All of these studies are pretty much worthless as well, based on translation rates to humans
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There’s no way further animal testing is a good thing, it’s barbaric, and needs to stop. It also affects the human researchers and labworkers.
I can’t find the X thread but long ago someone compiled the massive amounts of threads on reddit from labworkers having nightmares and affected by the work they’re doing.
AI, in-silico, in-vitro medicine, validated pathways in MR studies, these are good enough. These useless animal experiments are not.
" Students interested in STEM should probably know that if you create an anonymous forum for biologists, you get constant posts from people having existential crises over being pressured into mass mouse murder 
" https://x.com/invitrofuture/status/1830093094399648026
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I won’t read the article because it will make me too sad, but because it seems to me most people don’t even give it a thought, it gives me comfort to see others (meaning, you @A_User) also can see how barbaric it is.
I’m frankly glad it gives them nightmares… it should. If it didn’t, there would be no incentive for them to find alternatives.
I don’t know why more people don’t just say no. I actually failed my science class in high school because I walked out during the pig dissection. The teacher threatened me and I said be my guest…fail away.
I also easily passed on a job offer from US Surgical (a plum job for me at 24) because I would have had to show docs how to use the equipment on (already dead) animals. I said sorry, I won’t participate in that. No, such an easy word unless you are starving and desperate.
And thank you for posting this because with no sunlight on this topic, nothing changes…
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I think it depends on the animal-model used. Macaques, for example, are good-ish models for HIV medication/vaccines and hairloss treatments while mice are not.
But other primates are even more concious and aware and can suffer the most?
Perhaps the world should accelerate the development of non-concious “primate” and even “human” bodyoids:
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From the article:
Recent advances in biotechnology now provide a pathway to producing living human bodies without the neural components that allow us to think, be aware, or feel pain. Many will find this possibility disturbing, but if researchers and policymakers can find a way to pull these technologies together, we may one day be able to create “spare” bodies, both human and nonhuman.
We already use bodyoids, it’s just that they’re just grown in the status quo way, born, and comes with a brain, experience, emotion, and behavior. It’s 110 million every year that’s used for laboratory research. People haven’t accepted the fact that the normal state of affairs is very much not normal.
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It’s an extremely complicated issue IMO. I think most bioscience researchers will agree with you that mice in particular are not a great model. But I think it needs more nuance than because there are so many different types of “animal model”, and the alternatives are also pretty weak right now.
Some models are definitely rubbish - like you get female mice, inject a bolus of human breast cancer cells (typically a standardised cell line like MDA-MB-231 or MCF-7) into the mammary tissue, and the mice “dies from cancer” 3-4 weeks later. (Actually the tumour will just grow so comically large that the mouse can’t even carry it and it’s almost bursting out of the skin). And that’s your testing platform for new drugs, nanoparticles or whatever. But that’s not even close to how a real human develops or dies from breast cancer. We have thousands of papers curing breast cancer from a few cell lines in mice, which have no value to human patients whatsoever.
Sometimes metastasis is modelled by just injecting tumour cells intravenously and they will sporadically take up root in different tissue. But again, it has almost nothing to do with real metastasis, distal signalling, pre-metastatic niches etc. The models are good because of standardisation, repeatability, and speed (nobody wants to wait a year for the mouse to die). But they’re bad because they don’t actually tell you anything about the real effectiveness of the treatment. I think what we can learn from that sort of study is unfortunately almost nothing. I teach a course on in vitro models to replace animal testing, and I basically call this the “mouse as a Petri dish” model, where the mouse is just a living host for the cancer cells, and it isn’t realistic at all.
Same thing with diabetes research. You get young, healthy mice, inject them with a compound called STZ which obliterates their beta cells, and their blood sugar goes up. But does it bear any resemblance to how a real patient becomes diabetic with insulin resistance, derangement in the liver, skeletal muscle etc? Of course not. So I feel that a lot of that research is also totally pointless.
Most neurodegeneration models are also terrible. Mice don’t get Alzheimers, and loads of papers can cure mouse neurodegeneration and have almost no translational value for humans.
However, if you have developed your new molecule, nanoparticle etc, you are simply not going to be able to publish your work without animal models. Any top journal will not accept your work without animal models to provide evidence that your treatment works, period. I have tried, and you can argue until you’re blue in the face, and they don’t care.
I would argue that some models are actually pretty decent, such as traumatic wound healing, infections etc. There, animals make quite realistic hosts and the principles of those diseases are more similar to the processes which occur in humans. In my field, we give mice heart attacks by suturing the coronary artery. It’s definitely not perfect, because the mice are otherwise young and healthy and don’t have atherosclerosis like human patients. But the general trajectory of inflammation, cell death, scar formation etc is similar to humans though on an accelerated time scale. Now, we could make the research a lot better and realistic by giving them crappy diets to make them metabolically unhealthy and waiting until they are older - however, it will cost 2x more, take 3-4x longer, and we will not be rewarded with better papers, more grant money, more recognition or anything else. So from that perspective, investing in “better” experiments is a total waste of resources which won’t benefit my students, me, the university, the funding agency or anybody else. In fact, if you deviate from the standard (8-12 week old B6 mouse), reviewers get suspicious, ask why, and they want the B6 data anyway. That’s the sad reality.
In terms of alternatives, there honestly isn’t that much. We can do some fancy things with cell culture, like growing multiple cell types together, or changing the microenvironment. But they’re quite labour intensive, lack standardisation (i.e. one lab protocol versus another lab protocol, having low reproducibility), and the results still don’t have high translational value. I am very very sceptical that in vitro models will ever really replace animal testing outside of a few edge cases. One successful example is in skin testing, where we have decent in vitro models that can predict basic things about the penetration or irritation of a compound.
But still, we have no way of modelling any sort of “systems” - cardiovascular system, nervous system, immune system, or the interactions between them using in vitro models. And trying to build those from the ground up in vitro using isolated cells is just insanely complicated and will never happen IMO. For example, you could never develop an in vitro system for testing a vaccine because there’s no way to build up all the parts that you need for it to work.
IMO, the possible answer will be simulations, once we can build up a high resolution picture of cells, tissue, organs, and have enough computing power. But I think we are still an incredibly long way away from that too unless some unexpected revolution happens. From what I know in the field, we are still very very basic even in terms of “easy” things like modelling blood flow through vessels, let alone trying to predict how a particular antigen might sensitise your immune system to a particular cancer.
What I think is realistic should be more acceptance of the value of studies that don’t have animal testing. And we probably need to change the mentality that having “an animal study” is automatically stronger or an advantage and we should look at the quality and translational relevance of the animal study. Testing on 50 young healthy B6 mice is arguably less useful (IMO) than testing on 6 elderly wild-type mice.
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I don’t like the sound of any of these, it’s similar to what was described in the article.
I have to think about it more, but possibly the very static system of animal experimentation could be replaced today by going straight to phase 1 trials in humans with informed consent, if we think about the ethical side of things. The only thing I can think of is the lack of safety data, and I don’t know if current methods could provide enough information for informed consent for volunteers, though even that unknown risk there can be volunteers for. It would be interesting to know how well safety could be assessed pre-phase 1 trials in other ways.
I read on X that because of the low translation rate of animal studies we might even miss efficacious treatments.
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Ugh I will not be able to get the images of those poor suffering mice out my head…
@relaxedmeatball you offered a good explanation and I realize you feel handcuffed by the system…
The system simply needs to change… many of the awful things that used to happen in this world just kept on going only because they were the accepted way… until they weren’t.
Most things don’t change without enough pushback. Without a collective effort, it’s just not happening… decade after decade… the only reason some cosmetic companies have changed their ways was solely due to public pressure and boycotts… not because they felt the same formula of mascara that has been used for 20 years in the US needed to be tested again in China.
I also realize nothing I could ever say on this topic will have any impact whatsoever, but I feel voicing my opinion is a microscopic token of support that might give air cover to someone else who feels they are alone or too intimidated to share their feelings. Saying nothing normalizes it.
And aside from offering better alternatives, like Ghislaine Maxwell, I don’t have a any other viable ideas to offer.
And yes @A_User , when I was a pharm rep, we came out with a new blockbuster drug… was on the market for all of 1-3 months… it turns out the animal testing didn’t show how many people were going to die (and obviously the limited human trials). 35 years later and we are still here.
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It can’t change until there is a viable and superior alternative. Just stopping animal testing because of ethics would be disastrous to progress.
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That is a fair point. Granted, if I could end it all I would, but as relaxed meatball explained, it’s even done when they know it’s not the best method because publications demand it, etc… so a lot of it is still just done out of habit and not that it advances medicine.
I think a great first step would be to only do it when the top scientists feel it will yield the best results.
All it would take is for the top scientists to collectively refuse… it would change just like that, “snap”.
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Progress would slow to a halt if we had such a bottleneck. I really hope that does not happen.
Alternatives will arise in the near future anyway. But I hope we don’t rush to ban animal testing until those alternatives are thoroughly proven.
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You are in luck, I don’t think animal testing will be banned in my lifetime because too few people care what happens to them.
I’m old enough to remember when it was common practice for pets to be routinely be taken from the animal shelter and sold to labs for testing… It’s better now, but I still think it’s legal in most states… so nothing is stopping soon.
Maybe not banned but alternatives will come.
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Well, I can reply and add a bit more information.
I don’t think there is a lack of “caring” exactly. I don’t even think it’s accurate to blame “the system” because there’s no real rules saying that we have to do animal testing. However, it’s the expectation.
Well, the problem is that something like myocardial infarction is essentially impossible to replicate with in vitro cells, or to simulate with software. So there literally is no alternative. We still don’t really understand the disease processes in anywhere near enough detail to be able to simulate it or predict outcomes.
I am very sceptical that phase I trials could tell us anything, because those small trials are only really assessing short-term safety (i.e. is this drug or treatment going to cause some sort of dangerous show-stopping side effect or toxicity). They are never powered to determine efficacy. However, the major goal of pre-clinical animal experimentation is about finding things which do have efficacy.
I would also point out that efficacy is not the same as effectiveness. Many things have efficacy in carefully run pre-clinical experiments, but fail in the real world because of patient variability and disease variability. In my lab, every mouse gets the same heart attack from the same ligation of the same artery for the same duration. In the real world, patients get blockages in all sorts of places, and some are faster or slower than others to get to hospital, and of course vary by age, disease status etc. So the animal testing is more like a screening test - i.e. if something can’t at least demonstrate efficacy in the animal test, it doesn’t have a chance of ever working in humans. To get efficacy data, you need huge trials due to the inherent variability of people, and that costs incredible amounts of money.
And I would also point out that while yes, I believe many experiments are pointless, wasteful etc, medical progress is absolutely massive within our lifetimes. Heart attacks used to be largely fatal, and now they’re totally survivable, largely due to experiments giving animals heart attacks and figuring out the best courses of treatment. Pacemakers, LVADs, stents etc couldn’t exist without people having some lots of trials on animals. For example, the body responds to implanted biomaterials and it took decades to figure out what is safe to implant, can function stably etc.
So it’s overall a very difficult issue. I’m not “pro” animal testing, but I also don’t think ideological stances against it are supportable if we want medical science to keep progressing. It’s definitely flawed, but overall we still learn a lot. I would also point out that regulation is getting stricter and stricter and the 3R principles are generally taken seriously. Nowadays, ethics committees want to see in vitro evidence first, want to see why you calculated a particular dosage, how you’re going to monitor animal suffering/pain etc. If my students deviate from the approved plan, or are found mis-treating animals, it’s against the law and all of us can be fined, I’d lose my job, and there can even be prison sentences. It’s not a free-for-all where people just do whatever they want.
Yes and no IMO. Cosmetics were a specific thing, where all we actually care about are two things: acute irritation and toxicity, and skin permeability. In the case of cosmetics, the product must not penetrate the skin (otherwise it is a transdermal drug), and obviously it should not cause harm, and those two things are all that the law (in Europe) called for. So around the 2000s the EU started moving towards restricting animal testing for cosmetic products, and several in vitro equivalents were developed. But those are pretty simple layers of cells that can be used to make basic predictions. This did demonstrate the point that you can move away from animal testing and come up with alternatives, but trying to apply this to something like a myocardial infarction or tumour metastasis is an order of magnitude more complicated.
IMO one of the most promising technologies are iPSCs, and some countries are building biobanks of cells to represent their populations, and one day you might be able to do a “clinical trial in a dish” with 1,000s of cells from different genetically diverse patients. As one more example, when screening drugs this sort of platform is already used for detecting cardiotoxicity by something called hERG inhibition which can cause drug-induced long QT syndrome, and drug companies already moved over to using in vitro iPSC-based assays rather than the crappy assays they used before.
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