3 ms·

You're absolutely right that this is the mentality that future treatments need to take. Yeah, and I'm sure our regulatory infrastructure will catch up sometime

by moldbug 15y ago

You're absolutely right that this is the mentality that future treatments need to take. Yeah, and I'm sure our regulatory infrastructure will catch up sometime in the Obama administration. That is, the Malia Obama administration... If this time frame were possible this would be ideal, however, unfortunately each of these steps (if they are possible) takes significantly longer than an evening, and typically far longer than a patient has. Then speed them up! You might have heard the story of Steve and Gorilla Glass: http://en.wikipedia.org/wiki/Gorilla_Glass http://en.wikipedia.org/wiki/Gorilla_Glass You're not going to tell me the actual chemical reactions are slow. It's all human labor. The speed of any organization is limited by the schedule on which results are demanded - compare the Manhattan Project to the new Bay Bridge. This is a risky game. How do I (the scientist) know which drugs were effective? How do I know how they'll react with one another? If my focus is Steve, then do I really want to risk killing him through an unexpected cross reaction of my 30-40 untested drugs? Yes, because Steve knows he's at risk of dying anyway. Being an intelligent person, Steve compares the risk of dying from neglect, versus dying from treatment, as apples to apples. Do you? There are (apparently) 1210 billionairs in the world. So say they all get cancer and get this team of doctors - if any of the patients survive then some aspect of the treatment worked. If they don't some aspect failed. It would be impossible to determine which is which. It would be impossible to determine which is which by the present statistical standards. Ie, it would be impossible to absolutely absolutely 10^7 know which was which. It might be possible for an intelligent person to make a good guess, however. This is how technique advances in any technical field that can't be reduced to pure mathematics. If you're limited to advancing on the basis of perfect truth that absolutely * 10^7 knows it's right (even if when tested in practice, it's 90% irreproducible), you can barely advance at all. Guess what - we're barely advancing at all. A combined focus of translational and basic research is essential, with a frequent and effective dialogue between the two. The best way to have a frequent and effective dialogue is to make basic researchers part of the teams treating patients. The distinction is imaginary, anyway. This was I believe the case for Steve, but not even for Steve could they do personalized drug development as described. They couldn't even try drug candidates which other developers and/or researchers had abandoned along the way - an enormous library of molecules, if properly collated. Ultimately, your argument assumes the rate of discovery will be constant. You need to consider the research in the broader picture. Cancer is a genetic disease (in terms of pathological origin, not necessarily in hereditary terms). It cost the (publicly funded) human genome project $3bn to sequence a human genome in about 12 years. Now it costs $5000 in a week or so, and both the cost and the time is coming down. It's a separate discussion, but you're actually making the argument against investing in basic cancer biology. Rather, all the investment should be in sequencers, etc. Reason: consider the studies you did with the tools of 10 years ago. What was difficult then is trivial now. So in what way did it contribute to what you know now? In no way, which makes it useless - if you hadn't done the work then, expensively, you could do it now, trivially. Now, consider the studies you'll do with the tools of 10 years from now... Of course, the practical effect of funding cancer biology is to fund tools development. But it's a somewhat indirect way to accomplish the objective...

polyfractal 14y ago
>You're not going to tell me the actual chemical reactions are slow. It's all human labor. I'm going to tell you that you are, in fact, wrong. Chemical reactions (pharmacodynamics) may be fast, but pharmacokinetics may very well be slow. There is a reason you have to take antibiotics for at least two weeks, or wait three months to see an effect from SSRIs. These things literally take time. Not all processes are instant in your body, many take time for their physiological effects to be materialized. Biology is biology and not everything is instant, no matter how much you wish it was. >Then speed them up! You might have heard the story of Steve and Gorilla Glass: This is such a naive comment I'm not really even sure how to address it. First, you can't just "hack" a molecule in a night. 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. Second, even supposing we can make a specific molecule overnight, the chance that molecule is going to kill your patient is really damn high. The human body does not get along well with most chemical compounds. There is a reason we have extended, long clinical safety trials. While you can make an argument they are too long, "overnight" is far, far too fast. You'll never know if you cured your patient's cancer when he drops dead tomorrow from your sulpho-cholorinated-methyl-mercury superdrug cocktail that you synthesized last night.
- 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?

by moldbug 15y ago

polyfractal 14y ago

>You're not going to tell me the actual chemical reactions are slow. It's all human labor. I'm going to tell you that you are, in fact, wrong. Chemical reactions (pharmacodynamics) may be fast, but pharmacokinetics may very well be slow. There is a reason you have to take antibiotics for at least two weeks, or wait three months to see an effect from SSRIs. These things literally take time. Not all processes are instant in your body, many take time for their physiological effects to be materialized. Biology is biology and not everything is instant, no matter how much you wish it was. >Then speed them up! You might have heard the story of Steve and Gorilla Glass: This is such a naive comment I'm not really even sure how to address it. First, you can't just "hack" a molecule in a night. 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. Second, even supposing we can make a specific molecule overnight, the chance that molecule is going to kill your patient is really damn high. The human body does not get along well with most chemical compounds. There is a reason we have extended, long clinical safety trials. While you can make an argument they are too long, "overnight" is far, far too fast. You'll never know if you cured your patient's cancer when he drops dead tomorrow from your sulpho-cholorinated-methyl-mercury superdrug cocktail that you synthesized last night.

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?