The case for free-range lab mice
newyorker.com
newyorker.com
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.
The rulers of the country would take 99% of the profits and 0% of the costs.
Think Tuskegee syphilis experiments or Dengvaxia.
Isn't part of it also just that the long hanging fruit has already been picked?
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-...
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.
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.
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.2021.7985...
> "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.
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.
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.
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.
Why is conciousness even the deciding factor?
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.
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.
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.
I also don't mind when someone extracts a tissue from mu body for testing. it's not connected to a "whole", these tissues alone don't make life.
I think our differences stem from how we charactarize individual cells.