No need for anger - I think we're mostly in (violent) agreement here. :)
Maybe the one area we would significantly disagree is that I don't think it's simply that "the people working on it are not smart enough and are more interested in stoking egos and careers than doing real science".
Honestly, I've had discussions with so many mid-level smart trusted colleagues who always think that the higher-ups are making stupid decisions, and they'd do better. They're right that some of the decisions might be stupid (and you're probably right about "stoking egos and careers") some of the time, but people are promoted, decision-makers come and go, and the decisions (and failure rates) don't really improve. I (think I) see it for what it is, and agree that we lack meaningfully informative pre-clinical models, but I'm also comfortable to acknowledge the weaknesses of the system and be honest that I don't have all of the answers. At the moment, it's a heinously inefficient crap-shoot, but it's the best we've so far come up with.
But, prove me wrong. There are likely countless molecules that have been discarded that have therapeutic benefit waiting to be realised. (I don't mean to sound facetious here but) If you can do better, and are smarter than and will make better decisions than everyone else in the industry, you'll be a billionaire in short order, as this is literally the golden ticket in this industry that everyone else is missing.
I would love to prove my point by actually becoming a billionaire, but my point is that the system is stacked against folks like me. Gotta have a nature paper to get a job in Genentech fresh out of PhD. Who gets nature papers? People who join labs that already publish nature papers. Who gets to join there? Valedictorian Who undergrad in top schools. Apparently the odds are stacked the moment you slack off in eigth grade lol.
I have done my PhD, I need to take a break to actually take care of my family and immigration. I hope to get back to this field at some point, in my own terms, and see if I can succeed. If it works, it works! If not Who cares right! Let's see.
Maybe the one area we would significantly disagree is that I don't think it's simply that "the people working on it are not smart enough and are more interested in stoking egos and careers than doing real science".
Honestly, I've had discussions with so many mid-level smart trusted colleagues who always think that the higher-ups are making stupid decisions, and they'd do better. They're right that some of the decisions might be stupid (and you're probably right about "stoking egos and careers") some of the time, but people are promoted, decision-makers come and go, and the decisions (and failure rates) don't really improve. I (think I) see it for what it is, and agree that we lack meaningfully informative pre-clinical models, but I'm also comfortable to acknowledge the weaknesses of the system and be honest that I don't have all of the answers. At the moment, it's a heinously inefficient crap-shoot, but it's the best we've so far come up with.
But, prove me wrong. There are likely countless molecules that have been discarded that have therapeutic benefit waiting to be realised. (I don't mean to sound facetious here but) If you can do better, and are smarter than and will make better decisions than everyone else in the industry, you'll be a billionaire in short order, as this is literally the golden ticket in this industry that everyone else is missing.