"I don't know, they seem pretty determined to protect each other."

March 30, 2020 9:00 PM

A sunbeam from XKCD: "... but now humans are adapting too fast." (SL-XKCD-P) (explainxkcd)

alt text: "We're not not trapped in here with the coronavirus. The coronavirus is trapped in here with us."

posted by WCityMike (45 comments total)

;___;
posted by longdaysjourney at 9:01 PM on March 30, 2020 [1 favorite]

This is great! Also the ones before this are good too- I like the one called Sabotage
posted by freethefeet at 9:12 PM on March 30, 2020

I've never cried at an XKCD comic before, but here we are.
posted by Aquifer at 9:33 PM on March 30, 2020 [23 favorites]

Mmmmm, pasta...
posted by Greg_Ace at 9:40 PM on March 30, 2020 [7 favorites]

Wait hold up how long would everyone have to socially isolate to cure every disease? Because I'll keep wearing the same thing everyday and not showering for humanity.
posted by iamck at 9:42 PM on March 30, 2020 [43 favorites]

The XKCD comic refers to the immune system as the scariest thing ever, which made me think of "Cells at Work". It's an anime where the operation of the human body is portrayed as a city, with the cells as human characters. I'd recommend watching it to anyone who has time. The various white blood cells are portrayed as almost psychotically violent, and I don't know, I'm kind of less anxious about viruses when I can picture my immune system as angry men with knives who really want to destroy any foreign pathogen.
posted by Grimgrin at 10:02 PM on March 30, 2020 [32 favorites]

Isn't the tall skinny guy a bacteriophage? Paging Blasdelb, would Blasdelb come to the white courtesy phone please.
posted by Joe in Australia at 10:07 PM on March 30, 2020 [4 favorites]

That's REALLY great, and I don't think I would have seen it if you hadn't posted it here.

Thank you for sharing this warm blast of hope, WCityMike!
posted by kristi at 10:19 PM on March 30, 2020 [4 favorites]

There was a recent post in Smithsonian Graphs (which I now, of course can't find) charting the infection spikes for the 1918 flu - long story short, cities that put in closures and isolation early and aggressive had much fewer deaths then cities that didn;t.
posted by The Whelk at 10:38 PM on March 30, 2020 [6 favorites]

And it was good that he drew a protozoan since he mentioned malaria.
posted by Ivan Fyodorovich at 10:49 PM on March 30, 2020 [1 favorite]

The Whelk, I think that this National Geographic story/blog post is what you're thinking of.
posted by ElKevbo at 10:56 PM on March 30, 2020 [4 favorites]

This is beautiful.
posted by jenfullmoon at 10:57 PM on March 30, 2020 [1 favorite]

"I wondered what those were for!"
posted by The Underpants Monster at 11:27 PM on March 30, 2020 [6 favorites]

As someone with lifelong allergies and general autoimmune issues, I picture my white blood cells less as violent men with knives and more as crazed backwoods farmers, just sitting on the porch with an iced tea and intermittently hallucinating and screaming about varmints as they spray buckshot wildly in every direction. I mean, glod help the poor bastard pathogen if they ever get their hands on a real one but I do wish they aimed better.
posted by Scattercat at 11:50 PM on March 30, 2020 [136 favorites]

The XKCD comic refers to the immune system as the scariest thing ever, which made me think of "Cells at Work". It's an anime where the operation of the human body is portrayed as a city, with the cells as human characters.

I've been watching this also! Was excited that they represented my absolute favorite thing that happens in the human body, the Hunger Games style test that immature T cells are subjected to before being allowed in the body at large, in which attacking an innocent cell results in test failure & also death.

Although I was disappointed they didn't show the losing T cells being phagocytized by the macrophages, who in the series are serene axe-murdering cafe maids... look it's anime af ok
posted by taquito sunrise at 12:08 AM on March 31, 2020 [6 favorites]

eutrophil (好中球, Kōchūkyū) / White Blood Cell (U-1146) (白血球, Hakkekkyū)
Voiced by: Tomoaki Maeno[4] (Japanese); Billy Kametz[5] (English)
A type of white blood cell, whose job is to kill pathogens infecting the body. Despite his ruthless occupation, he's quite soft-spoken and gentle. When he was still in school as a young cell, he saved AE3803 from a bacterium after she got lost in a training exercise.

ded
posted by away for regrooving at 12:22 AM on March 31, 2020

Bacteriophages feed off bacteria. Hence the name! They can't infect humans, and it's scientifically inaccurate to depict them as being concerned about human resistance.

Also, they don't make charts.
posted by Joe in Australia at 12:44 AM on March 31, 2020 [7 favorites]

I picture my white blood cells less as violent men with knives and more as crazed backwoods farmers

The reality is less kind than that; autoimmunity is like a beloved family member who's gotten super gun happy and doesn't recognize anyone anymore - and take unkindly to everything they don't recognize anymore.

In the worst cases, they only recognize family, but only as monsters out of delusions that they must slay.

Neighbours know not to visit, but family still got to...

My sympathies.
posted by porpoise at 1:14 AM on March 31, 2020 [6 favorites]

SARS-CoV-2 does a pretty good job of getting your immune system to kill you even as the virus is waning. It would be much more scared of quarantine than macrophages (which it can infect handily).
posted by benzenedream at 1:47 AM on March 31, 2020 [3 favorites]

A lovely strip. Thanks for posting it, WCityMike.

"They saw what we were doing and changed their behavior to stop us...."

"It's not over, right? They can't sustain this. They must be bored and tired. Will they give up?"

"I don't know. They seem determined to protect each other."

Yes. Not just ourselves, maybe not so much ourselves (for some of us), but each other.
posted by brainwane at 4:03 AM on March 31, 2020 [9 favorites]

The XKCD comic refers to the immune system as the scariest thing ever, which made me think of "Cells at Work". It's an anime where the operation of the human body is portrayed as a city, with the cells as human characters.

Funny, it reminded me of Once Upon a Time... Life, a french animated series from the 80's.

The body sentinels
posted by Pendragon at 6:11 AM on March 31, 2020 [2 favorites]

Speaking of animation...psst, hey buddy, wanna see some RNA transcription at real-time speed? (about 3min in but the whole thing is good)
posted by sexyrobot at 6:14 AM on March 31, 2020 [10 favorites]

An earlier visual commentator was disturbingly prescient.
posted by sammyo at 6:49 AM on March 31, 2020 [2 favorites]

Wait hold up how long would everyone have to socially isolate to cure every disease? Because I'll keep wearing the same thing everyday and not showering for humanity.

Unfortunately many diseases have animal reservoirs (like hansens disease) or can happily reside in the soil for decades and then infect humans when conditions are right (like anthrax).
posted by Mitheral at 6:51 AM on March 31, 2020 [5 favorites]

Love this. Thank you for posting.
posted by widdershins at 6:52 AM on March 31, 2020

Grimgrin, I fucking love Cells at Work. It's peak anime in its ridiculousness but that just makes it all the more fun. I like to imagine all these battles raging inside of me.

I contain multitudes, and they are anime.

This was a great XKCD comic and I appreciate the: We're not trapped in here with the coronavirus. The coronavirus is trapped in here with us.
posted by Fizz at 6:57 AM on March 31, 2020 [2 favorites]

"Cells at Work" on Netflix
posted by ShooBoo at 7:49 AM on March 31, 2020 [3 favorites]

❤
posted by supermedusa at 7:55 AM on March 31, 2020

Why, yes, I DO have a lot of pasta....and, ha ha!!! I have the means to make more!
Thanks for posting.

And drinking wine at home. That helps too, right?
posted by winesong at 7:59 AM on March 31, 2020 [3 favorites]

Bacteriophages feed off bacteria. Hence the name! They can't infect humans, and it's scientifically inaccurate to depict them as being concerned about human resistance.

Sheesh. Allow the guy some poetic license.
posted by Aardvark Cheeselog at 8:52 AM on March 31, 2020

Thanks for this great post!

Yay Cells at Work, which is getting a second season on Netflix! Also, the Internet Archive has is the manga available to read online. Or some of it. I'm not sure. I'm a platelet.

Yay pasta!
posted by danabanana at 9:10 AM on March 31, 2020 [4 favorites]

Also, check out the StoryBots "How do people catch a cold?" episode, which has adorable T cells, B cells, and a studio ghibli-inspired lymphocites.
posted by Hermeowne Grangepurr at 10:27 AM on March 31, 2020 [3 favorites]

The narrating bacteriophage reminded me of something from Steven Universe. Creatures in the nursery?
posted by doctornemo at 11:48 AM on March 31, 2020

Bacteriophages feed off bacteria. Hence the name! They can't infect humans, and it's scientifically inaccurate to depict them as being concerned about human resistance.

The only way they could get anything done at their infect all humans meetings was to get someone otherwise neutral and uninvolved to run it, or else it just degenerates into infighting.
posted by ckape at 12:47 PM on March 31, 2020 [9 favorites]

Also check out Disney's 1940s version of this, "Defense Against Invasion," in which a society of adorable blood cells responds to the warning of a vaccine with all their factories churning out vast numbers of bombs, tanks, and war planes to destroy the scary invaders when they attack.

(As told by Dr. White Lab Coat to an assortment of concerned boys and their doggy.)
posted by straight at 12:47 PM on March 31, 2020 [1 favorite]

Isn't the tall skinny guy a bacteriophage?

Those bacteriophages are always trying to stick their ideas into bacteria.
posted by straight at 12:51 PM on March 31, 2020 [3 favorites]

This reminds me of a book I found in our attic once when I was young, Huber the Tuber. Pretty much an illustrated explanation of what tuberculosis was, how it spread and its lifecycle, and how it was treated back in the day. Published in 1942, it must still be under copyright as I had to really search around to find a copy online, but its out there if you want to take a look. I remember my mom being upset when she found me reading it, which confuses me to this day, but its explanations and descriptions of how this little microorganism did its thing stuck in my memory.
posted by Blackanvil at 2:23 PM on March 31, 2020

Joe in Australia: "Isn't the tall skinny guy a bacteriophage? Paging Blasdelb, would Blasdelb come to the white courtesy phone please."

The tall skinny guy is indeed a very iconic representation of a Myovirus, a morphology of tailed bacteriophage!

I've talked about the history of phage therapy before, the process of using these viruses that infect bacteria to treat bacterial infections. We tend to think phage as friends these days because of the exciting prospect of it, having forgotten how much they helped us understand the nature of life, as they will hopefully allow us to treat infections we can't otherwise due to things like biofilm development, allergies, resistance, or other complications. However, I am particularly excited as they could be a solution to the exponentially growing antimicrobial resistance crisis that may just become the number one cause of death by 2050, beating cancer even in the context of an older world. Indeed, these projections don't just predict antimicrobial-resistant bacteria causing significantly more annual deaths than WWII did within the lifetimes of most of us here, they also predict grinding poverty. While we tend to think of charismatic wealthy white patients, the impact of this will not be distributed equally, and the developing world will be hit hardest.

We've been in a moment like this before, in the 1950s and '60s educated observers were predicting a similarly terrible future in store for anyone who didn't live in a society with the unlooted and mechanized agriculture of the US or Europe. Populations were exploding everywhere and there were no feasible ways to increase agricultural yields enough to keep up without massive investments from wealthy countries that would never happen, and the inevitable result was a global famine that would kill on an order that would overshadow all the wars of the previous thousand years. That didn't happen because a small group of determined people led by an obscure plant pathologist from Iowa kept it from happening. It's important to keep in mind that the billion lives that the invention of dwarf strains of staple crops and the accompanying Green Revolution saved aren't just an abstract number. Cities like Seoul, Shanghai, Jaipur, and Jakarta aren't just filled with the grown people that lived because they could eat the products of these crops, but also their children, their grandchildren, and all the culture, wealth, and sovereignty that a billion people and their descendants can create. The Green Revolution changed who we are as a global people, and it set us down a path where we at least had a solid shot at achieving peace and prosperity with justice.

Today we're rapidly approaching another crossroads where we desperately need another technical solution because, as rapidly as the developing world is developing, the massive transfers of wealth and infrastructure needed to even minimally address the problem with current solutions in time will just never happen. What we need is a heat and humidity stable solution for killing target bacteria that comes from a limitless reservoir that can be cycled to outrun resistance faster than small molecule antibiotic development and that can be manufactured cheaply. If we can get it to work, phage may just be the friends we need who can help us out, and bring us a world that both more of us get to live in and that is more worth living in.
posted by Blasdelb at 2:41 PM on March 31, 2020 [21 favorites]

Joe in Australia: "Bacteriophages feed off bacteria. Hence the name! They can't infect humans, and it's scientifically inaccurate to depict them as being concerned about human resistance."

There is an important caveat to this though that perhaps makes Munroe more right that he could be expected to know. There are in fact quite a few diseases that are, from a particular perspective that many microbiologists and research-minded ID physicians might benefit from, caused by phages that absolutely have a deeply antagonistic ecological relationship with us.

Many strains of pathogenic S. aureus, E. coli, Shigella, V. cholerae, C. botulinum, C. diphtheriae, Streptococcus, and a whole bunch of described shrimp and insect diseases are in a sense not really caused by those bacteria, but by the phages that infect them. All phages can go through what is called a lytic life cycle when they infect a cell. In this life cycle they shut down the host bacteria's metabolism to substitute their own, replicate their genetic material, construct and pack 30 to 3000 viral particles, and then lyse the cell for the new particles to hunt for more cells. This is obviously extremely lethal, and part of what makes phages so attractive when we have problematic bacteria to take care of. However, some phages, known as temperate phages, can also go through a second kind of life cycle where instead of shutting down the hosts' metabolism, they turn off their genomes and wait. This creates what are call lysogens, sort of a phage/bacteria hybrid, where the phage hides and lets the host replicate it with its own chromosome when the host divides. While hiding, these temperate phages have an interest in their hosts doing well and sometimes have exotic genes, which get expressed independently of the host-lethal ones, that often contribute to host success in weird situations, like pathogenesis.

Thus, for example, cholera isn't really caused by Vibrio cholerae like you may have heard, but instead by the CTX-φ and TLC-φ phages. Vibrio are, for the most part, planktonic bacteria content to scavenge for low levels of organic substrates in bodies of water and leave us well enough alone. However, when infected by the temperate CTX-φ or TLC-φ phages, Vibrio cholerae suddenly gets a pathogenicity cassette of DNA with a type IV pillus and the cholera toxin. Indeed, Vibrio cholerae is harmless without a temperate phage, but CTX-φ gives it the recipe for a poison-syringe/grappling-hook along with the most potent mucosal immunogen yet identified. This provides it with the tools it can use to feed off your guts while forcing you to spray hideous concentrations of it into the water supply of all of your friends.

These kinds of phage that are capable of going through this second type of lifecycle are pretty trivial to detect and avoid in pure phage stocks intended for therapy using classical microbiological techniques and modern sequencing. However, it is important to keep in mind that not all phages are our friends, and that many have the potential to kill on the order of the worst of those less charismatic Eukaryotic viruses.
posted by Blasdelb at 3:20 PM on March 31, 2020 [26 favorites]

I must be an old, this discussion reminds me of Norman Spinrad's Carcinoma Angels.
posted by a person of few words at 3:20 PM on March 31, 2020 [2 favorites]

Vibrio cholerae is harmless without a temperate phage, but CTX-φ gives it the recipe for a poison-syringe/grappling-hook along with the most potent mucosal immunogen yet identified.

Might there be a way of immunising the cholera bacteria against the phages that make them toxic? Or treating cholera patients with something that interferes with phage reproduction in the cholera bacteria, much like HIV can be treated with drugs that interfere with viral reproduction in human cells?
posted by Joe in Australia at 5:03 AM on April 1, 2020 [1 favorite]

Thanks to this thread my nesting partner and I devoured the first 5 episodes of "Cells at Work", and found it highly enjoyable.
posted by saveyoursanity at 9:23 AM on April 1, 2020 [2 favorites]

Vibrio cholerae is harmless without a temperate phage, but CTX-φ gives it the recipe for a poison-syringe/grappling-hook along with the most potent mucosal immunogen yet identified.

I tend to think of selection happening at the gene level, I would assume there are circumstances where Vibrio cholerae has lost its phage elements and stabilized its pathological toxins (e.g. a medieval sewer system where it can be endemic and the ability to flip/flop isn't being selected for). Is it the case that pathogenic Vibrio cholerae always retains the phage elements?
posted by benzenedream at 2:42 PM on April 1, 2020 [1 favorite]

Joe in Australia: "Might there be a way of immunising the cholera bacteria against the phages that make them toxic? Or treating cholera patients with something that interferes with phage reproduction in the cholera bacteria, much like HIV can be treated with drugs that interfere with viral reproduction in human cells?"

There are a variety of systems that bacteria employ to gain immunity against phage like the famous CRISPR systems, or these systems described in one of the more groundbreaking recent phage papers, or classical homoimmunity.

If we'd be talking about doing something to environmental Vibrio, it's important to keep in mind that these temperate phages are incredible engines for promoting the spread of genomic material when they are induced, and I'd be concerned about how we would be playing with an ecological fire that we don't fully understand. The idea of doing something in the environment to something as fundamentally wild and unpredictable as a temperate phage, particularly when it carries such horrifying tools, would be a bit terrifying. I'd imagine that most things targeted enough to detect and cure the relevant prophages (the kind of genomic element that a temperate phage becomes in the cell when it hides in the genome of its host cell) could just as easily kill the relevant cells, which would somewhat reduce the potential for unintended consequences?

If we'd be talking about doing something inside patients, while many lytic phages carry their own polymerases, temperate phages just use the ones conveniently proved by their hosts during a lysogenic cycle - so we wouldn't have a convenient phage-specific foreign enzyme to target with a small molecule like for HIV. There are already a bunch of antibiotics that target bacterial RNA and DNA polymerases, which are different enough from our own to make great targets, but that doesn't really treat the phage independently of the bacterial host. However, there is good reason to at least be cautious about trying to attack the phage independently of the bacterial host, because at least many will be holding patients hostage as part of an odd ecological relationship that they can have with Infectious Disease physicians.

On a molecular level, temperate phages are able to undergo a lysogenic lifecycle by encoding a transcriptional repressor that binds to the parts of the phage genomes that promote expression of almost all of the phage genes, keeping them from turning on. This specifically includes all of the host-lethal genes that start a lytic lifecycle and make infectious phage particles. At the beginning of infection, when temperate phages first inject their DNA into a host cell, a fundamentally stochastic decision is made between the two types of lifecycles depending on how much repressor is made. If enough is made, then the phage prevents the expression of most genes excluding the repressor, as well as often an integrase that stitches the phage genome into the host genome and sometimes payloads like the dangerous ones we are concerned with. The phage then effectively hides, with the host replicating the phage genome whenever it replicates its own, tying their evolutionary fates together. However, if the lysogen ever fails to manufacture enough repressor, something associated with DNA damage and various types of bad times for the phage/bacterial hybrid, the phage will have a chance to stab its host in the back attempting to escape, by inducing all of the host-lethal genes and the lytic lifecycle.

E. coli is a commensal that belongs in your lower intestinal tract and plays an important role in keeping it anoxic. In healthy people, eating food contaminated with human-adapted E. coli aught be more uncomfortable and hilarious than tragic as the bug wreaks gassy havoc trying to play a role adapted to your colon in your small intestine while triggering the heck out of your intestinal immune system. However, the pathogen E. coli O157:H7 is particularly dangerous for even healthy people to catch from contaminated meat because it carries the Shiga toxin on a prophage. The Shiga toxin causes hemolytic uremic syndrome by destroying red blood cells, which then clog the kidneys causing them to fail. Attempting to treat E. coli O157:H7 with at least most antibiotics has been shown to induce the prophage, stimulating the production of the toxin by the lysogen, such that even though you might be curing the infection, the damage you cause to the kidneys in doing so might be worse than the benefits you make to the patient. Indeed, whether or not to treat O157:H7 with antibiotics has been controversial for some time, with different ID physicians coming down on either side of what ends up doing less harm, though it is now looking like that some antibiotics like quinolones may more unambiguously help in the end by directly inhibiting expression of the prophage while simultaneously killing the bacterial host.

If we directly target the prophages that infect the bugs infecting our patients, we could very easily just be inducing them to escape, which could both activate exactly what makes the bug so dangerous while at the same time spread the dangerous phage elements to new bacterial hosts... Incidentally, My own work showed something that classical phage biologists had long suspected, that prophages seem to be very sensitive to induction by lytic phage infection, which would suggest to me that phage therapy might not be appropriate for diseases like this, particularly E. coli 0157:H7.
posted by Blasdelb at 3:40 AM on April 3, 2020 [5 favorites]

benzenedream: I tend to think of selection happening at the gene level, I would assume there are circumstances where Vibrio cholerae has lost its phage elements and stabilized its pathological toxins (e.g. a medieval sewer system where it can be endemic and the ability to flip/flop isn't being selected for). Is it the case that pathogenic Vibrio cholerae always retains the phage elements?

I think this might be mostly a question of vaguely pedantic taxonomy, the best kind of taxonomy.

If we look at the genomic elements that we find in bacterial genomes that are obviously of temperate phage origin, being packed on a cassette with unambiguous phage genes and things like different codon bias and different GC-skew, but are also obviously no longer capable of either supporting a lytic infection or getting packaged into a phage particle no matter how much you poke them. We call these elements 'cryptic prophage,' but are they phages? What exactly is a phage anyway? I'd tend to define phages functionally as genomic elements that are capable of spreading between host bacteria by promoting a productive infection, either lytic or chronic, that generates packaged infectious particles. This can often, but not always, be usefully abstracted on a functional level as an ability to produce visible plaques on lawns of host bacteria. Truly cryptic prophages would not meet this definition, but the lines do get fuzzy.

A lot of genomic elements of obviously temperate phage origin can't produce infectious particles on their own no matter how much you poke them as they are missing essential tools, but they can produce infectious phage particles with help from a compatible phage that infects the sort-of-lysogen. These used to be called satellite phages, and I think that we kind of have to call them phages as the 'viral sex' that they need to reproduce is kind of an inherent part of the biology of most RNA viruses, as the very sexy papers below describe. Recently many have started very usefully thinking of these elements as being phages that infect phages according to the virocell concept, while pointlessly redefining them as 'virophages.'

For most prophage elements though, at least the ones that have been identified genomically, it isn't really obvious whether or not they are functional (or how functional), and you would kind of need to actually induce the damn things to really know for certain. At the same time, demonstrating a negative, that a genomic element can't generate a productive infection no matter how you might conceivably poke it, can be ontologically tricky in the best of circumstances. So, while the virulence factors that make cholera so awful might, as far as I know, always be carried on prophage-ey elements - are those elements always prophages? I think the best answer I can give might just be an apology for how messy our previously elegant functional nomenclature has turned out to be in the genomic era.

Fitness of RNA virus decreased by Muller's ratchet. Nature. 348(6300):454-5.
Why sex exists remains an unsolved problem in biology. If mutations are on the average deleterious, a high mutation rate can account for the evolution of sex. One form of this mutational hypothesis is Muller's ratchet. If the mutation rate is high, mutation-free individuals become rare and they can be lost by genetic drift in small populations. In asexual populations, as Muller noted, the loss is irreversible and the load of deleterious mutations increases in a ratchet-like manner with the successive loss of the least-mutated individuals. Sex can be advantageous because it increases the fitness of sexual populations by re-creating mutation-free individuals from mutated individuals and stops (or slows) Muller's ratchet. Although Muller's ratchet is an appealing hypothesis, it has been investigated and documented experimentally in only one group of organisms--ciliated protozoa. I initiated a study to examine the role of Muller's ratchet on the evolution of sex in RNA viruses and report here a significant decrease in fitness due to Muller's ratchet in 20 lineages of the RNA bacteriophage phi 6. These results show that deleterious mutations are generated at a sufficiently high rate to advance Muller's ratchet in an RNA virus and that beneficial, backward and compensatory mutations cannot stop the ratchet in the observed range of fitness decrease.

Prisoner's dilemma in an RNA virus Nature
The evolution of competitive interactions among viruses was studied in the RNA phage phi6 at high and low multiplicities of infection (that is, at high and low ratios of infecting phage to host cells). At high multiplicities, many phage infect and reproduce in the same host cell, whereas at low multiplicities the viruses reproduce mainly as clones. An unexpected result of this study was that phage grown at high rates of co-infection increased in fitness initially, but then evolved lowered fitness. Here we show that the fitness of the high-multiplicity phage relative to their ancestors generates a pay-off matrix conforming to the prisoner's dilemma strategy of game theory. In this strategy, defection (selfishness) evolves, despite the greater fitness pay-off that would result if all players were to cooperate. Viral cooperation and defection can be defined as, respectively, the manufacturing and sequestering of diffusible (shared) intracellular products. Because the low-multiplicity phage did not evolve lowered fitness, we attribute the evolution of selfishness to the lack of clonal structure and the mixing of unrelated genotypes at high multiplicity.
posted by Blasdelb at 5:10 AM on April 3, 2020 [1 favorite]