5 ms·

The case for free-range lab mice

68 points by cocacola1 4y ago

superkuh 4y ago
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 single cell tests (or just chemical binding assays) in a micro-well array has less predictive power and useful outcome than testing 10 compounds in monkeys. At least when it comes to figuring out which things will work in human disease. The giant massively abstracted studies also generate false positives that waste time. But they do generate publications so they're selected for at the funding level. That's part of the reason biological research was so much more productive per $ input last century.
- kanzure 4y ago
  What's that old joke about mice benefiting from all the research but not humans? Maybe we can switch back to (this time voluntary) human experimentation at some point.
  - teddyh 4y ago
    If human experimentation was that more useful, wouldn’t a lot more scientific results be available from countries with more lax laws against it?
    - xwdv 4y ago
      Problem is those countries suck at research.
    - runnerup 4y ago
      Most likely a small handful of backwater countries would allow it. Most of the test subjects would get $500 from pharma giants and horrible disabilities from the side effects. There would be local organizations owned by relatives of politicians that would be statutorially required to be used for oversight, coordination, recruitment, etc. The rulers of the country would take 99% of the profits and 0% of the costs. Think Tuskegee syphilis experiments or Dengvaxia.
- klipt 4y ago
  > That's part of the reason biological research was so much more productive per $ input last century. Isn't part of it also just that the long hanging fruit has already been picked?
- beebmam 4y ago
  I don't find this very convincing. Do you have any evidence for this claim breaking down all the different costs for the research and quantified the change in those costs over time, or is this just an apriori argument?
  - superkuh 4y ago
    I apologize for my answer being in the form of a youtube video. I hate and ignore it when people link me youtube videos. It's a terrible format for information and discussion. But... https://www.youtube.com/watch?v=1u6ZkAVQfPA https://www.youtube.com/watch?v=1u6ZkAVQfPA "Jack Scannell - Why was biopharma so much more productive in 1950 I DeSci.Berlin" - The main points is the need to formally evaluate biological models. https://www.science.org/content/article/fda-no-longer-needs-require-animal-tests-human-drug-trials https://www.science.org/content/article/fda-no-longer-needs-...
- gpcr1949 4y ago
  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.
- refurb 4y ago
  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.
lofatdairy 4y ago
Similarly, cell lines are known to have variations and make replication difficult, especially after a few passages at the lab. FBS also being essential to media but being notoriously difficult to standardize makes things even trickier.
aaron695 4y ago
[dead]
photochemsyn 4y ago
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 complex tissues consisting of multiple cell types (2021): https://www.frontiersin.org/articles/10.3389/fimmu.2021.798552/full https://www.frontiersin.org/articles/10.3389/fimmu.2021.7985... > "In this review, we will emphasize the transitions from immortalized cell lines to stem cells and describe their use in combination with gut-on-chip models. These “on-chip” models are defined as three-dimensional (3D) cell cultures arranged as multiple cell layers actively perfused by microfluidics for medium exchange to enable an improved tissue formation with increased lifespan. We will highlight selected applications of these gut-on-chip models to understand gastrointestinal diseases and forthcoming strategies to investigate human gut physiology." This looks to be superior to animal testing on multiple grounds - first, animal models don't respond to drugs and don't develop identical disease states to humans, second 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.
- tsol 4y ago
  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
- refurb 4y ago
  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.
  - photochemsyn 4y ago
    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.
fuzzythinker 4y ago
https://archive.is/FMo6r https://archive.is/FMo6r
tspace2k 4y ago
Hmm saw article on c60 pills on lab mice it's effects on increasing life expectancy and bought bottles of it based on that scientific research... Just won't ever really know just got to try it on faith

68 points by cocacola1 4y ago

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 single cell tests (or just chemical binding assays) in a micro-well array has less predictive power and useful outcome than testing 10 compounds in monkeys. At least when it comes to figuring out which things will work in human disease. The giant massively abstracted studies also generate false positives that waste time. But they do generate publications so they're selected for at the funding level. That's part of the reason biological research was so much more productive per $ input last century.

kanzure 4y ago
What's that old joke about mice benefiting from all the research but not humans? Maybe we can switch back to (this time voluntary) human experimentation at some point.
- teddyh 4y ago
  If human experimentation was that more useful, wouldn’t a lot more scientific results be available from countries with more lax laws against it?
  - xwdv 4y ago
    Problem is those countries suck at research.
  - runnerup 4y ago
    Most likely a small handful of backwater countries would allow it. Most of the test subjects would get $500 from pharma giants and horrible disabilities from the side effects. There would be local organizations owned by relatives of politicians that would be statutorially required to be used for oversight, coordination, recruitment, etc. The rulers of the country would take 99% of the profits and 0% of the costs. Think Tuskegee syphilis experiments or Dengvaxia.
klipt 4y ago
> That's part of the reason biological research was so much more productive per $ input last century. Isn't part of it also just that the long hanging fruit has already been picked?
beebmam 4y ago
I don't find this very convincing. Do you have any evidence for this claim breaking down all the different costs for the research and quantified the change in those costs over time, or is this just an apriori argument?
- superkuh 4y ago
  I apologize for my answer being in the form of a youtube video. I hate and ignore it when people link me youtube videos. It's a terrible format for information and discussion. But... https://www.youtube.com/watch?v=1u6ZkAVQfPA https://www.youtube.com/watch?v=1u6ZkAVQfPA "Jack Scannell - Why was biopharma so much more productive in 1950 I DeSci.Berlin" - The main points is the need to formally evaluate biological models. https://www.science.org/content/article/fda-no-longer-needs-require-animal-tests-human-drug-trials https://www.science.org/content/article/fda-no-longer-needs-...
gpcr1949 4y ago
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.
refurb 4y ago
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.

lofatdairy 4y ago

Similarly, cell lines are known to have variations and make replication difficult, especially after a few passages at the lab. FBS also being essential to media but being notoriously difficult to standardize makes things even trickier.

aaron695 4y ago

[dead]

photochemsyn 4y ago

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 complex tissues consisting of multiple cell types (2021): https://www.frontiersin.org/articles/10.3389/fimmu.2021.798552/full https://www.frontiersin.org/articles/10.3389/fimmu.2021.7985... > "In this review, we will emphasize the transitions from immortalized cell lines to stem cells and describe their use in combination with gut-on-chip models. These “on-chip” models are defined as three-dimensional (3D) cell cultures arranged as multiple cell layers actively perfused by microfluidics for medium exchange to enable an improved tissue formation with increased lifespan. We will highlight selected applications of these gut-on-chip models to understand gastrointestinal diseases and forthcoming strategies to investigate human gut physiology." This looks to be superior to animal testing on multiple grounds - first, animal models don't respond to drugs and don't develop identical disease states to humans, second 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.

tsol 4y ago
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
refurb 4y ago
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.
- photochemsyn 4y ago
  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.

fuzzythinker 4y ago

https://archive.is/FMo6r https://archive.is/FMo6r

tspace2k 4y ago

Hmm saw article on c60 pills on lab mice it's effects on increasing life expectancy and bought bottles of it based on that scientific research... Just won't ever really know just got to try it on faith