Why Drugs That Work in Mice Don't Work in Humans • Hacker News Board

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

#31

Post by tapland » Thu, Feb 28, 2019, 11:37 AM UTC

rajadigopula wrote: post #25

dtech wrote: post #2

Except for maybe the last paragraph, this is not new information to basically anyone performing studies. The problem is we don't have any ethically and scientifically better alternatives.

There is an alternate. To wake up from the ignorant direction the so called studies are taking the human kind to. And stop calling it science. Dr. B.M. Hedge suggested long ago that all the studies done on animals or humans are wrong and inefficient in so many fronts. His words - According to ayurveda, human body can be classified into around 200 types based on the K/P/H balance of a body. A medicine that works for o…

We know that there are things in humans that make them react differently to medications. We know _why_ this because of rigorous science.

Typing out that you are prepared for downvotes doesn't really change who has drank the Flavor Aid.

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

#32

Post by rajadigopula » Thu, Feb 28, 2019, 11:49 AM UTC

fifnir wrote: post #29

rajadigopula wrote: post #25

Earlier quoted context omitted.

There is an alternate. To wake up from the ignorant direction the so called studies are taking the human kind to. And stop calling it science. Dr. B.M. Hedge suggested long ago that all the studies done on animals or humans are wrong and inefficient in so many fronts. His words - According to ayurveda, human body can be classified into around 200 types based on the K/P/H balance of a body. A medicine that works for o…

Here's a nice smackdown which I don't have the time or knowledge to offer myself: "He abandons [Dr. B.M. Hegde] all rational thinking and embraces fantastical belief systems. The sad thing is I personally know many people delaying cancer treatment being swayed by his speeches and ending up with incurable metastasis later." https://www.quora.com/Do-you-agree-with-the-controversial-vi...

Understood. May be the modern world needs another wim hof to become a subject to the existing science - validity though current limited existing medical tools to prove/validate that humans can get access to autonomous nervous system and heal themselves (which was thought to be impossible in modern days). The approach Dr. hedge took is not registering with the rest of the world according to the comments above. May be he should have proven his claims subjecting to the existing methods just to give that level of confidence who trusts it like wim hof did.

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

#33

Post by chiefalchemist » Thu, Feb 28, 2019, 12:08 PM UTC

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).

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

#34

Post by AbyormPiranha » Thu, Feb 28, 2019, 12:10 PM UTC

Because mice aren't humans.

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

#35

Post by interfixus » Thu, Feb 28, 2019, 12:12 PM UTC

klmr wrote: post #30

interfixus wrote: post #23

Earlier quoted context omitted.

We are closer related to rodents than to pigs. Whether this is an argument for one thing or for another or for nothing at all, I really have no idea.

This isn’t quite true. The issue is that rodents evolve a lot quicker due to effective population size and generation time. As a consequence, the genetic divergence between rodents and humans is in fact greater than that between humans and pigs (see e.g. https://europepmc.org/abstract/pmc/pmc1142312 ), even though pigs branched off earlier than rodents.

Had a vague that something like that might be in play. I obviously have some reading up to do. My assumption was, that our branch would, until quite recently, have been rapid breeders too. And the pigs' one as well.

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

#36

Post by jonlucc » Thu, Feb 28, 2019, 12:31 PM UTC

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).

I work in pre-clinical pharma research, and this isn't really true in my experience, but there are a couple caveats. At least in my experience, we wouldn't run the same study again, but we might change the model. There are a few models that all point to a similar indication, so we might try both. If a treatment works in one but not the other, it's definitely seen as less strong evidence of efficacy, unless there's some very compelling mechanistic reason. That's not quite as crazy as it sounds, though, because translation from mouse to human is already poorly understood, so it can be hard to know which model will suggest positive effects in clinical trials.

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

#37

Post by jonlucc » Thu, Feb 28, 2019, 12:34 PM UTC

narrator wrote: post #3

What about drugs that work in humans, but not in mice? Could you ever get them into trials without animal data?

There is some work in this direction that is based on work with human cells (preferably primary cells) and building an otherwise compelling case. You have to be incredibly careful to do the appropriate safety studies and find some way to show efficacy in animals before you put the treatment into humans still due to FDA (and ethics) requirements.

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

#38

Post by Amygaz » Thu, Feb 28, 2019, 12:38 PM UTC

klmr wrote: post #22

bayesian_horse wrote: post #21

Earlier quoted context omitted.

Organoids do count as in vitro. And as I said, synthetic biology, automation and machine learning help in improving these methods. Nothing can replace certain studies in Humans completely. We can only hope to make those more effective by better choice of candidate drugs.

Absolutely. My phrasing wasn’t clear, I was contrasting organoids with the cell cultures mentioned in your reply, not with in vitro studies in general.

Organoids, organ-on-chip, 3D cell cultures, have all shown to be equivalent to each other, and better than standard 2D cell culture. Ultimately they are not very complex, definitely more than a monoculture, but no where near an organism that evolved from a single cell.

They haven’t shown to be a good proxy for a whole organism.

On term of disease model, they are typically artificial in the sense that genetically engineer the cell with a specific mutation that may or may not represent the disease or the population.

And if an experiment doesn’t work the way you want, you are a new set and sometimes it works the way you want.

The only two things they have over mice is that they can be from human origin, and sometimes that human origin might be in a disease state that you want to study, which might be the only way to generate a model for complex disease...

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

#39

Post by shawnz » Thu, Feb 28, 2019, 12:40 PM UTC

rajadigopula wrote: post #25

dtech wrote: post #2

Except for maybe the last paragraph, this is not new information to basically anyone performing studies. The problem is we don't have any ethically and scientifically better alternatives.

There is an alternate. To wake up from the ignorant direction the so called studies are taking the human kind to. And stop calling it science. Dr. B.M. Hedge suggested long ago that all the studies done on animals or humans are wrong and inefficient in so many fronts. His words - According to ayurveda, human body can be classified into around 200 types based on the K/P/H balance of a body. A medicine that works for o…

I don't get it. If you can't trust researchers who perform studies to validate their results, then what is it which makes this guy trustworthy to you? He has done strictly less than that to validate his results.

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

#40

Post by Amygaz » Thu, Feb 28, 2019, 12:45 PM UTC

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 are all central to aging.