Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

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

thelri.org

Post reply on HN
Print view View original

21–30 of 116 posts

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

#21

Post by bayesian_horse »

klmr wrote: post #20
bayesian_horse wrote: post #11

Earlier quoted context omitted.

We are getting there. In-vitro methods, often involving cell cultures, are gaining traction. In-silico, also. Robotic automation and synthetic biology help with that a lot. Machine learning can help make sense of more limited data, for example predicting toxicity and other parameters for drugs so that you can better choose what to forward to Human trials.

In vitro studies have been done for ages, but are often a worse model than closely related organisms. For instance, there are various human cancer cell lines and while these are routinely used to study various aspects of biology (cancer being just one of them), they are generally a poor model for drug trials. The current research trend goes towards developing organoids — cell cultures with a distinct 3D organisation…

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.

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

#22

Post by klmr »

bayesian_horse wrote: post #21
klmr wrote: post #20

Earlier quoted context omitted.

In vitro studies have been done for ages, but are often a worse model than closely related organisms. For instance, there are various human cancer cell lines and while these are routinely used to study various aspects of biology (cancer being just one of them), they are generally a poor model for drug trials. The current research trend goes towards developing organoids — cell cultures with a distinct 3D organisation…

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.

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

#23

Post by interfixus »

ggm wrote: post #14

I'm not arguing for pigs over mice but I ask since transgenic pigs are often said to be future potentially viable transplant sources would not trials in pigs be a better model? (Ethical nightmares)

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.

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

#24

Post by danieltillett »

distant_hat wrote: post #12
danieltillett wrote: post #5

While mice are not humans (who would have known), we could do a lot better by moving away from using inbred mice. More positively we could make a lot more use of domestic pets in research. If we started to treat more pets as research subjects we could really do a lot of great research.

The thing with inbred mice is that the results are more consistent (or at least more so) than with regular mice. This allows you to use less mice and get statistical significance. If you do not use those than the sample size you'd need drastically increases. Animal research is plenty expensive as it is.

Yes I know why inbred bred mice are used, but the end result is often a more accurate result that is meaningless. Use more outbred mice and do fewer experiements.

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

#25

Post by rajadigopula »

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 one may be totally neutral for another. So, you read a paper that claims it got awesome results on a random blindfold study, the question Dr. Hedge asks is what type of the 200 human body types is it efficient? Apparently there is a body type that gives neutral or negative results (ignoring side effects). Talk about working it on animals first! (-ve downvotes welcome)

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

#26

Post by danieltillett »

bayesian_horse wrote: post #10
danieltillett wrote: post #5

While mice are not humans (who would have known), we could do a lot better by moving away from using inbred mice. More positively we could make a lot more use of domestic pets in research. If we started to treat more pets as research subjects we could really do a lot of great research.

The purpose of inbred strains is to isolate the effects of the drug and the environment from the genetic effects. Drugs are routinely tested on multiple such strains. There is a huge variety of mouse strains in use and under development. Basically anything you would see in a "fancy mouse" you can have as a strain. Pets, like cats and dogs, owned by private owners, are used for studies all the time. And not just for v…

The problem is in most cases a new drug is not tested on multiple strains. Often we get the result for the CL57/black mouse and nothing more. The end results is often meaningless since it is strain specific.

Yes I know pets are used in studies, but we use pets to only a fraction of their potential. We have 10s of millions of pets and we use a few thousand at most every year. I am lamenting the waste.

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

#27

Post by danieltillett »

BostonEnginerd wrote: post #13
danieltillett wrote: post #9

Earlier quoted context omitted.

People are really keen to allow their pets to be used in research as long as they understand the importance. Pets are a massive resource that is just being wasted.

My cats are certainly not being wasted. Who else would step across my keyboard when I’m typing?

You should consider yourself lucky to be able to use your cat's keyboard while she is taking her afternoon stroll.

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

#28

Post by bonzini »

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…

> According to ayurveda, human body can be classified into around 200 types based on the K/P/H balance of a body.

Maybe you'd first need peer-reviewed research to prove that...

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

#29

Post by fifnir »

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…

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...

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

#30

Post by klmr »

interfixus wrote: post #23
ggm wrote: post #14

I'm not arguing for pigs over mice but I ask since transgenic pigs are often said to be future potentially viable transplant sources would not trials in pigs be a better model? (Ethical nightmares)

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.
Post reply on HN