4 ms·

I'm going to throw this out there not knowing much about the specifics in this case. Academic biologists suffer from tunnel vision when it comes to developing d

by apo 8y ago

I'm going to throw this out there not knowing much about the specifics in this case. Academic biologists suffer from tunnel vision when it comes to developing drugs. Here's a script I've seen play out way too often. Molecule exhibits interesting behavior. Molecule is examined more closely in vitro and in vivo. Effects appear to be for real. More studies are done. Years go by. And at no time was a single close analog made. Nor was a medicinal chemist ever consulted. Little to no structure-activity relationships were performed. The molecular mechanism of action remains mostly unknown as a result. The thinking seems to be that drugs are discovered (by biologists), not developed (as in software through an iterative process). Some drugs are discovered, but most are developed. The compound that biologists are interested in right now isn't the good part. The good part is the underlying mechanism and how amenable it will be to actual drug development.

sametmax 8y ago
Making the mechanism of action known open the door to alternatives and competition. If a firm pour millions into a project, they want exclusivity. In our current system it's more important than good science or choosing what's best for humanity.
- thereisnospork 8y ago
  But for the academics their prestige rests on publishing that mechanism of action. Determining x drug works via inhibiting such-and-such transferase via pi-pi interactions (for example) is how careers are made, and in cases where the learning is important enough to shutter away, typically the academic will license it out or go into business for themselves -- which is just fine because that means we get a drug out of it, if there was one to be had. The problem is that the academic side isn't generally focused on things that matter about getting a drug to market(e.g. what happens when you swallow it? Does inhibiting such-and-such transferase actually do anything meaningful? What does it metabolize into? etc.) Lots more glitz and glamor (and lots cheaper) to make a compound inhibit something or kill cancer in a petri dish. Its vaguely as if say computer science academics were studying code golf.
phkahler 8y ago
>> The thinking seems to be that drugs are discovered (by biologists), not developed (as in software through an iterative process). Some drugs are discovered, but most are developed. >> The compound that biologists are interested in right now isn't the good part. The good part is the underlying mechanism and how amenable it will be to actual drug development. You're not wrong, but some important drugs were actually discovered - Aspirin and Statins come to mind. The reason for "drug development" is often due to a desire for a fresh patent to keep profits high. The reason a lot of those academic discoveries are not pursued is the lack of patentable derivatives. Go create a new opioid for example that's more addictive and see how much money it makes! There's no money in growing poppies. Medicine does not require novelty, just results. Having said that, I do feel that understanding mechanisms is a good idea. But then look at all the psych medications where the mechanisms are often not really understood - SSRIs are an exception, though how serotonin actually affects how you feel is not well understood.

by apo 8y ago

sametmax 8y ago

Making the mechanism of action known open the door to alternatives and competition. If a firm pour millions into a project, they want exclusivity. In our current system it's more important than good science or choosing what's best for humanity.

thereisnospork 8y ago
But for the academics their prestige rests on publishing that mechanism of action. Determining x drug works via inhibiting such-and-such transferase via pi-pi interactions (for example) is how careers are made, and in cases where the learning is important enough to shutter away, typically the academic will license it out or go into business for themselves -- which is just fine because that means we get a drug out of it, if there was one to be had. The problem is that the academic side isn't generally focused on things that matter about getting a drug to market(e.g. what happens when you swallow it? Does inhibiting such-and-such transferase actually do anything meaningful? What does it metabolize into? etc.) Lots more glitz and glamor (and lots cheaper) to make a compound inhibit something or kill cancer in a petri dish. Its vaguely as if say computer science academics were studying code golf.

phkahler 8y ago

>> The thinking seems to be that drugs are discovered (by biologists), not developed (as in software through an iterative process). Some drugs are discovered, but most are developed. >> The compound that biologists are interested in right now isn't the good part. The good part is the underlying mechanism and how amenable it will be to actual drug development. You're not wrong, but some important drugs were actually discovered - Aspirin and Statins come to mind. The reason for "drug development" is often due to a desire for a fresh patent to keep profits high. The reason a lot of those academic discoveries are not pursued is the lack of patentable derivatives. Go create a new opioid for example that's more addictive and see how much money it makes! There's no money in growing poppies. Medicine does not require novelty, just results. Having said that, I do feel that understanding mechanisms is a good idea. But then look at all the psych medications where the mechanisms are often not really understood - SSRIs are an exception, though how serotonin actually affects how you feel is not well understood.