Secrets of the Great Plague

come SARS bird flu the Ebola virus aids throughout history infectious disease has been the number one killer on the planet and today the threat is as great as ever there may not be a vaccine capable of fully immunizing our citizens from the new influenza virus during the first several months of the pandemic but as scientists and world leaders brace for the next disaster some experts are looking for help in the most unlikely place the past this is the story of how an ancient killer might just save your life in the winter of 1665 the Great Plague swept through London killing a third of its population defect of the plague was as devastating as a biological weapons attack would be on a modern city and yet out of the devastation came survivors super survivors men and women mysteriously resistant to this deadly disease why did they survive why didn't everybody die now through a series of groundbreaking experiments and archaeological discoveries one man is hoping to find the answer the descendants of the super survivors still walk among us they would have maybe 15 or 20 doctors just literally staring at me and scratching their heads everyone I knew was sick and I wasn't sick does the Great Plague hold the key to surviving today's infectious diseases and can our own bodies teach us how to outsmart nature's most vicious killers Stephen O'Brien is a medical detective his work is part of a global struggle to find new ways of fighting infectious diseases diseases that have the potential to sweep through our communities and kill millions but dr. O'Brien doesn't just have a professional stake in this fight for him it's personal aids killed his brother in 1994 losing a brother to AIDS is clearly focused my concentration in seeing people struggling and reaching for hope it sort of crystallizes your resolve to get to the end of the study and not worry about the details or the the vagaries and the niceties of the process he's come to believe that the key to saving other lives to countering the diseases that threaten the soul may lie within our own DNA we might be able to discover natural hardwired defenses that scientists couldn't have thought of but which nature did he believes that the place to look is among the survivors among people who have witnessed death and suffering on a scale we can barely imagine who came into contact with deadly infection and lived did they manage to pass on their immunity to their descendants O'Brien's quest will take him across continents and centuries because to truly unlock the mysteries of today's killer diseases he will need to come face-to-face with some of the most misunderstood and terrifying moments in human history I can't think of an epidemic quite so devastating that we know about in history until you reach back to the great plague December 1660 for London England a city that didn't realize it was on the verge of disaster in southwark a clergyman named John Allen traveled to the home of the Phillips family Mary Phillips had suddenly been taken ill she had a fever she was delirious Allen was a physician as well as a priest and one specific symptom made him very afraid on her neck was a huge dark boil a Bubo it was the calling card of the disease that would surely take Mary Phillips his life and it's the line for the arendelle now Allen stayed with Mary Phillips threw her excruciatingly final hours later he wrote about what he saw in a letter to his brother in this fetid grimy City this poor soul departed this life in the greatest agony she tossed and turned this way and that shouting for her deliverance at four of the morn the pestilence burst forth from the boils destroying her at once Allen prayed for her soul for the people of the city and for himself because the plague had returned to London but they had no idea what caused it to them plague was a disease of bad air what they called a miasma a mysterious illness creating substance that spread through the atmosphere it was a complete mystery to them and yet its effects had been documented time and time again this is why Allen was terrified three centuries earlier the plague known as the Black Death first swept through Europe leaving as many as 30 million dead then it kept returning there were waves of plague that ravaged Europe almost every generation up until the Great Plague of the 17th century each time the symptoms were the same fever the mysterious black inflammations and death often in a matter of days by the mid 1600s London was once again under attack in the winter of 1660 for in a spring of 1665 London was a disaster waiting to happen it's one of the largest cities in Europe probably four hundred thousand people there is a teeming mixture of all sorts of people from the very very wealthy the aristocrats the court down to the marginal figures the beggars the vagabonds the water men transporting people over London all of the waste disposal from those four hundred thousand people goes into the River Thames most of the water that that community drinks comes out of the River Thames you can imagine the sort of cycles of infection and disease that are there as endemic all the time throughout the following year Alain documented death on an extraordinary scale Bills of mortality weekly records of the dead were nailed up in public places in an average week one might be expected to bury perhaps three to five people in an average week in the plague period you would be expected perhaps to bury 200-300 in some of the suburban parishes perhaps even 800 people a week now that that's a lot of dead bodies this is a devastating effect upon the City of London as a biological weapon would be released in the center of New York between April and December about a hundred thousand people were recorded as dying from plague and those are just the people who are actually accounted for the true figures probably nearly half as much gain the city authorities did what they could under a form of martial law they began to enforce a brutal and basic quarantine if you're identified with the disease the entire household is shut up everybody who is in there when the watchman turns up with his padlock and attaches it to the front door is locked in there together the sick and the healthy are in the same space this was an act of desperation it meant that some healthy people who wanted to get away couldn't as a result entire households were wiped out and yet in the midst of it all there was a mystery the plague killed many people but it didn't kill them all some people emerged unscathed despite living side by side with the dying and the dead in their survival Stephen O'Brien sees an extraordinary opportunity but why did they survive why didn't everybody die why is that the 2/3 of the people in London survived to stop an infection spreading you have to understand how it spreads the 17th century physician John Allen saw hundreds of cases his unflinching descriptions of what he witnessed provide vital clues for modern science during the Great Plague there were chroniclers of the infections that were describing it in some detail medical characteristics of the epidemic and in many ways today scientists are really standing on the shoulders of these early observers these medical giants if you will the raging thirst the fever the delirium most of all the agonizing black swellings accounts of these symptoms allow modern-day scientists to identify this disease the bubonic plague it is a disease that is caused by a bacterium called Yersinia pestis that was discovered really in the late 19th century the bacteria followed a complicated path they are initially carried by infected rats a flea bites a rat and picks up the bacteria the flee then infects a human being once under the victims skin the plague bacteria moved quickly to the lymph glands the bacteria multiply and cause the glands to swell they spread through the lymph system eventually reaching the heart at this point they enter the bloodstream and are spread around the entire body at the same time the swollen lymph glands begin to break down they become inflamed cells die bloody debris is released small clots form break away and travel through adjacent blood vessels eventually they get stuck in smaller vessels this can block the blood supply to fingers and toes turning the skin black gangrene sets in as the extremity start to rot meanwhile more lymph glands begin to swell and burst as infected blood travels around the body the victim develops a high fever becomes delirious though he is in terrible pain he starts to lose consciousness vital organs shut down and the patient dies but the plague wants to continue it wants to multiply so before the victim dies the bacteria has another trick up its sleeve it finds a way to leap from human to human once bubonic plague became established in a very close community a number of cases would develop pneumonia and cough up the organisms and subsequent cases would pick that up as pneumonic plague in other words plague in the lungs now one person can affect another and the mortality of pneumonic plague is greater than 90% its effect upon a population would be devastating when you Manik plague strikes a population statistics indicate that it should kill nine out of every ten people it infects the death toll in London in 1665 was massive it reached 150,000 1/3 of the population but it should have been much more you would expect the disease to go on and on and on and devour that community but it doesn't this is the real enduring mystery of the Great Plague how so many people came into contact with the most deadly bacteria known had no access to medicine and still survived scientists who are today on the frontline against infection would dearly love an answer but for years the question was brushed aside the theory was simply that the outbreak had largely confined itself to London's underclass one of the great sort of arguments about who died and when they died is that it's the poor that die and the arguments fairly straightforward the poor live in the most marginal and filthy of circumstances plague is a disease that's created by dirt and rats and fleas therefore it's the poor that's I this was an easy answer and it was widely accepted the poor lived in cramped squalor their living conditions brought the plague upon them people higher up the social scale was shielded but was survival really just a matter of Klaus a chance discovery in modern-day London put this convenient theory on trial in the heart of the city workers digging on the site of an old church have uncovered fifty-seven skeletons they have been perfectly preserved by deep heavy clay these bodies have been dated to the time of the Great Plague they challenge the accepted belief that people escape the plague because they were wealthier each of the bodies has been subjected to rigorous forensic examination to determine cause of death age and social status were these victims rich and did they in fact die of bubonic plague this individual is a female probably mid 30s to early 40s there is no sign of actual pathological disease on the skeleton so up until her the time of death she was relatively healthy the plague would have occurred far too quickly to actually make any visible sign on the skeleton evidence suggests that whatever killed these individuals was too Swift to leave marks it wasn't violence or prolonged illness it took people of all ages the clues point a plague but were these victims also members of London's underclass a biological anthropologist can tell a lot about a person's social status from their bones a tough life will leave its mark the examiners look for signs of deprivation the effects of hard work and the kind of diseases associated with poverty during that time period it is possible to see diseases such as tuberculosis or syphilis there's no indication of that on on the skeleton at all other diseases that might be indicative of working-class individuals is arthritis which is not indicated on this particular scale again it's the lack of marks there are none of the signs you expect to see on the bones of someone who lived in poverty and there's an even more compelling piece of evidence the burial itself if these were poor plague victims they would most likely have been buried in mass graves this person are based on where they were buried within the church was not a poor individual they were buried within the church in an individual grave and that didn't occur among the poorer classes they couldn't afford to do that so this was certainly somebody that had some kind of social status at that time this woman seems to have been from the upper classes it's the same with the other skeletons their discovery and others like it appear to call into question the argument that well for a high quality of life was any real protection against the bubonic plague that argument that the poor are the the greatest and really the only casualties of the plague epidemics I think has shown to be flawed I think every time an epidemic begins people who watch it hope that it's going to be limited to a few individual with time I think all these diseases begin to show that they do not respect class they do not respect social status they do not respect ethnicity they do not respect age they simply spread whenever they get a chance if social class is not the answer then what makes the difference between a victim and someone who survives and can solving this puzzle shed new light on today's deadliest threats why is that the 2/3 the people in London have survived and 2/3 of the people in Europe survived when people get infected with something like HIV 95% of them die within 10 or 15 years more than 3 centuries apart dr. Stephen O'Brien and the clergyman physician John Allen share the same goal they both want to understand why some people seem to be shielded from infectious disease and they both want to find a way to harness that natural power to save others throughout the time of the Great Plague Allen labored to produce a cure an elixir or medicine that would ward off the sickness at one point he genuinely believed he had found an answer a potion based on a secret recipe Jan Allen's elixir was an attempt to use a natural product in order to treat a disease and this kind of exercise even continues today I call it our importable a this medicine will cure the world of plague and many other diseases besides what it appears to be some sort of distillation of a herb or a fungus run through gold or some base metal that he's created he isn't an eccentric he's at the cutting edge if you like of modern contemporary science whether it works who knows for Allen the possibility is there I myself have taken to drinking a vial of my elixir to ward off the evils of the pestilence it has thanks be to God preserved me from the grave pioneers of medicine were simply tinkering around and trying to think of better ways to develop treatments or elixirs if you will modern commentators and scientists have tended to write off the work of men like Alan as amateurish or superstitious but is it possible that he was right is the medicine of the time somehow more effective than we 300 years later are prepared to believe scientists never know what their research is going to provide otherwise they wouldn't have to do it and Alan was not alone hundreds of would be healers proclaimed that they had found the answer they offered their own potions therapies and masks stuffed with spices that would allow the wearer to breathe bad air and emerge unscathed many of these treatments do have their modern equivalents but after years of investigation medical historians agree that most provide little help allons elixir proved incapable of protecting against the ravages of bubonic plague he learned that the hard way on the 15th of June 1665 the play claimed one more of his patients his own brother Peter I'm sure the plague approaches me for it is please God to take from me the best friend I ever had in the world is my brother Peter who is abroad on Lord's Day last in the morning towards the evening a little ill then took something to sweat which night brought a stiffness under his ear where he had a swelling he died Thursday last Stephen O'Brien also lost someone to an infectious disease his brother Danny died from an AIDS related illness he respects Allen's attempts to find an answer I don't sneer at people who are trying to be creative and try and looking for novel solutions but despite the failure of Alan's elixir something had to explain the fact that John Allen himself was exposed to hundreds of victims and never caught the plague one of the remarkable facts about Allen's life is that despite being intimately involved with the dead and the dying he survived unlike many other doctors knew that he knew he went on to live to a ripe old age of 64 he died in in the mid 16 70s so there was something about him and others like him that meant he was resilient or anew Steven O'Brien has come to wonder whether men like Allen did carry the key to combating deadly diseases not in the form of some miraculous potion but within their own bodies did these people carry unbeknownst to them specific genetic endowments that they had been handed down from their ancestors that allowed them to defend a little bit better against that bacteria from that flee from that rat that had bit them and infected them did these people develop natural defenses that they passed on to their generations waiting for the next outbreak to come along science has shown that surviving the plague wasn't about social class or hygiene or medicine but could it have been directly related to genetics of the thousands of genes that survivors like John Allen carried was there one which would confer immunity to certain infections and can Steven O'Brien and his colleagues find it in the early 1980s a medical disaster struck which would radically alter the way researchers looked at infectious diseases aids hit America's cities although our original and first detection of AIDS illnesses was in the community of gay men there was a second population that became infected at around the same time but for very different reasons and these were young boys who were born with the blood disease hemophilia hemophilia is a condition where the blood doesn't clot properly sufferers live under the constant threat of fatal internal bleeding they rely on regular injections of a chemical clotting agent called factor 8 in the 80s this put them at particular risk from HIV because factor 8 was extracted from donated blood crucially anyone unit of factor rate could contain blood products from hundreds of donors if just one of these people had HIV then the entire batch was contaminated the result was the accidental infection of a large proportion of the haemophiliac population the hemophiliacs were carrying a virus that was very deadly killing 90% of the people it infected more deadly if you will than a bullet to the head but again as with the great plague in London some people who should have died survived Bill Jameson is one such survivor he saw firsthand what hiv/aids was doing to the people around him it turned out that the products that we used to actually control our bleeding were actually the products that would turn out to kill most of us like every haemophiliac Jameson was faced with a terrible dilemma take-two factor 8 and risk dying of AIDS oh don't take it and face the possibility of bleeding to death what do you do what do you do I had a wife I had kids i under business I had responsibilities so an order is provide for them I decided to take that risk and continue to use that product Jameson assumed that he would contract HIV and die I would go in they would have maybe 15 or 20 doctors just literally staring at me and scratching their heads trying to figure out this guy took this product everybody else is positive but you're as healthy as an ox and that was the big question the same question intrigued dr. Stephen O'Brien I wondered whether or not there was a difference in certain genes that allowed them to defend and clear the virus more efficiently than the individual who did become infected O'Brien decided that if a gene did exist which gave it scarier resistance to AIDS he was going to find it of the many personal experiences that have influenced my work the loss of my brother who died of AIDS in 1994 was one of the more important ones it does make you work harder if you get up every day and you realize that if today is the day that the advance takes place that's worth discovering every day that you delay it there is more dying there's a thousand people a day who die from hiv/aids even today O'Brien joined the human genome project the global task force working to map out the immensely complex genetic code that makes up a human being Human Genome Project was a international collaboration of many countries and many scientists to unravel the three billion base pairs or letters specifying about 25,000 genes that are present in a generic human being O'Brien soon began what some called a fishing expedition hunting out the one mutated gene in 25,000 which would make the difference and make people like Bill Jamison resistant to AIDS most mutations particularly when they occur inside of genes are not very good for you it's a little bit like taking a hammer to the engine of a mercedes-benz and just whacking something well most of the time you do damage maybe one time in a million you might do some good and make the car run a little bit better it was two days before Thanksgiving in 1997 that I got a call from my treatment center and they said Bill you know we found out why you never became HIV positive I said well okay you know let's let's find out what this big mystery is as it turns out Jamison had inherited a genetic mutation they called it Delta 32 when HIV infects a normal cell it does so by latching on to a protein called a receptor this receptor is the virus's doorway into the cell in Bill Jameson's case the Delta 32 mutation knocks it out there's no receptor and no way for HIV to enter the cell so the chance of infection is blocked after years of searching had O'Brien and his colleagues finally found what they were looking for when we first discovered ccr5 Delta 32 it was a whopper it was basically the equivalent of pulling out a 300-pound Marlin out of the sea on our fishing expedition because it cost complete resistance to HIV in all of the people who carry two copies of it one from each parent they now understood what the mutation was that you inherited it from both parents and that it gave you immunity to HIV but to help non-carriers they wanted to harness the power of Delta 32 that meant understanding everything about it why did some people carry this mutation where did it come from according to the theory of evolution mutations are produced by mistakes in the genetic code if they provide a positive benefit to the carrier they survive into the next generation so Delta 32 must have helped previous generations in some way long before aids arrived on the scene geneticists call it selective pressure something in the environment that favored the people who carry this mutation either reproductively had more babies or in survival there was no evidence of increased fertility amongst Delta 32 carriers so O'Brien knew he was looking for an event in the past that had spared those with the mutation and killed off the rest we were looking for some sort of breathtaking cataclysmic event that basically wiped out millions of people but differentially according to whether or not they carried this gene we thought it probably was an infectious disease of some sort like HIV but we knew it wasn't hiv/aids because that disease has only been around for less than two generations the answer again lies in the DNA if you know how to read the genetic code correctly it will point back to the time in the past when the mutation developed when carriers survived and non carriers didn't the length of an segment around the Delta 32 is a surrogate if you will for time so we examined that variation we estimated the time elapsed since Delta 32 was last strongly favored and that number came up to be 700 years smack in the middle of the 14th century this is a major revelation Delta 32 had a significant impact in the middle of the 14th century the time when bubonic plague the Black Death first began to terrorize the populations of Europe the black death was probably the greatest epidemic in history something of the order of 25 to 30 million Europeans have died O'Brien began to wonder if Delta 32 carriers were better equipped to survive bubonic plague and that was when he connected another part of the puzzle the last major outbreak of bubonic plague in Europe was the Great Plague of 1665 a much higher proportion of people seem to have survived that epidemic than survived earlier outbreaks of the disease is this evidence of the Delta 32 mutation at work it could have been that the survivors of the Black Death passed down genes that protected their descendents from the Great Plague of the 17th century if O'Brien is right Delta 32 doesn't just confer immunity to AIDS it is even more powerful the next step is to try and find a group of people who are directly descended from plague survivors if the theory is correct tests will show that a high number of them are Delta 32 carriers the challenge is tracking these people down in the three centuries since the Great Plague London has changed in measurably because there's a lot of migration in in human populations in and out of London you're going to get other genes coming in and genes going out from the gene flow very few people in today's London can trace their ancestors back as far as the time of the Great Plague and that is a major problem if O'Brien is going to demonstrate the power of Delta 32 he will have to look elsewhere and find a community where people can trace their ancestry right back we're looking for a town which had been succumbed to the disease but which had not really changed much in terms of immigration of people in and out a time capsule if you will of the survivors of the actual event O'Brien found his time capsule here 120 miles north of London deep in the valleys of the English Peak District lies the village of E and three centuries later the mark that the plague left on em is still there the day it came was the 9th of August 1665 to the South Londoners were dying in their thousands but so far eeeem was spared what the villagers didn't know was that a biological time bomb was about to be planted among them a traveling salesman named George Vickers arrived from the capital he had come to sell bales of cloth needing a bed for the night he was welcomed into the home of the Cooper family this single act of charity led to the near destruction of an entire community accounts suggested that Vickers bales of cloth were infested with fleas as he shook out his wares to display them he was bitten for days everything seemed normal vicars went from house to house selling cloth tailoring clothes but on the night of the 2nd of September Mary Cooper heard her house guests screaming Vickers had a fever he was vomiting blood and bleeding from the nose five days later he was dead and he was just the first ten days later Mary Cooper's infant son died the villagers realized what was happening the parish priest called a meeting as more and more people became sick the healthy gathered together they made a decision of tremendous courage in the knowledge that they might be sentencing themselves to death they decided to place the village in quarantine no one would try to run no one would leave or enter until the epidemic had run its course in an incredible gesture of self-sacrifice the population of em sealed off the village in order to stop the plague spreading further so what we have is a very small tightly knit community which remains at a connect community to this day where they were completely able to control people coming in and out of the village for Stephen O'Brien this event also has huge scientific importance while many small towns suffered the plague the story of what em went through has been meticulously recorded not only that but many of the people living there could trace their roots all the way back to the 1665 outbreak for O'Brian's purposes een is perfect when I first learned about him where most of the people that lived there were descended from the survivors directly I became very fascinated with what I perceived as a scientific opportunity O'Brien enlists the help of historian John Clifford the leading expert on the villages unique story now this this is the vanished register of the plague years and if you turn to the right-hand page you see here this pointed finger indicating and here follow us the names a number of the people who died during the plague and the first victim on the 7th of September in 1665 was George Vickers called the play came to aim in the late summer of 1665 lasted for fourteen months and killed something like two hundred and sixty residents out of a population of around about eight hundred every year the descendants of the plague survivors take part in a procession to keep alive the memory of what their ancestors went through Joan plant is one of them I first heard and that we were related when we put together this family tree and traced it back to Margaret Blackwell and who was a famous heroine if you like in the plague Margaret Blackwell's story has become part of Eames folklore she had lost five members of her family when she herself fell ill it is said that one day she staggered from her sickbed entered the kitchen of her home and either out of delirium thinking it was water or out of desperation thinking it would end her life more quickly she drank a jug of hot bacon fat look she wanted and collapsed but then somehow she began to get well she recovered I asked Jonas she believed that the bacon fat had actually saved Margaret Blackwell and she said she thought probably did and I told John I thought I had a different idea Stephen O'Brien believes that Margaret Blackwell was one of the lucky ones but she had inherited Delta 32 from both her parents and it had saved her life if he's right if the mutation did save her and the other survivors many of their descendants should carry it will O'Brien get his proof is the ability to fight off killer infections actually being handed down from generation to generation and is the way open to harness this power in our own modern battle with infectious disease the evidence is starting to point towards a genetic link between immunity to bubonic plague and immunity to the HIV virus if O'Brien is right a higher than average percentage of these people should carry the Delta 32 mutation his plan is to take and analyze samples of their DNA and then we take this back to the laboratory where DNA is extracted that is suitable for analysis of any genes we might be interested in or you might give us permission to test the DNA of each volunteer is analyzed for the presence of Delta 32 and the results seem to confirm O'Brien's theory looking for dolphin 32 in that sample we collected from you we actually collected something like 85 individuals to see who had Delta 32 who had two copies who had one copy and when we genotype them we discovered about 15 percent of them were Delta 32 from iam which is about 50 percent higher than the surrounding regions around em which had not had the same history of like so that was exciting and the number of people that had two copies was twice as high as we expected the evidence strongly suggests that carriers of the Delta 32 mutation are immune to bubonic plague but the next step provides a brand with even further proof under laboratory conditions cells have been exposed to the plague bacteria Yersinia pestis Delta 32 does appear to offer immunity if you take normal cells that have the normal parent molecule of Delta 32 a gene we called ccr5 they do take up your Suniya pestis quite rapidly if you take cells which have the equivalent of Delta 32 they're resistant to your sania pestis they do not take it up after years of research O'Brien and his colleagues finally appear to have their answer Delta 32 really does seem to be an almost miraculous mutation it protected people from bubonic plague for centuries in Europe and carried by their descendants it has also helped defend against the modern plague of hiv/aids now that scientists understand Delta 32 how it works and where it comes from they are beginning to learn how to mimic its effects so if we could discover why patient a fights off AIDS or a bola or SARS or bird flu and patient B doesn't then we could imitate the process by developing new pills or therapies or drugs that we can give to the patient who wasn't lucky enough to be born with them these new generation medicines are already being tested spike Rhodes has been hiv-positive for twenty years he was close to death when he was given the chance to try the first in a new class of drugs called fusion inhibitors just like Delta 32 they stopped the virus by blocking the portal through which it enters cells for spike the results have been extremely encouraging within weeks of first taking the drug the t-cells that support his immune system began to recover my t-cell counts doubled and my viral load had gone undetectable which was I also quite a surprise and within the next three months after that my viral load stayed undetectable my t-cells doubled up again if it hadn't come into my life I probably wouldn't be here AIDS SARS leukemia prostate cancer breast cancer Alzheimer's Parkinson's the litany of diseases that fill our hospitals discovering how these defenses work explicitly pinpointing the exact gene giving us a mechanism well then we know what to go after then we know how to develop treatments that are effective and clear out these hospitals from these chronic diseases that we cannot treat we're in the middle of a scientific revolution that could change the way we treat sickness it's a revolution that began in death and suffering centuries ago and as threats continue to emerge from all corners of the biological world it may be the mysteries and miracles of the human body itself that provide our ultimate line of defense you you

Channel: TheOfcar

Views: 799,713

Rating: 4.7154489 out of 5

Keywords: europe black plague, selective mutation, The Great Plague, Black Death (Disaster), fourteen'th century

Id: bQ8JQZwiwWE

Length: 50min 23sec (3023 seconds)

Published: Tue Dec 11 2012

Reddit Comments

[u/YOUREABOT]

Europe during this time period was basically the perfect environment for a Plague transmitted by fleas / rats. Modernisation had led to large concentrations of people in urban areas, yet the sanitation technology of the day was simply way too backwards to support this trend safely. London, in particular, was famous and well known all over Europe for it's extraordinary number of rats ,as well as it's high population density areas of the poorer classes. It was simply a recipe for disaster ,and it eventually happened.

[u/dogbotherer4]

She looks quite healthy for having the plague. Must be a good secret!

/s