Animal research for ME

Now that I remember, @PeterW, we used to call it the Yak Dung Effect in the lab in 1980. Give a mouse or a rat anything and the graph will shift with p<0.01. Or at least one of your graphs will and that is the one to publish.

 

Can you provide a source that distress doesn't happen at slowly increased flow rates?

The effect of carbon dioxide flow rate
on the euthanasia of laboratory mice, 2014

Nitrogen gas produces less behavioural and neurophysiological excitation than carbon dioxide in mice undergoing euthanasia, 2019

One interesting thing - while humans and many other animals can not directly detect low oxygen environments directly and are actually detecting high CO2, some animals apparently can sense low oxygen without high CO2:

Wikipedia: Inert gas asphyxiation

You might be right about price. Though on this Reddit thread, a few people who work with lab mice say the difference is a time cost. Nitrogen takes much longer to kill a mouse.

 

I find the idea of animal models at this stage, to be grossly unethical and at best a waste of time.

there is no such thing as an 'animal model' of ME. It simply cannot currently exist. We dont know what causes ME so its impossible... IMPOSSIBLE to accurately simulate one.

Exercise to exhaustion plus psychological stress does not = ME/CFS. If only it were! But no, that is just a common but woefully inaccurate, misconception.

So any experimentation on torture of, animals based on such ideas will not lead to any insight into ME/CFS. Any more than injecting a animals in the leg with lidocaine to create intermittent numbness, would lead to insight into MS. That wouldnt be an 'animal model' of MS, and scientists would laugh at the idea it could yield anything useful.

The whole thing is absurd and vile. Its one thing doing experiments to save lives, when it might actually save lives, (I mean i not sure of the ethics of doing even that but its a more difficult & nuanced decision).... but doing it for this?!?

I feel angry and outraged about it.

Not to mention the tragic waste of time and money that could be spent on something useful.

 

The study I am referring to was not an animal model of ME/CFS, they injected mice with extracts of blood from ppl with LongCovid, and those mice then exhibited symptoms.

Having used mouse poison in the past, I don’t have an issue with undertaking studies which result in the death of mice.

Perhaps having seen animals being slaughtered the old fashioned way (knife to throat and bleeding out), I don’t have such a horrible opinion of it. I think there are worse ways to go than these.

 

ah, well, as you can tell from my comment i was referring to studies using an 'animal model' of ME/CFS - of which there are quite a few & seem to be growing in number. Its those studies i object to.
The one you mention where they injected IgG... Is that the one you mean? I feel agnostic about that, but the poll just says 'research uisng animals', and there is no 'on the fence'/not sure, option.

 

That's what we call an animal model. LC maybe, but I think the assumption is that they are trying to model something like ME/CFS.

 

many pigs in the UK are slaughtered using CO2 asphyxiation. That doesn’t disprove your point (about which I simply have no insight) but I do eat pork which will have been slaughtered that way.

 

Yeah, I'm not a fan of food animals being treated inhumanely either. One organization I think is doing great work in this field is the Humane Slaughter Association, and I believe has had some big wins in changing industry in Europe. Though I think they only deal with farm animal slaughter, not lab animals.

https://www.hsa.org.uk/news-events/...lternatives-must-now-be-urgently-implementeda

 

A load of our current medications were developped before we had any understanding of the mechanism underpinning them.

While the idea of building-up a formal mechanistic understanding to support drug development is very attractive, is that how many major drugs have been developed, or is there a need for serendipidy here?

 

I'm confused... I cant follow your reasoning... What i'm talking about is researchers exercising animals to exhaustion & then testing things on them, and assuming their results tell us something about ME. Whatever the results are they will only be results on what works (or doesnt), for treating a mouse who has exercised to exhaustion, & therefroe possibly a human.

Since ME does not = having exercised to exhaustion, i dont see how it can serendipitously tell us anything about it. It can only tell us something about what happens in a mouse body when they have swam until the point of collapse (Or sometimes they stress them out psychologically as well or instead of, the exhaustion).

Its like giving a bunch of mice very nasty psychological shocks, until they start trembling & shaking with it, & then expecting experimentation on them in that state to tell us something about parkinsons, just because it looks superficially similar. Its illogical.

I eat meat, with guilt but i do eat it, but i do not find it acceptable to kill more animals than we need for food (i know that happens but the question was what we find acceptable). Neither do i find it acceptable to do all kinds of experiments on animals hoping to discover something out of the experiments 'serendipitously'.

Yes we are going to need a pretty big stroke of luck to get anywhere, but i dont see it as necessary to toy with extreme cruelty, with animals, until we have a damn good reason to do so. I'm not certain i find it ethical even then, but that for me would be a different question.

Again, to be clear i am talking ONLY about studies on animals where researchers try to simulate ME/CFS - i dont believe that is possible, so to my mind research on animals with simulated ME/CFS is wrong and a waste. Playing around with them hoping for a stroke of luck is appalling.

The example you gave of injecting an infected person's blood to see if it will give them symptoms... well that is slightly different, i dont know about that, but i defer to Jonathan's comments both here and on the thread about that study, since it is all a bit scientifically beyond me.

All i'm saying is : No experiments on animals that are exercised to exhaustion , and or stressed to collapse, that are being performed because the researchers are too ignorant to know that that is simply not what ME/CFS is. I wish it were that but it isnt, it only looks a little like that to people who confuse it with CF or TATT.


LOL I honestly cant eat my ham sandwich now, i didnt think about that pig's death when i bought it. I dont find it acceptable to treat animals inhumanely during life or slaughter, and try to buy my meat accordingly, but i dont always, so i need to face that and stop it.
I only started eating meat for ease when i got too ill to cook for myself & was cutting out all kinds of other things trying to 'nutrition' my way out of this hell. But i carried on eating it even when i resumed bread etc, because it tastes good and it is easier.

Sorry if that was very waffly i not good at succinct even before the fog descended

 

I would agree with you that animals exercised to exhaustion are not in any way a proxy for ME/CFS.

The question is, if insights can be gained from animal testing, should we be doing it?

that is significant as the UK ME/CFS charities all refuse to fund animal research.

This would include injecting the blood of people with LongCovid into mice to see if they exhibit symptoms.

I feel that is legitimate animal research, and I am disappointed it has not been done before.

 

I tend to ask myself for anything involving animals, would this be acceptable to do to a human? Would society be okay with injecting healthy humans with LC blood, trying to induce LC symptoms? If not, what's the reason it feels okay to do to an animal?

 

Well, on a practical level, many of us do eat meat, poison and trap mice, kill slugs etc. All things which our society does not accept being done to other humans.

So many of us do differentiate between human and non-human animals on a daily basis.

 

That's true. So I'd go to the question, why does it seem okay? Is it because there's actually some difference that matters morally in all these cases, or does it just feel that way because animals are so different?

To me, it mostly seems like the latter, as well as because that's how it's always been done.

 

Well many people have thought about that.

So the question of morality of testing on animals (and whether it should be done in ME/CFS) essentially boils down to the simple question of “are you vegan”?

 

I think the situation is more nuanced.

All immunology, from which we have to build theories of disease, has involved animal experimentation to establish how the immune system normally works and responds to stimuli.

ME/CFS charities are happy to fund research that makes use of that knowledge. They fund research that involves use of lab reagents generated in animals.

What they are not happy to do by and large is fund studies where animals are deliberately caused distress. How strict they are and how open to change in policy they might be I do not know but that would be a reasonable position if history has told us that such studies are by and large useless.

And that is the case.

Research is not legitimate if there isn't snowballs chance in hell of it telling us something useful. Giving a mouse a slug of human IgG is a bit like giving a human two pints of mouse IgG. Since all of it (not just some extra mysterious 'thing in the blood') is foreign protein there will inevitably be a reaction. So testing mice for symptoms vaguely compatible with ME/CFS or fibromyalgia after injection of human IgG is going to be pretty hard to interpret. Moreover, people did hundreds of experiments like this in the 1970s and 1980s and ended up none the wiser.

Small molecule drug development is still very dependent on being able to simulate things like inflammation in animals for early efficacy testing. For biologic drugs this doesn't necessarily apply. But in ME/CFS and fibromyalgia we have no inflammation to simulate and anyway the drug companies would do that sort of study - and only once a pathway had been identified. We don't have any identified pathways.

 

Not quite right - this thread was first started after 2 UK ME/CFS charities stated to me, quote “our position on using animals in research is unequivocal - we don’t fund it”. Another said similar.

Regarding the limitations of different research methodologies - you will know these better than me but, I would note that many research institutions and larger research funders do have a less restrictive approach:

Oxford Uni: https://www.ox.ac.uk/news-and-events/animal-research/research-using-animals-an-overview

Parkinson’s UK: https://www.parkinsons.org.uk/about-us/animal-research-at-parkinsons-UK

Vs Arthritis: https://versusarthritis.org/researc...r-approach-to-research/our-research-policies/

When we look at research funding in the UK, we see that ME/CFS funding is insufficient both from government agencies (see Prof Danny Altmann’s recent comments that funders are “not interested”) but also from the UK charity sector (which funds even less research than government does).

It is worth querying whether the UK charity sector is being too dogmatic around the research that it will fund. It is also worth querying whether fixed ideas about methodologies including animal research has, or in the future could, get in the way of understanding this disease better or testing potential therapeutics.

 

Well, having been on the steering committee of a research group funded by such a charity that had to use reagents derived from laboratory animals I can say that things are not so unequivocal. You cannot do any immunology without doing that. And there wouldn't even be any immunology if there hadn't been background animal studies. The charities mayn't realise that but I suspect they do and I don't actually think they would object. Charles Shepherd would be aware of the situation for instance, as would the people from MERUK I have met.

 

It is worth querying but I can assure you that as someone who once had a specific interest in animal models I think the ME charity policy is exactly right. There are not experiments that involve direct harm to animals as disease modelling exercises worth doing in ME/CFS and I doubt there ever will be. Oxford has had a reputation for having a pretty borderline ethical policy, hence the animal rights episodes around 1990. Versus Arthritis has a long history of funding animal model studies that I consider totally unjustifiable and a complete waste of time.

Worth querying, yes, but I wouldn't get too bothered about it. It is not where the problems lie. The last thing we want is for people's money to go into the sort of pointless me-too research that dominates the scene these days. DecodeME is a rock solid project. There have been other good searching exercises in immunology that have come out negative. The metabolic studies make sense but it seems unlikely they will turn up much when we know so much of the metabolism is normal. Otherwise our main problem is that we do not have leads. Setting up animal models with no leads is futile because you can always set up a model that does what you manipulate it to do and it still has nothing whatever to do with the disease in hand.

 

Animal research is often more for exploring than for proving. In diseases with unknown aethiology like ME/CFS, just reliably reproducing the disease would be a huge step towards understanding and solving the problem. And you can't do that with humans for obvious reasons. If you have to justify by proving the significance first, no such exploration will never take place.