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  • Covid Origins: Lab leak hypothesis

    It hasn't been possible to discuss this openly since the big orange man endorsed it last spring. But its taken some time for things to shake loose since the usa election and the constantly delayed WHO report. Hoping to finally see that published soon.

    This stories begins in 2014 when Obama called a multi year moratorium on certain types of gain of function research (lifted under the trump admin) that was due to a letter signed by many scientists called the cambridge working group.

    Recent incidents involving smallpox, anthrax and bird flu in some of the top US laboratories remind us of the fallibility of even the most secure laboratories, reinforcing the urgent need for a thorough reassessment of biosafety. Such incidents have been accelerating and have been occurring on average over twice a week with regulated pathogens in academic and government labs across the country. An accidental infection with any pathogen is concerning. But accident risks with newly created “potential pandemic pathogens” raise grave new concerns. Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control. Historically, new strains of influenza, once they establish transmission in the human population, have infected a quarter or more of the world’s population within two years.

    For any experiment, the expected net benefits should outweigh the risks. Experiments involving the creation of potential pandemic pathogens should be curtailed until there has been a quantitative, objective and credible assessment of the risks, potential benefits, and opportunities for risk mitigation, as well as comparison against safer experimental approaches. A modern version of the Asilomar process, which engaged scientists in proposing rules to manage research on recombinant DNA, could be a starting point to identify the best approaches to achieve the global public health goals of defeating pandemic disease and assuring the highest level of safety. Whenever possible, safer approaches should be pursued in preference to any approach that risks an accidental pandemic.
    http://cambridgeworkinggroup.org

    Its not easy to shut down a multi billion dollar industry which is important to the welfare of humanity so you can imagine it had an impressive group of scientists support it. The trigger was gain of research on ferrets in the netherlands and the USA that made the H5N1 FLU virus easily transmissible, which possess an immune system similar to humans, if it escaped could spark a flu pandemic. Scientists for Science oppossed the cambridge group and made the value argument. During the moratorium China became an even more important centre for this type of research. but even before the ferret research there has been an argument raging on specific types of gain of function research and its risk reward ratio, splashed across top scientific journals like Nature throughout the years. This has always been a mainstream argument that has divided the community. And the research has been an international collaboration led by scientists in the west and china. Any leak, anywhere, will partly rest with this collective community and the risk reward analysis they have conducted.

    You can make the argument that its the correct call even if a pandemic is sparked if the probability analysis was sound. In other words, hindsight bias is unfair, we did the right thing but just got unlucky. As opposed to we didnt estimate the risk correctly. The reward component is a separate analysis and also hotly debated ove the years between scientists. I will follow up here with some more thoughts/posts.

  • #2
    As with the opening post I am hoping to first discuss the kinds of things we need to think about that have their origins pre covid. So we can see they arent tainted by political discourse of the USA of the last year.

    Its worth thinking about the risk that labs pose in the first instance. Consider what Marc Lipsitch said in 2014

    It’s the one that I can quantify. We don’t know how bad the bad guys are, how many of them there are, and how that will change over time. What we do know is that there is a 20 percent risk that at least one laboratory worker will get infected over 100 laboratory years of work in a Biosafety Level 3 lab, which has special safety features for handling lethal agents.

    If one worker gets infected, that doesn’t mean the world is at risk. The pathogen would have to become widespread, and the only published estimate for that occurrence is in the 10 to 20 percent range. I would expand that range to 5 to 60 percent, because it depends on things that are hard to predict: how long a person is infectious, how many contacts they have, whether their infectiousness is reduced by antivirals.
    https://www.hsph.harvard.edu/news/ma...tens-humanity/

    This article from 2019 is a decent summary of western lab errors
    https://www.vox.com/future-perfect/2...llpox-bird-flu

    No matter how you define it, there have been hundreds of serious incidents to local outbreaks as a conservative estimate.

    For fairly obvious reasons we can assume that the long list of lab errors is massively under reported as people dont what to admit to them and the vast majority of errors end without a negative outcome of any kind.

    Its also worth noting there have been 2 widely accepted lab leak escapes that went big, 1977 H1N1 that killed 700,000 (soviet union lab) as well as the escape of Venezuelan Equine Encephalitis. By 2014 SARS escaped labs atleast 6 times globally, several in China, sometimes leading to deaths before it was controlled.

    https://armscontrolcenter.org/wp-con...17-14-copy.pdf

    A very annoying part of the discussion is lab leaks are incredibly rare so we can rule it out for the most part logic...

    We can rule out a statue of the virgin mary crying beacuse the probability that the correct arrangement of atoms forms a drop of water exiting the statues eye by accident exceeds the number of atoms in the known universe. Lab leaks are rare in the way you dont expect them to happen often, not never. And that the risk reward evaluation invites a risk that is much smaller than the risk of a natural pandemic, which over a long enough period of time is a near certainty. At least thats the theory.

    So as to state the obvious, rare events do happen, just not often.

    Edit. I meant to also link this summary of american lab accidents that predated this pandemic

    https://eu.usatoday.com/story/news/2...ents/26587505/

    From 2006 through 2013, labs notified federal regulators of about 1,500 incidents with select agent pathogens and, in more than 800 cases, workers received medical treatment or evaluation, limited public data in program annual reports show. Fifteen people contracted laboratory-acquired infections and there were three unintended infections of animals, according to the reports, which do not identify labs and mostly provide aggregated counts of incidents by type. Reported incidents involve events ranging from spills to failures of personal protective equipment or mechanical systems to needle sticks and animal bites.
    Last edited by tantalus; 28 Mar 21,, 20:07.

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    • #3
      To round up the pre covid considerations is the january 2018 diplomatic cable sent by Us diplomats and scientists raising concerns about lab safety having visited wuhan. They were worried enough to send the cables concerned of the risk of "sars-like pandemic" having witnessed protocols in the labs around bat research. This is hardly a smoking gun but adds further merit to seriously considering a lab leak for covid 19. And at the very least suggests we need a global moratorium on certain types of research until a global treaty of lab safety, research and reporting of outbreaks, irrespective of the origins of this pandemic can be arranged and signed.

      I will follow up with several posts when I have th chance that will deal with events from the autumn of 2019 and will be tainted by political and personal narratives.

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      • #4
        Before going into detail I want to add some disclaimers and discuss some probability.

        First this could be natural origin, obviously. Or it could be a lab worker got infected with a natural origin virus while out collecting in the field, thats a grey area because without the research you don't get the interaction. Or it could be a lab leak of a natural origin, or a lab leak of an gain of function virus. I am not by any stretch ruling out natural origin. For whats its worth back in february, 2020, I just assumed it was a rerun of the wet markets and sars 1, pangolins etc. Made perfect sense, 2003 all over again, those god damn wet markets. But once I realsied the research conducted in the city the doubts crept in.

        And a warning, some evidence can look like its natural but actually still be lab. And vice vearsa. We need to be careful how we analyse data. While the chinese have offered no signs of a zoonotic source yet in a wild animal population, we should expect to find a virus closely related to sars cov 2 somewhere in the wild, natural or lab, there is a closely related virus in the wild and that is the ultimate beginning, And its not plausible we will not find some closer relative eventually.

        Now with regard probability. We have a pandemic that was in the sars group, not a hot favourite for the next pandemic, in a city that does not have a bat population known for having sars viruses that jumps to humans, at a time of the year the bats are hibernating. To be fair its unclear what time of the year the virus jumped but taking the ccp timeline, which to be honest we know is a lie, they would be. The closese bats are in southern china. When the chinese led by Shi Zhengli (fondly known as the bad lady as she is respected for her work around sars) sought a control group against southern chinese communities (published research that was studying how much coronavirus viruses were jumping into humans - by seeing if there was history of coronviruses infections in people in southern china) they used the wuhan population as a control, logically they assumed they wouldnt have any evidence of infection in the control and they were correct. This is why Shi is on the record of having said she was surprised when she heard an outbreak was underway in Wuhan and she was initially worried about the wuhan labs.

        Now shi is also on the record of picking a corona virus as a possible future pandemic as a curve ball possibility when asked to pick a non traditional candidate for the next epidemic. She didnt pick a sars virus specifically, alpha or betacornavirsus. Note Mers was not a sars virus. It seems nobody, even Shi, could pick any one part of the coronavirus phylogenetic tree as the source of the next coronavirus trouble maker. It could be any branch. So ask this, was sars a logical place to expect the next one, we had sars 1 right, no it seems, but if you imagined a sars pandemic would emerge in a city for conducting research specifically on sars viruses things get more interesting. If we has a sars pandemic elsewhere we could have said, we should have realised after sars one to see this coming, warning shots in 2003. But cant seem to realise that when it occurs in the actual city doing the research and before the fact sars wasnt singled out we cant connect the dots.

        In quotes below we can consider multypling the probability of the wuhan population by the number of branches in the phylogenetic coronavirus tree to help us think about the chances of a sars virus emerging within a a trip to the shop for some milk... (I consider it flawed but its simplicity is an aid here in helping us think about if we should give the lab leak hypothesis a serious look)
        Given these provisos, and knowing that (1) bats and other animals which harbour coronaviruses are found practically all over the world, and (2) that the population of Wuhan is 11 million, and that (3) the global population is 7 billion, we can calculate the likelihood of Wuhan being the epicentre of a natural zoonotic coronavirus pandemic: The chance of a person from Wuhan being patient zero is approximately 1 in 630....

        If each Alpha and Betacoronavirus species is equally likely to spill over to humans, which is consistent with our understanding, then the probability of a virus from the SARS-related coronavirus species starting a zoonotic pandemic is 1 in 28. (And if there are undiscovered coronavirus species––pretty much a certainty––the number will be greater still)....

        while Zheng-li Shi at the WIV focused on virus collection, above all, she dedicated her research to understanding zoonotic spillovers to humans of one species alone: the SARS-related coronaviruses....

        So, if one accepts as reasonable the assumptions made above, the probability of Wuhan being the site of a natural SARS-related coronavirus outbreak is obtained by multiplying 1 in 630 by 1 in 28. The chance of Wuhan hosting a SARS-related coronavirus outbreak is thus 17,640–1

        The criticism will doubtless be made that the geographic and the phylogenetic evidence described here are circumstantial–mere coincidences. But critiquing evidence as circumstantial is based on a common logical misconception–that circumstantial evidence represents a special category of evidence. As the philosopher David Hume first argued, all evidence of causation is composed of coincidences. All an observer can do is to add up the coincidences until they surmise that the threshold of reasonable doubt has been surpassed. Conclusions are always provisional, but in the absence of evidence to the contrary, anyone open to persuasion ought at this point to conclude that a probability of 17,640–1 far exceeds that threshold. A lab escape should at this point be the default hypothesis.

        Such a conclusion is only reinforced by much of the important information that has emerged since the outbreak began. We now know, for example, that, at the time of the outbreak, Zheng-li Shi and her colleagues had in their freezers the virus sample known as RaTG13. Among all the known coronaviruses, including within the SARS-related coronaviruses, RaTG13 is by far the closest relative of SARS-CoV-2. We also know that Zheng-li Shi implied she had not actively studied RaTG13 prior to the outbreak (in Zhou et al, 2020). We now know this was false and they had been studying it since at least 2017 (Zhou et al. 2020 addendum). These facts again do not support a natural zoonotic origin.
        https://www.independentsciencenews.o...andemic-virus/

        And to quote Scott Gottlieb on face the nation
        It looks like the WHO report was an attempt to try to support the China narrative, Chinese narrative around this- this origin of the vaccine. You know, the lab leak theory doesn't seem like a plausible theory unless you aggregate the biggest collection of coronaviruses and put them in a lab, a minimum-security lab in the middle of a densely populated center and experiment on animals, which is exactly what the Wuhan Institute of Virology did. They were using these viruses in a BSL-2 lab and, we now know, infecting animals. So that creates the opportunity for a lab leak. It might not be the most likely scenario on how this virus got out, but it has to remain a scenario. And I think at the end of the day, we're never going to fully discharge that possibility. What we're going to have here is a battle of competing narratives.
        https://www.cbsnews.com/news/transcr...march-28-2021/


        I want to touch on RatG13 in the next post, the closest known wild relative to sars cov 2.
        Last edited by tantalus; 28 Mar 21,, 21:42.

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        • #5
          Ratg13 is the closest known relative to sar cov 2, at almost 97%. Sounds close but its not that impressive, My understanding is Ratg13 is not the original virus as some have suggested, I read an analysis that placed the evolutionary divergence in the wild from sar cov 2 as decades ago. Dont know if that a trustworthy analysis.

          What is interesting is the fact this closest relative was found in 2013 after it infected 6 workers in a bat cave in southern china, killing 3. At the time it was not reported as a sars like viral event but eventually Shi and the wuhan labs went down and sampled it and brought it back to Wuhan and studied in no later than 2017. We have a thesis online that the CCP missed that helped us connect RATG13 to the mine deaths as Shi was not forthcoming, she changed its name in later report and "confusion" led to the initial understanding she had sequenced and studied if after the pandemic has started, not before. We now know they had another 8 other wild viruses, of which the ccp have not relased their genetic codes. We also have reaonss to belief that they have sequenced thousands of other viral strains and kept them in a wuhan database that the CCPhas taken offline in early 2020 and have refused to share the sequences.

          So we have the worlds leading sars lab in wuhan with the closest known relative under study and the ccp have taken the database offline for "security" reasons.

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          • #6
            I want to talk a little bit more on my expectations of the early pandemic phase before wading it on the political, intelligence aspects and ccp obfuscation.

            We would expect a virus that jumps to humans to enter an initial phase of trying to adapt to humans and get better at adapting over time at spreading in a new host.

            One of the reason why even the ccp abandoned pangolin theory so quickly imo is they knew we would test it in pangolins cells where it does very poorly. This has also been found to be the case in bats and mustelids (like mink).

            In a side-by-side comparison of evolutionary dynamics between the 2019/2020 SARS-CoV-2 and the 2003 SARS-CoV, we were surprised to find that SARS-CoV-2 resembles SARS-CoV in the late phase of the 2003 epidemic after SARS-CoV had developed several advantageous adaptations for human transmission. Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV
            https://www.biorxiv.org/content/10.1....073262v1.full

            Sars 1 followed this pattern of adapting to humans over time. Sars cov2 appears ready and well adapted immeidiately to human cells, but poorly adapted to pangolins (intermediate host), bats (direct host), ferrets (mustelid like mink). As a result, we should consider serial passaging though humanised mice in the lab as a possible origin of a rapid emergence of a sars cov 2 that more closely resembles a late stage sars 1 virus that a newly emerging virus adapting to a new host.

            For futher reading on sars cov's 2 adaption to cells see https://link.springer.com/article/10...11-021-01211-0

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            • #7
              So now things get a little hairy and I am looking forward to the ever delayed WHO report.

              Pompeos fact sheet http://2017-2021.state.gov/fact-shee...ogy/index.html


              “That was a very carefully crafted statement, carefully crafted so as not to overstate the case that it was making,” Pottinger said. “The case it was making was for following up on these important leads.”

              In a talk he gave last month at Florida International University, Pottinger said the Jan. 15 fact sheet was vetted and cleared for release by the State Department, the White House, the Department of Health and Human Services and U.S. intelligence community leadership

              After reviewing the Trump administration’s underlying evidence, none of which has been released publicly, the Biden State Department determined that some of the facts in the Jan. 15 statement are supported by either U.S. government information or public sources, a senior State Department official told me. But that doesn’t mean the Biden team is endorsing Trump’s or Pottinger’s assertion that the lab was probably involved.
              https://www.washingtonpost.com/opini...an-lab-claims/

              So everybody understands that us intelligence doesnt know the origin and the biden admin seems to not be denying any of the points on the sheet just that its only making the case for lab and not for zoonotic. I delayed posting as this was too hot to touch when released, I dont know if wabbits are comfortable with the fact sheet currently.

              But it now seems that Marion Koomans, WHO has confirmed that the chinese have admitted that there were sick reasearches in autumn 2019 in the lab (which she described as normal and no problem) and the the WHO are trusting chinese reports that these workers tested negative for covid 19. https://www.nbcnews.com/nightly-news...9-104497733806
              Last edited by tantalus; 28 Mar 21,, 23:11.

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              • #8
                The way I see it we have a pandemic that clearly emerged earlier than the chinese are claiming and from what the WHO team have already reported we cant take seriously the December dates for the first covid patients in Wuhan as the actual first people infected in Wuhan.

                Whats more the ccp refused to give WHO access to blood donated in wuhan in autumn 2019 for covid seroprevalence testing (data privacy as an explanation, dark humour coming from the CCP) and the wuhan authorities informed the WHO after they asked for them that they had destroyed the sewage water sampling so we cant test for covid 19 in the samples. Apparently nobody thought they might be important. We also have Mike ryan, WHO, on the record of saying the ccp were not forthcoming in January, lying about if there was human to human transmission, the CCP refused to release a sequence of sars cov 2, until a university official sent the sequence to a colleague in Australia, who sent it to Scotland where they posted it online. The CCP supressed internal doctors and scientists, and used the chinese military over the chinese CDC in the early days to manage the outbreak. The chinese CDC have close ties with the americans and presumably couldnt be trusted, They also pointed quickly to the market, ordered samples destroyed, and have engaged in a disinformation campaign regarding the origins of the pandemic. For a list of some ccp actions see here https://jamiemetzl.com/origins-of-sars-cov-2/
                Last edited by tantalus; 28 Mar 21,, 23:14.

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                • #9
                  The reality is by serial poassaging scientists can alter viral sequences that realsitically are not detectable. The earlier spring papers by western scientists that shaped the media narrative fail to point this obvious reality and sar cov 2 has features that are known in the scientific community to help make them spread in humans. They could have occured naturally through recombination but since sar cov 2 disccovered tricks we are aware of and not some new novel approach it equally means it could be lab.

                  Controversially, right in the middle of the spike gene of SARS-CoV-2 lurks a surprise. Unlike other SARS-like coronaviruses so far described, including RaTG13 and the pangolin viruses, SARS-CoV-2 has an extra 12 digits inserted, creating a “furin cleavage site”. This is a feature found in other pathogenic coronaviruses such as Middle Eastern Respiratory Syndrome (MERS), and is known to make viruses more capable of infecting different tissues in the body. Yet, this remarkable insertion was not mentioned in either of the WIV’s first covid-19 papers despite a close analysis of the spike gene. It will be near impossible to definitively determine whether this furin cleavage site arose naturally or artificially. However, its omission from key WIV covid-19 papers is curious.

                  The practices of building chimera coronaviruses (made from parts of multiple viruses), sometimes leaving no trace of manipulation, or inserting a furin cleavage site into the spike protein of SARS virus, are not new. These experiments have been conducted in select laboratories such as at the WIV for the purpose of understanding how novel SARS viruses could spill over into humans. The ultimate goal is to create a universal vaccine for all SARS-like viruses.

                  The scientists might find it unbearable if they instead caused a pandemic. But they did not find it unthinkable. In a 2015 article co-authored by Dr Shi and Dr Ralph Baric of the University of North Carolina at Chapel Hill (the heads of two leading SARS coronavirus research groups) these words appear: “scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue… the potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens.”
                  https://www.rationaloptimist.com/blo...pe-from-a-lab/

                  Comment


                  • #10
                    Finally its worth pointing out that all known and unknown possible origins of covid 19 should add up to 1 or 100%. So as the probability of one theory weakens based on exisiting evidence or the absence of evidence as a function of time, the other theories become more likely even if no evidence has emerged for them.

                    The ccp have said they have sampled a very large series of possible animal origins in china (waiting for full details in WHO report) (although hardly exhaustive and that takes time to be fair) and found nothing. They have pushed the narrative of frozen food and that the virus was imported into China. If we place a very low probability on a person being infected by frozen food (which seems mainstream), than the odds that one of the very first people infected is by frozen food and that they cause the first noticable outbreak by flying into wuhan, but not where the outbreak originated, is ridiculously low. I am reluctant to give that hypothesis serious consideration.

                    The fact that 13 to 19 months since the virus found into way into the human population and we have no hint in the wild or breadcrumb trail hurts the zoonotic theory and increases the chances of lab origin, there is time for that narrative yet to change, and always time for a late discovery to blow things open, but as I warned previously we should expect to find wild relatives no matter the origin. However if the lab is the original source of the pandemic it is possible the CCP wont even release the wild samples, for fear of lab workers being traced to them.

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                    • #11
                      Why this matters? It's worth taking a moment to consider the gravity of possibly having caused one of the worst disasters in the modern era while trying to prevent it. Its symbolically a huge blow to humanity, progress, science and technology of which I still remain a great subscriber to the idea that these are the greatest forces in the world, along with both the free market and a drop of socialism for good measure.

                      There are far more dangereous pandemics out there in the future, some already lurk in labs, others will come to be in future labs and mother nature will always have nasty combinations for us. A highly contagious 60% mortality flu pandemic is a modelled possibility and would represent a danger to the very stability of civilization. We need to take all possible future pandemic origins seriously but its obviously vital to know if we caused this one ourselves. We need to be able to assess what went wrong. We need an open discusioin on security, risk reward of research, incentives both financial (free market isnt always a friend) and reputational, as well as international agreements on early and open reporting.

                      And we need to consider new emerging technoligies in biotech and AI and the threats they pose to all of us. Covid 19 can be the trial run for something far more serious.

                      Comment


                      • #12
                        What do you mean trial run? We've been hit again and again with plagues. COVID-19, if anything, is much more benign as compared to the plagues of the past - Spanish Flu, the Black Death, and let's not forget that the Poxes wiped out entire Central and South American civilizations. The Spanish Flu killed 50 million worldwide, inclduing 625,000 Americans. The fact that the Americans are approaching this number while worldwide deaths is ~3 million is a testament to the walking clusterfuck of Trump, not the lethality of the diesease.

                        We will be hit with plagues again and again and there is zero defence we can prep for. We don't know the nature of the future germ and it will be nothing we've seen before, mainly because we already got immunity from those we know. We don't know if it will be airborned, carried by bugs (good luck in getting rid of the musquitto population and even if you do, what kind of ecological damage will you do?). We don't even know if quarrantine will work in a future plague (malaria).

                        At that point, all we can hope for is that some of us can survive the plague to rebuild our societies, ie the Black Death.
                        Last edited by Officer of Engineers; 29 Mar 21,, 07:49.
                        Chimo

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                        • #13
                          Originally posted by Officer of Engineers View Post
                          What do you mean trial run?
                          A trial run for managing pandemics in modern times. So we are better prepared for one of the nasty ones you listed. Everything from supply chains of small pieces of medical equipment uo to how to scale factory production for drug and vaccine production. We need to consider organisation from the local to state to federal, private and public. We need a deep dive on testing systems and distributuion and how we can ramp and concentrate human experitise. Science communication, effficient and well targeted economic responses, food supplies etc Basically a pandemic war games. Countries like South Korea were better prepared due to taking lessons from 2015 Mers outbreak they had but Iam not sure many countires would have fared even decent in a severe pandemic.


                          Originally posted by Officer of Engineers View Post
                          . The fact that the Americans are approaching this number while worldwide deaths is ~3 million is a testament to the walking clusterfuck of Trump, not the lethality of the diesease.
                          That goes to the point there is a sliding scale of responses. That said if the usa mortality methodology was applied globally there would be quite a number of countries up there with the USA, . Still i agree it was a clusterfuck given the resources and talent and geogrpahy at the USAs disposal.

                          Originally posted by Officer of Engineers View Post
                          .

                          We will be hit with plagues again and again and there is zero defence we can prep for. We don't know the nature of the future germ and it will be nothing we've seen before, mainly because we already got immunity from those we know. We don't know if it will be airborned, carried by bugs (good luck in getting rid of the musquitto population and even if you do, what kind of ecological damage will you do?). We don't even know if quarrantine will work in a future plague (malaria).

                          At that point, all we can hope for is that some of us can survive the plague to rebuild our societies, ie the Black Death.
                          There is alot we can do to improve our response, but it has its limitations. We will also have many new technolgies at our disposal, new weaponary to deploy, depending on the timeframe. The RNA vaccines is a brand new technology that just happent to be well suited to tackling covid 19 as its caused by a RNA virus. We only started using mRNA tech to try to treat cancer starting back in 2011.

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                          • #14
                            Bubonic plague.
                            Chimo

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