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The case for free-range lab mice

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Re: The case for free-range lab mice

#11

Post by tsol »

photochemsyn wrote: post #10

If you're going to look for cures for diseases in humans, you should be using human genetic and cellular models. Since running experiments on human beings is frowned upon, what with control groups and the post-experimental 'sacrifice' of the test subjects for tissue analysis and so on, what to do? Happily, modern technology allows for development of human stem cells into a variety of cell types - even lately into com…

Tissue in a lab is not equivalent to a whole organism in drug testing, and what works in one may not work at all in the other. It's a step forward but it still has limited use

Re: The case for free-range lab mice

#12

Post by gpcr1949 »

superkuh wrote: post #2

It's even worse than the un-life like conditions of allowed animal models leading to bad results. With the increasing regulatory burden and outright outlawing of animal models in scientific research biological studies are moving to new far-abstracted models that are much cheaper, easier, higher N, and counterintuitively, way, way less predictive of the actual results in human bodies. Testing 1,000,000 compounds in si…

High-throughput screening (HTS), i.e. testing a large amount of compounds in simple biochemical assays can't be compared with testing 10 compounds in monkeys. The point of HTS is finding active substances in a large collection of compounds (finding needles in the haystack), and then using this as the initial step of a whole chemical optimization research program that may lead to a new drug candidate down the line.

Conversely, the 10 compounds tested in monkeys will usually be advanced drug candidates just before phase 1 trials in humans. If you would give monkeys 10 compounds from a HTS collection you would learn nothing about what works in human disease because most compounds are inactive at a given target.

Every large pharma company has HTS infrastructure and uses this for early discovery (in addition to animal experiments at later stages of drug discovery campaign) - and these companies are interested in making profit by discovering new drugs that meet the requirements to get approved, not in generating publications or boasting about their fancy HTS robot.

Re: The case for free-range lab mice

#13

Post by refurb »

superkuh wrote: post #2

It's even worse than the un-life like conditions of allowed animal models leading to bad results. With the increasing regulatory burden and outright outlawing of animal models in scientific research biological studies are moving to new far-abstracted models that are much cheaper, easier, higher N, and counterintuitively, way, way less predictive of the actual results in human bodies. Testing 1,000,000 compounds in si…

There is no replacement for live animal tests at this point.

There have been advances in cell models, but they are not a replacement for whole organism tests. They are proxies for living organisms and often not very good ones. There is too much complexity in living organisms to be modeled.

It's going to be that way for a long time.

Re: The case for free-range lab mice

#14

Post by refurb »

photochemsyn wrote: post #10

If you're going to look for cures for diseases in humans, you should be using human genetic and cellular models. Since running experiments on human beings is frowned upon, what with control groups and the post-experimental 'sacrifice' of the test subjects for tissue analysis and so on, what to do? Happily, modern technology allows for development of human stem cells into a variety of cell types - even lately into com…

Testing isolated human tissue is in no way comparable to a whole organism.

Even if you tested all different human tissue types separately, you haven't accounted all for interactions between tissues. Say liver metabolism to a molecule that is toxic to bone marrow.

Re: The case for free-range lab mice

#15

Post by lofatdairy »

photochemsyn wrote: post #10

If you're going to look for cures for diseases in humans, you should be using human genetic and cellular models. Since running experiments on human beings is frowned upon, what with control groups and the post-experimental 'sacrifice' of the test subjects for tissue analysis and so on, what to do? Happily, modern technology allows for development of human stem cells into a variety of cell types - even lately into com…

Yeah these have been the hot thing for a minute. Nina Tandons TED talk came out 10 years ago and minus a few more detailed developments, I think it holds up really well as an introduction. The main challenges are related to the fact that cell cultures and tissue cultures are also not easy to standardize (passaging and media variations) and also introducing mechanical stimuli to more accurately model living systems. Serum free media is one area where there's been a bit of development, and recreating function mechanically has been a really interesting field. Dongeun Huh's paper I think he did while a postdoc in Donald Ingbers lab is pretty canonical and still is incredibly impressive but stretching is only part of the deformations these tissues undergo.

Re: The case for free-range lab mice

#16

Post by photochemsyn »

refurb wrote: post #14
photochemsyn wrote: post #10

If you're going to look for cures for diseases in humans, you should be using human genetic and cellular models. Since running experiments on human beings is frowned upon, what with control groups and the post-experimental 'sacrifice' of the test subjects for tissue analysis and so on, what to do? Happily, modern technology allows for development of human stem cells into a variety of cell types - even lately into com…

Testing isolated human tissue is in no way comparable to a whole organism. Even if you tested all different human tissue types separately, you haven't accounted all for interactions between tissues. Say liver metabolism to a molecule that is toxic to bone marrow.

Ideally one could construct a whole model of the human circulatory system in this manner, with a digestive tract module, a liver module, a kidney module, etc. Probably still a bit sci-fi at this point.

Re: The case for free-range lab mice

#17

Post by Dalewyn »

photochemsyn wrote: post #10

If you're going to look for cures for diseases in humans, you should be using human genetic and cellular models. Since running experiments on human beings is frowned upon, what with control groups and the post-experimental 'sacrifice' of the test subjects for tissue analysis and so on, what to do? Happily, modern technology allows for development of human stem cells into a variety of cell types - even lately into com…

>it's needlessly cruel to animals, particularly when there are now better approaches utilizing technology that should be capable of producing muscle, lung, heart, even brain tissue models based on human stem cells.

What is the difference between "animals" and "cells"?

No, seriously. Answer me. I'll wait.

If you're actually serious and sincere about "cruelty", it shouldn't make any difference whether it's a whole animal or a cell: They're both living entities.

Re: The case for free-range lab mice

#18

Post by photochemsyn »

Dalewyn wrote: post #17
photochemsyn wrote: post #10

If you're going to look for cures for diseases in humans, you should be using human genetic and cellular models. Since running experiments on human beings is frowned upon, what with control groups and the post-experimental 'sacrifice' of the test subjects for tissue analysis and so on, what to do? Happily, modern technology allows for development of human stem cells into a variety of cell types - even lately into com…

>it's needlessly cruel to animals, particularly when there are now better approaches utilizing technology that should be capable of producing muscle, lung, heart, even brain tissue models based on human stem cells. What is the difference between "animals" and "cells"? No, seriously. Answer me. I'll wait. If you're actually serious and sincere about "cruelty", it shouldn't make any difference whether it's a whole anim…

Consciousness.

Re: The case for free-range lab mice

#19

Post by refurb »

photochemsyn wrote: post #16
refurb wrote: post #14

Earlier quoted context omitted.

Testing isolated human tissue is in no way comparable to a whole organism. Even if you tested all different human tissue types separately, you haven't accounted all for interactions between tissues. Say liver metabolism to a molecule that is toxic to bone marrow.

Ideally one could construct a whole model of the human circulatory system in this manner, with a digestive tract module, a liver module, a kidney module, etc. Probably still a bit sci-fi at this point.

Thats pretty much a human then.

For example livers arent made up just liver cells (hepatocytes) there are 3 other major cell types.

In vitro heptacytes are commonly used today to measure metabolism and toxicity and you get a lot of good info, but they dont substitute an actual liver.

Re: The case for free-range lab mice

#20

Post by Dalewyn »

photochemsyn wrote: post #18
Dalewyn wrote: post #17

Earlier quoted context omitted.

>it's needlessly cruel to animals, particularly when there are now better approaches utilizing technology that should be capable of producing muscle, lung, heart, even brain tissue models based on human stem cells. What is the difference between "animals" and "cells"? No, seriously. Answer me. I'll wait. If you're actually serious and sincere about "cruelty", it shouldn't make any difference whether it's a whole anim…

Consciousness.

What is your reasoning that cells do not possess conciousness?

Why is conciousness even the deciding factor?

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