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Why Drugs That Work in Mice Don't Work in Humans

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Re: Why Drugs That Work in Mice Don't Work in Humans

#81

Post by ennisthemennis »

klmr wrote: post #59
Amygaz wrote: post #40

Any mice trial should use 4 different breeds: one of the academic hallmark (black6 or balb/c) for publication purpose, one that represent your model (or so you think) because that’s the logical thing to do, and a truly wild type one (captured in the wild) to capture the noise. Even this bias longevity piece needs to do that. This 4 breeds will all have different immune system, cognitive behavior and lifestyles, which…

The issue with that approach is that you’d multiply the number of sacrificed animals by 3 (or 4, did you forget a breed?), for limited gains in insight. Your approach would be a lot more defensible if it didn’t involve killing vastly more animals, and a fairly large increase in research cost. These things are always a balance, and there’s no evidence that always using your approach would be worth it.

I agree "any mice trial" is too strong a statement, and also 4 groups is kind of infeasible. But I do think there is not enough research on how these particular inbred mouse strains might bias research. Even the same strain sourced from different companies have produced different results, due to microbiome differences [1]. It's possible that we are way "overfitting" to these particular academic mice

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870873/

Re: Why Drugs That Work in Mice Don't Work in Humans

#82

Post by shawnz »

rajadigopula wrote: post #56
pcnix wrote: post #54

Earlier quoted context omitted.

It's not about giving confidence to people, the existing methods are part of the fundamental idea of the scientific method. Dr. Hegde's claim of body types doesn't really mean anything until there's evidence to back it up. And modern medical trials are crafted and investigated with a wide variety of statistical tools to determine the exact impact of a treatment method. Only if his claims can stand up to this rigorous…

Agree. Unfortunately, this is never going to happen. The few still practicing Ayurveda properly come from a background where they learned it from their ancestors within their family and practicing it for free and never allow commercialization of their knowledge. But they can gladly share the knowledge to people who want to learn. Food, Education and Medicine/health are the 3 things the practitioners in Indian culture…

> Unfortunately, this is never going to happen. The few still practicing Ayurveda properly come from a background where they learned it from their ancestors within their family and practicing it for free and never allow commercialization of their knowledge. But they can gladly share the knowledge to people who want to learn.

How is it possible that they could have prevented that information from ending up in the hands of profiteers even after all these years? And no profit hungry pharmaceutical company has ever been able to rediscover and commercialize those techniques, even though the details of them are mostly freely available on the internet?

Re: Why Drugs That Work in Mice Don't Work in Humans

#84

Post by SubiculumCode »

magicalhippo wrote: post #68
woliveirajr wrote: post #48

Earlier quoted context omitted.

That makes 3...

The 4th is a group of dead mice, to make sure you don't accidentally start a zombie apocalypse.

Jokes are discouraged on HN, but you did make me snort out loud.

Re: Why Drugs That Work in Mice Don't Work in Humans

#87

Post by Balgair »

leemailll wrote: post #42

Model animals are used in researches mostly due to two reasons: cost, which is always a big hurdle for academic studies; and reproduction, especially for inbred mice. The use of inbred mice often is because the behavior and activity of the mice is well-characterized, high availability, and genetically more consistent. However, the second part nowadays is often challenged and they are not that consistently genetically…

For those that are interested, the Animal Welfare Act of 1966 (an the many amendments to it) specifically spell out the animals that can be used for research and testing. There aren't that many of them, hence why rats and mice are so popular, as they are some of the few animals that can be used for testing. The AWA is structured such that all animals are covered by default, and only a few species are specifically excepted. It's an expansive law that also covers herding, meat processing, cosmetics, hunting, etc.

In general, the AWA is very restrictive in terms of animal testing for scientific research. Getting exceptions to use an animal for research is very intensive and highly regulated, taking years to get the approval. Getting approval for studies that may involve studying intentional pain, harm, etc to an animal can take up to a decade for approval, and with much study and research on other possible methods. Internal Review Boards (IRBs) are required to include local lay people, clergy, other non-scientists, etc in order to approve a study. Vivariums are also highly regulated and frequently inspected.

The US, at least nowadays, takes the welfare of animals extremely seriously with stiff fines and real consequences for breaches and lapses in protocol.

https://www.aphis.usda.gov/animal_welfare/downloads/AC_BlueB...

https://en.wikipedia.org/wiki/Animal_Welfare_Act_of_1966

Re: Why Drugs That Work in Mice Don't Work in Humans

#88

Post by nonbel »

hjk05 wrote: post #64
nonbel wrote: post #46

How many of these drugs actually do work in mice? Every study that comes out on the topic shows at least 50% and often closer to 90% of preclinical research does not replicate or even is not replicable in principle.

Research and drug development are pretty different leagues. A research paper might be 3 researchers with 20 mice. When your looking at preclinical trials it’s more like 300 people and 5000 mice per trial and god knows how many trials before something goes through. The reproducibility crisis is happening in academia. There isn’t that much room for uncertainty when it comes to industrial drug development. You won’t fin…

> "When your looking at preclinical trials it’s more like 300 people and 5000 mice per trial and god knows how many trials before something goes through."

This is sampling to a foregone conclusion. It is guaranteed to yield unreproducible effects.

> "You won’t find drugs making it all the way to market only for “another group” to be incapable of reproducing the effect."

I doubt this from the description above.

Re: Why Drugs That Work in Mice Don't Work in Humans

#89

Post by toiletfuneral »

Balgair wrote: post #87
leemailll wrote: post #42

Model animals are used in researches mostly due to two reasons: cost, which is always a big hurdle for academic studies; and reproduction, especially for inbred mice. The use of inbred mice often is because the behavior and activity of the mice is well-characterized, high availability, and genetically more consistent. However, the second part nowadays is often challenged and they are not that consistently genetically…

For those that are interested, the Animal Welfare Act of 1966 (an the many amendments to it) specifically spell out the animals that can be used for research and testing. There aren't that many of them, hence why rats and mice are so popular, as they are some of the few animals that can be used for testing. The AWA is structured such that all animals are covered by default, and only a few species are specifically exc…

I wouldn't praise the US too much on this subject:

https://www.washingtonpost.com/news/wonk/wp/2018/05/14/usda-...

Re: Why Drugs That Work in Mice Don't Work in Humans

#90

Post by nabnob »

chiefalchemist wrote: post #33

I'm not sure how common the practice is, but I've been told (by a trusted source) that if a med study doesn't get the desired results they just get a new set of mice and try again. That is, results can vary based on the mice used for reasons not understood (but gut bacteria perhaps).

Wouldn't that introduce the possibility that a study gets the desired results just due to randomness?

If you roll a die enough times, eventually you'll get a 6.

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