4 ms·

My impression formed from my time in cancer drug discovery is that bro science is, within practical bounds, a perfectly reasonable option for one arm of a compr

My impression formed from my time in cancer drug discovery is that bro science is, within practical bounds, a perfectly reasonable option for one arm of a comprehensive plan for treatment. A lot of things that sound like bro science are actually broadly supported in the literature. But studying this stuff is hard because of all of the usual issues with human subjects, the less than complete reliability of our epistemic institutions, and the infeasibility of running enough trials to address every indication in every subcohort. So if anecdata supports some intervention that that isn't aggressively inconsistent with basic theory, won't make you miserable for what might be the rest of your life, and which you could try with the sober understanding that your One Weird Trick might not work, why not? If nothing else, a well-documented case study with good adherence tells us of one more thing that didn't work, which is hardly the worst parting gift to the world.

lambdaphagy 2y ago
To give a practical example, grapefruit juice contains some compounds that inhibit CYP3A4, a metabolic enzyme that influences the metabolism and absorption of many drugs, which is why many prescriptions tell you not to drink it while taking a given medication. This interaction was not discovered until 1989, and not reported until two years after that. So before 1991, a simple dietary intervention that affected like half of all drugs and that could in principle have been noticed by patient who felt bad after drinking a common household beverage, was bro science. Which is not to say "and therefore just do whatever", but just to point out that there's plausibly a lot of low-hanging fruit still left if you can figure out where to pick it.
- 7e 2y ago
  The problem is you can't figure out where to pick it; it's lost in a sea of superstitious noise. Even if you could find this fruit easily, "a food that cures cancer when eaten" does not exist. That would surface in epidemiological studies very quickly.
  - lambdaphagy 2y ago
    I admire your optimism in epidemiology. In point of fact, though, we have a rough natural experiment in the form of a food that doesn't cure a disease, but rather makes half of all drugs worse. That's very valuable knowledge, and under ideal epistemic conditions it might have been discovered within a few years of organized drug discovery as such. Yet was not widely known until the 1990s. So that's a failed positive control, which suggests that our practical capabilities to detect these kinds of effects are limited. Understandably so, given that there is no general requirement for dietary logging in clinical trials. That said, "a food that cures cancer when eaten" is not the bar for experimentation. More realistic might be something like "a dietary or behavioral protocol that, in some way, ameliorates this or that illness". For organisms with our body plan, "a cure for cancer" is like talking about "a cure for defection". But clearly there's "stuff that is efficacious against particular instances of cancer", a lot of which we found through techniques like natural product screens, i.e. "just trying stuff", rather than via rational drug design.
    - pama 2y ago
      It is indeed somewhat surprizing why it took so long to figure out grapefruit juice (and it was by accident during the study of the effects of coffee on a drug). Some of the early drugs that interacted with grapefruit juice where short-term agents like antibiotics, and others like channel blockers didnt have obvious detrimental toxicity though they might have had effects that were above the range of typical human variability. Powerful statins became household items a bit later, and all the cancer drugs were invented after this association was already known.
  - s1artibartfast 2y ago
    I think there is a lot of efficacy left on the table with modern studies, clinical trials, and drug development. Most of the work is looking for treatments that work for the majority of the population. If a treatment was effective than standard care for 10% of people, it would be discarded. It is more economical to start over looking for something that works for 90% of people. Drugs an treatments aren't evaluated and discarded when proven worthless. The bottleneck is the number of treatments in development, so they are discarded when something else has a better ROI.
- EVa5I7bHFq9mnYK 2y ago
  Is it juice specifically that should be avoided? What about grapefruit in solid form? Pomelo?
  - youngtaff 2y ago
    All grapefruit… my wife has clear instructions on this for her heart meds
hsuduebc2 2y ago
I love that someone asks for advice. Even for individual experience because he is miserable and some people are basically like "Nah just die. It would be uNeThIcaL."
- potsandpans 2y ago
  It's incredible. People are completely out of touch.
- totallynothoney 2y ago
  Time is precious.
_DeadFred_ 2y ago
Every single person I know who died from cancer young went down this route, from trying weird cures to going and seeing John of God in Brazil. Zero cured or delayed the cancer. All delayed acceptance and GREATLY regretted wasting that time and wishing they had had more time in the acceptance phase not the 'this can't be real' 'I can't die' 'There has to be something' denial. This can and does hurt them, and is cruel. If they want to inflict in upon themselves, that is one thing. But to do it because OP has had enough losing friends is selfish. You will never stop losing friends to death, in fact, it will only accelerate from here on out. It will never get easy. In fact, it compounds as more and more joy/light/goodness leaves the world and those you turned to for support are gone. It's part of the deal they made when our parents volunteered us for this existence.
- lambdaphagy 2y ago
  My own view is not that self-experimentation is an appropriate, let alone likely efficacious, substitute for reconciliation to the idea of one's death. I certainly don't endorse interference in others' treatment, however well-intentioned. If you want to say: "you shouldn't treat your terminal illness like a science fair project unless you possess extreme sang froid and are precommitted to the acceptance of your death", I'd find that totally reasonable. But my own view is rather that institutional epistemology is somewhat overrated, and self-experimentation somewhat underrated, relative to the conventional wisdom. (Though some people go too far in this direction.) This leads to general overconfidence in epistemic efficient market hypothesis arguments ("if a protocol were worthwhile, someone would have found it already") and underconfidence in the value of crowd-sourcing trying a bunch of stuff and writing it down. This view was principally informed by developing cancer drugs for a living and coming to appreciate that it's really hard, your knowledge of what's going on during a clinical trial is highly abstracted, and you can't be everywhere at once. It was secondarily informed by watching people do bro science on certain important questions and making interesting progress in large part because they could move much faster than academic or corporate research. If we recast the point of contention as: "what is the largest effect size that could be found by an institution outside of academia or industry?", my position is that it's plausibly non-zero. I'm sorry for your friends and I hope they found peace.

lambdaphagy 2y ago

To give a practical example, grapefruit juice contains some compounds that inhibit CYP3A4, a metabolic enzyme that influences the metabolism and absorption of many drugs, which is why many prescriptions tell you not to drink it while taking a given medication. This interaction was not discovered until 1989, and not reported until two years after that. So before 1991, a simple dietary intervention that affected like half of all drugs and that could in principle have been noticed by patient who felt bad after drinking a common household beverage, was bro science. Which is not to say "and therefore just do whatever", but just to point out that there's plausibly a lot of low-hanging fruit still left if you can figure out where to pick it.

7e 2y ago
The problem is you can't figure out where to pick it; it's lost in a sea of superstitious noise. Even if you could find this fruit easily, "a food that cures cancer when eaten" does not exist. That would surface in epidemiological studies very quickly.
- lambdaphagy 2y ago
  I admire your optimism in epidemiology. In point of fact, though, we have a rough natural experiment in the form of a food that doesn't cure a disease, but rather makes half of all drugs worse. That's very valuable knowledge, and under ideal epistemic conditions it might have been discovered within a few years of organized drug discovery as such. Yet was not widely known until the 1990s. So that's a failed positive control, which suggests that our practical capabilities to detect these kinds of effects are limited. Understandably so, given that there is no general requirement for dietary logging in clinical trials. That said, "a food that cures cancer when eaten" is not the bar for experimentation. More realistic might be something like "a dietary or behavioral protocol that, in some way, ameliorates this or that illness". For organisms with our body plan, "a cure for cancer" is like talking about "a cure for defection". But clearly there's "stuff that is efficacious against particular instances of cancer", a lot of which we found through techniques like natural product screens, i.e. "just trying stuff", rather than via rational drug design.
  - pama 2y ago
    It is indeed somewhat surprizing why it took so long to figure out grapefruit juice (and it was by accident during the study of the effects of coffee on a drug). Some of the early drugs that interacted with grapefruit juice where short-term agents like antibiotics, and others like channel blockers didnt have obvious detrimental toxicity though they might have had effects that were above the range of typical human variability. Powerful statins became household items a bit later, and all the cancer drugs were invented after this association was already known.
- s1artibartfast 2y ago
  I think there is a lot of efficacy left on the table with modern studies, clinical trials, and drug development. Most of the work is looking for treatments that work for the majority of the population. If a treatment was effective than standard care for 10% of people, it would be discarded. It is more economical to start over looking for something that works for 90% of people. Drugs an treatments aren't evaluated and discarded when proven worthless. The bottleneck is the number of treatments in development, so they are discarded when something else has a better ROI.
EVa5I7bHFq9mnYK 2y ago
Is it juice specifically that should be avoided? What about grapefruit in solid form? Pomelo?
- youngtaff 2y ago
  All grapefruit… my wife has clear instructions on this for her heart meds

hsuduebc2 2y ago

I love that someone asks for advice. Even for individual experience because he is miserable and some people are basically like "Nah just die. It would be uNeThIcaL."

potsandpans 2y ago
It's incredible. People are completely out of touch.
totallynothoney 2y ago
Time is precious.

_DeadFred_ 2y ago

Every single person I know who died from cancer young went down this route, from trying weird cures to going and seeing John of God in Brazil. Zero cured or delayed the cancer. All delayed acceptance and GREATLY regretted wasting that time and wishing they had had more time in the acceptance phase not the 'this can't be real' 'I can't die' 'There has to be something' denial. This can and does hurt them, and is cruel. If they want to inflict in upon themselves, that is one thing. But to do it because OP has had enough losing friends is selfish. You will never stop losing friends to death, in fact, it will only accelerate from here on out. It will never get easy. In fact, it compounds as more and more joy/light/goodness leaves the world and those you turned to for support are gone. It's part of the deal they made when our parents volunteered us for this existence.

lambdaphagy 2y ago
My own view is not that self-experimentation is an appropriate, let alone likely efficacious, substitute for reconciliation to the idea of one's death. I certainly don't endorse interference in others' treatment, however well-intentioned. If you want to say: "you shouldn't treat your terminal illness like a science fair project unless you possess extreme sang froid and are precommitted to the acceptance of your death", I'd find that totally reasonable. But my own view is rather that institutional epistemology is somewhat overrated, and self-experimentation somewhat underrated, relative to the conventional wisdom. (Though some people go too far in this direction.) This leads to general overconfidence in epistemic efficient market hypothesis arguments ("if a protocol were worthwhile, someone would have found it already") and underconfidence in the value of crowd-sourcing trying a bunch of stuff and writing it down. This view was principally informed by developing cancer drugs for a living and coming to appreciate that it's really hard, your knowledge of what's going on during a clinical trial is highly abstracted, and you can't be everywhere at once. It was secondarily informed by watching people do bro science on certain important questions and making interesting progress in large part because they could move much faster than academic or corporate research. If we recast the point of contention as: "what is the largest effect size that could be found by an institution outside of academia or industry?", my position is that it's plausibly non-zero. I'm sorry for your friends and I hope they found peace.