen. And macrophages seem to act in the prenatal skin as sort of construction engineers for the blood vessels.
Wow, that's amazing. Immune cells that normally deal with invaders from the outside world are repurposed. They're doing something else to help develop blood vessels inside the womb. Exactly, exactly. Tell me about the development of scarring in this tissue. Yeah, so scarring is quite interesting. So before birth, the skin has the unique ability to heal without scarring, but only in the first and in the second trimester.
And we were quite interested to see what conveys this ability to prenatal skin to heal without scarring. So what we did is we looked at these time points and we compared the prenatal skin over time and with adult skin. And we observed some key differences. So prenatal fibroblasts are geared towards reducing inflammation and promoting tissue regeneration.
In contrast, the adult fibroblasts were prone to triggering inflammation and collagen deposition, which leads to scarring. And as the skin develops, the fibroblast subtypes that we see start to shift towards a more pro-inflammatory scar-promoting state in the later stages of gestation. And this kind of coincides with the clinical observation that the skin starts to scar. Well, if this prenatal skin can heal itself without scarring...
Can we take advantage of that and try to apply it to adult skin when we get wounded? That is the hope. So we are not completely there yet. There is no off-the-shelf treatment yet. But by understanding what type of fibroblasts we need to prevent scarring, we can try to reproduce this then, for example, after a surgical incision. So that is the hope. Are these immune cells also involved in this healing without scarring process?
Yes, so what we did is we used an in vitro model to kind of look at the effect of macrophages on these fibroblasts. And we kind of scratched fibroblasts to create an artificial wound. And when we added macrophages to that, the wound closure improved actually. So the macrophages really seemed to improve the scarring as well.
Again, it's like these immune cells have nothing to do because they're in a sterile environment in the wound. So let's do something else. Let's help make blood vessels. Exactly. Let's prevent scarring. How will this prenatal skin map and the skin organoid that you developed help open up what we can research in the future? So one thing we are super interested in researching in the future are certain genetic skin diseases and hair follicle diseases.
that our skin organoid very closely resembles the prenatal skin and also expresses these genes that are associated with these diseases. And this really opens up the opportunity to use this skin organoid to study these diseases further, to understand the precise mechanisms behind them and to test even therapies on them. Dr. Vinhein, thank you so much for your time.
Thank you so much for having me here. Dr. Elena Vinheim is a postdoctoral research fellow in immunology at the Wellcome-Sanger Institute in Cambridge in the UK. And that's it for Quirks and Quarks this week. If you'd like to get in touch with us, our email is quirks at cbc.ca or just go to the contact link on our webpage at cbc.ca slash quirks where you can read my latest blog or listen to our audio archives.
You can also follow our podcast, get us on SiriusXM, or download the CBC Listen app. It's free from the App Store or Google Play. Quirks and Quarks was produced by Rosie Fernandez, Amanda Buckowitz, and Sonia Biting. Our senior producer is Jim Lebens. I'm Bob McDonald. Thanks for listening. For more CBC podcasts, go to cbc.ca slash podcasts.