(🧵2/5, HISTORY): What does history teach us about pandemics? This is a topic that's been covered by others, but much of what's been said is worth taking a closer look at, in context. Let's look at some historical pandemics/epidemics & see what we can learn. (1/)

It's worth starting by defining what a pandemic is- and isn't. To quote Michael Osterholm (in '09): “(A) pandemic is basically a…novel agent emerging with worldwide transmission.” It's an epidemiological, not a social, construct. Pandemics don't go away if you ignore them. (2/)

In the last 🧵, we looked at what biology tells us about emergent pathogens. The key take-home: the evolution of their virulence is unpredictable- it often increases. Host & pathogen are locked in a Red Queen's Race (3/). It's not a stable equilibrium. https://t.co/LrdIobC3Ur

Pandemics are (re)emergence events - their timelines have historically been variable- they can run for decades or centuries. (Later in this 🧵, we'll discuss why some pandemics end in a couple of years & others last for generations.) We'll look at 3 historic pandemics. (4/)

The 1st of these is Plague, specifically the 2nd Plague Pandemic (1347-1657), starting with the Black Death (1347-1352). Plague, caused by the bacterium Y Pestis, has a CFR of 40-60% if untreated. Y pestis emerged ~5000yrs ago, causing a pandemic that lasted generations. (5/)

Y Pestis evolves slowly (it's clonal). The Black Death was driven by emergence out of rodents (marmots) of a highly virulent & transmissible Y Pestis clone. Sudden evolutionary jumps like this (punctuated equilibrium) are common when a pathogen (re) emerges from a reservoir. (6/)

Detailed death records & paleogenomic sequencing allow a surprisingly detailed picture of the 2nd Plague Pandemic. We know there were repeated waves at roughly generational intervals- makes sense as plague immunity is lifelong. New waves were seeded from the reservoir(rats). (7/)

Y Pestis slowly evolved to become more transmissible over the years. The pandemic persisted until societal changes eliminated the conditions for it (living with rats/ fleas). "Learning to live with" the plague caused millions of deaths, basic hygiene got rid of the problem. (8/)

Next, let's look at Smallpox (an endemic, not a pandemic, disease). Smallpox was instrumental in the collapse of indigenous North American cultures- the smallpox epidemic in Tenochtitlan killed 40% of the population in a year, paving the way for Cortes' defeat of the Aztecs. (9/)

Why were the conquistadores spared? The CFR in Europe (15-30%) was lower than in Mexico, & smallpox mainly killed small kids. We can infer the adult CFR as 2.5%. Similarly, we can infer ~10% of Spaniards were immune. So the expected no. of conquistadore deaths in 1521? ~1 (10/)

Living with smallpox for millennia likely provided a genetic basis for resistance. In other words, despite the popular narrative that immunity to smallpox was what provided the Spaniards with an advantage, age structure & evolved resistance are more plausible explanations. (11/)

As a side point, intrinsic CFR for smallpox was bimodal. Variola major & variola minor, which coexisted for centuries, were two clades of smallpox with a ~30% & a ~1% CFR respectively. Viral CFRs are not carved in stone, even for slowly evolving viruses such as smallpox. (12/)

Next, let's discuss the 1918 Flu pandemic. The influenza virus has a segmented genome, favoring the mix & match of antigenic determinants. Seasonal flu evolves relatively slowly in humans (undergoing "antigenic drift"), and has fairly low transmissibility & virulence. (13/)

Pandemics are caused by "antigenic shifts", when flu re-emerges from animal reservoirs. These are punctuated equilibrium events, characterized by big jumps in transmissibility &virulence relative to seasonal flu. Pandemic flu clades burn out quickly,as they run out of hosts (14/)

The clade of H1N1 responsible for the 1918 Pandemic may have been circulating in pigs at the turn of the 20th c. A single-nucleotide change in the HA gene was sufficient to kick off the pandemic, with the virus now possessing increased virulence & transmissibility (15/)

Notably, the 1918 spring & fall waves appear to have been caused by different clades of the virus, both of which went extinct at the end of the pandemic. Several phylogenetic studies have shown that seasonal H1N1 is not descended from pandemic flu (see screenshots for more) (16/)

Much of what gets said about 1918 influenza is just wrong. Influenza pandemics end with herd immunity, which (combined with NPIs) drives the pandemic viral clade to extinction. 1918 Flu didn't "attenuate", in fact the 2nd wave (different clade) was deadlier than the 1st. (17/)

In summary: 1. Punctuated equilibrium is a common threat. 2. Pandemics can be self-limiting (flu) or not (plague). 3. Pandemics can run for generations. 4. Even endemic disease can cause societal collapse. 5. CFRs are not carved in stone. 6. NPIs can help end pandemics. (18/)

A popular trope in recent years has been that ignoring a pandemic is the best course "for the economy". But pandemics are intrinsically violent events, and history doesn't support the idea that they benefit societies. (There are whole books written about this subject, btw). (19/)

Pandemics can destabilize governments. Not surprisingly, mass death events often catalyze riots, revolts & civil war. (The examples in the screenshot will be fleshed out later with references in our blog posts & articles. Some of these events are well known). (20/)

Pandemics can lead to military defeats, as they rarely impact both combatants equally. (And even when they do, they can tip the balance of power unpredictably by allowing one or the other side a transient military advantage, as we saw with Cortes &. Aztecs). (21/)

Complex, labor-intensive systems can fail during pandemics. Mass death & disability can cause famines, labor shortages & supply chain disruptions. Not surprisingly, GDP contractions & inflation (stagflation) have been shown to arise repeatedly during historical pandemics. (22/)

Historical pandemics have often been part of or a cause of polycrises (the intersection of infectious disease, climate change & civil war). These are repeated historical patterns,not coincidences. (Again, refs in upcoming posts/articles - these examples are well documented) (23/)

Pandemics are incredibly bad for business & social stability- they're harbingers of social collapse. We've known about these things for millennia- there's a good reason why the Bible talks about the Four Horsemen of the Apocalypse (plague, famine, civil unrest & conquest). (24/)

Much of the popular narratives around pandemics have been shaped by (misinterpretation of) the 1918 Flu Pandemic. In some aspects, 1918 Flu was a best-case scenario- it was limited by herd immunity &human behavioral changes were effective. We can't always count on that. (25/25)

Many* H/t again, to @TRyanGregory & @madistod for stimulating conversations that gave rise to much of this material, and to @gckirchoff & @0bj3ctivity for helpful feedback. This is actually part 3 of a series of 6 🧵s, links to the first two parts are below ⬇️

@TRyanGregory @madistod @gckirchoff @0bj3ctivity Part 0: Foreword https://t.co/2GKik3j4tk Part 1: Emergence https://t.co/P9CfYkD5Dg

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