6 ms·

FTA: "But until now, scientists have been unable to determine how, exactly, the drug works." Try that next time you submit a PR: Yeah... it works, but "I am un

• Trasmatta 2y ago
  That's very common actually! The mechanism of action for many drugs is unknown. And then it gets even weirder with psychoactive drugs: eventually the answer is "this drug effects this neurotransmitter which gives you this subjective first person experience, and we don't really know why". It brings up a lot of philosophical and existential questions!
  • lordnacho 2y ago
    How do people come to find these drugs then? If you don't have a theory about how something works, what would make you test whether it works?
    • MaxDPS 2y ago
      Sometimes there is a theory, but it’s also possible for a drug to help in other (unrelated) ways as well.
    • pitpatagain 2y ago
      In the case of metformin, the direct line is from guanidine in french lilac being used since the middle ages for diabetes. Guanidine is effective, but long term liver toxic. Once actual chemistry broke open our ability to analyze that drug, related chemicals could be synthesized and studied, which led to biguanidines, of which metformin is one, which were tested in animals. Many drugs are found this way by looking at chemicals related to ones we already know about, and then testing on animals and humans. Self testing of new drugs by researchers used to be very common. How did folk medicine come to know the effects of guanidine? Dunno.
      • groby_b 2y ago
        > How did folk medicine come to know the effects of guanidine? Dunno. The same way we know a lot about other things in the chemistry domain - somebody tasted it, just to see what happens. "Mendeleyev's Dream" is a great book that contains many fascinating anecdotes of people going "let me just lick this, just to try". (Or, if you want to go more modern, the history of hallucinogens is pretty fun too) Humans seem to have a strong tendency to stuff unknown things into their mouth, just because they can.
        • falcor84 2y ago
          Indeed. I would assume that this is one of the traits that survives due to group selection [0] - it would be bad if everyone in the population was such a risk taker, but groups that have a small percentage of these people will adapt better. [0] https://en.wikipedia.org/wiki/Group_selection https://en.wikipedia.org/wiki/Group_selection
          • elcritch 2y ago
            That's my belief on why ADHD has such similar levels of prevalence (between 5%) around the globe despite drastically different cultures and varying genetics. It's great for the group as a whole as the ADHD members tend to be natural entrepreneurs, inventors, etc. However it often sucks for the individual ADHD folks and leads to higher rates of, well, everything. So the equilibrium settles to a stable fraction of the overall population.
    • hmottestad 2y ago
      I think it’s more often «we know that this drug lowers X in blood results, cause we saw that when we trialed it for something a few years ago that didn’t work out, now we’ve found out that disease B shows high values of X…»
    • robocat 2y ago
      A fabulous book on this is Phenethylamines I Have Known and Loved (PiHKAL) which can be found as a PDF online (the link I had has died but try Google and filetype:pdf). Summary: a chemist is interested in psychedelics so he starts creating candidate psychoactive substances, and he then tests them on himself and friends. He wrote a lovely book about his journey.
      • amanaplanacanal 2y ago
        Also its mate Tryptamines I Have Known And Loved.
    • a_wild_dandan 2y ago
      Expected utility, just like anything else. It's why our ancestors ate willow tree bark (aspirin), for instance.
    • sjducb 2y ago
      Mostly enormous libraries of compounds. You take a cell culture model for the disease and see if the compounds affect the cells. Then try it in animals, then humans. Repeat this process until you have good safe drugs for all of the diseases.
    • mtlmtlmtlmtl 2y ago
      Sometimes by accident. The original serotonergic antidepressants were antibiotics that happened to have MAO inhibition as a side effect. Initially developed to treat tuberculosis, doctors noticed the drugs had a stimulating side effect. A year later, a psychiatrist decided to trial them for depression, and found some success. It's actually the other way around. They didn't have very serious theories about the etiology of depression back then, the only clue they had was from the pharmacology of these drugs, which led to the situation where for many years the leading theory on depression was that it was caused by low levels of monoamine neurotransmitters(serotonin, norepinephrine and dopamine). The main evidence for this initially was the fact that these drugs seemed to work, and that they increased the levels or effects of monoamines. This theory has since become discredited as we've learned more, although the connection between monoamines and depression is still strong. It's just not the whole picture.
• profunctor 2y ago
  If your pr deploys a machine learning model then that would be a suitable comment. I suppose the idea is similar, we can determine that this drug helps so a (hopefully) statistically significant degree so even if we don’t know how it works we want to use it.
• renewiltord 2y ago
  Does it sound crazy? Most startups don’t understand why their product gains traction. They have less comprehension by this standard than the scientists with drugs. One of the beautiful things about knowledge is this: you don’t need knowledge of components to know the whole.
  • vlod 2y ago
    Sure. However the implications if your stupid sass app [0] fails or not is not in the same league (IMHO) as messing with humans biology. [0]: Yes there may be medical sass apps that are more serious
• justinko 2y ago
  Sorry bro, human biology is infinitely more complex than your CRUD app.
  • vlod 2y ago
    Oh... I agree.. I'm just shocked at the attitude. i.e. "We don't quite know how it works... but statistically we think it will help, with these side-effects.. good luck" <gasp>
    • glial 2y ago
      Yes, I remember learning about this issue with psychiatric medications and being similarly dismayed. There is a sub-field called Computational Psychiatry [1] trying to do better. And interestingly, a person could argue that randomized controlled trials for medicine are only really necessary because we don't have good enough theory and/or good enough measurement devices. If we did, we could reliably predict the effects of a medication without the trial. [1] https://www.nature.com/articles/nn.4238 https://www.nature.com/articles/nn.4238
• mft_ 2y ago
  The process for approving a new drug essentially requires proving that they are safe and also have sufficient efficacy, and usually also that the balance of the two (aka benefit:risk) is an improvement over a reasonable existing comparator. There are plenty of drugs I can think of (even relatively modern, specialised drugs) for which we kinda understand some parts of the mechanism of action, but not other parts. Also, given how difficult and competitive developing new drugs is, the incentive is to do the minimum (as above) for approval in the shortest time possible.
• aftbit 2y ago
  I've submitted just such PRs before, usually with a comment along the line of "this hack is dumb and I do not yet understand why it is necessary, but it works now, tests prove it works, and I have more urgent things to do." Sometimes this is unacceptable but often it is just what the doctor ordered. Of course, unlike with biology, it is usually not beyond my skills to eventually understand the whole system, but it may be beyond my time availability. With biology, the whole thing is just too complex to grok.
  • falcor84 2y ago
    Reminds me of the classic story about the 'more magic' switch - http://catb.org/jargon/html/magic-story.html http://catb.org/jargon/html/magic-story.html
• inglor_cz 2y ago
  Biology is a result of billions of years of constant evolutionary struggle on a planetary scale, without rhyme or reason, very much not intelligently designed. Whatever random mutation worked, worked. We the IT people love to complain about esoteric interplay of hardware, OS, apps and network. There is a lot more phenomena in constant interplay even in mere amoebas, not to speak of human bodies. Not to mention that you just cannot put breakpoints into a living organism and read its current status on screen. I find it positively crazy that we know something about biology at all. The intrinsic obstacles are just so much higher than in software.
• aftbit 2y ago
  What's the alternative? Never develop or deliver a life-improving medication until we can fully understand it from first principles? Gonna be waiting a long time IMO.
• pedalpete 2y ago
  It's the same with neurology. We pretend we understand how the brain works, but much of what we are understanding is our current conceptual knowledge, so it's theoretical. We work with Phase-targeted auditory stimulation to enhance deep sleep (https://affectablesleep.com https://affectablesleep.com). We know we can stimulate the brain during sleep and measure the increase in electrical activity which is the result of increased synchronous firing of neurons, but the reason why we are able to create this result is just a theory. However, the behaviour itself is consistent, and replicated.
• xkcd-sucks 2y ago
  It's completely rational just inverted -- Our understanding of biology is based on testing hypotheses of how drugs work, mostly. Some of the best practical understanding comes from "phase 4 clinical trials" i.e. those performed informally by the market
• tippytippytango 2y ago
  Evolution just pushes straight to master.
  • falcor84 2y ago
    But with a very gradual rollout, with automatic rollback
• groby_b 2y ago
  Welcome to medicine and biology. We have no idea how a lot of stuff works (ask an anesthesiologist how anesthesia actually works, if you don't mind being freaked out). We just know it seems to reliably work. This extends all the way to surgical procedures, which often amount to "should fix your issues, IDK" especially when it comes to soft tissue. I like to think of it as a stochastic discipline. (Which means that you want doctors who understand probabilities. Many don't. Filter well)
• marcellus23 2y ago
  Tell me you've never worked on a huge production codebase without telling me you've never worked on a huge production codebase. Sometimes you need to fix a problem and you just don't have days to spend finding out the root cause.
• devilbunny 2y ago
  We have some clues but not much real, deep understanding of how general anesthetics work. Process that for a second. They've been in use since at least the early 19th century. We have had a bunch of them (though in humans, at least, we pretty much only use 4 or 5 in developed countries these days). We do this every day in surgical suites around the world. People expect to be unconscious during surgery. But we don't really know how they do it. Or take antipsychotics: the companies were looking for antihistamines and noticed psychotic patients got better on some of them. If it works... you keep using it until something better shows up.
• JALTU 2y ago
  Yes! I am a "glaucoma suspect" meaning that short of going blind, I have the eye and eyesight degeneration characteristics that suggest I have the disease - no known causal factors. So I am treated with an expensive eye drop drug, rhopressa. In the fine print of the paper that comes with the drops is, and I paraphrase, a disclaimer stating the drug's active mechanism is "unknown." But my ocular pressure is definitely 30% lower than when not using rhopressa! (shrug)