Astral Codex Ten

Australians

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Australians

Article

Australians is a recurring place in the Astral Codex Ten archive, appearing 2 times across 2 issues between September 02, 2021 and July 12, 2024. The archive places it in contexts such as “do you think those Australians who got infected with Q fever”; “Yet as soon as the Australians arrived”; “The Australians had hoped to ‘modernize a Stone Age people’“. It most often appears alongside Australia, UK, 1980s.

Metadata

  • Category: Places
  • Mention count: 2
  • Issue count: 2
  • First seen: September 02, 2021
  • Last seen: July 12, 2024

Appears In

Source Context

Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.

Long COVID: Much More Than You Wanted To Know
September 02, 2021 · Original source
This is terrible. Recovery rates in the single digit percentages over the space of years. You would think at least some patients would get placebo recoveries, or forget how it felt to be well, or otherwise Lizardman themselves into fake complacency, but no. This is f@#$ing awful. Maybe COVID won’t be this bad? One ray of hope comes from this Australian study, where doctors record the rates of recovery from postviral fatigue after various rare diseases they encounter (Epstein-Barr, Q fever, Ross River virus). They find that 35% of these patients have postviral fatigue after six weeks, but only 12% after six months, and 9% after twelve months. This sounds a lot better than chronic fatigue. In fact, these people do the kind of weird task of figuring out how bad different diagnostic labels for fatigue are, even though some might argue that all the labels refer to the same underlying reality. They find an official diagnosis of “CFS/ME” (chronic fatigue / myalgic encephalitis) is much worse than “postviral fatigue”. Using the weird measure of “days per year of followup with diagnosis” (I’m not sure I fully understand their reasoning for why this is good), they find a median length of 80 for CFS/ME vs. 0 for PVF (…huh?). Using the more comprehensible measure of percent who still complain of fatigue after 7-12 months, they find it’s 24% vs. 10% (which super contradicts the above study saying that basically nobody with a CFS/ME diagnosis ever recovers). My guess is that this study had much lower criteria for a CFS/ME diagnosis (some doctor diagnosed it and put it on the insurance records) compared to the ones above (some specialist confirmed it by official criteria). The conclusion I draw is that, while official CFS/ME is horrible and hopeless, there are a lot of things that unofficially look kind of chronic-fatigue-ish which have pretty good prognoses. Since there’s no good reason to think post-COVID fatigue is official CFS/ME as opposed to just some chronic-ish fatigue-ish thing, probably it will have a better prognosis, more like weird Australian viruses. …which we still don’t know, because AFAICT nobody has done any good studies on postviral fatigue lasting more than a year. 5. Psychosomatic symptoms probably aren’t the majority of long COVID. I mean, I’m not seeing too many people claiming that they are. There are a lot more people worried that someone else might be claiming that, than people actually making the claim. Still, the Wall Street Journal opinion section is always up for slathering itself in glue and rolling around in a haystack until it becomes the straw man everyone else warned you about, and they do have an article on The Dubious Origins Of Long COVID. They point out that long COVID was first thrust into the public consciousness in surveys run by Body Politic, who self-describe as “a queer feminist wellness collective merging the personal and the political”. I agree this is a weird source for something to come from, but Hans Asperger was a Nazi and I still use his diagnosis, so I probably have to accept these people’s as well. More relevantly, WSJ points out that many of the people complaining of Long COVID symptoms test negative for COVID, or at least never tested positive. This complaint conflates the fact that not everyone was able to get a COVID test at all, with the fact that sometimes you get the acute COVID test after you’ve recovered from acute COVID and it’s negative, with the fact that COVID tests don’t have a 100% success rate, with the fact that yeah, okay, some people who didn’t have COVID are probably imagining Long COVID symptoms. I feel like some of the case-control studies above, which clearly show that seropositive people have higher rates of Long COVID than seronegative people, are pretty convincing here. But also - the people with lung scarring clearly have lung scarring, and most of them have weird x-rays consistent with lung scarring. If you have lung scarring, then you have trouble breathing, you’re fatigued, and you probably have lots of other stuff downstream of that. The people with smell/taste disturbances clearly have smell/taste disturbances, testable with the stupidly named but scientifically venerable Sniffin Sticks test - and also, who even cares enough to make up olfactory problems? Fatigue and brain fog are the only symptoms here that can’t be easily objectively confirmed, and, well, do you think those Australians who got infected with Q fever and had twelve months of postviral fatigue are faking? What about all those post-Epstein Barr fatigue people? Lots of viruses cause postviral fatigue, it’s not really surprising that COVID should also. (WSJ also spends a while arguing that CFS/ME is just a psychiatric disorder, which I think is not really in keeping with the best recent evidence. Also, as a psychiatrist, I’m very against this conclusion, mostly because if it were true, then people would expect me to cure CFS/ME patients.) One point WSJ didn’t bring up but could have was that most Long COVID patients are women. Probably this is somewhere between 60 and 80% - I suspect on the lower end of this, because I think women are more likely to talk about these kinds of things than men, and much more likely to eg join Facebook groups. This is noteworthy, because women are traditionally more prone to psychosomatic illnesses - so much that the ancients attributed these to the uterus and called them hysteria (note shared root with eg “hysterectomy”). Women are about 2x as likely to get diagnosed with panic disorder, anxiety disorders, phobias, etc, about 2.5x as likely to get chronic Lyme disease, widely regarded as an entirely psychosomatic condition, and 3-5x more likely to be diagnosed with fibromyalgia. So the female preponderance is suspicious. But women are also somewhere between 2x and 4x more likely to get autoimmune disorders than men (it varies by disorder - the ratio for Sjogren’s is as high as 16x). There are some pretty crazy hypotheses for why this is - for example, maybe women’s immune systems are permanently upregulated to be prepared for attempts by the placenta to secrete immune-downregulating chemicals during pregnancy, as part of the creepy shadow war between mother and fetus to regulate the maternal environment. I don’t know, do you have a better idea? Anyway, women have more autoimmune issues and more upregulated immune systems, so if there was any good way to assess gender ratio in true postviral fatigue excluding all psychosomatic cases, that would probably be female-biased too. Probably some Long COVID cases are psychosomatic just like some cases of anything are psychosomatic, but I don’t see too many signs that this is too important in explaining the phenomenon. …and please allow me a moment of preachiness here. Chronic fatigue sounds really fake to anyone who doesn’t have it. I think this is because it’s related to willpower. Willpower itself would sound fake to anyone who didn’t have to worry about it. “Oh, so you can go partying with your friends whenever you want, but as soon as it comes time to write a ten page report, your ‘lack of willpower’ prevents you from doing it? A likely story!” Still, all of us (except Bryan Caplan) recognize how real and important willpower is - how having more of it is better than having less of it, and how some condition that caused you to have pathologically little of it would be a huge disaster. In the comments section to the rough draft of this post, CJ wrote: I will say - I was one of those types of men to scoff with skepticism at people claiming to have chronic fatigue and the like. I would have called those people lazy and would have been adamant they were faking it or feeling like crap because of unhealthy lifestyle choices. Unfortunately I have learned the hard way the severity of neurological conditions, what it feels like to have brain fog, what chronic fatigue feels like, and how difficult it can be to communicate neurological symptoms to others. I now start from a position of listening to people who are willing to open up about their symptoms and trust that they are being honest. There are millions of people suffering in silence with untreated and undiagnosed disorders - those people are not all faking it or just dealing with psychosomatic conditions. I would recommend Jennifer Brea's documentary, Unrest. Thank you for shedding some light on the subject. Heron added: I second the suggestion to watch 'Unrest,' and to consider the many unseen ill whose symptoms are deemed to be imagined. Until this last year, I had little patience with, and doubted, people who I saw as hypochondriacs. Then I became the thing I hated. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID do have similarities from what I've read, since becoming ill in August 2020. At that time, here in Northern Ireland, there was scant availability of COVID tests; after spending three days trying to get hold of one, (by which time I'd stopped teaching my post-grad online classes & I haven't worked since) I became too ill to do anything. I figured if this was COVID I'd gotten off lightly, mostly constant severe headache, inability to think, a new experience of fatigue, high temperature, insomnia, hypersomnia, paresthesia, no smell or taste etc Debilitated but not dead. Except for the fact that I still have the aforementioned symptoms a year on and whilst they fluctuate in type and severity, the fatigue, headaches and cognitive difficulties are real. A brain scan, an appointment for brain and spinal MRIs (waiting lists, even when going private [as NHS has 3-8 yr waiting lists here in NI] are lengthy), rare virtual doctors and neurologists suggest my ailments constitute a post-viral thing, maybe Long C, they can offer nothing but pills for pain. There is no test for ME/CFS yet, nor a Long C test, symptoms and presentation are so varied. Given a widespread lack of knowledge and resources regarding these ailments, you're on your own. Maybe I've developed ME, I certainly have post-exertional malaise which my very prominent neurologist hadn't heard of. Looking at the history of ME/CFS* and a dearth of research surrounding it, I hope that rather than dismiss the lives of sufferers of this or the long-lasting aftermath of COVID, that those experiencing such difficulties will be heard and learnt from. I only understood when I had no alternative. I don’t think I ever actively pooh-poohed CFS, but like everyone else who encountered it, I underestimated just how bad it was until I met some patients with the condition. It is real and really bad. For whatever reason it is hard to think about and take seriously, but it really is as bad as people say. </preachiness> 6. Long COVID is probably rare in children This matters a lot, because children are (currently) ineligible for the vaccine, and also likely to encounter the virus at school. But children usually have mild cases of COVID and don’t die from it, so it’s tempting to just not worry about them. But if they could get Long COVID, that would make it much less tempting. Preliminary Evidence On Long COVID In Children sounds like a good paper to draw conclusions from. It says 42.6% of children with COVID experience long-term follow-up symptoms, which would be higher than the rate for adults. But it has no control group, and most of the symptoms it finds don’t seem very COVID-related (eg rashes, constipation). The most common symptom (20%) is insomnia, which better studies in adults fail to associate with real Long COVID. The rate of known long COVID symptoms (eg taste and smell problems) is only about 3-4%, and no higher or lower than anything else. Probably these kids are just having problems at the usual rate and attributing them to their recent COVID. Blankenburg et al do the correct thing and ask a thousand children about potential symptoms, then compare the number who say yes vs. no among COVID-seropositive and seronegative subjects. They find no difference between the two groups. Both are reporting a lot of insomnia, etc. They reasonably attribute this to pandemics being a stressful event that it’s natural to lose sleep over. This is really reassuring, but it can’t rule out a somewhat rarer syndrome. The authors say that they might miss symptoms with a prevalence of less than 10%, and one of them gives his own personal guess that it’s 1%. An English team says there’s a Long COVID rate of 4.6% in kids. But there was a 1.7% rate of similar symptoms in the control group of kids who didn’t have COVID, so I think it would be fair to subtract that and end up with 2.9%. And even though the study started with 5000 children, so few of them got COVID, and so few of those got long COVID, that the 2.9% turns out to be about five kids. I don’t really want to update too much based on five kids, especially given the risk of recall bias (ie you might notice / care about your symptoms more if you know you had COVID before getting them). My overall conclusion here is that long COVID is rarer in children than adults, and may not exist at all. The studies tell us it’s probably somewhere less than 5% of kids, but so far we can’t conclude anything stronger than that. 7. Vaccination probably doesn’t change the per-symptomatic-case risk of Long COVID much Here’s a complicated Twitter thread about this. Of vaccinated people who got symptomatic COVID, about a third ended up with Long COVID symptoms, the same rate as in unvaccinated people. Of course, vaccinated people are much less likely to get symptomatic COVID. But even conditional on getting it, they’re still much less likely to go to the hospital, die, etc. It would have been nice if the same was true of getting Long COVID. But it doesn’t look that way. (all this information is from an online poll by a sketchy group of COVID “survivor” activists. But they wrote up their poll in the scientific paper font, as a PDF and everything, so I say we count it anyway) This NEJM study wasn’t exactly designed to look for Long COVID in vaccinated people. But they found it anyway, at a rate of 19% after 6 weeks. This also fits within the (wide) range reported for unvaccinated people. They don’t give a symptom breakdown beyond “prolonged loss of smell, persistent cough, fatigue, weakness, dyspnea, or myalgia”, which sounds like the usual set. These studies are pretty weak, and you could argue that given that vaccines decrease the average severity of COVID infection, and infection severity is linked to Long COVID risk, we should have a strong prior on vaccines decreasing Long COVID risk. And just before publishing this, someone sent me this study, which very preliminarily finds vaccines might decrease Long COVID risk by a factor of 2. I think a factor of 2-3 is believable; one of 10 or 20, less so. Weirdly, there are some claims that vaccines can help relieve symptoms of existing long COVID. Sounds kind of like sympathetic magic to me, but the researcher quoted in the linked article said it might “improve symptoms by eliminating any virus or viral remnants left in the body” or by “rebalancing the immune system”. So yeah, sympathetic magic. 8. Your risk of a terrible long COVID outcome conditional on COVID is probably between a few tenths of a percent and a few percent. My original calculation went like this: About 25% of people who get COVID report long COVID symptoms. About half of those go away after a few months, so 12.5% get persistent symptoms. Suppose that half of those cases (totally made-up number) are very mild and not worth worrying about. Then 6.25% of people who get COVID would have serious long-lasting Long COVID symptoms. After doing that calculation, I read this essay by Matt Bell, who tries to figure out the same thing. He is much more optimistic. He agrees that about half of long COVID cases go away after a few months, but adds another 50% decrease from “few months” to “lifelong”, kind of on priors, admitting there’s not too much positive evidence for this. Then he adds another factor-of-two decrease from vaccination, based on very preliminary studies from the UK. He estimates that someone with my demographics (vaccinated man in his 30s) has a 2% risk of Long COVID conditional on getting COVID at all. Then he divides by five for the true worst case scenario, based on studies showing that a fifth of people with Long COVID report that it affects their daily activities “a lot”. So by his final number, I have an 0.4% chance of getting really terrible long COVID, conditional on getting COVID at all. My friend AcesoUnderGlass also did a writeup of this, published after I did my first-draft calculation, which seems to be thinking of this very differently, based entirely on hospitalization rates (which of course are very low in vaccinated people our age). She accordingly concludes that risk is very low. I don’t really understand her reasoning here, but I trust her a lot and am working on trying to converge with her on this. What’s my yearly risk of getting COVID if I try to live a normal life? This site says only 0.1% of vaccinated Californians have gotten COVID after their vaccination. But vaccination was pretty new when that survey was done, so we might want to take this as a per one-to-two-months estimate. That would mean a risk of 0.5 - 1 percent per year. But not all these people are living normal lives, so my risk might be higher. MicroCOVID gives me a good sense of how careful I’d have to be to stay within a risk budget of 1% COVID risk per year. When I play around with it, I think I am about 5x - 10x less careful than that, which would mean a risk of about 5%/year. This tracker suggests my area has recently had about 1 new case per thousand people per week, which would imply 5% per year. But most of those people are probably unvaccinated, so my risk would be significantly lower than that. I’m going to round all of this off to about 1% - 10% per year of getting a breakthrough COVID case (though obviously this could change if the national picture got better or worse). Combined with the 0.4% to 6.25% risk of getting terrible long COVID conditional on getting COVID, that’s between a 1/150 - 1/25,000 chance of terrible long COVID per year. How does this compare to other risks? My ordinary risk of death per year, just from being a man in his 30s, is about 1/700 (though this includes drug abusers and stunt pilots, so my real risk might be lower, let’s say 1/1000). Here are some other risks, courtesy of the BMJ: In this context, I find the 1/150 risk pretty scary and the 1/25,000 risk not scary at all, so, darn, I guess there’s not yet enough data to have a strong sense of how concerned I should be. 9. This is hard to compare to other postviral syndromes Going into this, I wondered if we might be able to ignore Long COVID. The argument would go like this: all viral diseases have a risk of postviral syndromes. Colds, flus, mono, lots of stuff that’s going around all the time. Lots of people get those postviral syndromes, and either recover or don’t, but either way we don’t make a big deal out of it. Since COVID’s considered “newsworthy” in a way flu isn’t, we obsess over its postviral syndrome even though it’s no worse than anything else’s. This wouldn’t make Long COVID any less bad, and maybe we would be wrong to not panic more about colds and the flu, but it would at least give us some context and make things feel less scary. Unfortunately, I can’t find anything supporting or opposing this picture. The only relevant study is a meta-analysis by Poole-Wright et al, who (contra nominative determinism) don’t pool the studies by condition, which makes it hard to draw conclusions. I think all of their examples of postviral syndrome after flu are from severe hospitalized cases, so any comparison with COVID would be unfair. Although there do seem to be scattered reports of post-flu problems, they’ve never been formally studied or quantified. Mononucleosis is an infectious disease caused by the Epstein-Barr virus, affecting about 1/2000 people per year in developed countries. It has a famously nasty postviral syndrome, which this paper describes as “almost one-half of the group had substantial ongoing symptoms 2 months after onset and… ∼10% had disabling symptoms marked by fatigue lasting ≥ 6 months”. Flu is as common as COVID, but nobody really talks about it having a significant postviral syndrome so probably it’s not that bad. Mono has a worse postviral syndrome than COVID, but it’s rare enough that it doesn’t cause massive society-wide effects. COVID is right in the middle: more common than mono, and (probably) worse postviral syndrome than flu. I think it’s fair to say that we may not have encountered a condition with this exact combination of risk factors and can’t dismiss it as similar to conditions we currently ignore. One potential analogue might be the Spanish Flu of 1918. It was an equally widespread pandemic, and seemed to have some kind of postviral syndrome. From TIME: In what is now Tanzania, to the north, post-viral syndrome has been blamed for triggering the worst famine in a century—the so-called “famine of corms”—after debilitating lethargy prevented flu survivors from planting when the rains came at the end of 1918. “Agriculture suffered particular disruption because, not only did the epidemic coincide with the planting season in some parts of the country, but in others it came at the time for harvesting and sheep-shearing.” Kathleen Brant, who lived on a farm in Taranaki, New Zealand, told Rice, the historian, about the “legion” problems farmers in her district encountered following the pandemic, even though all patients survived: “The effects of loss of production were felt for a long time.” The 1918 flu seemed to have lots of psychiatric effects: “Norwegian demographer Svenn-Erik Mamelund provided such evidence when he combed the records of psychiatric institutions in his country to show that the average number of admissions showed a seven-fold increase in each of the six years following the pandemic, compared to earlier, non-pandemic years.” Coronavirus doesn’t - the excellent Amin-Chowdhury study above finds nothing. Still, this is the scale of thing I’m worried about. The worst case scenario here is really really bad. If a few percent of COVID patients get long-term unremitting genuine CFS/ME, that has the potential to overwhelm government welfare budgets and long-term depress the economy. I think there’s a 90% chance the real situation isn’t that bad, but it’s scary that we can’t entirely rule it out. Aside from the somewhat different 1918 case, I don’t think we have any historical experience of dealing with postviral syndromes at this scale. The medium case scenario is something more like “a few percent of infected people get moderate fatigue, which doesn’t really prevent them from working, and goes away after a few years”. I don’t know whether the level of media attention paid to this would converge on “boring and nobody notices” or “giant disaster”, and I think it would be compatible with either. 10. Conclusions 1. Long COVID is many different issues without a common mechanism. 2. Some of these are straightforward and not surprising, eg lung scarring and post-ICU syndrome from severe infection, and would happen in any disease of this severity. Others seem to be more like the poorly-understood postviral syndromes associated with several other diseases. While some symptoms may be psychosomatic, most are probably organic. 3 The three major categories of symptoms are straightforward cardiovascular-pulmonary issues, straightforward smell and taste issues, and more mysterious neurological issues. 4 Although these get better with time in some people, in a significant number (maybe ~50% of people who had them at six weeks) they persist for as long as anyone has been able to measure them (a few months in the case of COVID, a year or two in the case of comparable syndromes). 5. Post-COVID fatigue is particularly concerning. This would be very bad if we analogized it to CFS/ME, and still pretty bad if we analogized it to other known postviral syndromes. There is no proof that this always gets better over the long term, although no study has looked at them for more than a few years. Facing postviral fatigue on this scale is a new problem. 6 . Children probably get Long COVID less than adults, probably at a rate of less than 5% of symptomatic cases. But we don’t know how much less, and we can’t rule out that some children get pretty severe symptoms. 7. Although vaccination decreases the risk of symptomatic COVID, it probably doesn’t decrease the risk of Long COVID per symptomatic COVID case by very much, though it might decrease it by a factor of 2-3. 8. Your chance of really bad debilitating lifelong Long COVID, conditional on getting COVID, is probably somewhere between a few tenths of a percent, and a few percent. Your chance per year of getting it by living a normal lifestyle depends on what you consider a normal lifestyle and on the future course of the pandemic. For me, under reasonable assumptions, it’s probably well below one percent. EDIT: Here are some other people who tried to do this same analysis. I learned about all of these after I wrote the first draft of this, so you can consider the basic thought process here to be independent of them - but I edited some things to account for what I learned from them before writing the final version. AcesoUnderGlass: Long COVID Is Not Necessarily Your Biggest Problem
Inline links: Lizardman, this Australian study, these people, The Dubious Origins Of Long COVID, weird x-rays, Sniffin Sticks test, somewhere between 60 and 80%, somewhere between 2x and 4x more likely, for example, the creepy shadow war between mother and fetus, Bryan Caplan, wrote, added, Preliminary Evidence On Long COVID In Children, Blankenburg et al, one of them, English team says, Here’s, the scientific paper font, This NEJM study, infection severity is linked to Long COVID risk, this study, vaccines can help relieve symptoms of existing long COVID, this essay, a writeup of this, This site says, MicroCOVID, This tracker, the BMJ, https://substackcdn.com/image/fetch/$s_!yL40!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F1eea7cfa-df08-4c67-acf2-da24ce860ae3_713x373.png, a meta-analysis by Poole-Wright et al, scattered reports, this paper, postviral syndrome
Your Book Review: The Family That Couldn’t Sleep
July 12, 2024 · Original source
(This report was, as it happens, published in the exact same month as The Family That Couldn’t Sleep.) DTM came to know the family well. He befriended them by way of two members of their younger generation, Lisi – a woman terrified by the shadow of the disease, and Ignazio – the doctor she had married, who was more terrified by the shadow of the disease. Ignazio put together the pieces of the family puzzle, consolidating all the disparate diagnoses into a single disorder and filling out a lot of blank spots on family trees. When DTM came along, he was able to help Ignazio make the case that the family would benefit from the spotlight – that greater awareness of FFI could lead to a cure both for them and for a slew of other prion diseases. As it so happens, he is one of those nonfiction authors who serve as a character in their own story. DTM has some form of progressive muscular palsy. He is, or at least was in 2006, not entirely sure what it is. The relatively unimpressive state of genetics at the time had not identified his causative mutation, though it looked a lot like one of the rarer forms of Charcot-Marie-Tooth disease2. DTM is pragmatic about this, the way everyone chronically ill is either pragmatic or doomed. Whatever he has, it is a defect in protein structure; his peripheral nerves decay not because of a problem with the nerves themselves but an inability of their scaffolding to hold them together, as he puts it. The last chapter of the book dwells on this, on the web of connections popping up between a thousand disorders. DTM’s disease is something vaguely similar, if you squint, to an exceptionally slow-progressing motor neurone disease; if you jump another level out, you see amyloid plaque diseases like Huntington’s and Alzheimer’s, and if you jump yet another level out, you see something like prions. His interest in the Venetian family was driven by this. Some of its members thought this a beautiful act of sympathy; others thought him a grotesque parody of themselves, an onlooker, a gawker, peddling their tragedy to salve his relatively insignificant problems. They are, he thinks, both right. That’s the beginning, and that’s the end. What happens in the middle? --------------------------------------------------------- The Venetian family lends the book its title, but they’re really more of a framing device. The Family That Couldn’t Sleep is separated into four parts, of which the first and fourth – the shortest by far – deal with the family. Part 2 is kuru, the king of fucked up diseases you read about in clickbait Weird Medicine listicles. Let’s talk about kuru! Kuru, is, famously, the prion disease you get if you eat another person’s brain. Well, not quite. It’s a prion disease that became endemic amongst women in the Fore society, who ritually ate brains, one of which had an inherited or spontaneous prion disease. This is an important note – there’s a tendency (which the book’s later chapters engage in) to assume cannibalism just has a Prion Disease Generator attached. If you eat people who don’t have prion diseases, you won’t suddenly get one. Uh, don’t eat people. Anyway, part 2 is DTM’s historiography of Fore-Westerner first contact. It’s hilarious. Papua New Guinea is a frankly ridiculous place; one of the all-time best Lyttle Lytton winners (worst first sentence from a hypothetical or, in this case, real work) was “Papua New Guinea is so violent that more than 820 languages are spoken there”. The native residents were so hostile to outsiders that all the colonial empires had cut their losses – and when you think about the places they colonized, that says something. After the First World War, PNG was ripped from its nominal German ‘owners’, but no one else wanted the place. So, of course, they gave it to the Australians. It was thirty years and another war before we actually made contact. 1940s Australia was as ‘settled’ as it’d ever be; the cities were bustling and the interior was mapped. The kind of explorer who two centuries before would be heading to new continents had to console himself with Pacific islands. Console he did. The native peoples of the PNG coasts were hostile enough to the wannabe-colonialists that the Australians, flying planes overhead, were the first people to discover that the island’s inland was populated too. No one had broken through on land. In all this deep and angry rainforest, the Fore were the furthest out. They lived far into the island’s mountainous interior; DTM describes their territory as “nearly vertical”. Calling people primitives is a bit passe these days for understandable reasons, but no other term comes to mind. The Fore had no name for themselves; we call them by an exonym, “the people to the south”. They weren’t, to be clear, hunter-gatherers – they were slash-and-burn agriculturalists, but very well-fed ones. Despite the tendency in grain-focused cultures for poor agriculturalists to be stunted/malnourished, the Fore were a remarkably healthy people. Well, except for the famous bit. The first remarkable thing about the Fore was just how quickly they wanted to assimilate. Most PNG tribes weren’t particularly enthused by Western offers of injections/tractors/radios/Christianity. Yet as soon as the Australians arrived, the Fore made ceasefires in their wars with other tribes, volunteered to help large-scale Australian projects on the coast, started planting and trading coffee, and enthusiastically participated in censuses. It’s the only first-contact narrative I’ve seen where the colonizers were concerned about how badly the other guys wanted to be colonized. The next was the one that got their names in the history books. Australian officials started to notice a remarkable lack of women in Fore camps. Some tribes sequestered their women, particularly when Westerners were around, so at first they thought nothing of it. The high rate of unpartnered young men, though, was way out of PNG norms. DTM tells this part fantastically. The Fore chapters drip with the dread of dramatic irony. When the first breakthrough comes, you have to catch your breath: “Tiny” Carey noted something in the middle of August 1950 that deepened this mystery. He noticed that near the village of Henganofi there had been an unusual number of deaths. “It appears,” he wrote his superiors, “natives suffer from stomach trouble, get violent shivering, as with the ague, and die fairly rapidly.” [...] McArthur investigated a little more [...] One day in August 1953 he ran into more of the shivering people Tiny Carey had seen several years before: “Nearing one of the dwellings, I observed a small girl sitting down beside a fire. She was shivering violently and her head was jerking spasmodically from side to side.” It would be quite some time before anyone figured out what caused it – but the problem, as DTM notes, was that its cause wasn’t possible. Everyone priored that the weird undescribed disease in the Fore lands was some nocebo sorcery-sickness. Vincent Zigas, the first actual doctor sent to work with the Fore, tried to placebo-effect them and failed miserably: On the way, Apekono stopped at a hut and showed Zigas his first kuru victim. “On the ground in the far corner sat a woman of about thirty,” the doctor wrote. “She looked odd, not ill, rather emaciated, looking up with blank eyes with a mask-like expression. There was an occasional fine tremor of her head and trunk, as if she were shivering from cold, though the day was very warm.” It was almost exactly the tableau McArthur had witnessed in 1953. Zigas, though, was a doctor. He could do more than look—or so he thought: “I decided I might as well try my own variety of magic,” he remembered. He rubbed Sloan’s Liniment, a balm for sore muscles, on her and declared to her family and his guide: “The sorcerer has put a bad spirit inside the woman. I am going to burn this spirit so that it comes out of her and leaves her. You will not see the fire, but she will feel it. The bad spirit will leave her and she will not die.” The lotion penetrated the woman’s skin and she writhed in pain. “Get up! Walk!” Zigas commanded theatrically. “The woman struggled feebly as if to rise, then, exhausted, started to tremble more violently, making a sound of foolish laughter, akin to a titter.” That evening Apekono asked Zigas not to try to cure any more kuru victims; “Don’t use your magic medicine anymore. It will not win our strong sorcery.” This was a disaster. The Fore were so cooperative precisely because they hoped “Western magic” could conquer theirs. As it became clear it couldn’t, they turned hostile. The Australians had hoped to “modernize a Stone Age people”; now all their subjects were dropping dead before their eyes, from what they could only assume was a “hysterical reaction” to colonization itself. So, to solve this, they needed a batshit insane American. Carleton Gajdusek is one of the characters who dominates The Family That Couldn’t Sleep. He couldn’t not. You could put him in a car commercial and he’d dominate it. Gajdusek was a physician with a rare, intense combination of science and practice. He was a romanticist, a field worker, and a lover of everything strange. He’d been an army doctor, a government conspiracy-cover-upper, and a postdoc under Linus Pauling who described his intent as “to straighten out Pauling’s ideas about proteins”. He hated civilization, in a slightly-to-Ted’s-centre sense, and was passionate about “primitives and isolates”. He jumped at the chance to work in Papua New Guinea; he planned to conduct a multi-site study on child development in such cultures, and relished the opportunity to live in a “primitive” environment himself. He did all this so he could rape kids. Oh, he did it for the scientific curiosity and love of medicine, but he also did it so he could rape kids. Gajdusek was a pedophile in the actual-lifelong-exclusive-paraphilia sense, as opposed to the “metonym for child molester” sense. Some people who roll snake-eyes on the Sexuality Dice repress it, but some are perfectly happy to act on it; Gajdusek was #2 in its fullest form, the kind of guy who believes that a well-lived life includes raping some kids. DTM doesn’t shy from this, not for a moment. It’s the first thing he tells you about Gajdusek. It couldn’t not be; you couldn’t talk about why he went to PNG otherwise. When Gajdusek landed in PNG, he first found the place too civilized. He’d been promised a land of “cannibal savages” – where were they? After some traipsing, he found them, right where he was promised. The Fore were perfect for Gajdusek. They had some kind of medical mystery that’d been lost on everyone else. They ate each other, in exactly the way he loved detailing in his diaries (“”Women and children, particularly, partake of the human flesh,” he noted with pleasure”). As kuru cases popped up, he aggressively recorded them. He wrote lovingly detailed notes that he sent back to his Australian advisor. He wrote with intensity, with exclamation marks, with the joie de vivre of a man just where he wanted to be. Gajdusek smothered the Fore with ‘cures’ that never worked, but they didn’t get angry at him. As DTM dryly puts it: “Their children trusted him, and that was enough for them.” At some point, someone suggested sending an anthropologist...or an epidemiologist...or literally anyone with more credentials than Gajdusek and Zigas3. Gajdusek threw a shitfit, convinced this one-and-a-half-man team was enough to Solve The Problem Forever. But he got bored eventually – running off with another tribe with, as his diary notes at length, an apparent custom of youths ritually fellating older men – and Zigas, I dunno, the book neglects him a bit here. So they managed to sneak in some anthropologists. The husband-and-wife team of Robert Glasse and Shirley Lindenbaum4 were the first involved parties to give a shit about the Fore as people, rather than as colonial subjects/medical mysteries/walking sex toys. What they uncovered was fascinating. The Fore were cannibals, yes, but they were recent cannibals. They didn’t have an ancient tradition of eating their dead, like the other visitors assumed. They happened to be in contact with some cannibal groups, and after a Fore man died of “sorcery”, they thought: well, what would happen if we ate him? “People tasting it expressed their approval. ‘”This is sweet,” they said, “What is the matter with us, are we mad? Here is good food and we have neglected to eat it.”” If not for the wild coincidence that the first Fore cannibalism victim had a prion disease, kuru would never have existed. Glasse and Lindenbaum started to put together the pieces. They’d been sent down to rule out a genetic explanation – to track the kinship ties of the Fore and see how the disease ran through families. It didn’t run through families in any coherent sense, but it sure did run through cannibalism. The clincher was the age distribution. The Fore, ever enthused by colonialism, quit eating each other as soon as the Australians arrived. Children stopped dying of kuru shortly after; they simply weren’t exposed to the infectious agent. The couple sent the news to Gajdusek, who was off raping kids somewhere else. In the next part of the book, DTM runs through Gajdusek’s many conjectures of kuru’s cause – more like sketches or abstract paintings than like true hypotheses. Gajdusek was annoyed that someone else was doing something he “totally could’ve done”, and even more annoyed that another lab was running similar experiments – an attempt at a vaccine for a particular sheep disease had accidentally created a prion generator. But he was happy to swoop in and claim the credit for what he was starting to think of as “slow viruses”, an infection that somehow lays dormant for years. DTM portrays Gajdusek perfectly, in that “real life has no need for verisimilitude” way. Gajdusek was at once a brilliant man, an all-consuming narcissist, an entertaining character, and a monster beyond redemption. A lesser book might pick one or two. The Family That Couldn’t Sleep portrays him as all four, and on a personality level (as opposed to a scientific one), the Gajdusek-focused parts are some of the most gripping. --------------------------------------------------------- Outside of the jumps between the Venetian family and everything else, The Family That Couldn’t Sleep is not siloed. The narratives of all prion diseases are deeply intertwined. This is what makes it a great book. It’s 300 pages of dramatic irony. You read the whole thing, waiting for the eureka moment – the point everyone realizes they’re looking at the same cause. It does, however, make it a tad difficult to review or synopsize. The book’s story is so weird – and, often, so at odds with conventional wisdom that trickles down about the Fore et al – that you have to recap quite a bit, and the book steadfastly resists recapping. The next couple chapters after we depart from Gajdusek’s credit-claiming are mostly about experiments with various prion diseases. They’re scientifically fascinating. Unlike some medical-books-for-general-audiences (cough, How Not to Study a Disease), DTM never talks down to the reader. He assumes someone reading a 300-page book about prions is smart and wants to learn about prions. He also has – you can feel it in his words – the agonizing experience of spending his life on the other side of the doctor’s desk, trying to beat into whoever he’s talking to that no, seriously, you don’t need to lie to him or try explain a complex disease at a fourth-grade level. The first prion disease studied was scrapie. Scrapie was a big deal – it starved and killed large shares of British sheep flocks, making it a serious economic problem. Veterinary researchers had tried to prevent or cure it for centuries. It was a veritable graveyard of ambitions: Quintessential was D. R. Wilson at the Moredun Institute in Scotland, who worked in the middle of the last century for more than a decade trying, with mounting frustration, to kill the scrapie agent. He found that it survived desiccation; dosing with chloroform, phenol, and formalin; ultraviolet light; and cooking at 100 degrees centigrade for thirty minutes. The scrapie researcher Alan Dickinson told me he remembered Wilson at the end of his career as “very, very, very quiet. Of course, that was after his breakdown.” “Now it is our turn to study prions. Perhaps we should approach the subject cautiously.” The problem, as DTM explains, is that prion diseases were impossible. They violated 20th-century understandings of biology. Proteins “were no more alive, and no more infectious, than bone”. Prion diseases seemed to have too many causes – genetic, infectious, and sporadic. They looked infection-like in some ways, but patients didn’t produce virus antibodies. Sheep exposed to scrapie, or chimps infected with kuru, took years to develop symptoms. Their facts did not fit together. In the 1960s, people started wondering. The unifying trait of prion agents was that they had to be denatured to be destroyed. Was this a particularly small virus defined by its protein coating? Or – even more outre – was it pure protein, no DNA at all? No one could figure out quite how the latter worked, but it was tempting. Gajdusek, by now a major figure in this field, kept a foot in both worlds. He didn’t want to stake his reputation on a no-DNA hypothesis, but he certainly sympathized. Enter Prusiner. Stanley Prusiner was Gajdusek’s counterpart. Where Gajdusek seemed permanently manic, Prusiner was deliberate and exacting. He entered Gajdusek’s “slow viruses” field in the early 1970s after a chance encounter with a CJD patient. He relished the laboratory in a way Gajdusek didn’t at all, and set out to optimize the hell out of his projects. Prusiner set out to isolate the smallest infectious particle in the scrapie agent. He injected tons of hamsters (hamsters got sick faster than mice) with increasingly tiny scrapie proteins, hoping to determine whether the Minimum Viable Scrapie was DNA. By the mid-1980s, he’d produced something so small it couldn’t possibly be a virus. Denaturing it destroyed it; exposing it to nucleic acid dissolvers actually made it stronger. Emboldened by this discovery, Prusiner set out to anoint himself the King of Prions. Here emerges something of a Voldemort-Umbridge distinction – the difference between cartoonish villainy and banal evil. Gajdusek is a bad guy because he rapes kids. Prusiner is a bad guy because he is the most grotesque stereotype of the Advisor/Peer Reviewer from Hell made flesh. Everything Prusiner did was to build his reputation atop a pile of skulls. When recruited as a peer reviewer for other prion papers, he wrote negative reviews to undermine their authors. He worked his grad students to the bone and intentionally destroyed their careers, telling them he’d “ruin them” if they entered prion research as competitors. He lied about the origin of the protein-only hypothesis, claiming he originated it a decade after it was actually conjectured. But hey, he was good at getting grants. I was surprised reading a lot of this, because for all the time I’ve been aware of it, the cause of prion disease has seemed settled. “Oh yeah, it’s a protein that gets all fucked up.” But DTM goes through just how unsettled it was right up through to The Family That Couldn’t Sleep’s publication. Serious confirmation only arrived a couple years later. Many people were deeply critical of the prion hypothesis – often, it seemed, because they loathed Prusiner too much to go along. Throughout the book, he cuts an uncharismatic figure. Gajdusek and Prusiner both won the Nobel for discovering prions, decades apart. This tells you something – the “discovery” of prions can be construed quite a few ways. Gajdusek formulated the hypothesis; Prusiner proved it. Gajdusek was grievously offended by Prusiner’s Nobel, perceiving his rival – not inaccurately – as a follower who never originated any ideas of his own. But Gajdusek was offended from a federal prison cell, so how’d that work out for him? Fascinating as all this is, no one published a book about prions in the mid-2000s because it was about kuru or FFI. They published books about prions because teenagers were dying, and people wanted to know why. DTM lays the seeds for part 3 – the mad cow section – in part 1. This is a discussion of scrapie, the longstanding prion disease of sheep. Scrapie was a medical mystery for centuries (remember poor D. R. Wilson), precisely because of the intuitive implausibility of prions. The scrapie chapter is a great history-of-science piece, covering the agricultural productivity revolutions of the 18th century, the surfeit of bizarre origins veterinarians concocted, and the treatments that never worked. Scrapie is not transmissible to humans – well, we hope. It’s concerningly transmissible to primates. But it’s been around for a long, long time, and it doesn’t epidemiologically look like humans get it...we hope. Anyway, you ever tried to generalize from one example? The British government did! In the mid-1980s, strange reports started coming out of the UK’s farms. Farmers were describing a new disease where dairy cows – incredibly docile creatures, under normal circumstances – turned hostile, kicking them as they went into the milking stalls. The symptoms looked to all the world like scrapie. Epidemiologists tracing the outbreaks found a unifying link with “cake” – animal protein feed sweetened with molasses. The scrapie-like symptoms must have traced to an infected sheep. But scrapie doesn’t transmit to humans, so it must be okay to keep slaughtering them, right? We all know how this ended. The best term for the British response to the mad cow outbreak is “cacklingly evil conspiracy”. The agricultural industry really, really didn’t need a huge zoonotic outbreak – so it decided it didn’t have one. They first suppressed all mentions that the disease looked like scrapie, then – when this became impossible – hyped up that scrapie doesn’t transmit to humans, so there’s nothing to worry about. The formal name of the disease, “bovine spongiform encephalopathy”, was supposedly chosen to optimize for unfamiliarity – it wouldn’t fit well in a headline. They emphasized, extensively, that there was nothing to worry about. Ever. At some point, people started asking questions. If there was nothing to worry about, why was the agricultural industry panicking so hard? As things became ever more worry-inducing, this turned down ludicrously twisting paths: Meanwhile, the Southwood Working Party and the experts who advised it were learning on the job. They learned, for instance, that the BSE agent entered the animal through the mouth and then followed the digestive tract into the organs that try to filter out infections—the tonsils, the guts, and the spleen—and from there traveled into the peripheral and central nervous system, and finally arrived at the brain. They also learned that pasties, meat pies, and even some baby foods contained tissues from a lot of those organs. So the Southwood Working Party recommended banning these organs, but only from baby food. This started a chain reaction of consumer doubt: if infected cow organs were unsafe for babies, how could they be good for adults? The government then banned offal, as the organs were collectively called, in all human food but gave the industry a grace period to get it out of the feed supply. Then pet food manufacturers began to wonder if what drove cows mad might not also drive dogs, cats, and parrots mad. The feed they sold came from concentrate made of the same sick animals that had previously made up the meat and bone meal farmers used. Their trade group decided to put a similar ban in place—immediately. So for five months it was safer to be a dog than a human in Britain. DTM spends pretty much this whole section of the book making fun of the British government. To be fair, they deserved it. They killed hundreds of kids in agonizing and preventable ways – they could take some ribbing. This is all throughout the mid-1980s to early-mid 1990s. Through this period, it wasn’t yet clear that mad cow could spread to humans. The panic was clear, and deserved, but it didn’t yet have a match for its powder keg. It would alight. The first suspected case of vCJD – human mad cow – was in 1994. Fifteen-year-old Vicky Rimmer developed a sudden, strange disease. Doctors gave her months to live...until she died in 1998. A couple other suspected cases trickled down through the mid-90s, including a young man who made meat pies for a living, whose grieving mother received a letter from the Prime Minister that “humans do NOT get mad cow disease”. (That must’ve been fun.) Soon, they couldn’t deny it any longer. On March 20, 1996, Stephen Dorrell, the health secretary, stood up in Parliament to announce the news that had already appeared as a tentative conclusion in scientific journals and as rumor in newspapers for the previous two years: British beef was killing British teenagers. The first confirmed death was that of Stephen Churchill, a nineteen-year-old student from Wiltshire, who died in May 1995. Back in 1989, at the Southwood Working Party’s suggestion, the government had set up a surveillance unit in Edinburgh to watch for any evidence that BSE had crossed to humans. One worry had been that if BSE passed to humans, how would anyone know it? How would you recognize something you had never seen? It turned out to be easy: Churchill and the nine other teenagers who had gotten sick had spectacular amyloid plaques in their brains, chunks of dead protein almost visible to the naked eye. If sporadic CJD was a whisper, BSE-caused prion disease was a shout. The investigators sat open-mouthed looking at slides whose damage, they feared, portended the most severe epidemic in modern British history. This part of the book is not fun. It lacks the insane personalities and duelling careers of the other entries. It is an honest chronology of the vCJD epidemic – a gruesome failure of the agricultural industry, the one system that everyone is vulnerable to. The government and industry had completely violated their duty of care to citizens and consumers. They were paying the price. No one would buy British beef anymore – not while they watched their children die. Now here’s the thing: this is ethnography, not historiography. The Family That Couldn’t Sleep is a book from the mid-2000s. The epidemic was not at all in the rear view mirror. There were piles of unanswered questions that DTM constantly alludes to. We have eighteen years more hindsight than he did then. What do we know now? --------------------------------------------------------- In 2006, the vCJD epidemic looked like it was going to be a lot better than the worst fears. BSE itself was a huge problem for the cattle industry, but honestly, no one is too sympathetic to the cattle industry. People were not going to die in anywhere near the numbers believed. We had all sorts of reassuring data coming out about this, which DTM chronicles. We were learning that only some genotypes seemed susceptible to vCJD. We didn’t see any older people die of the disease. We were seeing numbers drop, such that vCJD must have a pretty short incubation period. Anyway, all of this is wrong! The Family That Couldn’t Sleep was written in the candidate gene era. Back then, the nascent field of human genetics was sure it was about to Solve Polygenism. Yes, the simple Mendelian monogenic patterns popular a few decades back clearly didn’t apply to common diseases, but how many variants could there be? We were about to discover the five genes influencing 20% of Alzheimer’s risk each, the five genes influencing 20% of heart disease risk each, etc., and once we were done we’d just do gene therapy and cure Alzheimer’s. A paper on autism genetics from 1999 was so outre as to speculate there might be as many as fifteen genes involved. The fact we are now using the term “omnigenic model” should tell you roughly how well this worked out. Do you remember SNPedia? If you were a 2014 Slate Star Codex reader, you might. 2014 was still pretty candidate gene. People were out there publishing papers saying a single variant could increase your life expectancy by 15 years. SNPedia was a site that beautifully categorized all of these, so you could do 23andme or whatever, look up your results on SNPedia, and make horrible life choices.5 It was eventually bought out by one of the consumer DNA companies, so no one ever edited it again, making it a great time capsule of early-mid 2010s behavioural/medical genetics takes. SNPedia will excitedly explain to you that common genetic variants make you immune to vCJD. They cite a 2009 post from the now-archived 23andme blog titled “No Good Evidence That Potential Pool of Mad Cow Disease Victims Is Expanding”, explaining how fears of late-onset vCJD are clearly debunked by new Scientific Knowledge. Everyone who developed vCJD in the 1990s and 2000s had an M/M genotype in a particular part of the PRNP prion gene, so the roughly half the population with M/V or V/V genotypes were immune. The Family That Couldn’t Sleep buys this, too. In fact, it buys it in an even more agonizingly 2000s way. The first sign that transmissible prion diseases weren’t genotype-restricted should’ve been the growth hormone kids. You might have heard this story – from the late 1950s through mid-1980s, human growth hormone produced from brain tissue was used as a treatment for pituitary dwarfism, until it turned out to spread CJD if the originating brain was infected. DTM discusses this, to set the scene for the genetics thing. He mentions what was the state of the art at the time – that a disproportionate share of both the growth hormone kids and sporadic CJD cases were V/V homozygotes. This, uh – so the book was written in the mid-2000s, yeah? Yeah. The conclusion DTM drew – and this was a common conclusion at the time – was that homozygosity somehow made you more vulnerable to CJD, and M/M homozygosity made you vulnerable to BSE-borne CJD in particular. We cannot criticise the author for not predicting the future, but we live in the future, and can say how this worked out. Turns out, nope, M/V heterozygotes totally get vCJD. After a British man in his 30s died of CJD in 2016, he was found to have vCJD and an M/V genotype. He was tested for vCJD only because he was exceptionally young for someone with a sporadic prion disease – meaning people developing it later in life would be missed6. Did you know up to 1 in 2000 people in the UK have latent vCJD? There is one line in The Family That Couldn’t Sleep that stopped me dead in my tracks when I read it: What happens to the Italian family in the end depends less on their own actions than on the world’s interest in prion diseases, which they cannot control. If lots of people are afraid of getting variant CJD, the family benefits. If fear of prion disease goes the way of the fear of swine flu or Ebola, then they will be orphaned again. THIS BOOK IS FROM 2006! Three years before the swine flu pandemic! Eight years before the Ebola pandemic! “If you’re looking for a sign, this is it.” --------------------------------------------------------- The last section of The Family That Couldn’t Sleep addresses BSE fears in America and a nascent internet subculture DTM calls “Creutzfeldt Jakobins” – people who track American CJD cases, trying to spot vCJD patterns. When reading his description of the Creutzfeldt Jakobins, my mind constantly, uncontrollably turned to covid. Here it was – an online community of people deeply skeptical about a disease’s official story, tracking every contradiction, every implausibility, every statistic that failed to apply to the individual. Self-described “redneck hippies” and “soccer mom Republicans” teaming up to find the truth hidden behind an impossible world. You know what they’re doing now. I’ve always combined a deep interest in medicine with a healthy distrust for it. People who are constitutionally inquisitive, anti-authoritarian, and suspicious about official narratives tend to end up skeptical of at least some mainstream claims in the field. This is not to say I think you should take bleach enemas or something, just that I understand the impulse behind concluding the US government was covering up a local vCJD wave. Traditionally, sporadic prion diseases are said to have a prevalence of one in a million. (Hold on to that for a second.) The last section of the book is a chronology of Americans finding bizarrely more than one in a million of their friends dying of sporadic CJD, often at inexplicably young ages, sometimes in geographical clusters. This is understandably suspicious. Then DTM goes on to reassure us by saying none of these cases were confirmed to have an M/M genotype, which OH GOD OH FUCK A number of high-profile people in the prion world, including Gajdusek, are clarified as not believing sporadic prion diseases exist. You get the impression DTM doesn’t, either. Now, how common are prion diseases? Eric Vallabh Minikel has an answer for you! Eric and his wife Sonia are prion researchers from a rather unique background – after Sonia was diagnosed as having a single-gene mutation with ~100% penetrance for prion disease, they left their previous jobs to dedicate their lives to curing it. It turns out, when you run the numbers, you get not one in a million but 1 in 5000 people dying of prion diseases. This is best described as “nightmarishly high”. I’m normed on genetic disorders. A genetic disorder that affects one in five thousand people is pretty common! I have known, in person, completely unselected, just from “random people I’ve met in my life in a non-medical context”, someone with a ~1/250k syndrome and someone with a ~1/50k-100k syndrome. I don’t think anyone in my extended family knows someone who died of a prion disease. I feel like it would’ve come up if they did! Prion diseases have distinctive phenotypes. Not distinctive enough, apparently, to avoid a lot of CJD being misdiagnosed as Alzheimer’s – but diagnosis is consistently insane. Something DTM reiterates throughout The Family That Couldn’t Sleep is just what prion dementia looks like. The characteristic dementia in prion diseases spares something – “self” or “recognition” or “reflection” – that is not spared by Alzheimer’s, or by most common dementias. Shouldn’t this be, uh, noticeable?7 They kill rapidly, often over the course of months, and often onset in midlife. ALS shares this pattern and is way, way more common than prion diseases; you hear about ALS far more in the “disorder people actually have” sense. What am I missing here? Anyway: 1 in 2000 prevalence of latent vCJD in the UK + extreme lack of clarity over whether scrapie is human-transmissible + blood donations spread vCJD + sporadic CJD prevalence keeps going up = ??? (Yes, I am annoyed that most countries have lifted their ban on UK blood donors, thank you for asking!) --------------------------------------------------------- But back to the book. The “American chapter” is one-third about the country’s response to vCJD, one-third about the Creutzfeldt Jakobins, and one-third about chronic wasting disease. The last part is the most interesting. Chronic wasting disease is a prion disease of deer. Like scrapie, it “probably, we hope” isn’t human-transmissible (eat venison at your own risk). Under natural circumstances, deer shouldn’t get prion diseases: A prion plague should not be possible among ruminants in the wild. Deer are not cannibals, as the cows that spread BSE were forced to be; and, because deer and elk are not domesticated, they do not have enough contact with one another to spread a prion infection the way sheep are thought to spread scrapie. But deer do not live as they used to live, humans having once again brought their ambitions to bear on the natural course of things. The Family That Couldn’t Sleep is a book of medical anthropology. Anthropology of the Veneto, anthropology of Papua New Guinea, anthropology of 1990s Britain. Here, it is an anthropology of America. Americans, having won the world, still fight to win their own backyard. The North American continent is geographically diverse, cutting through rain-snow-shine, mountains jutting over plains, cities sprawling into wilderness, habitations criss-cross dotted with surprisingly few empty zones. Go somewhere like Denver, the Mile High City, three million people fighting against nature. Few other countries have anything like this; geographically vast polities usually have uninhabitable blocks. Australians are twenty-five million people clustered against the shore. It still surprises me, after all this time, how every US state has a meaningful city8. Midcentury Denver, growing and sprawling out across its mountains, started to run into their natural inhabitants – deer. Starvation is one way nature adjusts the deer population to the available food supply. People did not usually see this process, but in the 1950s and 1960s Colorado became more densely settled, reducing forested areas and forcing deer to look longer and harder for food. At the same time, the state enacted conservation laws, limiting when and where hunters could shoot. Soon emaciated deer began wandering onto the lawns and through suburban streets looking for a meal. People began to feed them, only to find that they died anyway. They would drop dead by haystacks, along highways, and in flower beds. In the late 1960s, a young biologist named Gene Schoonveld tried to figure out why the deer starved even when they were fed.9 He deprived some deer of food for a while, “[h]e cut windows in their stomachs to see what went on inside, and then he began to feed them”. While this was going on, he had a control group of healthy, well-fed deer as backups in case anything went wrong. It did...but not to the experimental group. The pen in which the deer were kept also housed sheep, which, it turned out, were scrapie carriers. The deer somehow acquired scrapie – there’s a huge unanswered question here, which DTM doesn’t address. How did they get scrapie? They didn’t eat the sheep, presumably. Did it somehow transmit from casual contact? This is not supposed to happen. And yet: the deer in the sheep pen started dying of a mysterious scrapie-like disease, one never reported before, that would go on to infect thousands. These deer were released into the wild. Ten years later, the first reports of chronic wasting disease came out. The disease spread across deer and elk in the western half of the country. By the turn of the millennium, cases were exploding – and lost all geographical restriction. DTM can report up to 2005, at which point it was floating around Upstate New York. This kind of spread doesn’t track natural deer migration. That’s irrelevant, because nothing about CWD’s spread is natural. We shift gears into an anthropology of the American hunter. The hunter wants to shoot the most impressive buck, to bag himself one with as many “points” as possible – one whose antlers branch out most. A “ten-point buck” has five branches on each horn: Original by Ric McArthur Nature doesn’t make enough bucks with perfectly symmetrical ten-point horns. To fill the demand, the market had to step in. Thus was born the deer farm industry, which raises captive deer in better genetic and nutritional conditions than Nature permits, then ships them across the country so hunters who couldn’t get legit ten-point bucks get the taxidermy piece for their wall. These are controversial amongst hunters and illegal in numerous states – but the industry is big enough to spread CWD. (The kind of hunter who needs a deer shipped to his house is the kind of hunter who will fumble killing it.) Another problem is supplemental feeding – leaving out protein-enriched food for deer to eat. This produces “trophy class animals at an earlier age”, but again, what’s in that protein? (“It is much like feeding your cows 41 percent protein cottonseed cake during the winter to raise the protein level in the cow’s diet to a level that will maintain acceptable production”, says that article from 1991.)10 The book segues into a vignette. CWD was new in Wisconsin in the early 2000s, and the state’s Department of Natural Resources was optimistic it could eradicate it. In a state with a love of hunting, you could, in theory, recruit people to kill every single deer in a 400-square-mile radius: In many states, the state would have had to call out the National Guard for such an onslaught, but hunting is a passion in Wisconsin. Hunters shoot 450,000 deer every year, more than in any other state. “I’m looking for ardent hunters to help us, unless fear or their wives keep them away,” one DNR official told a Milwaukee magazine. The state extended the normal hunting season and waived the usual limit of one buck per hunter, and the hunters came out in force. The whole affair was gruesome – one official called it “hunting for slob hunters”. If you’re trying to eradicate a prion disease, you can’t very well let people take the carcasses home to eat. Bodies piled up in control stations, decomposition mingling with bleach. The 2002 hunt established a base rate of 2% for chronic wasting disease in Wisconsin deer, with the most affected areas getting up to 10%. Further hunts in 2003, 2004, and 2005 spread to wider and wider areas – and didn’t move the needle one bit. This is to say that CWD is quite a bit more common in the American deer population than BSE ever was in British cattle. Since publication, it’s popped up in Norway and South Korea. Notably, Norway doesn’t allow for the import of cervids, raising numerous questions about how it got there. There are no unambiguous cases of CWD transmission to humans, and in vivo/in vitro primate studies have mixed results. There sure are some unusually young hunters with sporadic CJD, though. But don’t worry, most of them aren’t M/M homozygotes! There is an absolute ton going on in this book. I’ve had to skim over whole sections. Parts that couldn’t be easily slotted into a narrative review include: When Gajdusek was invited to a party at Prusiner’s house, he was horrified to find his rival had purchased hundreds of New Guinean statues – all with the genitals removed.
Inline links: 2, Lyttle Lytton, 3, 4, a couple years later, concerningly transmissible to primates, omnigenic model, you might, 5, SNPedia, a 2009 post, https://substackcdn.com/image/fetch/$s_!N93S!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fced2eca3-ec58-40b8-8c13-debdb559ab8f_651x601.png, Yeah., nope, M/V heterozygotes totally get vCJD, 6, up to 1 in 2000 people in the UK have latent vCJD, bleach enemas, has an answer for you, 7, blood donations spread vCJD, going, up, 8, 9, not supposed to happen, https://substackcdn.com/image/fetch/$s_!0J8B!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F2a64b287-a7c6-4d82-bbe1-da949fc93118_1024x683.png, Ric McArthur, controversial, amongst, hunters, illegal in numerous states, trophy class animals at an earlier age, 10, Norway, South Korea, mixed results, sure are
Yeah. The conclusion DTM drew – and this was a common conclusion at the time – was that homozygosity somehow made you more vulnerable to CJD, and M/M homozygosity made you vulnerable to BSE-borne CJD in particular. We cannot criticise the author for not predicting the future, but we live in the future, and can say how this worked out. Turns out, nope, M/V heterozygotes totally get vCJD. After a British man in his 30s died of CJD in 2016, he was found to have vCJD and an M/V genotype. He was tested for vCJD only because he was exceptionally young for someone with a sporadic prion disease – meaning people developing it later in life would be missed6. Did you know up to 1 in 2000 people in the UK have latent vCJD? There is one line in The Family That Couldn’t Sleep that stopped me dead in my tracks when I read it: What happens to the Italian family in the end depends less on their own actions than on the world’s interest in prion diseases, which they cannot control. If lots of people are afraid of getting variant CJD, the family benefits. If fear of prion disease goes the way of the fear of swine flu or Ebola, then they will be orphaned again. THIS BOOK IS FROM 2006! Three years before the swine flu pandemic! Eight years before the Ebola pandemic! “If you’re looking for a sign, this is it.” --------------------------------------------------------- The last section of The Family That Couldn’t Sleep addresses BSE fears in America and a nascent internet subculture DTM calls “Creutzfeldt Jakobins” – people who track American CJD cases, trying to spot vCJD patterns. When reading his description of the Creutzfeldt Jakobins, my mind constantly, uncontrollably turned to covid. Here it was – an online community of people deeply skeptical about a disease’s official story, tracking every contradiction, every implausibility, every statistic that failed to apply to the individual. Self-described “redneck hippies” and “soccer mom Republicans” teaming up to find the truth hidden behind an impossible world. You know what they’re doing now. I’ve always combined a deep interest in medicine with a healthy distrust for it. People who are constitutionally inquisitive, anti-authoritarian, and suspicious about official narratives tend to end up skeptical of at least some mainstream claims in the field. This is not to say I think you should take bleach enemas or something, just that I understand the impulse behind concluding the US government was covering up a local vCJD wave. Traditionally, sporadic prion diseases are said to have a prevalence of one in a million. (Hold on to that for a second.) The last section of the book is a chronology of Americans finding bizarrely more than one in a million of their friends dying of sporadic CJD, often at inexplicably young ages, sometimes in geographical clusters. This is understandably suspicious. Then DTM goes on to reassure us by saying none of these cases were confirmed to have an M/M genotype, which OH GOD OH FUCK A number of high-profile people in the prion world, including Gajdusek, are clarified as not believing sporadic prion diseases exist. You get the impression DTM doesn’t, either. Now, how common are prion diseases? Eric Vallabh Minikel has an answer for you! Eric and his wife Sonia are prion researchers from a rather unique background – after Sonia was diagnosed as having a single-gene mutation with ~100% penetrance for prion disease, they left their previous jobs to dedicate their lives to curing it. It turns out, when you run the numbers, you get not one in a million but 1 in 5000 people dying of prion diseases. This is best described as “nightmarishly high”. I’m normed on genetic disorders. A genetic disorder that affects one in five thousand people is pretty common! I have known, in person, completely unselected, just from “random people I’ve met in my life in a non-medical context”, someone with a ~1/250k syndrome and someone with a ~1/50k-100k syndrome. I don’t think anyone in my extended family knows someone who died of a prion disease. I feel like it would’ve come up if they did! Prion diseases have distinctive phenotypes. Not distinctive enough, apparently, to avoid a lot of CJD being misdiagnosed as Alzheimer’s – but diagnosis is consistently insane. Something DTM reiterates throughout The Family That Couldn’t Sleep is just what prion dementia looks like. The characteristic dementia in prion diseases spares something – “self” or “recognition” or “reflection” – that is not spared by Alzheimer’s, or by most common dementias. Shouldn’t this be, uh, noticeable?7 They kill rapidly, often over the course of months, and often onset in midlife. ALS shares this pattern and is way, way more common than prion diseases; you hear about ALS far more in the “disorder people actually have” sense. What am I missing here? Anyway: 1 in 2000 prevalence of latent vCJD in the UK + extreme lack of clarity over whether scrapie is human-transmissible + blood donations spread vCJD + sporadic CJD prevalence keeps going up = ??? (Yes, I am annoyed that most countries have lifted their ban on UK blood donors, thank you for asking!) --------------------------------------------------------- But back to the book. The “American chapter” is one-third about the country’s response to vCJD, one-third about the Creutzfeldt Jakobins, and one-third about chronic wasting disease. The last part is the most interesting. Chronic wasting disease is a prion disease of deer. Like scrapie, it “probably, we hope” isn’t human-transmissible (eat venison at your own risk). Under natural circumstances, deer shouldn’t get prion diseases: A prion plague should not be possible among ruminants in the wild. Deer are not cannibals, as the cows that spread BSE were forced to be; and, because deer and elk are not domesticated, they do not have enough contact with one another to spread a prion infection the way sheep are thought to spread scrapie. But deer do not live as they used to live, humans having once again brought their ambitions to bear on the natural course of things. The Family That Couldn’t Sleep is a book of medical anthropology. Anthropology of the Veneto, anthropology of Papua New Guinea, anthropology of 1990s Britain. Here, it is an anthropology of America. Americans, having won the world, still fight to win their own backyard. The North American continent is geographically diverse, cutting through rain-snow-shine, mountains jutting over plains, cities sprawling into wilderness, habitations criss-cross dotted with surprisingly few empty zones. Go somewhere like Denver, the Mile High City, three million people fighting against nature. Few other countries have anything like this; geographically vast polities usually have uninhabitable blocks. Australians are twenty-five million people clustered against the shore. It still surprises me, after all this time, how every US state has a meaningful city8. Midcentury Denver, growing and sprawling out across its mountains, started to run into their natural inhabitants – deer. Starvation is one way nature adjusts the deer population to the available food supply. People did not usually see this process, but in the 1950s and 1960s Colorado became more densely settled, reducing forested areas and forcing deer to look longer and harder for food. At the same time, the state enacted conservation laws, limiting when and where hunters could shoot. Soon emaciated deer began wandering onto the lawns and through suburban streets looking for a meal. People began to feed them, only to find that they died anyway. They would drop dead by haystacks, along highways, and in flower beds. In the late 1960s, a young biologist named Gene Schoonveld tried to figure out why the deer starved even when they were fed.9 He deprived some deer of food for a while, “[h]e cut windows in their stomachs to see what went on inside, and then he began to feed them”. While this was going on, he had a control group of healthy, well-fed deer as backups in case anything went wrong. It did...but not to the experimental group. The pen in which the deer were kept also housed sheep, which, it turned out, were scrapie carriers. The deer somehow acquired scrapie – there’s a huge unanswered question here, which DTM doesn’t address. How did they get scrapie? They didn’t eat the sheep, presumably. Did it somehow transmit from casual contact? This is not supposed to happen. And yet: the deer in the sheep pen started dying of a mysterious scrapie-like disease, one never reported before, that would go on to infect thousands. These deer were released into the wild. Ten years later, the first reports of chronic wasting disease came out. The disease spread across deer and elk in the western half of the country. By the turn of the millennium, cases were exploding – and lost all geographical restriction. DTM can report up to 2005, at which point it was floating around Upstate New York. This kind of spread doesn’t track natural deer migration. That’s irrelevant, because nothing about CWD’s spread is natural. We shift gears into an anthropology of the American hunter. The hunter wants to shoot the most impressive buck, to bag himself one with as many “points” as possible – one whose antlers branch out most. A “ten-point buck” has five branches on each horn: Original by Ric McArthur Nature doesn’t make enough bucks with perfectly symmetrical ten-point horns. To fill the demand, the market had to step in. Thus was born the deer farm industry, which raises captive deer in better genetic and nutritional conditions than Nature permits, then ships them across the country so hunters who couldn’t get legit ten-point bucks get the taxidermy piece for their wall. These are controversial amongst hunters and illegal in numerous states – but the industry is big enough to spread CWD. (The kind of hunter who needs a deer shipped to his house is the kind of hunter who will fumble killing it.) Another problem is supplemental feeding – leaving out protein-enriched food for deer to eat. This produces “trophy class animals at an earlier age”, but again, what’s in that protein? (“It is much like feeding your cows 41 percent protein cottonseed cake during the winter to raise the protein level in the cow’s diet to a level that will maintain acceptable production”, says that article from 1991.)10 The book segues into a vignette. CWD was new in Wisconsin in the early 2000s, and the state’s Department of Natural Resources was optimistic it could eradicate it. In a state with a love of hunting, you could, in theory, recruit people to kill every single deer in a 400-square-mile radius: In many states, the state would have had to call out the National Guard for such an onslaught, but hunting is a passion in Wisconsin. Hunters shoot 450,000 deer every year, more than in any other state. “I’m looking for ardent hunters to help us, unless fear or their wives keep them away,” one DNR official told a Milwaukee magazine. The state extended the normal hunting season and waived the usual limit of one buck per hunter, and the hunters came out in force. The whole affair was gruesome – one official called it “hunting for slob hunters”. If you’re trying to eradicate a prion disease, you can’t very well let people take the carcasses home to eat. Bodies piled up in control stations, decomposition mingling with bleach. The 2002 hunt established a base rate of 2% for chronic wasting disease in Wisconsin deer, with the most affected areas getting up to 10%. Further hunts in 2003, 2004, and 2005 spread to wider and wider areas – and didn’t move the needle one bit. This is to say that CWD is quite a bit more common in the American deer population than BSE ever was in British cattle. Since publication, it’s popped up in Norway and South Korea. Notably, Norway doesn’t allow for the import of cervids, raising numerous questions about how it got there. There are no unambiguous cases of CWD transmission to humans, and in vivo/in vitro primate studies have mixed results. There sure are some unusually young hunters with sporadic CJD, though. But don’t worry, most of them aren’t M/M homozygotes! There is an absolute ton going on in this book. I’ve had to skim over whole sections. Parts that couldn’t be easily slotted into a narrative review include: When Gajdusek was invited to a party at Prusiner’s house, he was horrified to find his rival had purchased hundreds of New Guinean statues – all with the genitals removed.
Inline links: Yeah., nope, M/V heterozygotes totally get vCJD, 6, up to 1 in 2000 people in the UK have latent vCJD, bleach enemas, has an answer for you, 7, blood donations spread vCJD, going, up, 8, 9, not supposed to happen, https://substackcdn.com/image/fetch/$s_!0J8B!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F2a64b287-a7c6-4d82-bbe1-da949fc93118_1024x683.png, Ric McArthur, controversial, amongst, hunters, illegal in numerous states, trophy class animals at an earlier age, 10, Norway, South Korea, mixed results, sure are
Let’s pretend for rhetorical purposes that somewhere like Cheyenne, Wyoming is a meaningful city. The metro area is 100k people – it’s meaningful enough. The equivalent spot in Australia has a population of “no one”.