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Transcript
0:00 · So, the Black Death.
0:01 · Pretty exclusively a "back then" thing, right?
0:04 · But if you’re descended from the European, Middle Eastern,
0:06 · and North African populations that experienced the plague, and you’re dealing with
0:10 · an autoimmune disease, for you it could be a "right now" kind of thing.
0:15 · That’s because evidence is emerging that gene variants that were beneficial
0:18 · as one of history’s worst plagues was killing off millions…
0:21 · well, those variants aren’t so hot now.
0:24 · So here’s how the Black Death and other plagues wrote themselves
0:27 · into our genes and why that turned out to be such a double-edged sword.
0:31 · [♪ INTRO]
0:35 · So let’s start with a brief history lesson.
0:37 · History’s most notable outbreak of bubonic plague, aka the Black Death,
0:41 · happened in Europe in the fourteenth century.
0:43 · It’s thought that a ship arrived in Sicily with rats already infected
0:47 · with the causative agent of the plague, Yersinia pestis,
0:50 · and the rats quickly spread the disease all across Europe.
0:53 · Victims often died within a week, and the death toll
0:56 · quickly rose to over 25 million people.
0:59 · In a 2022 article from the journal Nature, an international team of researchers
1:03 · hypothesized that, with a death toll that high, this likely acted as a gigantic
1:08 · natural selection event, where the survivors likely had some
1:11 · genetic advantage over those who died.
1:13 · And to investigate this they did what
1:15 · any good research team would: they went grave robbing.
1:18 · Or more appropriately, grave sampling.
1:20 · Working with museums who had access to a handful of cemeteries,
1:24 · the researchers were able to get DNA samples from
1:26 · several hundred people who died before, during, or after the plague.
1:30 · Notably, however, these gravesites were from London and Denmark,
1:33 · so even though the Black Death ravaged the Middle East and North Africa as well,
1:38 · this study focused only on Europeans.
1:40 · Their goal was to see if there were specific gene variants
1:43 · that were more common in the surviving population
1:45 · than in the pre-plague population.
1:47 · To find those "plague please spare me" varieties.
1:50 · As a quick refresher, many genes come in multiple flavors
1:53 · that can have slightly different effects.
1:55 · The same gene might come in regular, diet, or cherry vanilla.
1:58 · And we call those variants or alleles of that gene.
2:02 · Of all 20,000-ish genes in the human genome,
2:05 · the researchers focused on a pool of about four hundred immune-related genes.
2:09 · Which, admittedly, is still a lot of genes.
2:11 · But now they could analyze these few hundred genes to find ones
2:15 · whose frequency changed significantly pre to post plague,
2:18 · and specifically ones that became more common,
2:21 · since that would mean they had some protective effect.
2:24 · All of this narrowing down left them with four sections of DNA
2:27 · that likely helped the survivors, well, survive.
2:30 · And one gene in particular sparked their curiosity.
2:33 · They identified two versions of a gene called ERAP2,
2:37 · one that seemed to end up expressing a lot more of that gene’s product
2:40 · (and so presumably doing more work) than the other.
2:43 · And when the team dug a little deeper, they did indeed find that
2:46 · these two flavors of ERAP had a difference in how they functioned.
2:50 · One variant produced an A type of ERAP2,
2:53 · which coded for full length, healthy proteins.
2:55 · The other was associated with a B type of ERAP2,
2:58 · which produced protein products that cut off too soon,
3:01 · causing the cell to degrade them.
3:03 · So rest in pieces, ERAP2 type B proteins.
3:06 · Research has already shown that ERAP2 is important for helping to train other
3:10 · immune cells, clearing pathogens, and modulating inflammatory responses.
3:14 · Knowing that, the researchers hypothesize that the type A variant
3:18 · leads to more ERAP2 protein, and thus better immune training.
3:22 · Essentially, the variant would have helped the immune system
3:24 · more efficiently identify plague bacteria while also limiting inflammation.
3:29 · The scientists estimate that people who had two copies
3:32 · of the type A variant were 40% more likely to survive the plague.
3:36 · That’s a pretty huge advantage considering
3:38 · how it wiped out nearly half of Europeans.
3:41 · But while this might sound like a win for all of humanity, that’s not the full story,
3:45 · because that same protective version of ERAP2
3:48 · has also been associated with something else: Crohn’s disease.
3:52 · We don’t know exactly how it’s involved,
3:54 · but it might be that immune training function going a bit too paranoid.
3:58 · And when you back up to that bracket of four variants
4:01 · the researchers had originally identified as protective against the plague,
4:05 · a different one is associated with autoimmune diseases
4:08 · like lupus and rheumatoid arthritis.
4:10 · So our genetic superheroes are suddenly looking more like double agents.
4:14 · The vigilant immune variants that kept the plague bacterium in check
4:17 · are a little too trigger-happy and turning on our own bodies.
4:21 · And this isn’t unique to the genes identified in this study.
4:24 · It’s a well documented phenomenon known as antagonistic pleiotropy.
4:28 · Pleiotropy means that a gene has more than a single effect,
4:31 · and the word "antagonistic" highlights how these effects
4:34 · may be at odds with each other.
4:35 · So the ERAP2 type A variant would be an example of antagonistic pleiotropy:
4:40 · it may spare you from the plague,
4:42 · only to harm your descendants with an autoimmune disease.
4:45 · A study done in 2023 sought to discover how much
4:48 · antagonistic pleiotropy has affected us.
4:50 · They surmised that this double-edged sword may be more common
4:53 · than previously thought, creating an evolutionary tradeoff between
4:57 · infectious disease protection on the one hand, and autoimmunity on the other.
5:01 · And they did this by looking at 10,000 years of genomic data.
5:05 · When examining all this data, a trend appeared: the more fit our genes became in
5:10 · protecting us against infectious diseases,
5:12 · the more vulnerable we became to autoimmune diseases.
5:15 · They could even identify specific variants, such as one that increases the risk of
5:20 · inflammatory bowel disease or IBD while decreasing the risk of infection
5:24 · with noroviruses, or a separate one that is associated with protection
5:28 · against COVID-19 instead while also increasing the risk of IBD.
5:33 · And the researchers don’t think this is a coincidence.
5:35 · They tried to pinpoint when selective pressures started favoring
5:38 · these genetic variants, and they found that most of these changes have occurred
5:42 · since the start of the Bronze Age, around 4500 years ago depending on the region.
5:47 · This was a time when people were coming together to live in cities,
5:50 · traveling more, and raising more livestock.
5:52 · All of this would have exposed people to more pathogens,
5:55 · which led to selection for these infectious disease-protective traits,
5:59 · that just so happen to increase vulnerability to chronic diseases.
6:02 · Plus, this link does make sense.
6:04 · When faced with infectious diseases, we might want a strong immune response,
6:09 · something that ERAP2 helps with in various
6:11 · immune cells when exposed to the Black Death.
6:13 · But when that immune response gets too strong,
6:16 · it can end up harming us, like with Crohn’s disease.
6:18 · Which means a very, very long history of disease
6:21 · and survival is written into our DNA.
6:24 · It’s a curious balancing act, and it shows that
6:26 · the difference between a beneficial and a harmful trait is razor-thin.
6:30 · But it also shows us that we can keep surviving,
6:33 · and adapting to whatever comes next.
6:35 · Now 14th century victims of the plague would definitely have benefited
6:39 · from knowing more about subjects like bacteria… or basic hygeine.
6:43 · But at least you can learn more about them thanks to our spinoff podcast,
6:47 · SciShow Tangents, which has episodes about both of those things.
6:50 · Tangents is a lighthearted, lightly competitive podcast made by the same minds
6:54 · as those behind SciShow, and 100% of episodes
6:58 · are guaranteed to contain at least one fact about butts.
7:01 · If that sounds good to you, you can check out
7:02 · Scishow Tangents wherever you get our podcasts.
7:05 · [♪ OUTRO]

Blame China. That’s where it came from.

Conjecture of science, this is a maybe. Imagine dating current day health problems all the way back to the middle ages.

An implication of the strict version of the hypothesis, linked to the Black Death specifically, would be that autoimmune diseases would be less common in populations untouched by the Black Death. Does anyone know if that is true?

Better immune systems... It’s in the genes.

My 78 year old sister living in a nursing home and her 100 year old roommate both got Covid about a month ago... They tried to give her roommate oxygen and that poor old lady told them to go f*ck themselves. They’re both on DNR’s so neither of them received any serious treatment.

It’s been 5 weeks since then and neither of them suffered any ill effects from having Covid.

If they did receive treatment the first thing they would’ve done is intubate them... After that it’s pretty much over. If you get intubated you typically end up getting hospital acquired pneumonia and you’ll either survive that or die from that.

Pretty much everybody who gets intubated for more than a few days gets hospital acquired pneumonia. My brother was in an ICU for 21 days back in the 1990s with complications due to type 1 diabetes and got pneumonia twice... Luckily, he was young and healthy. Old people do terrible after being intubated.

Should we make sure not to wonder if vaccines cause autoimmune disease?

Transcript
0:00	·	So, the Black Death.
0:01	·	Pretty exclusively a "back then" thing, right?
0:04	·	But if you’re descended from the European, Middle Eastern,
0:06	·	and North African populations that experienced the plague, and you’re dealing with
0:10	·	an autoimmune disease, for you it could be a "right now" kind of thing.
0:15	·	That’s because evidence is emerging that gene variants that were beneficial
0:18	·	as one of history’s worst plagues was killing off millions…
0:21	·	well, those variants aren’t so hot now.
0:24	·	So here’s how the Black Death and other plagues wrote themselves
0:27	·	into our genes and why that turned out to be such a double-edged sword.
0:31	·	[♪ INTRO]
0:35	·	So let’s start with a brief history lesson.
0:37	·	History’s most notable outbreak of bubonic plague, aka the Black Death,
0:41	·	happened in Europe in the fourteenth century.
0:43	·	It’s thought that a ship arrived in Sicily with rats already infected
0:47	·	with the causative agent of the plague, Yersinia pestis,
0:50	·	and the rats quickly spread the disease all across Europe.
0:53	·	Victims often died within a week, and the death toll
0:56	·	quickly rose to over 25 million people.
0:59	·	In a 2022 article from the journal Nature, an international team of researchers
1:03	·	hypothesized that, with a death toll that high, this likely acted as a gigantic
1:08	·	natural selection event, where the survivors likely had some
1:11	·	genetic advantage over those who died.
1:13	·	And to investigate this they did what
1:15	·	any good research team would: they went grave robbing.
1:18	·	Or more appropriately, grave sampling.
1:20	·	Working with museums who had access to a handful of cemeteries,
1:24	·	the researchers were able to get DNA samples from
1:26	·	several hundred people who died before, during, or after the plague.
1:30	·	Notably, however, these gravesites were from London and Denmark,
1:33	·	so even though the Black Death ravaged the Middle East and North Africa as well,
1:38	·	this study focused only on Europeans.
1:40	·	Their goal was to see if there were specific gene variants
1:43	·	that were more common in the surviving population
1:45	·	than in the pre-plague population.
1:47	·	To find those "plague please spare me" varieties.
1:50	·	As a quick refresher, many genes come in multiple flavors
1:53	·	that can have slightly different effects.
1:55	·	The same gene might come in regular, diet, or cherry vanilla.
1:58	·	And we call those variants or alleles of that gene.
2:02	·	Of all 20,000-ish genes in the human genome,
2:05	·	the researchers focused on a pool of about four hundred immune-related genes.
2:09	·	Which, admittedly, is still a lot of genes.
2:11	·	But now they could analyze these few hundred genes to find ones
2:15	·	whose frequency changed significantly pre to post plague,
2:18	·	and specifically ones that became more common,
2:21	·	since that would mean they had some protective effect.
2:24	·	All of this narrowing down left them with four sections of DNA
2:27	·	that likely helped the survivors, well, survive.
2:30	·	And one gene in particular sparked their curiosity.
2:33	·	They identified two versions of a gene called ERAP2,
2:37	·	one that seemed to end up expressing a lot more of that gene’s product
2:40	·	(and so presumably doing more work) than the other.
2:43	·	And when the team dug a little deeper, they did indeed find that
2:46	·	these two flavors of ERAP had a difference in how they functioned.
2:50	·	One variant produced an A type of ERAP2,
2:53	·	which coded for full length, healthy proteins.
2:55	·	The other was associated with a B type of ERAP2,
2:58	·	which produced protein products that cut off too soon,
3:01	·	causing the cell to degrade them.
3:03	·	So rest in pieces, ERAP2 type B proteins.
3:06	·	Research has already shown that ERAP2 is important for helping to train other
3:10	·	immune cells, clearing pathogens, and modulating inflammatory responses.
3:14	·	Knowing that, the researchers hypothesize that the type A variant
3:18	·	leads to more ERAP2 protein, and thus better immune training.
3:22	·	Essentially, the variant would have helped the immune system
3:24	·	more efficiently identify plague bacteria while also limiting inflammation.
3:29	·	The scientists estimate that people who had two copies
3:32	·	of the type A variant were 40% more likely to survive the plague.
3:36	·	That’s a pretty huge advantage considering
3:38	·	how it wiped out nearly half of Europeans.
3:41	·	But while this might sound like a win for all of humanity, that’s not the full story,
3:45	·	because that same protective version of ERAP2
3:48	·	has also been associated with something else: Crohn’s disease.
3:52	·	We don’t know exactly how it’s involved,
3:54	·	but it might be that immune training function going a bit too paranoid.
3:58	·	And when you back up to that bracket of four variants
4:01	·	the researchers had originally identified as protective against the plague,
4:05	·	a different one is associated with autoimmune diseases
4:08	·	like lupus and rheumatoid arthritis.
4:10	·	So our genetic superheroes are suddenly looking more like double agents.
4:14	·	The vigilant immune variants that kept the plague bacterium in check
4:17	·	are a little too trigger-happy and turning on our own bodies.
4:21	·	And this isn’t unique to the genes identified in this study.
4:24	·	It’s a well documented phenomenon known as antagonistic pleiotropy.
4:28	·	Pleiotropy means that a gene has more than a single effect,
4:31	·	and the word "antagonistic" highlights how these effects
4:34	·	may be at odds with each other.
4:35	·	So the ERAP2 type A variant would be an example of antagonistic pleiotropy:
4:40	·	it may spare you from the plague,
4:42	·	only to harm your descendants with an autoimmune disease.
4:45	·	A study done in 2023 sought to discover how much
4:48	·	antagonistic pleiotropy has affected us.
4:50	·	They surmised that this double-edged sword may be more common
4:53	·	than previously thought, creating an evolutionary tradeoff between
4:57	·	infectious disease protection on the one hand, and autoimmunity on the other.
5:01	·	And they did this by looking at 10,000 years of genomic data.
5:05	·	When examining all this data, a trend appeared: the more fit our genes became in
5:10	·	protecting us against infectious diseases,
5:12	·	the more vulnerable we became to autoimmune diseases.
5:15	·	They could even identify specific variants, such as one that increases the risk of
5:20	·	inflammatory bowel disease or IBD while decreasing the risk of infection
5:24	·	with noroviruses, or a separate one that is associated with protection
5:28	·	against COVID-19 instead while also increasing the risk of IBD.
5:33	·	And the researchers don’t think this is a coincidence.
5:35	·	They tried to pinpoint when selective pressures started favoring
5:38	·	these genetic variants, and they found that most of these changes have occurred
5:42	·	since the start of the Bronze Age, around 4500 years ago depending on the region.
5:47	·	This was a time when people were coming together to live in cities,
5:50	·	traveling more, and raising more livestock.
5:52	·	All of this would have exposed people to more pathogens,
5:55	·	which led to selection for these infectious disease-protective traits,
5:59	·	that just so happen to increase vulnerability to chronic diseases.
6:02	·	Plus, this link does make sense.
6:04	·	When faced with infectious diseases, we might want a strong immune response,
6:09	·	something that ERAP2 helps with in various
6:11	·	immune cells when exposed to the Black Death.
6:13	·	But when that immune response gets too strong,
6:16	·	it can end up harming us, like with Crohn’s disease.
6:18	·	Which means a very, very long history of disease
6:21	·	and survival is written into our DNA.
6:24	·	It’s a curious balancing act, and it shows that
6:26	·	the difference between a beneficial and a harmful trait is razor-thin.
6:30	·	But it also shows us that we can keep surviving,
6:33	·	and adapting to whatever comes next.
6:35	·	Now 14th century victims of the plague would definitely have benefited
6:39	·	from knowing more about subjects like bacteria… or basic hygeine.
6:43	·	But at least you can learn more about them thanks to our spinoff podcast,
6:47	·	SciShow Tangents, which has episodes about both of those things.
6:50	·	Tangents is a lighthearted, lightly competitive podcast made by the same minds
6:54	·	as those behind SciShow, and 100% of episodes
6:58	·	are guaranteed to contain at least one fact about butts.
7:01	·	If that sounds good to you, you can check out
7:02	·	Scishow Tangents wherever you get our podcasts.
7:05	·	[♪ OUTRO]