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@velvetdemon I'm doing a full reply because I want to give this question the time and space it deserves, and I really do appreciate your curiosity about this.

The short answer: It is deeply unethical. There are nowhere near enough willing patients in the world to be able to do this, and it would be criminal to put them through this.

The long answer: The one side of the equation you're focusing on is: how much of a drug is too much, to the point where it will cause negative side effects or even death? And this is crucial to know. But it's not just a matter of finding out the lethal dosage of a heart cholesterol medication, you need to know that it can actually lower the cholesterol of any living thing. There is no way to know this without giving it first to...a living thing.

But beyond this, I need to emphasize: The goal of a drug trial is to effectively cure people who are already suffering from disease, who are living on limited time.

Drug trials don't just happen on any member of the public, they need to happen specifically on people affected by the disease you're trying to treat. There is at any time a very limited and very marginalized population of the world affected by early onset, familial Parkinson's disease. Because you cannot ethically induce disease in a human being, you are working with, speaking with, and helping patients and their families who are hopeful and desperate for a cure.

If you were to jump straight to human trials from petri dishes, not knowing absolutely anything about how the drug functions in a living, breathing animal body, it would look like this:

We didn't know that minute quantities of the drug interact lethally with x, y, z medication that people are commonly also taking. X number of patients have died as a result.

We didn't know that the drug is fatal to people with [common variant] in their genetics. X more patients have died.

We didn't know the drug exacerbates x, y, z chronic illnesses. X number of people have acquired permanent, lifelong disabilities.

We didn't know the best way to deliver the drug, so we tried multiple ways: the people who received it intravenously are now suffering from a painful, costly, and debilitating condition that did not happen with the ingested form.

I could go on, and on, and on.

The vast majority of these problems can be nearly or almost entirely averted by testing other animals first.

These are all people who possibly could have waited for the normal progression from animal testing to human testing and thus received better outcomes. Some people will pass away in the time it takes to get to that point, and that's heartbreaking, and we all wish science could be faster.

animal research is not the mad scientist wild west that PETA wants you to think it is. there are extremely strict federal laws in place to protect the well being of these animals. animal welfare organizations like AAALAC ensure that lab animals are treated with dignity & respect and are given enough specialized care & enrichment to be happy and content in captivity, just like AZA accreditation with zoos.

not a single animal from a zebrafish to a mouse to a dog to a macaque goes unaccounted for. if an animal gets moved to a new cage, paired for breeding, has a procedure performed on it, gives birth, gets sick or injured, dies, etc. it is legally required that this information is recorded and kept on file for the US federal government to access. failing to record & retain this information is very much punishable by US federal law.

let me tell you - if you abuse or kill an animal, even a mouse - you are almost certainly getting both fired & blacklisted from the industry. if you abuse or kill a more ‘advanced’ animal, such as a dog or monkey, you will likely face criminal charges. killing a monkey is as serious and disastrous as a nuclear meltdown. you are expected to reasonably explain every illness, injury, or death of an animal under your care. you must record all of this information. animals that are clearly suffering with low QOL are required to be euthanized according to AVMA guidelines.

research animals are highly expensive. yes, even the "lesser" animals like mice. the cheapest mice will run you a few hundred $ per individual, with some of the most expensive mice i've cared for being $25,000 per individual. in research we have the "three Rs" - reduction (reduce amount of necessary animals to a minimum), refinement (refine processes to ensure research is accurate and animals feel no pain or distress), and replacement (replace animals with non-living research models as they become available). i can assure you no proper research team is wasting animals (*do not* say "b-b-but elon musk--" his research team is actively being investigated for animal abuse by the government).

research methods that do not require live animals are currently being looked into & efforts spearheaded by - you guessed it - the animal research industry itself (notice how the animal rights people are strangely silent & unhelpful when it comes to this?) but current technology is rudimentary and does not compare to live animal models.

some research animal fun facts (US edition):

all species of animals are only allowed to have one single major surgery performed on them in their entire lifetime.

institutions with nonhuman primates must have a behavior program in place (run by knowledgeable primate specialists) to ensure that they are happy and receiving enough daily enrichment and social interaction.

institutions with dogs are required to have physical exercise programs in place. this means every individual dog gets a substantial amount of leashed AND free-roaming exercise daily, including playgroups with other dogs.

a majority of nonhuman primates get to retire to sanctuaries like peaceable primate sanctuary, and almost all dogs get retired and adopted out by organizations like homes for animal heroes. some institutions will also adopt out unneeded young rabbits, guinea pigs, rats, etc.

some strains of mice glow neon green (or orange or blue) under UV light. this is not harmful to them and is commonly seen in cancer research.

Nutrition experiments carried out on Canadian Aboriginal children in residential schools between 1942 and 1952, in which various control and experimental groups were deliberately malnourished. Also the Qu'Appelle BCG vaccine trial.

Basically everything the Australian government has done to the Aboriginal people, but especially experiments in the 20s and 30s, which tested basal metabolism by forcing subjects to lie still and breath through a rubber tube for hours, or those testing their response to pain.

Testing of a new antibiotic* on children in Kano, Nigeria, during a meningococcal meningitis outbreak, by Pfizer. The lawsuit the families and the Nigerian government brought against Pfizer also alleged that this further reduced the public's trust in vaccines and contributed to poor uptake of the polio vaccine.

The Tuskeegee Syphillis Study, which is a landmark in medical ethics fuckery that everyone should know about. The US has also carried out variations of this in so many places

Southam's experiments on prisoners using HeLa cancer cells** without their informed consent.

The Rawalpindi experiments carried out on members of the British Indian army to test mustard gas.

I'm not even going to talk about the Nazi ones.

*In this case they actually did do animal trials beforehand, which contraindicated its use in children, but I included this because it demonstrates how unethical research practice can impact public health.

FunFact! The facility/company is SO dedicated to the welfare of their subjects that techniques to reduce mental and emotional stress on the animals brought on by repetitive tasks, interpersonal/colony stressors, industrial setting, and a shitload of other work-related stressors that they EXTRACTED THAT SHIT OUT LATERALLY INTO HOW THEY SCHEDULE AND ORGANIZE THEIR STAFF.

Laboratory researchers in real life: put up memorial statues to remind humanity how much it owes to the lives of even mice

Stolen from the Electronic Frontier Foundation:

On Android 

With the release of Android 12, Google began allowing users to delete their ad ID permanently. On devices that have this feature enabled, you can open the Settings app and navigate to Privacy > Ads. Tap “Delete advertising ID,” then tap it again on the next page to confirm. This will prevent any app on your phone from accessing it in the future.

On iOS 

To see which apps you have previously granted access to, go to Settings > Privacy > Tracking. You can set the “Allow apps to Request to Track” switch to the “off” position (the slider is to the left and the background is gray). This will prevent apps from asking to track in the future. If you have granted apps permission to track you in the past, this will prompt you to ask those apps to stop tracking as well. You also have the option to grant or revoke tracking access on a per-app basis.

Utah transportation: “ Good news we could all use: the Parley's Wildlife Overpass is working.”

=

oh wow! hey if you take pills check this out. new medicine taking meta just dropped.

according to these models, out of the 4 tested postures, the best position to digest pills is laying on your right side. standing upright has a similar time to laying in your back at twice as much as laying on the right side, and laying on the left side is the slowest by far.

laying on right side: pill dissolves in around 10 minutes.

standing: pill dissolves in 23 minutes. laying on the back has a similar time.

laying on left side: pill dissolves in up to 100 minutes.

https://doi.org/10.1063/5.0096877

definitely worth a lot more research.

As a former cakewrecks lover, I figured sure, I’ll bite. Let’s see this cake. Literally nothing could have prepared me for this cake. 

They paid $49 for this “frog-themed” cake and honestly no amount of money in the world could be put on this masterpiece:

Eventually, as we grew up, this morphed into just saying "Valdez!" whenever we spilled something. As far as I was concerned "Valdez" was just a word for "oops!" specifically in this context.

I'm from Australia where we only have 7 states, as such I have the (objectively correct) opinion that 50 is too many states, so I decided to cut it down to 10.

A few notes on my improved US map:

•Despite Illinois making the cut, Chicago is now in Michigan, due to the state getting the entire bank of its namesake.

•Boston is also in Michigan due to special exception.

•New York is now the capital of Pensylvania

•Yes that's how you spell Pensylvania

•The border of California is just roughly the Rockies, no need to overthink it.

•Making Florida bigger actually dilutes it's power, but Texas must be abolished

•Colorado should still be a rectangle, that's my mistake, I just couldn't be bothered fixing it.

•Alaska has been returned to Canada with a hand written apology

•All the random ass islands that the US forgot to pretend they didn't colonise have gained independence

Please let me know if there are any more improvements you can think of.

Edit: As a number of you have mentioned, Alaska never belonged to Canada, and giving it to them would be incredibly wrong when the native people have been trying to gain independence all this time.

There was too much traffic today, and an ICE agent deployed a tear gas canister in traffic in response.

Spread this far and wide - there's no paywall.

ETA: If you're a US citizen and want to help, CONTACT YOUR REPRESENTATIVES.

I mean it, I don't know any plainer way to say it - they NEED to know how furious their constituents are about this entire shitstorm of fascist dictator behavior. It doesn't matter which state or which party. Call them. Email them. Hell, Resistbot lets you send faxes.

Contact your senators, your representatives, your governors, and your state legislators too. Can't hurt to contact your mayors, either, because if they know most of their city's residents are willing to run ICE out of town on a rail, that helps them to push back!

Tell them how fucked up, immoral, and illegal this is. Tell them you support any action that keeps ICE off our streets, and will vote accordingly.

Because Democrats need to know this is a platform worth running on (yes it might seem obvious but y'all always forget just how few of us actually show up to vote, that's why we're even in this mess) but Republicans also need to know it's going to obliterate their chances of reelection. That's the only way to possibly get any of them to reconsider their current position of falling in line with Cheeto Mussolini's appointed goons.

Be safe out there, and look after your neighbors.

Rio: …Tall

Aaron: …Miles…I love you, and I am proud of you…but you are somehow the smartest and dumbest boy I have ever known.

Miles: Says the man who used his big brain to become a criminal when he could’ve been a black Tony Stark with that gear he made. And thought working for the Kingpin, who everyone knows will throw his minions away like tissues, was a good idea!

Peter: He makes a good point, babe, you did kind of mess up first–

Also people in the comments:

Boys Problems, 519 words

How to Marry Your Fake Husband from Another Dimension (speedrun), 5008 words

I like high chances that I might lose, 8373 words

You’re a Sunflower (I Think Your Love Would Be Too Much), 14 827 words

Scared of the Unknown, 15 217 words

How Did We Get Here? 46 926 words

This isn't to say that more "complete" stories can't be extremely good. Discworld, while an incredible canon, has a relatively small fanfic base compared to less well-written fiction because you get what you want from the canon. Leverage leaves more gaps, in part because of intent, in part because we're well aware there are some things you simply won't be allowed to put on American television. And then there are very flawed canons that have just enough interesting content of some kind that we're ready to fix them to get more of the good stuff.