One thing I never understood is that if results in mice so often don’t carry over to humans, what about the opposite - treatments that might work for people but are discarded because they don’t work well with mice.
There are a lot of problems with medical testing, and much of it stems from simple ethics. It would be more effective to test on humans directly and who knows what amazing treatments we might find that don't work in rats. And yet.. that's hopelessly unethical.
It reminds me of a scene from House MD;
>People should not be testing drugs because they are desperate. But, people won't test drugs unless they are desperate. We need drugs to save children and puppies ergo we need desperate people ergo welfare kills sick children.
Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge
Exactly. Last group of researchers that tested directly on humans happened to work for a certain political party that unfortunately managed to dominate Germany around the 1930-1940's.
Their "testers" happened to be people unjustly persecuted by their bosses, ranging from children to women and elderly.
They weren't the last group, they (along with Unit 731[1][2]) were just the most utterly and unashamedly barbaric group of savages to have done so.
Other groups of people have done plenty of unethical medical experiments since then - also typically against marginalized people.
Take https://en.wikipedia.org/wiki/Chester_M._Southam, for instance - thanks to his contributions to the study of cancer (consisting of injecting cancer cells into people without their consent). Thanks to his, uh, contributions to the field, he was later elected president of the American Association for Cancer Research.
[1] Which is utter nightmare fuel.
[2] Most of the members of which were given immunity from war crimes prosecution by the United States. Utterly mind-blowing. The ones that the communists were fortunate enough to get their hands on were subjected to a helping of Soviet justice.
I did work on medical devices and we did test on humans for non-life threatening conditions. The treatment wasn't that invasive though and it would never have had too bad side effects, the risk could be sufficiently reduced and the suffering of patients was greater than what the therapy could inflict.
Personally I wouldn't advertise any patriotism here, it is very important not to take advantage of desperate people here as long as the experimental treatment cannot possibly help against their conditions. Otherwise you certainly would loose more than you would gain. I doubt there can be a general rule though, the right choice depends on the circumstances and the risk to the patient.
> Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge
It’s clear to me that modeling the human body would be complicated, but I don’t have any idea about the order of magnitude. Can someone chime in?
Well, to model organic interactions you basically need a molecule-level model of the body or even deeper - especially for extremely complex molecules like proteins (which can famously "fold" in extremely hard to predict ways).
So, to very accurately model the human body, you need a model that has as many parameters as there are molecules in a human body, give or take a few orders of magnitude.
I have no idea to what extent you could get away with more high-level models - i would expect they could work well for some kinds of problems, but not for very systemic interactions, like hormonal or aging-related issues, that affect each cell in the human body to some extent.
I really doubt you'd start with "Let's emulate every atom of the human body". That's a huge waste of time. The atoms in my toenail are not relevant to most models you'd care about.
You'd probably start off instead by emulating specific proteins. That's already really hard, but obviously a trillion times easier than what you're suggesting.
Once you can emulate a number of proteins you can start to emulate interactions of drugs with those proteins. That's probably going to get you to a good enough heuristic where you can say "ok let's try this on something alive" or "this clearly doesn't work".
This is, to my knowledge, the existing approach being taken. It's just that a single protein is extremely complex. A single protein is a series of amino acids linked by peptides - each amino acid is itself a pairing of numerous atoms.
As you go from atom -> amino acid -> poly peptide -> protein you get a massive increase in complexity.
I thought the question was about developing new drugs entirely using computer models, at least until the first human trials. If that is the goal, we would need a model of the proteins in the entire body to get an idea of how a substance could affect every protein they interact with in every organ they reach, what organs it could actually reach, and how the modifications to each protein would in turn cascade.
And the toe nails and similar things are why I was saying "give or take a few orders of magnitude". Not to mention, certain drugs could affect your toenail.
I still think it would be unnecessary to do anything more than what I described, but just at a larger scale. But not the scale of emulating a whole human being. For the most part you're going to be looking for "does this bind with X but not Y" and expanding your set of X and Y is what makes things safer.
I think you could get to human trials using just a computer if you had a sufficiently sized set of emulated X's and Y's.
I guess the most difficult part is modeling all possible interactions related to an infinity of chemicals, DNA variations, environment influences, past medical issues, etc, etc.
I bet this would require computational power equivalent to whatever is "processing" the govern of real-world interactions in our bodies.
Am I the only one that sees the beauty and simplicity of a world that allows drug research companies to pay giant piles of money to people for them to agree to be test subjects for new treatments? The equalizing effect this could potentially have over wealth inequality across generations is arguably staggering. Some days it feels like our nobility and pride and respect for life are just ideals we claim on paper but end up just being huge shackles that keep us from preventing suffering in the now. We allow huge amounts of actual suffering and denigration of life to happen right under our noses.
Your imagination has veered into the entirely wrong direction.
If such a thing were legal, human test subjects would be the lowest classes, who would accept a pittance to support their family, or worse, who would sell their children for drug testing to score another hit. The vast majority of early drug trials cause extreme harm, so in essence any such contract would be a game of Russian roulette, except bullets to the head are a quick death. The extremely powerful incentive for companies would be to misrepresentat the risks and pay a pittance for the earliest trials, since these are the least likely to lead to profitable new medications.
Not to mention, if we were to replace mouse models with human subjects, the cost to develop new drugs would skyrocket, as even the least pittance afforded to some slave laborer in the this world would be more expensive than a mouse.
I share your concerns about it, and there is definitely potential for it to be abused and for it to create an underclass. But even for those, why not at least explore the option and at the same time use regulation to make it safe and not open for abuse? We're perfectly fine doing all sorts of games of wack-a-mole with other areas that we're trying to regulate but the free-market is constantly working around, so why not here too?
But this is what we've done, right? Drugs are tested on people, but only after they've been proven to be (a) somewhat promising and (b) somewhat safe in animal models. This helps make human trials safe.
Secondly, we've removed the profit motive, so that people are not allowed to be coerced by money into trying out someone's drug, and drug companies are not incentivised to test their drugs exclusively on the poorest people - this helps prevent abuse.
Unfortunately when money is an incentive, and money is also a requirement for life, you're not far from threatening to kill people if they don't take your experimental drugs. This is already an ethical concern with human drug testing.
Also, one benefit of mice is, morbidly, that you can immediately kill and autopsy them after treatment. I hope we can all agree that this would probably not be the right call for humans.
This probably happens. We're searching for drugs that "help humans, and don't kill them". And limiting our search to "helps mice, and doesn't kill them" is much more viable than trying random drugs on people and seeing how they do.
It reminds me of a scene from House MD; >People should not be testing drugs because they are desperate. But, people won't test drugs unless they are desperate. We need drugs to save children and puppies ergo we need desperate people ergo welfare kills sick children.
Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge