GUEST: DR. BIRGITTA EVENGARD, DR. MELANDRI VLOK, DR. JEAN-MICHEL CLAVERIE
Tracking down diseases using genomics
Stop the presses! New research shows that viruses locked in the Arctic permafrost for thousands of years have the potential to infect present-day organisms. Accompanied with a warming planet, this issue is really starting to thaw out. So what can brave scientists and institutions on the frontlines of tracking diseases do about it? And how can understanding our genomic history with diseases over thousands of years better prepare us in the fight to overcome them?
Dr. Kaylee Byers starts our journey by slinking into a disease-tracking genomics lab at Simon Fraser University to meet Dr. Michael Trimble and Dr. Will Hsiao to understand the challenge of outpacing the rapid evolution of viruses. Then she pops across the ocean to speak with Dr. Birgitta Evengård and Dr. Jean-Michel Claverie about whether the Pandora’s box of ancient diseases frozen in the arctic have the potential to become the next global outbreak as temperatures warm. Plus, we unearth ancient burial sites in Vietnam with Dr. Melandri Vlok, to investigate how climate change exacerbates the tension between human health and pathogens.
Special thanks to Dr. Will Hsiao and Dr. Michael Trimble for allowing us to record with them at Simon Fraser University.
Dr. Birgitta Evengard, spotting diseases under thawing permafrost
Dr. Jean-Michel Claverie on what resuscitated ancient viruses means for humanity
Ancient disease detective Dr. Melandi Vlok solves a mystery of epidemic proportions
Dr Kaylee Byers: Recording, recording, recording. Recording, recording. Hey, it’s Kaylee. Today I decided to sneak into a lab at Simon Fraser University in Burnaby, British Columbia. I’ve actually been here before, and yet this place is a maze.
I mean, not really sneak…
Excuse me. Do you know where Will Hsaio …
I got a little lost.
Jerome: Yeah, I’ll walk with you.Read Transcript
Dr Kaylee Byers: Oh, great.
But luckily I ran into Jerome.
Thanks, Jerome, by the way. I’m working on a podcast right now if they keep some of the…
Jerome: I wrote that story on you.
Dr Kaylee Byers: Oh my God!
Jerome: I’m Jerome, by the way.
Dr Kaylee Byers: Hi, Jerome!
Jerome: It’s lovely to meet you.
Dr Kaylee Byers: Oh, great.
Jerome: They don’t just label I guess.
Dr Kaylee Byers: Oh, thank you so much. Thanks, Jerome.
Jerome: Yeah. No problem.
Dr Kaylee Byers: Bye!
And eventually, I found this guy. Who are you?
Mike Trimble: I’m, I’m Mike Trimble. I am the genomics lab manager for Dr. Will Hsiao here at SFU, the Center for Infectious Disease Genomics and One Health.
Dr Kaylee Byers: Mike and I are in the lab to talk about…
We have worked together on this bat guano project where we go around and we collect bat poop and we’re looking to see what’s in it.
Poop! How exciting.
What happens once I have gone to collect the poop and it comes here? How do we look for things like the genomics in that poop?
Mike Trimble: Well, once we get it from you guys, we put it in the freezer here, so -80 degrees [Celsius], so it’s very, very cold. We pull it out, we thaw it up a little bit, and then I separate out a few of the guano pellets and then I put it through a kit, a DNA extraction kit. And so we use chemicals to lyse the poo particles and all the other bio bits in the poop and put it over a filter, a special filter, and we collect all the DNA out of it.
And then, we wash away all of the stuff we’re not interested in, the proteins, the carbohydrates, ’till we just have pure, pure DNA.
Dr Kaylee Byers: And from that nice, clean sample scientists like Mike comb over it.
Mike Trimble: So, what we’re looking for is there’s a special gene inside of it.
Dr Kaylee Byers: They find that special gene.
Mike Trimble: So, we’re going to amplify this gene, and that’s what we’re going to sequence.
Dr Kaylee Byers: And now they can pull all sorts of information from it.
Mike Trimble: We kind of don’t really know what’s in there. And we know there’s a lot of different species in it.
Dr Kaylee Byers: It’s a bit like popping the lid off a treasure chest where genomics are the jewels.
Mike Trimble: Yeah, so once we sequence that, all that data goes into the computer, and then we have to have our bioinformaticians piece apart the data and see what we have.
Dr Kaylee Byers: And those gems of information can help us understand what bats are eating. In Canada, mostly bugs. But if we were to cast an even wider net to include all the DNA in a sample, we could also spot other organisms like bacteria and viruses.
Mike Trimble: If it’s bacteria, we’re going to be looking for antimicrobial resistance genes. We’re looking for virulence genes. A virulence gene is what genes help the bacteria. If you’re looking from a human, the genes help the bacteria make you sick. But if you’re looking from a bacteria point of view, it’s genes that help it survive.
Dr Kaylee Byers: Grabbing samples, extracting the DNA, sequencing it, and analyzing the results. It’s a basic formula for any genomics work. This isn’t just about bat poop. It can also be used for identifying and tracking bacteria and viruses that are all around us, and some which can even make us sick. Scientists around the world repeating these steps over and over are progressing our understanding of these microbes so we can stay ahead of them. It’s a train ride that isn’t slowing down anytime soon. And as we’ve seen recently, this issue is only just beginning to thaw out.
I hear them beep and it gives me nightmares. Do they give you nightmares?
Mike Trimble: Yeah. No, you don’t want to hear a freezer beeping when you come in the morning.
Dr Kaylee Byers: You’re listening to Nice Genes, where we peek into the world of genomics, sponsored by Genome British Columbia. I’m your host, Dr. Kaylee Byers, your doctor who’s who of diseases both past and present. In this episode, we’re looking into a race between humanity and teeny tiny microscopic adversaries.
Hello. I went to your office first.
Dr. Will Hsiao: Yeah, sorry about that.
Dr Kaylee Byers: That’s okay!
On my quest to understand the front lines of this issue, I met with a friend and colleague at Simon Fraser University who’s an expert in genomics methods, Dr. Will Hsiao.
Dr. Will Hsiao: Dr. Will Hsiao. I’m associate professor in the fact of health sciences at Simon Fraser University. My background is in microbial genomics and bioinformatics and the use of genomics information to track diseases and to understand microbials, pathogens better.
Dr Kaylee Byers: He’s the one whose name was on the lab door that I was at earlier. And as you heard, Will’s lab uses genomics to recognize and track microbes, which includes diseases. What is the biggest challenge of trying to track diseases?
Dr. Will Hsiao: I think the major challenge is to understand how fast or how quickly these pathogens can evolve. We’re already seeing how SARS-CoV-2 time and time again overcome the pressure we apply through treatment, and pressure we apply through the use of vaccines and new vaccines have to be made to respond to the new variants.
Dr Kaylee Byers: And another thing I was thinking about when you were talking about the evolution of something like a virus and we’re constantly keeping up and we’re putting new pressures. It reminds me of the ‘Red Queen’ hypothesis.
Briefly, the Red Queen hypothesis is a co- evolutionary hypothesis. Proposed in 1973, it discusses a sort of arms race between organisms and how they evolve. Each species is trying to outpace the other one, and in this case, the race is between humans and pathogens. As they evolve and change, we keep on trying to stay ahead of them with medicines and treatment, but they’re doing the same thing. Some gain antibiotic resistance, others become more infectious. We’re locked in a constant foot race and one that doesn’t appear to have a finish line.
The Red Queen, to my understanding, is just that we’re running forever but we stay in one place, right? We’re constantly, yeah, Alice in Wonderland. We’re just constantly trying and we’re staying in one place. That makes me think about tracking diseases in real time. How do we go about doing that quickly so that we can keep up so that we can stay on track of things as they spread?
Dr. Will Hsiao: My own belief is that if we can understand how microbes evolve and when you apply a specific pressure, how it’s going to respond. There are patterns out there that we can learn. But this is a pattern that has many, many factors that has what we call sort of a large problem, a large search space in order to identify the patterns. That’s where getting large data sets together and being able to interrogate large dataset is the way to go.
Dr Kaylee Byers: Tracking viruses and bacteria is tricky because they can evolve quickly. That’s what I want to look at today. Diseases like SARS-CoV-2, don’t start or stop at any one border. So for this episode, neither will we. To widen our reach, I decided to take an international approach.
Dr. Brigitta Evengard: Hello.
Dr Kaylee Byers: [In Swedish] Hello, how are you?
Dr. Brigitta Evengard: [Swedish]. You’re speaking Swedish. That’s fantastic.
Dr Kaylee Byers: First stop, Sweden, speaking with Dr. Brigitta Evengard.
Dr. Brigitta Evengard: Actually, I was the northernmost professor of infectious diseases for quite a few years until University of Greenland is expanding, and so they now have a professor of infectious disease.
Dr Kaylee Byers: Oh, how did that feel to have someone take your title a little further north?
Dr. Brigitta Evengard: Well, it was a bit irritating. Not really. It’s a good friend of mine.
Dr Kaylee Byers: Dr. Evengard has been working in the realm of infectious diseases for decades as well as on the front lines of public health for just as long.
Dr. Brigitta Evengard: So, I’ve had about 45 years of clinical experience focused on patients with infections.
Dr Kaylee Byers: And what was it like working with some of these outbreaks before?
Dr. Brigitta Evengard: I still remember, this is a very intense memory from a summer when two young men came to the hospital and they had fever, swollen glands, and we had no idea what it was. So we called it ‘lymphadenopathy syndrome’. And I remember my then professor said, Brigitta, I do think this could be a new virus. And then of course HIV was discovered and we learned how to deal with it. Thankfully. I’m so grateful for science and progress.
Dr Kaylee Byers: Dr. Evengard is also a member of the Arctic Council for Human Health and a mover and shaker in the realm of infectious diseases in the European Union. Back in 2019, she organized a large skill-share event in Hanover, Germany.
Dr. Brigitta Evengard: We pulled together 60 experts. I wanted to join if I could pull in Russians. So we had four Russians.
Dr Kaylee Byers: Scientists and experts from all around the world came together to discuss and share their research on the Arctic. Or rather, what lies beneath its frozen surface.
Dr. Brigitta Evengard: Whatever is in there, it could be anything. It’s Pandora’s box.
Dr Kaylee Byers: And what lies under there are microbes.
Dr. Brigitta Evengard: There was a Nature publication from the Finnish meteorological organization that shows that the climate change is occurring four times faster in the Arctic. So, this means that this is really more than we ever feared. Permafrost is frozen ground. So when this thaws, nitrogen oxide, methane gas, CO2 level, will be released. So, what’s frozen there could be microbes.
Dr Kaylee Byers: Some of them may be bacteria, viruses, and parasites with the potential to cause disease.
Dr. Brigitta Evengard: Viruses that are like 30, 000 years old and 15,000 years old. More than 90% of bacterias are unknown to us. They have not been cultivated. We don’t know what they’re doing. Some might be producing antibiotics, some might be producing antibiotic resistant strains.
My general feeling was that I was a bit shocked that 60 super experts pulled together from the whole globe, couldn’t come up with more. There has been some ancient viruses, not pathogenic for humans as far as I know, one 30,000 years old, and recently one 15,000 years old, that have been published. And there is a group in southern France that has published on this. But otherwise, from a human health point of view, we know very little. This is what I think will be on the headlines on the next five, ten years.
Dr Kaylee Byers: Whether or not these microbes that are frozen in time for thousands of years could pose a threat to humans and other animals is unknown. When they freeze these single cells lie dormant, neither dead or alive. But when they emerge from their frozen state, is it business as usual? Could they go back to reinfecting present day organisms?
Hi Dr. Claverie, thanks for joining me today.
Dr. Jean-Michel Claverie: Okay.
Dr Kaylee Byers: Dr. Jean- Michel Claverie is a professor of genomics in bioinformatics a University Aix-Marseille University in southern France.
Dr. Jean-Michel Claverie: I started in as being a theoretician in particle physics. So as you can see, I’m still doing with particles, but they are much bigger than the one before.
Dr Kaylee Byers: He and his fellow researchers are looking precisely at whether or not we should be worried about what thawing permafrost layers, due to warming temperatures, means for our health.
Dr. Jean-Michel Claverie: I created my lab in ’95, if I remember correctly. At this point, we started to work on the genomics of parasitic bacteria. This is a bacteria that cannot survive outside of the cells and infect it. And one day we found strange bacteria that we could not characterize very well. And for a long time we didn’t understand what was going on. And finally, we discover that it was in fact not a bacteria, but a virus. We discovered what is called now the first ‘giant virus’. Not all those are viruses that you can actually see under a regular microscopes. I’m talking about viruses which have more than 2,000 genes, when the regular virus like AIDS virus has 10, for example.
That was the beginning of a change of pace and direction in the lab. And so we started to say, “well that that’s interesting, there is a new branch of biology, those giant viruses,” when we discovered that this type of virus was extremely abundant in water, in any kind of humid environment. And one day, I saw a paper by a Russian group claiming that they had been able to revive a plant that was kept in permafrost for more than 30,000 years, which is pre-historical time.
Dr Kaylee Byers: Dr. Claverie’s lab was interested in whether you could resuscitate species from permafrost.
Dr. Jean-Michel Claverie: First, it is important to understand what permafrost is. This is not ice, permafrost is just regular soil. Which as you know, soil is full of bacteria, a lot of rotting things, this is just everything is decomposing over the years, okay? Except that after the one meter, it becomes below zero, and so there is no liquid water in that thing. And if there is no liquid water, all biochemical processes are stopped. And some of those bacteria die because of that, but many don’t. And they just enter into a stages that we call ‘cryptobiosis’, which is in fact, they are not totally dead, they are not totally living, they are just waiting for better time to get some liquid water again so we can restart the whole process.
And when I saw that paper, at the time we were looking for viruses in all kind of environment, I decided, well, if they can resurrect plants, we should be able to resurrect the virus. And so we just called them and we asked them to send us the same sample, in fact that, they used to isolate this plant. That was the beginning of the whole story about the permafrost viruses.
Dr Kaylee Byers: They decided to see if that same concept used on the plant samples could work with microbes, especially with their giant viruses. How were they going to do it?
They decided to test other ancient viruses on amoebas.
Dr. Jean-Michel Claverie: And it tells that amoeba are fantastic tools because they’re extremely resistant. For example, they’re resistant to bacterial infection because they in fact eat bacteria.
Dr Kaylee Byers: Amoebas might not look like much under a microscope, but they’re sort of one of the toughest of the tough in microbiology. They shimmy around in their little microbial town absorbing other microbes to quench their insatiable hunger. They’re good at what they do. They have a lot of internal mechanisms to help them process the many little bacteria they consume. But Dr. Claverie put these amoebas next to one of the dormant ancient giant viruses they had and…
Dr. Jean-Michel Claverie: They start dying. The amoebas start dying.
Dr Kaylee Byers: These tricky viruses disguised as bacteria latched themselves to the amoeba. And that was the end of our toughest cowboy in the neighborhood. So long partner.
Dr. Jean-Michel Claverie: It turns out that the virus that we isolated first was called Pithovirus, in totally the shape of the bacteria. So we thought that it was a bacteria, but we never saw it dividing like bacteria do. And so for a while we called that thing the ‘New Life Form’, we didn’t know what it was.
And so the code name in the lab was ‘NLF’ for New Life Form. But we had to isolate them, purify them, extract DNA, and do the sequencing. And when we add the sequence of that genome, we realized it was not a bacteria. It could not be a bacteria, it had to be a virus. Okay? The amoeba is going to be very happy, thinks that she’s actually engulfing a bacteria, but in fact not, this is a virus. So this is a virus that disguises itself as a bacteria. So basically, we use the amoeba as a detector of trouble. And trouble means virus.
Dr Kaylee Byers: And Dr. Claverie and the lab dubbed these resuscitated viruses as ‘zombie viruses’.
Dr. Jean-Michel Claverie: You just want to use, back that the time, that I like it because yes, this is zombie virus. We think they are dead, but in the fact, they can come back to life. No, I didn’t invent the term, the term was invented by the press.
By using viruses, which are not a threat to human, we are able to prove indirectly that that’s probably that very ancient viruses are still infectious in the permafrost that is thawing every day now, releasing more viruses. And those viruses, most likely, can infect human or animals.
Dr Kaylee Byers: Okay, so I mean, what does that mean? Should we be worried?
Dr. Jean-Michel Claverie: Maybe you’ve heard of that story in, it was in 2016. It was that the anthrax epidemic.
Newscaster: An outbreak of anthrax in Siberia has been blamed on a heat wave melting infected reindeer carcasses that were frozen in the tundra.
Dr. Jean-Michel Claverie: That kills a lot of reindeers, and a few people too. And this anthrax bacteria was just, it’s a bacteria. So again, this is not so dangerous because it can actually recede using antibiotics. In that case it was only 70 years old the bacteria. But it could be 700 years [old] bacteria because we know that there is a lot of people that have been buried in permafrost, in fact, and those corpse don’t decompose. And if you died from variola [also known as smallpox] 300 years ago, and if you are buried in permafrost, the variola virus is still there.
Dr Kaylee Byers: But when it comes to us, I mean, what can we do about it? Are you hopeful?
Dr. Jean-Michel Claverie: Unfortunately not, not really. I’m afraid that viruses are going to be a very long threat, for very long time. Bacteria, it’s okay. We have plenty of different antibiotics, so this is still not a really big problem. But with viruses, yes, I’m very worried. And so now since then, we’ve now about, I think even more cases of viruses that we’re able to isolate from different layers of permafrost. Some of them much older, up to 50,000 years ago. And 50, 000 years ago, why? It’s because simply this is the limit of radiocarbon dating. And so probably, there are viruses there in layers that are basically as ancient as 200 or 300,000 years ago. Many of them are still infectious after a very long time in permafrost. So this is the danger, and this is where things are getting wrong now with the global warming, because as you know with global warming, many of those Arctic coasts and the Siberian coast are becoming much more accessible.
And it is a big interest for the Russians because there is a lot of mineral resources there. And those people are going to do what, for example, open-pit mining. Open-pit mining means that you are going to excavate up to 2, 3, 400 meters of permafrost at once, which gets you back 400,000 years ago basically, and release viruses of which we know absolutely nothing. So, what we just want to recommend is that if one of those places, somebody gets sick with strange symptoms that nobody has ever seen before, don’t send them back by the next plane to Moscow. Use the very old concept of quarantine to see what’s going on. And so, it would be very important that all those industrial exploitation have a good medical facility before just sending back those people back to civilization.
Dr Kaylee Byers: I mean, okay, as a scientist, on the one hand, you want to be able to really understand the system, right?
Dr. Jean-Michel Claverie: Yeah.
Dr Kaylee Byers: You want to research it, you want to know every bit of knowledge there is out there.
Dr. Jean-Michel Claverie: Yeah.
Dr Kaylee Byers: But based on what you’re saying, I mean, is it better if we just leave this thing be?
Dr. Jean-Michel Claverie: Well, yes, no, absolutely. I’m very glad that we only work on amoeba viruses. We have now very good evidence that there are other type of viruses that probably could infect animal in the same sample, but we will never try to revive any of those viruses.
Yes, it is frustrating because our theory is that if our amoeba virus can survive, probably the other viruses will be infectious too. But I’m stopping short of proving that. I’m not going to take the risks of reviving a new plague, a new human plague, just for the sake of being, “okay, I told you so, I was right.” I think at this point we have to stop, and this is why I’m so, I’m a little worried about, as I told you, the Russians continuing along that path.
Dr Kaylee Byers: And of course, it gets complicated.
Newscaster: It is already Friday in Ukraine, and already, we are hearing reports of explosions being heard in the capital as Russian forces continue their assault.
Dr. Brigitta Evengard: Now of course things have changed.
Newscaster 2: Amid reports of fierce fighting and troops pushing into the country on three fronts. The casualties are mounting.
Newscaster: It is hard to confirm details.
Dr. Brigitta Evengard: And with the current political situation, we have no longer access to facts, what’s happening there, which is an even further tragedy besides the war. So my group and myself, we had a great Nordic Center of Excellence, a six- year project where we involved a lot of Russians that ended in March this year. But in February, we had just signed the contract for further expanding networks, focusing on the permafrost and other things in Russia. And of course that was in February, so the money was withdrawn due to the war. And we are working with our friends in Greenland and Northern Norway and Finland. So this is a very, very threatening event that will emerge.
Dr. Jean-Michel Claverie: And again, many of those things that are in the deep permafrost, which is let’s say 1 million year ago, we have no idea at all where those virus lives and how many of those were in fact involved in the extinction of species. There are some people that still believe that at least in some part of Siberia, the Neanderthal population that went there could be that some of those population have gone extinct because of infectious disease, including animals, including animal species. What are the chances that that happening? And for this, we have no number. I mean, it is probably, it will be very rare. So I cannot tell you that a huge epidemic coming from permafrost is going to happen in the next century or in a millennia or in a million years from now. But the only thing we can say is that the chances for that to happen is increasing because of more people getting there and because of permafrost thawing at acceleration. So we start from a very tiny probability and we know that probability isn’t crazy. I don’t want to make people totally crazy about this.
Dr Kaylee Byers: All right, one thing I want to emphasize is, even though the prospect of potential pandemics hidden under permafrost is chilling, both Dr. Evengard and I want to be clear that this is still an emerging field of research with a lot of questions that need to be answered first. We’re not here ringing alarm bells or screaming from mountain tops, but we are articulating where we are in this race to get ahead of potential outbreaks. So what can we learn about diseases from thousands of years ago that weren’t frozen in time, the ones that actually hit human populations?
You’re listening to Nice Genes!, a podcast all about the fascinating world of genomics and the evolving science behind it, brought to you by Genome British Columbia. I’m Dr. Kaylee Byers, your host, and we want to get more people listening to the genomic stories that are shaping our world. So if you like Nice Genes!, hit follow on Apple Podcast or wherever you get your shows. Unfreeze your podcast feed by sharing us with your friends.
Okay, let’s hit pause on permafrost and zombie viruses for just a moment. (Also, zombie viruses don’t actually mean viruses that turn people into zombies. They’re just sleepy viruses, but they do have the potential to become active once again.) So I want to hit fast forward on earth’s microbe history. I mean on a time scale between permafrost from hundreds of thousands of years ago to only several thousand years ago.
Hello, can you introduce yourself?
Dr. Melandri Vlok: My name is Dr. Melandri Vlok.
Dr Kaylee Byers: She’s what’s called a bioarcheologist.
Dr. Melandri Vlok: That’s someone that studies the bones of ancient humans to look at evidence of disease or evidence of the kinds of activities that someone did during their life.
Dr Kaylee Byers: Dr. Vlok studies ancient diseases and the communities that were hit hard by them thousands of years ago. What she discovered through her work may actually help us today. So rewind, how did you end up becoming a quote on quote “ancient disease detective” in the first place?
Dr. Melandri Vlok: Well, as young as I could remember, I was always interested in all the history books, like “Horrible Histories” for example, that were written for children. Then, by the time that I was in high school and looking for what I wanted to do in my life, I came across this TV show called Bones.
Dr. Temperance Brennan: Zack, the bones. What did you do with the bones?
Dr. Zack Addy: Nothing. Dr. Brennan, I left them on the table just like you asked.
Dr. Melandri Vlok: She’s a forensic anthropologist, Dr. Temperance Brennan. I saw myself in her. So I was very much dead set on becoming a forensic anthropologist. But you could use the same techniques that you used on solving murders, but you could look at people who had lived and died thousands of years ago and find out things that the world didn’t know yet. And for me, the story between how humans and our greatest enemies, which are pathogens, have co-evolved with each other, we’ve influenced the evolution of each other, it’s so fascinating to me and so complex that I just wanted to keep learning more.
Dr Kaylee Byers: Dr. Vlok’s work has taken her all over the place.
Dr. Melandri Vlok: I did a field school when I was only 19 years old, first time overseas, and the archeology of Southeast Asia was so interesting. The way people buried their dead. They would bury them in jars and being the person to excavate that was so incredible. We can learn so much about who we are today and who we might become from our ancestors. I’ve worked in the Philippines, Vietnam, I’ve worked on a skeleton from Indonesia that’s 31,000 years ago, Mongolia, Japan I’ve worked on, and Thailand as well.
Dr Kaylee Byers: One of her most recent assignments challenges a long-held view by epidemiological anthropologists.
Dr. Melandri Vlok: So the story of malaria is one that we teach a lot in universities to epidemiologists, to public health specialists, because with agriculture we have what’s called the ‘first epidemiological transitions’. The first epidemiological transition is a massive increase in infectious diseases and the rise of epidemics, basically, because of our transition from hunter gathering to agriculture and it’s a really nice story that can be boxed up. But the reality is that that didn’t happen like that.
Dr Kaylee Byers: What she and other bioarcheologists found was evidence that contradicted that theory. It came from ancient burial sites in two different locations, one in the northern side of Vietnam and the other to the south.
Dr. Melandri Vlok: So, 7,000 years ago, northern Vietnam was a lot more forested. The people would’ve lived as hunter gatherers at a time where the climate was slightly warmer and more humid. The resource turnaround in the forest was immense. Estuarine, flora and fauna, marine environments were nearby, forested environments… The animal bones that we find at this site are dramatic. From monkeys, there’s tigers, there’s even a whale bone that they used in their mortuary rituals that we found positioned specifically around a burial. And it was well enough for these hunter gatherers to be able to actually live all year round and grow quite large populations.
But by about 4, 000 years ago, the climate has changed a bit and it’s drier and the resource returns aren’t there anymore. So we believe that to be the ultimate reason why people start to adopt agriculture. But this idea of malaria is that with transition to agriculture, we did what’s called ‘slash and burn’ agriculture. So that’s where you slash down forests, and then you burn the area, and then you prepare it for agricultural land, basically.
What results from that is the fact that you have stagnant pools, and these stagnant pools mean that you are attracting the mosquito that contributes to malaria, which is called the Anopheles mosquito. So that may have been the case in the Mediterranean where a lot of work has been done, but that’s certainly not the fact in Southeast Asia because the Anopheles mosquito is the species that is the one that spreads malaria the most is actually a forest mosquito. So it doesn’t like being around agricultural fields. So we should have known that this story’s not quite right.
Dr Kaylee Byers: And buried away in the bones of these ancient people. They found a gene that protects individuals from harmful parasites like malaria.
Dr. Melandri Vlok: So the way I do my work is I lay out a skeleton in full. It’s important for me to understand that whole story of that person because when a disease affects your bone. By that point, you’ve likely had that condition for a really long time and it’s quite severe if it’s affecting your bones. And what we found is that both sites actually had evidence of this genetic anemia called thalassemia. And thalassemia is really interesting because if you get one non-thalassemic gene from a parent and the other one, a thalassemic gene from the parent, you don’t necessarily have the really bad effects that come with a genetic anemia. So a genetic anemia is something that means that your red blood cells are basically defective. They’re not working properly, they’re not shaped properly to be able to transport oxygen around your body properly.
Dr Kaylee Byers: Okay.
Dr. Melandri Vlok: But what it does do is it changes some of your red blood cells just enough that malaria can’t actually infect your red blood cells. So it’s actually protective from dying from malaria. So you are seeing this constant flow over thousands of years of thalassemia staying in the gene pool because of the fact that malaria is such a threat in Southeast Asia. And we saw that, not just at the site 4,000 years ago, but also in the bones of hunter gatherers 7,000 years ago. So, malaria has been a problem for humans well before agriculture in this part of the world and completely undermines this beautiful tied up story that we’ve been teaching for the last 60 odd years.
The same story with thalassemia is happening in Africa with sickle cell disease. So if you have sickle cell disease in its most severe form, obviously that’s also horrific, but in its mild form, it also is protective against malaria. So, the problem with evolution is that it isn’t a process in which to keep you healthy. We don’t respond evolutionarily to infectious diseases to stay healthy, it is to pass on our genes. And it seems to also be the case with some of these really horrible genetic conditions that we’re dealing with today.
The thing about thalassemia is exactly that there are areas where we’ve eliminated malaria, but that gene is still causing issues. And thalassemia, especially if you have the severe forms, requires constant blood transfusions, requires constant what’s called iron chelation therapy. So that’s where they remove the iron from your blood. So it’s actually an equity issue as well to look at these things from an evolutionary perspective.
Dr Kaylee Byers: You know, I was really hoping that somewhere in this story there was going to be an uplifting piece about how these genes could help us out.
Dr. Melandri Vlok: I mean, there are some genes out there. There, for example, there are some people that are less likely to be infected by mosquitoes, where some populations are less susceptible to getting bitten by mosquitoes than other populations.
Dr Kaylee Byers: I wanted to understand how ancient diseases in the past can help us in the present, especially when we’re dealing with the effects of climate change.
Dr. Melandri Vlok: So the thing about the evolutionary history of some of these diseases that have been around for thousands of years is the fact that they are very particular to certain types of temperatures and humidities, or their vectors are. So malaria’s what’s called a vector disease. So it isn’t passed directly from human to human, it’s passed via a vector, and that’s the mosquito. So then the mosquito habitats are really important for understanding the distribution of malaria.
With climate change, unfortunately, especially in the last five years, the literature is really showing that these mosquitoes are now appearing in areas where they weren’t before because of global warming. They’re creeping further north. So where these two sites were in northern Vietnam, where I studied malaria, doesn’t exist anymore and it’s because the Anopheles mosquito habitats aren’t there. But 4, 000 years ago they were, because the climate was still wetter and warmer, and so the forested habitats, that tropical habitat, was further north.
So we also can get a bit of a caution from what we’re seeing in the archeological record, which is, oh, hey, this was here in this region in the past at this temperature and humidity, that’s potentially what we’re dealing with when we’re going through climate change now. And that’s why we look at these things through, over thousands of years, even though as slow as they were, they had dramatic effects on people’s health and people’s lifestyles. When we are looking at the things in the past, we’re not simulating future climate change, we’re just simulating the potential effects that these fluctuations can have. But the problem that we have is that we’ve caused it at such a fast rate.
And then on top of that, we’ve also got consequences like new diseases emerging that we haven’t seen before. So Coronavirus is a perfect example of what we’re setting ourselves up for and it won’t be the last pandemic that we see. We will see an intensity in frequency and duration of pandemics because of climate change, but we can at least look at the past and we can try and understand, okay, how did people mitigate these issues? Because they didn’t have a World Health Organization back then, and governments, and advanced medical treatment, they were being affected naturally, and we can look at that. And so it gives us a bit of an understanding of what happens if we don’t do something about this.
Dr Kaylee Byers: Melting permafrost, a Pandora’s box of microbes, human genes that can’t adapt fast enough, mosquitoes transferring pathogens from the air, yikes! It’s a lot. So, if I can muster my global experts here, what do they say is the way forward? How do you think we should deal with these compounding issues of these unknown diseases and then tracking them?
Dr. Melandri Vlok: I’ve been thinking about this a lot. My career is built on this question, right? How can we actually deal with this situation? Yeah, part of it is learning from the past. Also, part of it also involves listening to communities where these things have been around for thousands of years. Indigenous knowledge is very powerful.
Dr. Brigitta Evengard: They have lived through periods where it’s been warmer and colder. We need to learn more from people with local knowledge and then we cannot lose hope. I mean, we all have to try to do our best.
Dr. Melandri Vlok: Sometimes we can feel really lost in it all, especially when there are governments that are the ones that make decisions, and there’s so much that’s out of our hands, that we can feel as just people like, okay, but what can we actually do about this? And we can at least, I guess, like I said, prepare our communities for action.
You know, when you’ve got communities looking out for each other, you’ve got sustainable communities within which you can build environmental responses to. And all these things mean that we have a much better ability to then put our brains to work to deal with this problem.
Dr. Will Hsiao: But to really address this problem. That’s the main reason we think data sharing and the ability to harmonize datas around the globe. So being able to bring large data sets together that consists of both host genomics, viral genomics, and also clinical outcomes or even population level outcome would help us solve this problem. So that’s why to me, the biggest task is to really bring together social science experts and biological experts to really work together.
Dr. Brigitta Evengard: And then as scientists we’ll have to go out there and speak up and say our things and take responsibility, even if it’s just a small thing, you do it.
Dr. Melandri Vlok: It’s not just an environment issue, it’s a social issue, and those two things need to be put together, and that goes beyond just infectious diseases. Infectious diseases is just one of the effects. There are so many avenues that we can take to actually deal with this issue. We just have to actually sit and listen and talk to each other and coming up with a plan of action before any of this is necessary.
Having these really strong connections that humans also have had for thousands of years with each other in a community, rebuilding relationships that were broken down, those kind of things actually do have an environmental impact.
Dr Kaylee Byers: What became clear to me in conversations with all of our guests today is that preparing ourselves for diseases and being proactive means that we need each other. From genomic data sharing that Dr. Hsiao mentioned, to listening to local communities living on the front lines of these areas that Dr. Vlok and Dr. Evengard spoke about, across the globe, together, with mutual respect, we can overcome these challenges and create a more sustainable and healthier planet for all of us. But we really need to reach out and come together on this.
Dr. Melandri Vlok: Right now, I’m at the airport in Bangkok.
Dr Kaylee Byers: I know this because that collaboration is already taking place.
Dr. Melandri Vlok: And I’m on my way to a conference that is the largest conference in the whole Indo-Pacific region for archeology. Between that is where collaborations happen, where the sparks happen, where we get these bright ideas because of the different kinds of research that’s happening around the region. I can’t wait to get onto the plane to Chiang Mai in order to do so.
Dr Kaylee Byers: My guests for today have been Dr. Brigitta Evengard, professor at the Department of Clinical Microbiology at Umea University, Dr. Jean- Michel Claverie, professor of genomics and bioinformatics at the School of Medicine at Aix- Marseille University, and Dr. Melandri Vlok, bioarcheologist, post-doctoral research associate at the Sydney Southeast Asia Center and a National Geographic Explorer. Special thanks to Dr. Mike Trimble and Dr. Will Hsiao from Simon Fraser University for letting me pop into the lab and begin this journey.
You’ve been listening to Nice Genes!, a podcast brought to you by Genome British Columbia. If you like this episode, go back and check out some of our previous ones wherever you listen from. Share us with your friends and leave us a review. You can also DM the show on Twitter by going to @GenomeBC. And we also have Learn-A-Long Sheets added to the show description.
Join us next time for part two of our climate change segment where we ask, can we repair the damage that’s already been done to the environment?
Can we solve climate change? What do you think?
Dr. Aria Hahn: I hope so. I mean, yes, I think we can. Will we is a different question. But I think we can.
Dr Kaylee Byers: Thanks for listening and I’ll catch you next time.
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