3 ms·

We have first hand experienced this - we couldnt induce disease in the same mice when our lab moved universities and we all knew the temperature was one of the

We have first hand experienced this - we couldnt induce disease in the same mice when our lab moved universities and we all knew the temperature was one of the biggest culprits. But there are others too - gut microbiome and other microbiomes/viromes change from facility to facility and this is a huge deal for pretty much every topic except hardcore neuroscience. Probably. Who knew the bugs inside us are a big deal for everything that happens in us! All of this notwithstanding the growing knowledge that no, you can't just give mice cancer/MS/autism and check if a drug works there, expecting the same result in humans. I'll chalk the majority of problems in our drug pipelines to this fallacy.

Wowfunhappy 6y ago
> All of this notwithstanding the growing knowledge that no, you can't just give mice cancer/MS/autism and check if a drug works there, expecting the same result in humans. ...to state the obvious, scientists aren't giving drugs to mice and then shipping them off to pharmacies. They're testing the drugs in mice first to see if it's worth testing in humans. Then, the human trials are used to determine efficacy. It's not a perfect system to be sure, but what is the alternative? Bypass animal testing and go straight to human trials? I'd have a lot of obvious ethical issues with that.
- ramraj07 6y ago
  I'd argue that minimally positive results in these experiments should not be taken as any indication that the same therapy will work in humans unless they can convince an _extremely_ skeptical and thorough committee of experts that this result is likely translatable. That would immediately disqualify all xenograft models, and probably most native tumor models as well. So what should we do then? If I have solved it I would be running a successful company selling that secret sauce. But if I were to bet money then I'd say the best approach would be to come up with well thought out in vitro (and some mouse model) experiments that will clearly test all the known ways this drug will interact with every system in the human body; especially the immune system if it's a monoclonal. The emphasis should be on complete declaration of bankruptcy on any hope of a model system showing therapeutic efficacy that's correlated with expected human efficacy.
- danieltillett 6y ago
  Test on pets. Seriously our pets get all the same diseases we do (as always there are some exceptions). Millions of pets every year get cancer (just one example) and we make almost no use of this resource. The other approach is to start testing in humans at a very, very low dose. While this would work it would require a change in the regulatory environment.
  - GordonS 6y ago
    A lot of testing maims, disabled and/or kills rats. Are you going to be happy with a researcher coming to your home and breaking your dog's back? Or injecting it with toxins to induce neuropathy?
    - danieltillett 6y ago
      Don’t be silly. I am talking about treating pets for the diseases they have, not having people torture my pet.
nwah1 6y ago
The gut-brain axis is a huge deal. Hardcore neuroscience is affected by probiotics. There is even a class of them called psychobiotics.
t_serpico 6y ago
Everyone is aware that it's an imperfect model system. We just have nothing better to go off of. Granted, it got us to where are today so it obviously has had practical utility, but we may have exhausted the benefits of simplistic animal models as we try tackle more complex diseases (cancer, neurodegenerative disorders, etc.).

Wowfunhappy 6y ago

> All of this notwithstanding the growing knowledge that no, you can't just give mice cancer/MS/autism and check if a drug works there, expecting the same result in humans. ...to state the obvious, scientists aren't giving drugs to mice and then shipping them off to pharmacies. They're testing the drugs in mice first to see if it's worth testing in humans. Then, the human trials are used to determine efficacy. It's not a perfect system to be sure, but what is the alternative? Bypass animal testing and go straight to human trials? I'd have a lot of obvious ethical issues with that.

ramraj07 6y ago
I'd argue that minimally positive results in these experiments should not be taken as any indication that the same therapy will work in humans unless they can convince an _extremely_ skeptical and thorough committee of experts that this result is likely translatable. That would immediately disqualify all xenograft models, and probably most native tumor models as well. So what should we do then? If I have solved it I would be running a successful company selling that secret sauce. But if I were to bet money then I'd say the best approach would be to come up with well thought out in vitro (and some mouse model) experiments that will clearly test all the known ways this drug will interact with every system in the human body; especially the immune system if it's a monoclonal. The emphasis should be on complete declaration of bankruptcy on any hope of a model system showing therapeutic efficacy that's correlated with expected human efficacy.
danieltillett 6y ago
Test on pets. Seriously our pets get all the same diseases we do (as always there are some exceptions). Millions of pets every year get cancer (just one example) and we make almost no use of this resource. The other approach is to start testing in humans at a very, very low dose. While this would work it would require a change in the regulatory environment.
- GordonS 6y ago
  A lot of testing maims, disabled and/or kills rats. Are you going to be happy with a researcher coming to your home and breaking your dog's back? Or injecting it with toxins to induce neuropathy?
  - danieltillett 6y ago
    Don’t be silly. I am talking about treating pets for the diseases they have, not having people torture my pet.

nwah1 6y ago

The gut-brain axis is a huge deal. Hardcore neuroscience is affected by probiotics. There is even a class of them called psychobiotics.

t_serpico 6y ago

Everyone is aware that it's an imperfect model system. We just have nothing better to go off of. Granted, it got us to where are today so it obviously has had practical utility, but we may have exhausted the benefits of simplistic animal models as we try tackle more complex diseases (cancer, neurodegenerative disorders, etc.).