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.
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.
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?
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 "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.
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.
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.
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.
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):
> "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.
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.
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.
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.
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
>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.
Cells are just biological automata, they are dead thing, just a bunch of robots exchanging messages, no more alive than a chair. However, when many types of cells come together, they form a living being.
Consciousness, or life, is an emrgent property that appeared due a collection of cells working together, it's more than the sum of its parts.
Where is the boundary? When do these automata become alive? We don't know, but we can be sure that monkeys and mice are alive, and they feel things. They feel pain, which is a property of the neural system.
To use another analogy, let's imagine a conscious robot. It's made of various metallic things, of nuts, bolts, alloys, wires, sensors, and let's assume it feels pain.
Performing stress testing on the individual bolts that make up its body (just bolts, like spare parts, from a toolbox) would not cause anything to feel pain.
I really recommend watching this kurzgesagt video [1] about cells, proteins, and how they interact.
>Consciousness, or life, is an emrgent property that appeared due a collection of cells working together, it's more than the sum of its parts.
A singular cell very much is a "life".
>They feel pain, which is a property of the neural system.
We know for a scientific fact today that plants can detect and even respond to stimulants like "pain", just not in the same way animals with nervous systems do.
Honestly, the only thing we understand about biology is that we understand almost nothing about it; and it's not for a lack of trying either. We really haven't gone beyond a very basic, distinctly human understanding of biology yet.
Basing judgments of cruelty on what are obviously just human biases with no objective basis serves to benefit nothing other than some humans' need to feel good about themselves. Saying we shouldn't test on live mice because its cruel but that testing on live cells isn't cruel is hypocritical and belies the vapid nature of the argument.
Extending your argument, why then should we not test drugs and medical procedures on human beings, if there's no distinct difference from humans to rats to microbes? It's fairly obvious that if the objection to rounding up a bunch of human beings for use in sacrificial drug testing and other research is based on rights, ethics, morality,legality and so on, then why doesn't that concept of of ethical morality extend to clearly conscious animals?
Objectively I have no objections with tests on human subjects, humans are just another animal in the animal kingdom and just another living being like any other living being.
The only difference, if we can call it that because it's superficial, stems from human biases where humans are "one of us" whereas other species are "not us". That's it. From an objective perspective of living being, there is no difference between humans and other species including singular cell organisms.
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.
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
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.