Just to expand on this for the audience. Even a perfectly reasonable synthesis of MPPP, a synthetic opioid, can produce MPTP[1], which will destroy all of your dopaminergic neurons and give you permanent brain damage. This was discovered entirely by accident. Or, Karen Wetterhahn, who got a single drop of organic mercury on her gloved hand and spent the next year suffering from her brain rotting from the inside out.

This only barely scratches the surface from what I can remember, but there's absolutely, unambiguously a lot of good reasons why these barriers are there. These are rules that have been put down through blood and tears.

[1]: https://en.wikipedia.org/wiki/MPTP

People frequently don't realize that thalidomide is a very good chemotherapy drug that's back on the market with the appropriate category X designation.

It treats multiple myeloma, graft-vs-host disease, various HIV associated disease and Kaposi's sarcoma, Leprosy and potentially TB.

People who are specialists in something other than economics often make this argument but it's often a very weak argument, IMO. Liability means that you are incentivized to be quite cautious in pushing a potentially dangerous product. Particularly with pharmaceuticals a class action can be easily and successfully argued in court. Moreover, a relatively small number of dangerous flops will tank your reputation with consumers. I would also add that you can't make any more money selling drugs to people you have killed.

The worst money incentive for drug manufacturers is that market forces push them towards recurring treatments for diseases that effect a large number of people. However that seems less than perverse to me.

d) elderly and infirm people are in a weakened state and so are less likely to recover from accidental complications your drug might introduce

e) sickness is itself a confounder for the toxicology effect of a drug. Suppose you take a drug and your liver shuts down - did the drug cause it or was it your underlying illness? This can lead to programs being prematurely shut down and actually prevent the development of treatments that might have gone on to succeed.

But yes, it was very effective as a treatment. When it was approved for cancer use, we actually had no idea how it worked, only that it worked really well. Thalidomide has saved a few orders of magnitude more lives than it took/damaged.

However the majority of a protein’s structure is functionally inactive. Only a relatively small region tends to be active and affect rate kinetics of various chemical reactions. Alternatively similar interactions affect the mechanical properties of other proteins.

We also know many of the pathways for most key biological processes. Of course we’re no where near simulating an entire human, however we could feasibly filter drug candidate drugs for strong affects on key biological pathways.

That’s not too different in a broad since than using surrogates like mice to test for toxicity across highly conserved pathways in metabolism, reproduction, liver function, etc. It’s a much more tractable problem as well.

We have a lot of experimental data for the effect of many proteins on important chemical pathways. Presumably drug companies have more information on how many drug candidates react with or interfere with key pathways.

My conjecture would be that we wouldn’t need fine grained interactions but that even coarse grained filtering could be valuable. As in sure drug XYZ is great for binding to serotonin but it also has high affinity to key stomach proteins. That could avoid expensive studies just to find out a promising anti-depression drug causes severe gastrointestinal issues in a lot of patients.

Even better if we could use genome variations to protein structure variations which could help differentiate between subsets of patients with or without severe side effects.