Posted on 11/15/2023 7:12:19 AM PST by SunkenCiv
The bubonic plague killed so many people in Europe, the Middle East, and North Africa that that natural selection event is still rippling through our genomes today. But the same genes that helped your ancestors survive the Black Death may be contributing to autoimmune disease today.
Have an Autoimmune Disease? Blame the Black Death | 7:16
SciShow | 7.77M subscribers | 572,860 views | November 7, 2023
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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.
I blame all vaxxes.
10 years ago I would have said that’s crazy talk.....now not so much.
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?
I saw a TV doc on The Plague that had a very interesting conclusion - people who do not contract the AIDS virus - even after having been knowingly exposed to it, often repeatedly, and seem to have a natural immunity from it - are descendants of those who survived The Plague.
Apparently those who don’t contract AIDS have the same kind of anti-bodies that fended off the plague in their ancestors.
Plague usually is talked of as starting in 1348. That’s when it hit England and got recorded. It was earlier elsewhere. Arab data suggests 10 yrs earlier in central Asia. Chinese records show origins in Mongolia. There is no confidence about where it started, but no one suggests China. It almost wiped out China.
The critical records of Plague are from Oxen Ford (now Oxford) in England. The church records would record deaths increasing from 5 a week to 10 a week to 20 a week and then suddenly a jump to 100s per week. This is clearly bubonic forms killing people by sepsis until one particular strong individual hung on long enough for it to reach his or her lungs. Then a single cough could infect 50 in a hall/dorm at some hospital. Yes, hospitals, so docs did not have to walk house to house. They had no idea about carrying infections house to house in those days.
Entire villages were wiped out. Records just stopped being kept. They were all dead.
Governments were wiped out, particularly in China.
In years to follow, the Plague deathcount kept increasing because the farmers had died. The were around hay and crops and so were the rats. There was no food.
If you look at a long term chart of human population there is only one place on the curves where there was a period of decline. Not for wars. Not for famines. The plague years. Human population actually shows a recorded decline — and note that happened even with total exclusion of the human civilizations in Central and South America.
Europe’s population was flat for decades. It could not grow. No food. Only when Columbus in 1492 brought back potatos to Europe did the food supply grow sharply and fund population gain.
That was 150 years of stagnation.
There are a few topics about that very thing in the short list of links above. :^)
I think I just read my first podcast lol
I would like a second opinion on the conclusions
The main consequences of the Plague in Europe was the disintegration of the feudal system, interest in the scientific method, the Renaissance, the Reformation, the rise of banking and capitalism, and the Age of Sail with European expansion across the Earth and worldwide trade.
The Plague hit a number of times, going back thousands of years, so it's likely to have had impacts on prehistoric societies as well, we just don't know what those impacts were.
My ancestors survived the plague.
Multiple times.
Survived the Spanish Flu.
Modern lifestyles, modern medicine...not so much.
Four keywords related to Crohn's, sorted, duplicates out:
Forgot the plurals:
Apparently those who don’t contract AIDS have the same kind of anti-bodies that fended off the plague in their ancestors.
Not quite. People do not naturally have antibodies against any disease until they have been exposed to it (or a vaccine against it) and their immune system has responded.
When people are exposed to a virus such as AIDS, the virus gets inside cells using cell surface receptor proteins located on those cells. If a person has a mutant cell surface receptor protein, the virus cannot enter or has a hard time entering the cell. They are resistant to AIDS, not immune to it.
The plague was caused by bacteria called Yersinia pestis. The mechanism of infection is different. Most bacteria do not enter cells. The mutation in the receptor that makes people resistant to HIV also changes how the immune system functions. This is hypothesized to help people survive the plague.
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.
I’ve seen a video on this and they say “yes”. Interesting issue.
Evolution has consequences. Who woulda thunk that?
Thank you for another series of interesting links here in Comment #9 and also in comments #15 and #16.
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