Comment by lambdaphagy

Comment by lambdaphagy 8 days ago

26 replies

View on Hacker News

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.

_DeadFred_ 8 days 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.

Reply View 15 replies
  • lambdaphagy 8 days 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.

    Reply View 10 replies
    • zmgsabst 8 days ago

      As a pure numbers game, I’d find it more surprising if “broscience” never found a result:

      - a lot of terminal patients are prone to experimenting

      - their overall number probably eclipses the total number of trial patients in a given year by at least one order of magnitude and I’d believe two or three

      - they don’t have institutional barriers to what they can try, eg, they’ll fund non-patentable treatments

      - a lot of their approaches are taking things from published papers and trying to recreate similar effects (eg, calorie control [1])

      That they’ve stumbled across at least one treatment that solved at least one case for at least one patient seems likely. Isolating that from incorrect null results is where the epistemological struggle is. And there’s a good chance that it won’t help you with your particular case.

      But what’s the harm in trying? — you’re probably going to die anyway.

      [1] - https://pmc.ncbi.nlm.nih.gov/articles/PMC8749320/

      Reply View 9 replies
      • ryandrake 8 days ago

        When you try someone else's "broscience", you're not really experimenting with the unknown, so it's unlikely you're going to stumble into a "result". They know it doesn't work. If it did work, they'd have patented it and licensed it to Merck or Pfizer.

        Choosing quackery is not experimenting.

        Reply View 3 replies
      • _DeadFred_ 7 days ago

        If this was the case there would be facilities in remote countries with lax law making billions off of curing cancer. While there are indeed facilities in countries with lax laws doing questionable medicine, none are known for actually working. Instead they are known for preying on people. The fact that successful facilities don't exist indicates to me that your hypothesis is incorrect.

        Reply View 1 reply
        • lambdaphagy 5 days ago

          As I’ve pointed out elsewhere, I don’t think curing cancer is the bar for sober self-experimentation. “Noticeable amelioration of disease” is.

          There is substantial regulatory burden that prevents US-based companies from doing what you suggest. In fact there is regulatory burden that prevents things that 99% of American voters would prefer, like having reciprocity agreements that allow you to take any drug that had already been approved in Europe. It’s instructive to look at the case of Halassy and notice how much reflexive resistance there is to even the most self-evidently good ideas.

          To make things concrete, here’s a practical idea: write down everything you eat while on a medication and rate your subjective well being everyday. Look for patterns. If anything jumps out at you, try eliminating it and seeing if your subjective wellbeing improves. Is this method fool-proof and without failure modes? Of course not. Is the prior probability that you’re eating at least one thing that’s unknowingly contraindicated for your condition / treatment pair very low? Also no.

          My model is that the rate limiting factor for spotting unknown contraindications mostly just individual attention / discipline, so EMH arguments are unresponsive to this factor.

          Consider the following argument: if obesity were such a big health problem, why is everyone fat? Mostly because losing weight is really hard, which I sympathize with but don’t take as an indication that it’s impossible to do anything about it.

          In fact we don’t even have to bring disease into it at all. I’m sure that if i did a systematic elimination diet i would find one or two common foods that really didn’t agree with me, which i could make noticeable differences in QoL by avoiding. Why don’t I? Mostly because I’m just too lazy, and I’m fine with copping to that. But i don’t think it’s crazy for someone to choose otherwise, especially if they had a higher upside.

          Reply View 0 replies
      • Earw0rm 8 days ago

        True. But for the highest-grade nasties, where median life expectancy is unfortunately short and progression near-universal, you don't need much signal to get above the noise.

        Anyone surviving more than a handful of years with something like that is an outlier such as to merit a full work-back, and at that point it's no longer bro science.

        Reply View 2 replies
  • potsandpans 8 days ago

    Your tone policing in this thread is offensive.

    Apparently you know many people that have died from cancer young, and this qualifies you to know how a terminally ill person should process that emotion.

    You have zero qualification. How dare you imply that you know best for someone going through this.

    Hopefully no one reading this is ever in that situation. But I'll defer to the individual who's facing the death count down to process it in their own way.

    Reply View 3 replies
    • _DeadFred_ 7 days ago

      Your tone policing in offensive. Psychological and quality of life in end of life situations are valid and necessary considerations to include when talking about life threatening conditions.

      I said nothing about how a terminally ill person should process anything. I stated what I have found to provide the best outcome when a person close to you has a terminal disease. If OP said 'my friend asked me to research...' I would have given a different response/no response.

      But when OP makes it look like this is an initiative OP took upon themselves, for themselves, because they have lost too many friends, then yeah, I'm going to highlight that might not be the best possible position to come from if OP wants the best outcome for their friend. My response about outcomes it totally valid since OP asked for help with outcomes.

      Reply View 1 reply
    • lambdaphagy 8 days ago

      OP has a reasonable concern, I just don't think it's the only consideration at play.

      Reply View 0 replies
lambdaphagy 8 days 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.

Reply View 6 replies
  • 7e 8 days 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.

    Reply View 3 replies
    • lambdaphagy 8 days 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.

      Reply View 1 reply
      • pama 8 days 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.

        Reply View 0 replies
    • s1artibartfast 8 days 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.

      Reply View 0 replies
  • EVa5I7bHFq9mnYK 8 days ago

    Is it juice specifically that should be avoided? What about grapefruit in solid form? Pomelo?

    Reply View 1 reply
    • youngtaff 8 days ago

      All grapefruit… my wife has clear instructions on this for her heart meds

      Reply View 0 replies
hsuduebc2 8 days 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."

Reply View 2 replies