Drug 'reverses' ageing in animal tests
bbc.com
bbc.com
My bet: this drug will be for sale on the internet illegally within a year (and probably fake half of the time). The demand for this exact thing is just too high. It doesn't even matter if it's shown to not work on humans, people will still try it "just in case".
It doesn't make sense that society doesn't blink an eye when we send our youth off to war to die, but heaven forbid if someone dies in the pursuit of knowledge, everybody goes batshit insane. At least if someone dies taking this stuff, we learn a lot. And if it actually ends up working, it benefits society tremendously.
We'd learn a lot more if they were being monitored as they took the stuff, though. And yet it's still considered unethical to run human trials without preceding animal trials, even when the alternative is people off doing those same trials to themselves without your assistance.
We understand this problem in other domains—that's why "safe injection sites" for drug-addicts exist. So why has pharmaceutical research not cottoned on and begun offering "safe self-experimentation sites", complete with medical researchers + monitoring equipment to capture data, and nurses to help with bad reactions?
You could try teaching these individuals experimental protocols if you like, but if you enforce them, that means you're the experimenter. You're not allowed to be the experimenter. You just have to hope they're doing something useful. Probably you'd point a lot of automated instrumentation at each room, rather than having any human observers giving anyone (costly) individual attention, because most of the experiments would be too mired in sources of error to tell you much.
But keep in mind that the point wouldn't be to capture subtle things like drug efficacy. The point would be to find out about side-effects that might otherwise not be found, by having people around when they suffer adverse reactions to the drug to help the person not-die, and then being able to pull reports directly from the people who helped the person not-die, to find out (in clear medical terms) what the adverse reaction was.
They are not "experimenting" on themselves, they are simply engaging in a chemically-mediated attempt at wish fulfillment. There are few, if any, actual experimentation protocols being used and whenever I check out the scene to see if it is any better Instill find a random collection of anecdotes and poorly gathered "data points." I see no baseline data, no blinding or controls, the worst sorts of confirmation bias in data gathering and assessment, and people entering these "experiments" with a random selection of pre-exisiting conditions for which they are attempting self-medication. This is just an exercise in generating noise, not data.
> [offer] "safe self-experimentation sites", complete with medical researchers + monitoring equipment to capture data, and nurses to help with bad reactions?
That's what this whole subthread is about.
A real experiment has access to much better populations, tendency of psych experiments to be done on psych students aside.
Volunteering and bringing your own drugs with you is a much stronger signal of intent and capability than just volunteering. You don't need a large cohort to find exceptional effects, negative or positive, so the bias toward stronger filtering seems fine to me. If you're looking for subtler effects, self-selection won't work anyway; you'd need double blinded clinical trials like usual.
* You can't run a randomized control trial in this fashion, which makes it harder to collect meaningful data.
* You can't select the populations of people who are in your test groups. It's possible the drug will only work well in certain populations.
* You can't monitor people as well for things like adherence or control their other behaviors. Perhaps they are taking 5 other compounds simultaneously which are having an effect or interfering with your compound of interest.
* You can't screen for toxicity or determine dosing meaning the drug could kill people en masse before the ideal dose is determined.
I think it's fine for people to take any compound they want as long as it's an educated decision, but I don't think what you're describing is a great source of data or a good substitute for animal trials.
You can, it just needs to be organized properly. You sign up for a test of a new drug/nootropic online, you get the pills, but you don't know if they work or not.
Then, you have to report the results.
> * You can't select the populations of people who are in your test groups. It's possible the drug will only work well in certain populations.
First of all, you can. Require filling a questionaire (or even genotyping) before sending the drug. Not only you will be able to analyse the statistics across populations, but you will no longer have problems with many drugs being only tested on white males.
If certain populations are missing from the data, the company could afford the therapy to them for free, or even pay them.
> * You can't monitor people as well for things like adherence or control their other behaviors. Perhaps they are taking 5 other compounds simultaneously which are having an effect or interfering with your compound of interest.
What has a higher chance - experiment subject lying about other meds he's taking, because he wants to get the drug (or money for participation in experiment), or a person who stands nothing to gain or lose from filling in the questionnaire truthfully?
> * You can't screen for toxicity or determine dosing meaning the drug could kill people en masse before the ideal dose is determined.
The idea would be to allow only drugs that passed initial trials to estimate toxicity and safety. But open the drug to public before efficacy is established.
By the way, every single day doctors prescribe drugs with "unproven" efficacy. While every drug had to be proven that it's good for "something", many of them have off-label use, which is currently totally not tracked.
I was prescribed Modafinil for ADHD. It's off-label, and there is some research proving that it helps. I feel it's helping me too.
Unfortunately, I have no way of filling any kind of detailed description of perceived effects, or my history. Nobody offered me an option for participation in double-blind study. There is so much lost potential there.
"The drug gave me a headache and made me feel moody, and increased my cravings for white chocolate and potato crisps."
That's what you're likely to get from self-reporting in that sort of trial. Especially given the scale implied by the interest in an anti-ageing agent, you can expect to gather bazoodles[1] of data, most of which will be absolute garbarge.
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[1] Bazillions of oodles.
Charging for any FDA regulated drug or therapeutic (or anything) before marketing approval, however, is a cardinal sin in the pharmaceutical industry because it incentivizes the exact kind of snake oil salesman behavior that the FDA was created to curtail. Gathering any kind of useful data (let alone keeping patients safe) for a few self-experimenters will be extremely expensive so unless this infrastructure is publicly funded, you're just recreating the conditions of the 1800s, except now with entire businesses built on finding gullible people who will try literally anything because... "science". Even if it's publicly funded, it will almost certainly end in disaster.
All it takes is a few desperate parents, a dead autistic kid, and some clickbait for an entire generation to lose trust in our pharmaceutical and healthcare industries. That loss of trust will lead to orders of magnitude more death and suffering than would be prevented by letting desperate people play Russian Roulette with what is essentially a fully loaded gun (that they think is empty).
The first phase of human clinical trials is literally giving a small group of healthy patients under constant supervision a steadily increasing dosage until more than half of them can no longer safely handle it. That's only after a safe dose has been established in animal trials so we're talking about serious complications or death in the single digits percent of cases after tens of millions of dollars have already been spent. Individuals hoping for a positive outcome have a better chance of winning the lottery.
I think those individuals have much better chances!
If any one wants to take one for the team lol
I'd bet insurance companies would fight hard to reject coverage for anyone who publicly takes a non-FDA drug. If society supported the use of them, then they'd also have to support the aftermath, just like veterans.
That's a great soundbite, but it rather ignores the long and continuing history of exploitation via the sales of snake-oil cures and "enhancements". I absolutely have problems with the existing pharmaceutical industry and the economics around that. But it's foolishness to fail to understand how we got here: countless centuries of people peddling fake cures (and even outright poison) to people in need.
Likewise, it's mostly really hard to do actual, legitimate human-studies science that has a solid chance of advancing human knowledge. Thus the presence of things like experiment design as a discipline, ethics review committees around studies on human subjects, etc. This article specifically mentions that human studies are in the works, by teams that presumably conduct them in ways that are 1) ethical and 2) have a hope in hell of yielding useful long-term knowledge. OTOH, I have about zero confidence that random internet self-experimenting yahoos will produce any knowledge ROI on their risk investment.
The expectation of course is that someone else will die. From my experience, very few people [edit: who know what they're doing] are willing to actually kill themselves for science, or, say, endanger their children on the off chance it would "benefit society tremendously".
That's just not morally tenable, if I may be so bold. If there is some sort of benefit to be had, society will benefit in the long run and it doesn't make any difference if the benefits come right now or in a couple of generations. Dropping safety procedures is only ever going to benefit individuals- and probably not the ones who willingly (and foolishly) step up to be human guniea pigs for unregulated "trials".
Case in point: 95% of the supplement industry.
The trick here is that the current state of assays for senescent cell presence in samples is pretty terrible if you're outside a lab, and there is little point in doing this without measuring the outcome.
I think you're being generous. Why would anyone bother selling the real thing on the black market?
These black markets or silk roads are not just a bunch of drug swinging deviants. A lot of the processes are very well thought out. As someone already mentioned their business relies heavily on their reputation so they tend to take care of it quite closely.
Who verifies the "independence" of the "3rd parties" and/or the reliability or honesty of their results?
> As someone already mentioned their business relies heavily on their reputation so they tend to take care of it quite closely.
Reputation is important to any business. Hence the practice of dishonest/insincere/bought and paid for reviews or endorsements.
Additionally, grey-market supply is guaranteed to be real, because anyone can sell it for nonpatented use cases and there will be a huge demand by researchers for it, as biochemists don't often do their own peptide synthesis.
Also, this effect has not even been reproduced, and they seem to be playing their cards very close to the chest, which is almost always a massive warning sign. Even the researchers themselves don't seem overly sure they're seeing a statistically significant effect, citing it works on some mice and not on others.
Odds are, there is very little to see here.
Great! Too many results have been previously reported just in genetically modified mice that weren't aging normally in the first place.
UNITY Biotechnology: using repurposed chemotherapeutic drugs like navitoclax to selectively drive senescent cells into apoptosis by suppressing on the mechanisms that prevents that fate. They also have antibodies and immunotherapies in their backlog of patents, but if they haven't got it to work by now, not likely to be a direction they take in favor of the drugs.
Oisin Biotechnologies: programmed gene therapy that assesses p16 levels in the cell and then induces caspase expression and apoptosis if it looks senescent.
SIWA Therapeutics: monoclonal antibodies.
Everon Biosciences: small molecule drugs and related immunotherapies.
There is a lot of money sloshing into the field of senescent cell clearance at the moment, and given that the target market is ultimately every adult human for a treatment undertaken every few years, I think there is plenty of room for more players.
Can an elderly body body replace these cells on its own, or would senescent cell clearing generally need to be paired with a stem-cell replacement protocol of some kind?
Stem cell replacement is something that should be developed for use in old people anyway; the more of that going on the better.
If they don't work in humans it will be a great surprise given the science to date - an unlikely outcome. The open question is the degree to which specific diseases are rolled back and life extended, given that this is only one of a number of mechanisms causing aging.
Or maybe their purpose is to make old people stop consuming the tribe's food so that there's more for kids and people who can still have kids.
We've got some historical modelling available - as life expectancy has increased family sizes have dropped accordingly. Maybe we'll have entire villages with a couple communally raised children every decade.
Useful for the genes in your cells. Not useful for you as an individual.
As for why the cells become senescent rather than merely dying -- well, even senescent cells retain some function. If damaged cells died rather than becoming senescent, it would presumably result in more deaths in situations where a large number of cells are damaged.
It may be that a drug which kills senescent cells results in a decrease in chronic disability but an increase in deaths... an interesting trade-off!
Like you said, cellular senescence is a trade-off -- the body doesn't want these damaged cells to keep dividing per se, yet they are still useful for continuing to covert sugar and oxygen into energy to use as needed.
We do have a mechanism for getting rid of damaged cells in general: autophagy. However, autophagy seems to be mostly triggered when there is an energy deficit, for instance during fasting or during intense exercise.
This is probably why fasting and exercise are proven over and over to be beneficial to health, they essentially trigger a "cleaning cycle" of cellular autophagy within the body. I'm not sure autophagy typically includes senescent cells, my understanding is that it's primarily targeted towards cells that have damaged mitochondria.
Or it might kill you from some weird reaction.
Nobody yet knows. But fasting is meant to be good for you in similar ways.
Given that the alternative is definitely dying, I'd take my chances with the pill after trials have shown it to be sensibly safe.
Granted stronger social bonds has often been linked to better health so maybe a bit more relying on each other is a good thing.
A lot of anti-immortality arguments reduce to this problem. Folks who advocate ending aging do not want us to just live forever as progressively more decrepit and cranky old codgers. The point is not to keep you at 90. It's to keep you at 25 (and put you back there if necessary).