3 ms·

Identifying the protein targets could be a lifetime's work. Identifying drug interactors is another big project, verifying efficacy takes time, synthesis takes

by moldbug 14y ago

Identifying the protein targets could be a lifetime's work. Identifying drug interactors is another big project, verifying efficacy takes time, synthesis takes time, verifying purity, determining best method of delivery to the patient, half life, dosage, interactions with other drugs, on and on and on. It all takes time. Look, I'm not an idiot. I know it takes 10-20 years to develop a drug. But I also know that many of the drugs we use now were developed before any of these processes existed. Aspirin anyone? Penicillin? All of the processes and techniques used by the present-day pharmaceutical industry are predicated on the cultural assumption that, as I said earlier, it's better to let a thousand patients die of neglect than kill one with a drug. In fact, three orders of magnitude may be understanding the asymmetry - it might as well be six. Once you learn how to do things incredibly slowly, incredibly expensively and incredibly carefully, you're going to be completely ignorant of any way in which they might be done "fast, cheap and out of control." Very much a parallel situation is the nuclear industry. Does it really take 20 years to design and build a nuclear reactor? Done the modern American way it does. And indeed, there's a much better argument for nuclear overregulation than cancer drug overregulation - still not a good one IMHO. There's plenty of experience from military programs, even from the other side of the Iron Curtain, that tells us it's not that difficult, slow or expensive to build a nuclear reactor. But if you ask any nuclear professional, you'll be asking someone who knows in great detail how to build reactors the ultra-paranoid way. As far as he's concerned, that's the only way to do it. Nobody in the pharmaceutical industry knows how to execute effectively with a short OODA loop. The knowledge and experience would have to be created, certainly at the cost of errors and lives. That's a far cry from saying that it cannot possibly exist. Think about the way weapons are tested and deployed, not in the play wars we fight now but in a real war like WWII. Many, many soldiers in WWII died from unanticipated weapons failure. But if weapons hadn't been developed with the tightest possible OODA loop, we'd have been fighting Tiger tanks with cavalry lances. We're not fighting a "war on cancer." The military psychology is entirely absent. We're playing a game. As an earlier poster said, "it's an exciting time to be a cancer biologist." Is it an exciting time to be a cancer patient?

polyfractal 14y ago
Well first, I don't think you're an idiot. I haven't downvoted a single one of your comments because I think they are all constructive and thought-provoking...even if I don't agree with many of your points. =) Regarding Aspirin, Penicillin, et al, many of those drugs are the low hanging fruit in pharmacology. We've already plundered many of the easy molecules. I would contest that many of the present-day pharmaceutical assumptions are predicated on the fact that the easy molecules have already been found. The reason many drugs fail is not because clinical trials are too long - its because the drugs themselves prove ineffective, unsafe or both. Is a 2% increase in survival rate worth a 20% increase in mortality due to complications and side effects? We are past the days that you can find compounds that mold poops out, and use it to cure 90% of humanity's ailments. I certainly agree that clinical trial regulations are too long, with too much bureaucracy. They could stand to be shortened considerably. BUT, they also exist for a reason - safety is important. Also consider the safety of the patient. Cancer patients are usually willing to try anything to avoid dieing of cancer. There needs to be some protection such that these people are not unduly taken advantage of. There is a fine moral line between allowing people to take risky drugs to cure their disease and allowing companies to treat cancer patients as expendable hamsters. *Side note: I am no fan of big pharma either. They are effectively marketing firms that sell pills, not research companies (anymore). But that is not really what we are discussing at present =)
- moldbug 14y ago
  It's because the drugs themselves prove ineffective, unsafe or both. Statements like this prove the systemic abuse of statistics that is pharma regulation. You've - quite unconsciously, no doubt - reversed the definition of proof, asserting that failure to prove a positive is equivalent to proving a negative. Of course you don't believe this. But your institutional jargon automatically generates the lie. Orwell had a point. Today's viable drug is a survivor in a winnowing process in which any of a thousand screwups - often mere failures of trial design - can kill it. Moreover, while some of these are corporate errors (not the drug's fault), many of the design failures are institutional and uncorrectable. For instance, testing cancer drugs of the "magic bullet" type against late-stage tumors is utterly ridiculous, as these genetic Cthulhus are the last place anything targeted is likely to work on. But this is the only place our testing paradigm is viable. The drunk looks under the lamppost for his keys, again and again. Advanced genotyping might reveal that a certain tumor has five pathways for evading apoptosis. Five different molecules are needed to shut them all down. In an individual trial, each molecule fails. It thus - to use your language - "proves ineffective." We are past the days that you can find compounds that mold poops out, and use it to cure 90% of humanity's ailments. It's a commonplace assertion that most of these older compounds (certainly aspirin and penicillin) would fail an early toxicity screen and never get close to a mouse, let alone a patient. I have no idea whether this is true. But if it is, Western medicine is objectively in the same position as NASA: it can no longer do the things it did 40 years ago. Welcome to Trantor.

by moldbug 14y ago

polyfractal 14y ago

Well first, I don't think you're an idiot. I haven't downvoted a single one of your comments because I think they are all constructive and thought-provoking...even if I don't agree with many of your points. =) Regarding Aspirin, Penicillin, et al, many of those drugs are the low hanging fruit in pharmacology. We've already plundered many of the easy molecules. I would contest that many of the present-day pharmaceutical assumptions are predicated on the fact that the easy molecules have already been found. The reason many drugs fail is not because clinical trials are too long - its because the drugs themselves prove ineffective, unsafe or both. Is a 2% increase in survival rate worth a 20% increase in mortality due to complications and side effects? We are past the days that you can find compounds that mold poops out, and use it to cure 90% of humanity's ailments. I certainly agree that clinical trial regulations are too long, with too much bureaucracy. They could stand to be shortened considerably. BUT, they also exist for a reason - safety is important. Also consider the safety of the patient. Cancer patients are usually willing to try anything to avoid dieing of cancer. There needs to be some protection such that these people are not unduly taken advantage of. There is a fine moral line between allowing people to take risky drugs to cure their disease and allowing companies to treat cancer patients as expendable hamsters. *Side note: I am no fan of big pharma either. They are effectively marketing firms that sell pills, not research companies (anymore). But that is not really what we are discussing at present =)

moldbug 14y ago
It's because the drugs themselves prove ineffective, unsafe or both. Statements like this prove the systemic abuse of statistics that is pharma regulation. You've - quite unconsciously, no doubt - reversed the definition of proof, asserting that failure to prove a positive is equivalent to proving a negative. Of course you don't believe this. But your institutional jargon automatically generates the lie. Orwell had a point. Today's viable drug is a survivor in a winnowing process in which any of a thousand screwups - often mere failures of trial design - can kill it. Moreover, while some of these are corporate errors (not the drug's fault), many of the design failures are institutional and uncorrectable. For instance, testing cancer drugs of the "magic bullet" type against late-stage tumors is utterly ridiculous, as these genetic Cthulhus are the last place anything targeted is likely to work on. But this is the only place our testing paradigm is viable. The drunk looks under the lamppost for his keys, again and again. Advanced genotyping might reveal that a certain tumor has five pathways for evading apoptosis. Five different molecules are needed to shut them all down. In an individual trial, each molecule fails. It thus - to use your language - "proves ineffective." We are past the days that you can find compounds that mold poops out, and use it to cure 90% of humanity's ailments. It's a commonplace assertion that most of these older compounds (certainly aspirin and penicillin) would fail an early toxicity screen and never get close to a mouse, let alone a patient. I have no idea whether this is true. But if it is, Western medicine is objectively in the same position as NASA: it can no longer do the things it did 40 years ago. Welcome to Trantor.