#1 kilogram

[maxlarens]

Hi ! As a pescatarian girly and as someone who has recently started to like Lando, I kept thinking about him with pescatarian!reader, because you know opposites attracts and also it made me think of the olive theory from 'How I met your mother', can be fic or smau

(also I'm the anon who requested the Charles fic and I was wondering if you gave names or emojis to your anons 🤔)

ahhh hi😇😇 thank u sm for sending another ask in. verrryy into this! ive never watched himym but i HAVE heard of the olive theory and genuinely think it can be so true. i also think like sharing food/giving certain parts of ur meal to ur partner is so sweet so i loved this a lot🥺🥺

also, tbh i have never had a consistent enough anon to name them/give them an emoji so i would loveee LOVE to do that🙏🏻 pls let me know what i should call u❤️ (and if anyone wants to be a regular/semi-regular anon and give themselves an emoji/name pls do!!!) ANYWAY alright i hope u enjoy— it’s a just a short ficlet 😌💖

LN: quid pro quo

pairing(s): lando norris x reader [read on ao3]

word count: 1.2k

“Eugh,” Lando says, feigning a gag as he looks at the plate of food set in front of you, “That’s disgusting. I don’t understand how you can put that in your mouth.”

Slowly, you raise an eyebrow at him, looking between your plate and Lando’s screwed-up expression; you point at your food, “Salmon? You think salmon is disgusting? Are you joking right now?”

He shakes his head fervently, a grimace still stuck on his face, “It’s gross.”

A laugh, loud and guffawing erupts from your mouth as you realise he’s being entirely serious. He’s fixated on your meal, frowning as if the fish has severely insulted him in some way. Quickly, you clap your hand over your mouth, concerned you’ll offend him if you keep laughing like that. This is one of a handful of dates you’ve been on together— clearly the first you’ve ordered seafood on— and you’re still trying to make a good impression on Lando.

“Wait,” you collect yourself, breathing deeply so you don’t fall into a fit of giggles again, “You’re not allergic are you?”

“No,” he shrugs, “I just hate fish. You’ve never heard that?”

You snort a little indelicately, already going back to eating your salmon, “‘You’ve never heard that?’,” you tease, “Do you think I stalk you on the internet, Norris?”

He grins that small sheepish grin you like so much as a light blush blooms on his cheeks. You’re very fond of him really. He’s cute in a scrappy kind of way; he’s funny and charming, a little bit dumb sometimes; and he’s into you, which is always a bonus. You’re not together— not quite— just seeing each other when you both have time, but it’s been going very nicely if you do say so yourself.

You like him.

He likes you.

Lando rolls his eyes, and purses his lips in an attempt not to let you see the smile that he’s trying to hide, “Don’t you? Stalk me on the internet?”

“Never,” you answer resolutely, thinking blatantly of that night after you’d first met him when you fell down a rabbit hole, spending a good hour watching thirst traps of him on Instagram before coming to your senses, “Not once.”

He hums, unconvinced, “Alright.”

Alright. You make a face, almost stick your tongue out at him but think better of it at the last second. He laughs— giggles— at you. You look away from him, down at your plate, trying to hide the smile that spreads and spreads behind your hair. God, you like him. You’re trying not to let it get away from you. You get the impression that he’s not huge on relationships, and you’re trying hard to be casual about him. It’s difficult— mostly because everything feels so easy when you’re together.

“So,” you start as you push a forkful of salmon and leafy greens around your plate, “Hate to break it to you, but I’m a pescetarian.”

“Um,” Lando asks around a mouthful of half-chewed food, “What’s that mean?”

You stifle a laugh, “Like a vegetarian, but I eat seafood.”

He swallows and makes another face, similar to the earlier one. You can see this is hard for him to process, he clearly dislikes seafood to a degree that you hadn’t quite understood until now. It’s funny. It’s another thing to add to the growing list of reasons you fancy Lando Norris. Though you would think that as a pescetarian you’d want him to like fish, but you suppose by not eating them he’s just saving all the sea animals that you’re not— quid pro quo.

“What about, like,” he waves his fork around, evidently still wondering why you’d eat seafood voluntarily, “just being a vegetarian?”

You shrug, “Vegetables are boring.”

“Right. Better than eating fish though.”

“I like fish.”

He shakes his head, “I don’t get it… It’s— they’re slimy and they smell and they’ve got fucking beady little eyes. It’s not natural.”

“Okay,” you laugh brightly at his despondent expression, “I do need to eat them, unfortunately. Otherwise, I’d probably die of malnutrition, or I dunno, scurvy.”

He groans, hanging his head so that all you can see of his face is that mop of brown curls. You think of your second date when you’d kissed him for the first time in your stairwell and how you’d threaded a hand into it— and they were soft and not heavy with product the way that you hate. The way he’d smelt like expensive cologne and tasted both smokey and sugary at the same time, just like the whiskey and cokes he’d been having at the bar. There’s a soft smile playing at your lips when he finally looks up.

“Does it bother you?” you ask, “That I eat fish.”

He shrugs, shakes his head in a non-committal way that could be either answer and does that little grin again. The one that means he’s going to say something that you’ll find either unbearably cute or embarrassingly funny.

“Yes,” he says, grin not subsiding, “How am I supposed to kiss you when you’ve got fish breath.”

Your eyebrows shoot up and a shocked laugh bubbles from your mouth, you try to ignore the stirring feeling in your gut at the words how am I supposed to kiss you in favour of responding to his lack of tact Try, being the keyword there. It somersaults in your head, how am I supposed to kiss you he said, like he was thinking of doing it again. Which, okay, of course, he’s thinking of doing it again. You understand what this is— but there was an unmistakable fondness there that you just can't shake.

Anyway, you push thoughts of kissing him aside, he’d still accused you of having fish breath, “Wow,” you say dryly, with no malice at all as much as you try to feign it, “You say that to all the girls?”

He blushes, his tan cheeks turning a very pleasant red as he properly realises what he’d said, “Shit. No— oh my god— I’m sorry. I just meant—”

You wave him off, laughing, “I know what you meant. You’re good, Lando.”

“Phew,” he lets out a breath of relief, his nervous laughter punctuating the air between you, without meaning to he says, “God, I thought I’d just fucked it.”

You furrow your brows and frown, confused, “No. You couldn’t.”

You watch him scrub a hand over his face, embarrassed, before it falls away and he gives you a sheepish little grin that says he’s happy to hear that. Toothy, eyes squinted and carving dimples into his cheeks. Your face feels warm and you smile back, biting your bottom lip on the smile so it doesn’t grow and grow to cover your whole face.

Later, after you’ve finished lunch and spent too much time talking over a too-sticky table in your favourite pub, Lando kisses you up against a tree in the park by your apartment. You put your hand in his soft curls and you smell cologne and taste what he’s been drinking as he presses his tongue into yours. The coarse hair of his moustache brushes against your lips and you kiss back with equal gusto. You pull away when it feels like you two are veering into too inappropriate territory for this public park. He chases you, but you laugh softly, pressing a perfunctory closed-mouth kiss to the corner of his mouth. He groans, laughs, and puts his forehead against yours.

You hum, “I guess my fish breath doesn’t bother you so much, huh.”

“Fuck,” he breathes, “You’re never going to let that go are you.”

You shake your head ever so slightly, “Not as long as I live, Norris.”

[unityrain24]

weighted blanket not heavy enough i need loki (525 lbs via marvel.com) to lay on top of me

[evilscientist3]

42

you just KNOW its a big sloppin' bowl of chili baby!!!!!!

[officialfurbyposts]

Posted by the Brazilian Furby Facebook account on the 7th of November, 2014

Description

Uhnnnnnnnnnnnn...

[crazydane666]

I'm gay but broke so instead of spending 240 dollars on Joffrey/Sandor Funko Pops I just made my own damn figures

And they're built to kiss <3

[erttv]

Zehir Tacirlerine" Yönelik 46 İlde Düzenlenen NARKOGÜÇ-42 Operasyonlarında 1 Ton 340 Kilogram Uyuşturucu Ele Geçirildi

İçişleri Bakanımız Sayın Ali Yerlikaya, uyuşturucu imal eden ve satan “zehir tacirlerine” yönelik 46 ilde düzenlenen Narkogüç-42 operasyonunda 364 şüphelinin yakalandığını açıkladı.  Emniyet Genel Müdürlüğü, Jandarma Genel Komutanlığı ve Narkotik Suçlarla Mücadele Başkanlığı koordinesinde, İl Emniyet Müdürlükleri Narkotik Suçlarla Mücadele Şube Müdürlükleri ve İl Jandarma…

[evilwizard]

i mean this in the best way possible, i believe if you were a salad you'd just be a kilogram of lettuce leaves and 1 paper thin cucumber slice hidden somewhere in the middle

next time just slit me open from throat to taint

[wellnesgreen]

Looking to lose weight fast? Learn how to lose 1-4 kilograms in a week with our effective techniques. From cutting calories to high-intensity interval training, we've got you covered. But is losing 10 kg in a week realistic? Find out the truth about fast weight loss and discover the healthiest approach to achieving your goals.

[morbidology]

Coconut crabs are extraordinary creatures that inhabit tropical islands across the Indian and Pacific Oceans, captivating researcher with their impressive size and unique behaviors. Known as the largest land-dwelling arthropods on Earth, these crustaceans play a crucial ecological role in their island habitats, despite their intimidating reputation.

One of the most striking features of coconut crabs is their immense size. Adult specimens can weigh up to 4 kilograms (9 pounds) and measure over 1 meter (3 feet) in length from leg to leg. This substantial size enables them to dominate their environment, including climbing trees to hunt for food and find shelter.

Coconut crabs are renowned for their remarkable ability to crack open coconuts with their powerful pincers. This feat, which requires immense strength and dexterity, allows them to access the nutritious meat inside the coconut, making them well-adapted scavengers in their coastal and forested habitats. Beyond coconuts, they have been observed feeding on a variety of foods, including fruits, nuts, and even carrion.

Despite their predominantly herbivorous diet, coconut crabs have earned a fearsome reputation for their occasional predatory behavior. They have been documented climbing trees to capture and consume seabird chicks and even small rodents, showcasing their opportunistic feeding habits and adaptability in resource-scarce environments.

[romanpaulov]

⚖️ Weighing of a Pallas's cat is an important procedure that allows zoologists to monitor the health of Pallas's cat kittens and ensure that the kittens are developing properly.

🍼 Newborn Pallas's cat kittens weigh only about 100-150 grams;

🔸 At the age of 1 month, kittens become about half a kilogram of fluffy happiness;

▫️ When they reach the age of 2 months, this happiness almost doubles, with an average weight of about 1 kg;

🔸 At the age of 3 months, Pallas's cat kittens weigh about 1.5–2 kg;

😺 The young Pallas's cat reaches its “adult” size and weight at the age of 1 year.

This video depicts an Eve's kitten at the age of one and a half months. All little fluffs are growing and developing according to all manul standards 📈😁

[nikustuffs]

jeszcze 1 kilogram i będzie 5 z przodu 🥹🥹🥹

[leadoodles]

I ran some calculations and discovered kai has the energy output of 3 nuclear power plants.

In the first episode of season 11, Kai is seemingly able to heat a bell full of water instantly from (presumably) 25 Celsius to 40.

If we assume the bell is a cylinder 2.5m in diameter and 3m deep, that gives us 59 cubic metres of water. Convert to kilograms and we get 58,728 kilograms.

The specific heat capacity of water is 4200 j/kg/°C. Rearrange and we get an energy output of 3 gigawatts/joules.

The average nuclear power plant produces 1 gigawatt, and according to back to the future, you need 1.21 gigawatts to travel through time. And he was RELAXING.

In conclusion, Kai and Nya didn't need to stowaway on the iron doom. Kai could also power Ninjago city. Kai is a god.

[bestanimal]

Round 1 - Phylum Arthropoda

(Sources - 1, 2, 3, 4)

Arthropoda is a phylum of animals that have segmented bodies, possess a chitin exoskeleton, and have paired segmented appendages. They are colloquially called “bugs” though this is often only used for terrestrial arthropods, and sometimes only used for insects specifically.

After Nematoda, this is the most successful phylum, and it is far more diverse, with up to 10 million species! Arthropods account for 80% of all known living animal species. The three major subphyla include the Chelicerates (sea spiders, horseshoe crabs, arachnids, and the extinct eurypterids and chasmataspidids), the Myriapods (centipedes and millipedes), and the Crustaceans (shrimps, prawns, crabs, lobsters, crayfish, seed shrimp, branchiopods, fish lice, krill, remipedes, isopods, barnacles, copepods, opossum shrimps, amphipods, mantis shrimp, entognaths, and insects).

Arthropods are so diverse in fact that it is next to impossible for me to describe a model arthropod. They are important members of marine, freshwater, land, and air ecosystems and are one of only two major animal groups that have adapted to life in dry environments, the others being chordates. All arthropods have an exoskeleton and must molt as they grow, replacing their exoskeleton. Some arthropods go through a metamorphosis in this process. They have brains, a heart, and blood (called hemolymph, though some crustaceans and insects also use hemoglobin). They sense the world through small hairs called setae which are sensitive to vibration, air currents, and even chemicles in the air or water. Pressure sensors function similarly to eardrums. Antennae monitor humidity, moisture, temperature, sound, smell, and/or taste, depending on species. Most arthropods have sophisticated visual systems ranging from simple eyes (ocelli) which orient towards light, to compound eyes consisting of fifteen to several thousand independent ommatidia capable of forming images, detecting fast movement, or even seeing polarized or ultra-violet light. Some arthropods are hermaphroditic, some have more than two sexes, some reproduce by parthenogenesis, some by internal fertilization, some by external, some have complex courtship rituals, some lay eggs, some give live birth, some have prolonged maternal care. The first arthropods are known from the Ediacaran, before the Cambrian era.

Propaganda below the cut:

Insects are the first animals to have achieved flight

The smallest arthropods are the parasitic crustaceans of the class Tantulocarida, some of which are less than 100 micrometres long. The largest arthropod is the Japanese Spider Crab (Macrocheira kaempferi) with a legspan of up to 4 metres (13 ft) long. The heaviest is the American Lobster (Homarus americanus), which can get up to 20 kilograms (44 lb).

Many arthropods are popular pets, including various species of crab, shrimp, isopod, crayfish, mantis shrimp, millipede, centipede, tarantula, true spider, scorpion, amblypygid, vinegaroon, mantis, cockroach, beetle, moth, and ant! Some are even domesticated, including silk moths and honeybees.

Many arthropods are eaten by humans as a delicacy, and farming insects for food is considered more sustainable than farming large chordates. These farmed arthropods are referred to as “minilivestock.”

Arthropods feature in a variety of ways in biomimicry: humans imitating elements of nature. For example, the cooling system of termite mounds has been imitated in architecture, and the internal structure of the dactyl clubs of mantis shrimp have been imitated to create more damage tolerant materials.

Spider venoms are being studied as a less harmful alternative to chemical pesticides, as they are deadly to insects but the great majority are harmless to vertebrates. They have also been studied and could have uses in treating cardiac arrhythmia, muscular dystrophy, glioma, Alzheimer's disease, strokes, and erectile dysfunction.

Shellac is a resin secreted by the female Lac Bug (Kerria lacca) on trees in the forests of India and Thailand. It is used as a brush-on colorant, food glaze, natural primer, sanding sealant, tannin-blocker, odour-blocker, stain, and high-gloss varnish. It was once used in electrical applications as an insulator, and was used to make phonograph and gramophone records until it was replaced by vinyl.

One of the biggest ecosystem services arthropods provide for humans is pollination. Crops where pollinator insects are essential include brazil nuts, cocoa beans, and fruits including kiwi, melons, and pumpkins. Crops where pollinator insects provide 40-90% of pollination include avocados, nuts like cashews and almonds, and fruits like apples, apricots, blueberries, cherries, mangoes, peaches, plums, pears, and raspberries. In crops where pollinators are not essential they still increase production and yield. Important pollinators include bees, flies, wasps, butterflies, and moths.

Many arthropods are sacred to humans. In Ancient Egypt, scarab beetles were used in art, religious ceremonies, and funerary practices, and were represented by the god Khepri. Bees supposedly grew from the tears of the sun god Ra, spilled across the desert sand. The goddess of healing venomous bites and stings, Serket, was depicted as a scorpion. Kalahari Desert's San People tell of a legendary hero, Mantis, who asked a bee to guide him to find the purpose of life. When the bee became weary from their search, he left the mantis on a floating flower, and planted a seed within him before passing from his exhaustion. The first human was born from this seed. In Akan folklore, the cunning trickster figure Anansi/Ananse is depicted as a spider. Western astrology uses the crab constellation, called Cancer, and the scorpion constellation, called Scorpio. Dragonflies symbolize pure water in Navajo tradition. In Anishinaabe culture, dreamcatchers are meant to represent spiderwebs and are used as a protective charm for infants. They originate from the Spider Grandmother, who takes care of the children and the people of the land in many Native American cultures. The Moche people of ancient Peru often depicted spiders and crabs in their art. In an Ancient Greek hymn, Eos, the goddess of the dawn, requests of Zeus to let her lover Tithonus live forever as an immortal. Tithonus became immortal, but not ageless, and eventually became so small, old, and shriveled that he turned into the first cicada. Another hymn sings of the Thriae, a trinity of Aegean bee nymphs. Native Athenians wore golden grasshopper brooches to symbolize that they were of pure, Athenian lineage. In an Ancient Sumerian poem, a fly helps the goddess Inanna when her husband Dumuzid is being chased by galla demons. In Japanese culture, butterflies carry many meanings, from being the souls of humans to symbols of youth to guides into the afterlife. Ancient Romans also believed that butterflies were the souls of the dead. Some of the Nagas of Manipur claim ancestry from a butterfly. Many cultures use the butterfly as a symbol of rebirth. And the list goes on…

cute crab eat a strawbebby:

[batboyblog]

Things Biden and the Democrats did, this week #9

March 9-15 2024

The IRS launched its direct file pilot program. Tax payers in 12 states, Florida, New Hampshire, Nevada, South Dakota, Tennessee, Texas, Washington, Wyoming, Arizona, Massachusetts, California and New York, can now file their federal income taxes for free on-line directly with the IRS. The IRS plans on taking direct file nation wide for next year's tax season. Tax Day is April 15th so if you're in one of those states you have a month to check it out.

The Department of Education’s Office of Civil Rights opened an investigation into the death of Nex Benedict. the OCR is investigating if Benedict's school district violated his civil rights by failing to protect him from bullying. President Biden expressed support for trans and non-binary youth in the aftermath of the ruling that Benedict's death was a suicide and encouraged people to seek help in crisis

Vice President Kamala Harris became the first sitting Vice-President (or President) to visit an abortion provider. Harris' historic visit was to a Planned Parenthood clinic in St. Paul Minnesota. This is the last stop on the Vice-President's Reproductive Rights Tour that has taken her across the country highlighting the need for reproductive health care.

President Biden announced 3.3 billion dollars worth of infrastructure projects across 40 states designed to reconnect communities divided by transportation infrastructure. Communities often split decades ago by highways build in the 1960s and 70s. These splits very often affect communities of color splitting them off from the wider cities and making daily life far more difficult. These reconnection projects will help remedy decades of economic racism.

The Biden-Harris administration is taking steps to eliminate junk fees for college students. These are hidden fees students pay to get loans or special fees banks charged to students with bank accounts. Also the administration plans to eliminate automatic billing for textbooks and ban schools from pocketing leftover money on student's meal plans.

The Department of Interior announced $120 million in investments to help boost Climate Resilience in Tribal Communities. The money will support 146 projects effecting over 100 tribes. This comes on top of $440 million already spent on tribal climate resilience by the administration so far

The Department of Energy announced $750 million dollars in investment in clean hydrogen power. This will go to 52 projects across 24 states. As part of the administration's climate goals the DoE plans to bring low to zero carbon hydrogen production to 10 million metric tons by 2030, and the cost of hydrogen to $1 per kilogram of hydrogen produced by 2031.

The Department of Energy has offered a 2.3 billion dollar loan to build a lithium processing plant in Nevada. Lithium is the key component in rechargeable batteries used it electric vehicles. Currently 95% of the world's lithium comes from just 4 countries, Australia, Chile, China and Argentina. Only about 1% of the US' lithium needs are met by domestic production. When completed the processing plant in Thacker Pass Nevada will produce enough lithium for 800,000 electric vehicle batteries a year.

The Department of Transportation is making available $1.2 billion in funds to reduce decrease pollution in transportation. Available in all 50 states, DC and Puerto Rico the funds will support projects by transportation authorities to lower their carbon emissions.

The Geothermal Energy Optimization Act was introduced in the US Senate. If passed the act will streamline the permitting process and help expand geothermal projects on public lands. This totally green energy currently accounts for just 0.4% of the US' engird usage but the Department of Energy estimates the potential geothermal energy supply is large enough to power the entire U.S. five times over.

The Justice for Breonna Taylor Act was introduced in the Senate banning No Knock Warrants nationwide

A bill was introduced in the House requiring the US Postal Service to cover the costs of any laid fees on bills the USPS failed to deliver on time

The Senate Confirmed 3 more Biden nominees to be life time federal Judges, Jasmine Yoon the first Asian-America federal judge in Virginia, Sunil Harjani in Illinois, and Melissa DuBose the first LGBTQ and first person of color to serve as a federal judge in Rhode Island. This brings the total number of Biden judges to 185

[ane-doodles]

What are the names of your shittens (and any facts about both of them would be appreciated 🐑💖🥺🐈‍⬛)

Well… that depends on which AU we're talking about.

If you are referring to CFP then their names are Tao and Avader, if you are referring to the Box AU then we only have Bem, and if we are talking about one of the alternative timelines of CFP (one in which the lamb does agree to sacrifice itself) then we have to the last two who still do not have a name. I will give you some information about each one:

Tao: He doesn't like vegetables, he likes to sleep, he accompanies Narinder and Avana during the crusades and often uses his horns to stab enemies.

Avader: has a crest of wool from his head to the tip of his tail, in theory he is a Devon rex, he once got scared during a crusade and ended up returning to the cult crying… which led him to end up working at the funeral home .

Bem: when she was born she didn't weigh more than a kilogram and she was quite small, her eyes are small and black so it is difficult to distinguish where she is looking, her face and part of her body can be divided like Narinder's face, she doesn't have many friends but He spends most of his time with Baal and Aym.

Shitten 1: the wool on her head is actually a mane, since she was little she has proven to be quite strong… and when she grew up she became even stronger! She fights with bare fists, she likes to visit the fields and help with the harvest.

Shitten 2: The red pattern on his ears is shaped like eyes and extends across the back of his head and back, his eyes glow in the dark, he only has two toes/pads on his hind legs, he is very good at playing tag hiding and lurking, it's a week younger than shitten 1.

[excalculus]

I saw some mentions of rabies going around again and have no clue what's set it off this time, but given recent scientific developments I want to revisit the idea of curing symptomatic rabies.

First things first: there is still no practical way to do this. The famous Milwaukee Protocol fails far more frequently than it succeeds, and even the successes are not making it out in anything like a normal state. It's been argued that it should no longer be considered a valid treatment [1] due to these issues; any continued use is because there's literally nothing else on the table.

However. There are now two separate studies showing it's possible to cure rabies in mice after the onset of symptoms. The lengths you have to go to in order to pull this off are drastic, to put it mildly, and couldn't really be adapted to humans even if you wanted to. But proof of concept is now on the board.

long post under the cut, warnings for animal experimentation and animal death. full bibliography at the end and first mention of each source links to paper.

Quick recap - rabies is a viral disease of mammals usually transmitted through the saliva of an infected animal. From a contaminated bite wound, it propagates slowly for anywhere from days to months until it reaches the central nervous system (CNS). Post-exposure vaccination can head it off during this phase, but once it reaches the CNS and neurological symptoms appear it's game over. There will typically be a prodromal phase where the animal doesn't act right - out at the wrong time of day, disoriented, abnormally friendly, etc. This will then progress to the furious (stereotypical "mad dog" disease) and/or paralytic phases, with death eventually caused by either seizures or paralysis of the muscles needed for breathing.

That's the course we're familiar with in larger animals. Mice, though, are fragile little creatures with fast metabolisms.

In the first study's rabies infection model, lab mice show rabies virus in the spinal cord by day 4 after infection and in the brain by day 5. Weight loss and slower movement start by day 7, paralysis starting from the hind limbs from day 8 on, and if not euthanized first they're dead by day 10-13. [2]

This study (fittingly conducted at the Institut Pasteur) had two human monoclonal antibodies, and wanted to see if there was any possibility they could be used to cure rabies after what we think of as the point of no return.

Injecting the antibodies into muscle saved some mice if done at days 2 or 4, and none if done later, even at high doses of 20 milligrams per kilogram of body weight of each. Conclusion: targeting the virus out in the rest of the body is no use if it's already replicating in the CNS.

Getting a drug past the blood-brain barrier is, to use a highly technical term, really fucking hard. It's the sort of problem that even the best-funded labs and biggest companies in the world routinely fail at. And that's for small molecule drugs, which are puny compared to antibodies.

But this isn't drug development for a clinical trial. This is a very, very early proof-of-concept attempt, which means you're willing to ignore practicality to see if this idea is even remotely workable. So you can do things like brute force the issue by cutting through the skull to implant a microinfusion pump, which lets you deliver the antibodies directly into the normally-protected space around the brain. Combine this with the normal injections, and you can treat both the CNS and the rest of the body at the same time. Here's a survival graph of treated mice. X axis is days, Y axis is percentage of mice in that group still alive.

Figure 2A from reference 2, accessed February 2024

The fact that the blue, green, and purple lines did anything other than sink horribly to zero is unheard of. When the combination treatment was started at day 6, 100% of the mice survived. Started at day 7 (prodromal phase), 5 out of 9 mice recovered and survived. Started at day 8 (solidly symptomatic, paralysis already starting to set in), 5 of 15 mice recovered and survived. And when they say "survived", they kept these mice all the way to day 100 to make sure. Some of them had permanent minor paralysis but largely they were back to being normal mice doing normal mouse things. So, success, but by pretty extreme means.

Enter the second paper [3]. This was a different approach using a single human monoclonal antibody against Australian bat lyssavirus (ABLV - closely related to rabies, similar symptoms in humans) to try for a cure without needing to deliver treatments directly into the CNS. They also made a luminescent version of ABLV that let them directly image viral activity, so they could see both where the virus was replicating and how much there was in a live mouse.

Figure 1 from reference 3, accessed February 2024

Mice infected with ABLV start showing symptoms around day 8. You can see in the figure that at day 3 there's viral replication in the foot at the site of infection, which has shifted into the spine and brain by day 10. So what happens if you give one of these doomed mice one single injection of the antibody into the body?

Done at day 3, the virus doesn't make it to the brain until day 14, and while disease does set in after that around 30% of the mice survive. Days 5 and 7 are much more interesting. Those mice still develop symptoms at day 8, but the imaging shows the amount of virus in their spines and brains never gets anywhere near the levels seen in untreated controls, and within days it starts to decrease. Around 80% of day 5 and 100% of day 7 mice survive.

Okay, sure, you can stop another lyssavirus, but technically you did start treatment before symptoms appeared. What about symptomatic rabies?

The rodent-adapted rabies strain CVS-11 starts causing symptoms as early as day 3 after infection, and untreated mice die between days 8 and 11. The same single dose of antibody saved 67% of mice treated on day 5 and 50% of mice treated on day 7. Without making the luminescent version of the virus there's no real-time imaging of the infection, but you can still track symptoms.

Figure 2 from reference 3, accessed February 2024. CVS-11 is the name of the rodent rabies strain and F11 is the name of the antibody.

Disease score is a combination of several metrics including things like whether the mice are behaving normally and whether they show signs of paralysis. In untreated mice it goes up and up, and then they die. If one of those lines starts coming back down and continues past day 10 or so, that's a mouse that recovered. The success rate isn't as good as against ABLV, but again, this is a rabies strain specifically adapted to rodents and treatment wasn't started until it was well-established in the CNS.

So how on earth is this happening? The antibody neutralizes both ABLV and rabies really well in a test tube, but we've already established that there's no way a huge lumbering antibody is making it past the blood-brain barrier without serious help. Something about the immune response is clearly making it in there though. And it turns out that if you start trying this cure in mice missing various parts of their immune systems, mice without CD4+ T cells don't survive even with the treatment. By contrast mice without CD8+ T cells take longer to work through the infection, but they eventually manage it and are immune to reinfection afterwards.

To grossly oversimplify the immune system here, CD4+ are mature helper T cells, which work mostly by activating other immune cells like macrophages (white blood cells) and CD8+ T cells (killer T cells) against a threat.

Normally, T cells are also kept out by the blood-brain barrier, but we know that in certain specific cases including viral infection they can pass it to migrate into the brain. In the brains of the infected mice for which antibody treatment either wasn't given or didn't work, you can find a roughly even mix of CD8+ and CD4+ T cells along with a whole lot of viral RNA. But in the brains of those successfully fighting off the infection, there's less viral RNA and the cells are almost exclusively CD4+. So the antibody doesn't work by neutralizing the virus directly - something about it is activating the animal's own immune system in a way that gives it a fighting chance.

Again, neither of these proof of concept treatments is really workable yet as a real world cure. The first one is almost hilariously overkill and still has a pretty good chance of failure. The second is less invasive but careful sequencing still shows both low-level viral replication and signs of immune response in the brains of the survivors even at day 139, so it may not be truly clearing the virus so much as trading a death sentence for life with a low-level chronic infection. But now we know that 1. curing rabies after symptoms begin is at least theoretically possible, and 2. we have some clues as to mechanisms to investigate further.

Not today. Not tomorrow. But maybe not never, either.

References:

Zeiler, F. A., & Jackson, A. C. (2016). Critical appraisal of the Milwaukee protocol for rabies: this failed approach should be abandoned. Canadian Journal of Neurological Sciences, 43(1), 44-51.

de Melo, G. D., Sonthonnax, F., Lepousez, G., Jouvion, G., Minola, A., Zatta, F., ... & Bourhy, H. (2020). A combination of two human monoclonal antibodies cures symptomatic rabies. EMBO molecular medicine, 12(11), e12628.

Mastraccio, K. E., Huaman, C., Coggins, S. A. A., Clouse, C., Rader, M., Yan, L., ... & Schaefer, B. C. (2023). mAb therapy controls CNS‐resident lyssavirus infection via a CD4 T cell‐dependent mechanism. EMBO Molecular Medicine, 15(10), e16394.