welcome to the tungle

@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.

At the moment, this is not a substitute for animal testing. Bodies are incredibly complex and interconnected environments that we're still scratching our heads about, and animal testing is in a lot of ways the most efficient and least harmful way of testing things like medications.

If anyone wants to read more about these subjects, here are a few starting points (you will probably learn some new words, this is okay!):

Advances and Applications of Predictive Toxicology in Knowledge Discovery, Risk Assessment, and Drug Development research topic by the Frontiers in Pharmacology journal

Novel methods and technologies for the evaluation of drug outcomes and policies research topic by the Frontiers in Pharmacology journal

Spotlight on Artificial Intelligence in Experimental Pharmacology and Drug Discovery research topic by the Frontiers in Pharmacology journal

The Emerging Discipline of Quantitative Systems Pharmacology research topic by the Frontiers in Pharmacology journal

PDF Drug Combinations: Mathematical Modeling and Networking Methods by Vahideh Vakil and Wade Trappe

PDF Machine learning-based drug-drug interaction prediction: a critical review of models, limitations, and data challenges by Flaviu-Ioan Gheorghita et al.

PDF A review of 3D bioprinting for organoids by Zeqing Li et al.

3D Bioprinting for Engineering Organoids and Organ-on-a-Chip: Developments and Applications by Yuqing Ren, Congying Yuan, et al.

3D bioprinting of human iPSC-Derived kidney organoids using a low-cost, high-throughput customizable 3D bioprinting system by Jaemyung Shin, Hyunjae Chung, et al.

And it pissed me off so badly that I spent the ENTIRE WORK DAY today compiling evidence from every project my team has ever done for her, pulling past emails she’d sent us, putting together an entire case proving that she had been the problem all along. That she got projects mixed up, that she’d made requests that were nonsensical, literally everything you could possibly imagine. Screenshots of emails, reports we’d submitted, EVERYTHING.

This woman in particular has been terrorizing my team for years, her name is almost a slur in my office, I had simply had ENOUGH of her.

I put all of this evidence together and sent it to all of my bosses at 4:30pm. Then I took a long break to eat a sweet treat and drink some tea.

After my break, my bosses all called in an emergency meeting with me and they said they read my report and fucking loved it. And I sat on a teams call with my boss’ boss as she wrote my nemesis the scathing email I had always fantasized about sending, using the evidence I’d compiled, and hit send.