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Comment by fabian2k | Hacker News Reader

There's certainly more that could be done to prevent bad or futile research on animals. But there are areas where there is no reasonable way to replace animal testing. How else would you test the safety of a new drug or other chemical? You can't do this in vitro, and going directly into humans is not an acceptable solution in my view.

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> But there are areas where there is no reasonable way to replace animal testing.

Two specific examples for which animal testing seems essential:

1. Prediction of nanoparticle clearance from in vitro studies does not correlate with clearance in vivo. If you want to know where the particles go (do they hit the target organ/tumor at all? do they ever leave the body?) you need to do in vivo testing.

2. Adolescent idiopathic adolescent scoliosis can now be treated by vertebral tethering and growth modulation, not just bracing or fusion. Zimmer Biomet Spine recently had a device approved to deliver this treatment [0]. Exploratory research to establish cause-effect relationships between tethering and growth modulation depended on large animal models. It's not good to accidentally make a patient's spine worse because you don't understand what's going on.

[0] https://www.fda.gov/medical-devices/recently-approved-device...

You do not cut out animal research but you push for a clearer path to safely start research in humans. Instead of repeated and overlapping pre-clinical studies, focus on designing studies to move as rapidly into humans as possible while retaining a reasonable risk profile. The longer people do work on animals the more they optimize for and are invested in the animal solution.

I mean company can always do better like giving animal better life before testing and not enthusiast after testing? But what happens now? Those animal are tortured, kept in worst condition and after testing is done you know what happens. Most of the testing is not harmful but the way companies handle the testing is worst to animal.

If something is going to human probably means it is safe which should mean safe for animals to some extent imo. But to save 1% of research cost you know researcher don't care about animal life :/

Is it actually better to keep them alive after testing? I would think many studies could leave them with issues. Not to mention they would just be sitting in a cage somewhere.

better animal life means higher research cost, drives drug price up, delays research speed, end up "costing" human lives, so which is more important ?

For what it's worth, I'm an in vivo pharma researcher, and the standard is to not euthanize unless we need tissue. Unfortunately, I'd guess that 99% of the time, we need to collect blood, spleens, livers, etc. and doing so reduces the number of animals needed in that study as well as the number of studies we run with animals. There are already a lot of pressures to keep animal numbers low, not least of which being that each of the cheapest mice is somewhere around $28 (you can see the prices yourself on their website, but I think my company gets some discount on those prices). Also, my time is valuable, and adding mice increases the amount of my time is spent working on that study.

I'm also on the IACUC for my company, and I can assure you that we do care about animal life. We go to great lengths to ensure that research is being done in ways that maximize animal welfare to the extent that is possible. The FDA requires animal studies for safety and efficacy, and we can debate the morality of testing in mice, then NHPs before humans, but the system as it exists prioritizes de-risking first human doses as much as possible. Given that system, it is the job of the IACUC to oversee and approve every procedure done to an animal in the facility or in our company's name at other facilities. It's a big job that, at least at my place, is taken very seriously by researchers and up the chain of management.

The article specifically talks about this and you haven't really made a concrete reply to anything they say.

The quality of discourse on HN goes up when we all meaningfully engage with the content. The goal shouldn't be to see who is fastest to post a dismissal of the headline.

The article doesn’t actually talk about it in any meaningful way. They talk about it in a statistical fashion: most animal studies are underpowered, most don’t publish, etc.

And sure, I think we can all agree that nobody should be doing useless experiments, whether on animals or not.

But that in no way proves the article’s argument, and it hardly even supports it.

Are we going to test out new CRISPR therapeutic delivery systems in humans? We don’t have a non-living system that replicates a circulatory system, an immune system, and a liver. If the author has a suggestion for how to do things like this safely and effectively without animals, I didn’t hear it.

Failing experiments and learning something in the process is the bread and butter of science

The article is makings lots of points, I don't find it well focused which makes it harder to make specific replies. For example it talks a lot about animal experiments in cosmetics, but one of the quotes mentions that those are already outlawed in the EU. So I'm not sure what the point is here, if it is to extend that ban to other countries the author should say so, and it's a point I'd certainly agree with.

The author also claims to some extend that animal experiments can be replaced by other methods. In the general case this is simply wrong, you cannot replace all animal experiments. There are cases where you can gain similar information from other experiments without animals, and those should certainly be further developed. But this is really hard to discuss in general, the specifics matter here and not all animal experiments are equal. Animal experiments are also expensive and time consuming, if there are established and reliable alternatives they will find their use.

> if it is to extend that ban to other countries the author should say so

The article explicitly states this in no uncertain terms as the final sentence in the paragraph you are talking about: "I see no good reason that [animal testing for cosmetics] should not be banned totally and everywhere."

I agree that the article is unfocused. However for the specific issues you are mentioning here, it is simple to search the article to see if the author has covered the relevant point you are making.

The article gives a lot of examples of cruel, useless or ineffectual animal testing but does not address useful or critical animal testing at all. They are simply implying all animal testing is in the former category.

> The quality of discourse on HN goes up when we all meaningfully engage with the content. The goal shouldn't be to see who is fastest to post a dismissal of the headline.

The same could be said about comments.

there are a number of replacement methods, though i don't know if they cover all the cases. these include using tissue cultures, diseased humans and software modelling. also, when drugs have been deemed sufficiently safe, they can be further studied using human volunteer trials.

We already do all of this in drug discovery research before putting things into animals. We try computer modeling (very inaccurate but a good pre filter) then cell culture, and only after that do we use animals. Not only is it ethically the right thing, it’s the economical thing. Animal studies are crazy expensive (each mouse costs a couple dollars per day just to keep alive and you need a lot of them) compared to cell culture and modeling.

The problem is that in your scenario, many many more humans would be harmed. While animal models are flawed, there are no cell culture tools that even come close to recapitulating the system wide effects you get in a whole organism. Without animal tests, all the drugs that hurt a mouse (and there are very many that fail in mouse tests for this reason) would instead do it to humans.

You can ban animal research, but if you do, know that virtually none of the medicines you take would exist. It really is that stark.

Ultimately I am ok with that, but I understand it is a difficult ethical question.

I am personally not ok with subjecting animals to torture, in order to extend human lifespans.

It’s not something I would want done to me if a more advanced alien species were to come along, but I suppose it is an easier decision to make when you are on the side that benefits.

> How else would you test the safety of a new drug or other chemical?

Use computer models first as much as possible, while we know they are imperfect. In vitro-studies before in-vivo. Then test on volunteers (paid), starting with very very small doses of whatever you want to test to reduce the risk to the maximum, and measure the effects on living systems as you go to better understand how it is metabolized.

As someone who has done drug development this is a horrific idea.

I remember using computer modeling - the lead said “oh yeah, tweak the molecule here and you’ll double the potency”. Cool, make the tweak and…potency was 1/10th.

And we do toxicity filtering already, before we get to animal models (why trying something you know will fail?). Despite this we have plenty of highly toxic molecule make it through. I remember the rats who testicles went necrotic after the first dose. Never saw that coming and thank god it didn’t happen in humans.

We’re so far away from even modeling molecules docking with receptors. Toxicity? You’d have plenty of phase 1 volunteers dying every year. Or being horribly harmed.

>Use computer models first as much as possible

Are we not doing this already? I would assume this is even cheaper than producing the thing and testing it. And I'm not sure how confident I would be with computer models since we don't know a whole lot about how biology works enough to simulate it (given the simulation would mostly be trying to replicate previous potentially flawed studies)

You are correct, if you could build a computer model that could even somewhat predict the efficacy of a drug you would instantly become the wealthiest person in the world.

I imagine the only real way to do such a thing would be to simulate physics on an atomic level and have a perfect atomic map of the body. Which we are no where near achieving yet. But once we have that sorted, all kinds of incredible simulations could be done.

You would need to do that, but not just for the target in question but the entire human body - there are so many feedback loops and mechanisms in the body to counter whatever your trying to do. Add on top toxicity and that’s why biology is so hard.

Reminds me of the story of Lyrica. Logic was it targeted GABA receptors - made sense too since it looked very similar to GABA itself. Sweet! And it had the same effect as a GABA agonist would. Pretty god damn smart people thought that one up!

Then a few years after approval someone figured out it actually worked on glutamate receptors.

Complete luck that it looked like GABA, behaved like a GABA agonist. It just didn’t work that way at all though.

What computer models? I can imagine that it is possible to predict some already known toxicological mechanisms for similar molecules. But we're certainly not even close to anywhere where we could predict unknown toxicological interactions.

And in vitro tests are very limited in that area. Of course they're still done and useful, but they can't replace animal tests. And testing on paid volunteers is still ethically problematic, you're targeting pretty desperate people if you remove animal experiments which could detect toxic compounds.

There is no computer model that is even close to being accurate enough. Science actually understands very little about the human body on a very micro scale.

IIUC, you are proposing

    computers -> petri dishes -> people

Whereas the status quo is

    computers -> petri dishes -> animals -> people

So you think safety testing should be less rigorous?

And that poor people who take up these positions should be the first line of defense in testing.

Safety of people matters a lot, but I keep thinking about the following observation - in drug trials we routinely see many drugs that work in vitro, work in mice but don't work in humans, and many drugs that seem safe for mice but have bad side-effects for humans. Shouldn't this cut both ways symmetrically? Does that imply that we have a bunch of drugs developed for as-yet-uncured diseases that work in vitro and would actually work for humans but just won't work on mice, so we never tried them on humans and will never know because it's unethical to try?

Do you work in this field? I don't, but even as a layman I'm quite certain that the research process is more involved than you appear to be suggesting. As far as I'm aware, trials in animal models don't stop at mice — I've heard of researchers testing for safety and efficacy on mice, and then progressing to guinea pigs and subsequently macaques. Some animal anatomies behave more similarly to humans when confronted with the same disease than others.

I know what I'm an expert in and it certainly isn't this. I trust actual scientists to know what they're doing.

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