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2d21h
Purified recombinant Reelin was injected bilaterally into the ventricles of wild-type mice. We demonstrate that a single in vivo injection of Reelin increased activation of adaptor protein Disabled-1 and cAMP-response element binding protein after 15 min. These changes correlated with increased dendritic spine density, increased hippocampal CA1 long-term potentiation (LTP), and enhanced performance in associative and spatial learning and memory.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166788/
Published 2011. It's been a while... I wonder what it would take to reach human trials.
From my layman's understanding, in the US, it is almost impossible to get FDA approval for drugs that "improve" or "enhance" human biology.
The tl;dr is if you invented a drug tomorrow that stopped human aging, you wouldn't be able to get FDA approval to sell it.
This sadly means that research into how to improve human life and potential are very limited.
An alternative explanation is that it may just be super hard to make into a useful pill or convenient injectable, limiting commercial viability! Most drug companies aren't going to dumping $ into a chemical that may cure a disease but has no practical way to get it to the target site!
What is the rationale for this?
You can only make drugs to treat medical problems of some sort. I think the argument is that the cost/benefit is never positive for drugs that aren't attempting to just bring you back to baseline.
Basically imagine you are perfectly healthy, and you take a drug that has a 99.9% chance of increasing your IQ by 20 points, or a 0.1% chance of reducing your IQ by 5 points.
The FDA would basically say "no way in fucking hell, you don't need the extra IQ points to cure any problem, and there is a risk of brain damage".
Now if that same drug was instead marketed towards helping people with traumatic brain injuries heal, then it could maybe get approval.
There was a petition a few years back to the FDA to change this to allow research into life extending drugs, but AFAIK it didn't go anywhere.
International competition will eventually force the US to change rules like this.
When everyone in China lives till 200 years old and they all have IQs of 130+, the FDA will be pushed aside.
If this great science fiction scenario were to come to pass, I’m pretty confident that it wouldn’t be only the FDA that would be pushed to the side.
The impact of a population in an organised, technologically advanced society being one standard deviation of intelligence higher than a strategic rival population … would be immense.
Even if just temporarily boosting intelligence, something like a militarised Flowers for Algernon scenario is pretty terrifying.
Why? It will only result in more and harder dictatorship, more direct terror and fear, and even more unhappy society. Democracy works best when people are easy to manipulate through mass media. Smart people will need to be coerced by force. Maybe in fact, to a degree this is what already happening. Superior education in China makes democratic transition next to impossible.
Maybe the observation that countries with the best education tend to be authoritarian is not because "dictators are good at educating people" but other way around - because it's a natural selection and if a highly educated country tries to transition to democracy, it either ruins democracy, or education, or country itself.
Any model of governance mainly solves the problem of "how to satisfy interests of the stakeholders - i.e. the elite - without ruining things"; there are many ways to ruin things (even elite itself can bring about it's own downfall), but the one everyone fears most is when people get too angry. Democracy is a good way to shift responsibility back to people itself, thus defusing this threat. But it requires people being sufficiently dumb to bite it.
Been there done that, it’s called Russia.
I don’t agree with your worldview, but if I was presented with the choice is between dumb, fake democracy and clever competent dictatorship, I might as well choose the latter. At least trains will run on time.
The clever, competent dictatorship is quite rare, though.
And short-lived
This is a huge statement that seems wrong to me. Democracy works best when the population are engaged and hard to manipulate.
Also the "observation that countries with the best education are authoritarian" seems wrong to me too. The data I see has the top 10 entirely filled with democracies, with Singapore as the first nondemocracy coming in at 11th place. Check the economist democracy index, the correlation between democracy and education is imperfect but strong.
And those are arguments based on data. There are also arguments based on logic. Authoritarianism and education are fundamentally opposed, because authoritarians hate the teaching of things that disagree with their own specific viewpoint and suppress it.
On what basis are you making this claim?
Someone I know pointed out that there’s a feedback effect: groups where everyone is smarter do better not just because of the first order effect but also because they can cooperate better. There’s a roughly quadratic effect on productivity.
Mass enhancement of the general population would have far reaching consequences.
The Chinese government ran a huge research effort to try and determine the genes for intelligence. From what I understand it was a failure, as the genetic causes of intelligence are too spread out and varied to be easily isolated.
I'm pretty sure if the project had succeeded that the Chinese government would have had no moral qualms about gene-engineering a population with an IQ of 130+ and the US would be permanently behind in every field forever after.
I think all sorts of assumptions are baked into that statement. Would the CCP even survive if the population IQ was 130+?
It would be a worthy ultimate sacrifice
The US is already a key brain-drain destination for Chinese elites, why would that change?
Anyone cares to shed a tear for IQ 85/90 people that have to navigate increasingly complex world?
Look at the amount of legal documents, EULA’s, software, and complex corporate structures that an average Joe has to deal with today vs 50 years ago. How long u till average person can no longer cope?
The entire drug research sphere outside of the US is miniscule. Unless you can sell the drug in the US there's very little point to investing in the large scale research needed to truly determine efficacy. Yeah there's some minimal state sponsored stuff outside of the US. BUt it's like comparing Little League to the MLB.
Where do you get this idea from? More than half of all major drug companies are based in Europe and Asia.
https://en.wikipedia.org/wiki/List_of_largest_biomedical_com...
Maybe from the fact that half of all pharmaceutical revenues come from the US (and likely a much higher share of the profits). Single-payer systems are more cost-effective but definitely provide less revenue to pharmaceutical companies.
“We can overcharge patients” in no way leads to the logical conclusion that “more medicine is developed here.”
It just means your pharma companies can get away with higher profit margins.
There's an assumption here that such drugs will exist. They might not.
Death is a medical problem, terminal disease really. Stopping aging stops death.
We can give a lab mouse any form of cancer and cure it. We can reverse their aging symptoms... yet we've only been able to extend their lifespan by a measly third at best. It's safe to say we're very far away from getting anywhere close to solving aging in humans if we can't even make an immortal mouse despite a century of throwing every possible thing at them without holding back.
I agree, but the pedant in me wants to point out that
is incorrect. IACUCs exist for a reason. We do hold back.
Also, a century? What did we have a century ago?
MRI was only invented in 1977, first commercial CT scanner came out in 1970’s, same for ultrasound. Before 1970’s we didn’t have antiviral drugs or DNA sequencing
Medicine a hundred years ago was brutal and medieval
Believe it or not, lab mice have been used for medical research for over 150 years.
We're all high and mighty with our moderns scanners, yet we still do surgery with chisels and hammers, drill teeth, put broken bones in plaster, have sick people congregate all in one place so they get infected with each other's diseases plus get some antibiotic resistant bacteria or two on top. And well, whatever the hell they do in the ER. Medicine is still pretty brutal when it comes down to it.
That may be so, but it's absolutely fundamental to know where to cut, and to cut in the right place. How are you going to diagnose cancer at an early stage if you have no way to scan and detect anything? Exploratory surgery?
I think the point was that the opposite would be true if it weren't for it government intervention.
This wasn't necessarily an informed opinion.
Note their "layman's opinion" qualification.
I recently spoke with someone in biotechnology who was doing a deep dive on "exercise pills". she told me that it would only be approved if it treated a specific disease, like muscular dystrophy, because the FDA views any potential negative side effect as too risky to approve for healthy people. Long term negative side effects are tolerable in Duchenne muscular dystrophy because those people are going to die without intervention. Once people with DMD show the safety profile it can be evaluated for more conditions.
Due to the chaos it would kick off, I'm assuming. The FDA just needs to ask themselves "What happens if we OK this?" and if the answer is "I have no idea." they withhold approval.
An interesting tangent is Australia’s FDA equivalent -the TGA - make decisions by a single Doctor called The Delegate
This is a single anonymous doctor chosen at random from a pool of qualified doctors usually from a TGA committee
So effectively all that is required is convincing one very powerful secret doctor
For instance this is why we are the first country to allow MDMA/psilocybin research to resume since Nixon sent the field underground
Amazing to think how powerful organisations have odd quirks
Is this choice made on a per-decision basis, or do they serve terms, or what?
Per-decision afaik
I think the rationale is to minimise both committee biases and corporate influence
I think only a handful of people know who The Delegate is at any one time. The Delegate remains anonymous after the decision is made
I don't see how it really addresses corporate influence; normal behavior from a corporation is to donate to every politician that might conceivably affect them.
You’d effectively have to lobby any and all related doctors, relevant organisations and politicians then
The Secretary can make anyone they wish the Delegate on any issue
I should probably rephrase corporate influence as targeted corporate influence
This seems more restrictive than "all related doctors"?
Also,
That sounds like what you want to do is lobby the Secretary. If you're in control of who gets to make the decision, then you get to make the decision.
lol, withholding it would cause massive riots
Drugs must treat disease, and the benefits must outweigh the risks.
With the exception of cosmetic surgery; for some reason Botox's "avoid face wrinkles" somehow outweighs the risk of permanent paralysis.
But this is a treatment for a serious disease, so I'm sure those standards aren't the barrier here.
But why? lol
Because our society is rooted in puritanical, old and crude notions of what it means to be human. This makes its way into legislation.
It is one of the reasons I despise the FDA, it is an incredibly narrow-minded institution. If you made a drug that immeasurably improved QoL for 99.99% of users, you still wouldn't be allowed to sell it. The administration sucks.
Botox was not originally developed for wrinkles or approved for wrinkles, and a lot of the ways it gets used today are off-label.
Botox was originally developed by a bacterium because: evolution.
It wouldn't matter; you'd still be free to sell it as an unregulated supplement. Medical insurance wouldn't cover that, but who cares?
Patent protections on supplements are very weak compared to the protections afforded to FDA approved drugs.
That alone limits research into supplements.
Also what counts as a supplement is limited, companies cannot just declare any random drug to be a supplement. Dietary supplements have to have some tenuous connection to being from a natural source. (Though obviously that line gets skirted a lot, such was with DMAA prior to 2013)
Why is that relevant? In the scenario under discussion, you've already invented the drug.
My thinking as well. I’m fine with the FDA not giving drug approval to a substance as long as they don’t ban it. There are a few drugs I take regularly that are not FDA approved in the US (I.e Moclobemide as there are no approved reversible MAOIs in the US) but I’m still legally allowed to import them and usually it’s pretty cheap.
Luckily, it's almost a certainty that a drug that slows down aging or improves cognition will also affect disease processes.
If there's a drug that improves cognition, it will likely get approved for Alzheimer's.
Studies won't be done on long term risks in young adults taking it.
Do you want to take a drug that rewires your brain but has had exactly 0 studies done on what happens to users after 20 years? Alzeimer's drugs don't need 20 year follow up studies because, with the exception of early onset, the patients are, to put it bluntly, dead.
Actually right now Namenda is being used off-label for cognition enhancing properties, and suffers from the exact issue that its impacts on healthy adults is mostly unstudied. (FWIW I had negative cognitive side effects with it to the extent that I had to abandon it, but plenty of people seem to like it!)
If you want to talk even higher risk profiles, there are plenty of substances that may very well increase neural growth if given to children, but there is no way in hell any ethical medical team is going to ever run those studies.
For one thing, we know that plenty of awful diseases are the result of too much activity in the brain. No one wants to be the lead author on a study titled "Boosting IQ by 10 points in adolescents, with only a 20% risk of seizures."
Sure, but treating Alzheimer’s is a big deal.
Would expect to see research focused on compounds that increase Reelin expression too, in addition to direct supplementation. A mouse study a couple years later showing nicotine increasing Reelin expression: https://pubmed.ncbi.nlm.nih.gov/23385624/
Nicotine has been really interesting for Dementia or Alzheimer's so this checks out. The one study I know that is ongoing is mindstudy.org. It's well tolerated, cheap, and widely available.
Not a Doctor but if I had a loved one at-risk or experiencing age-related cognitive impairment, it's probably worth trying rather than waiting for scientific consensus which may take years and will probably be blocked by the FDA so some pharma company can develop patented neuro-nicotine or whatever.
Huberman has also espoused nicotine's benefits, so before someone reading this runs headfirst into a nicotine addiction, please be aware of the withdrawl symptons.
https://www.reddit.com/r/QuittingZyn/
Yes please be careful here folks. Nicotine can also cause anxiety and panic attacks.
don't forget high blood pressure
Don't forget the many, many negative issues SOME people get from nicotine.
I loved nicotine, but it terribly exacerbates my rheumatoid arthritis in my hands, inflames blood vessels in my lower arms (to the point of waking with my arms completely numb in the middle of the night) and gives me terrible heart palpitations that woke me up (if I consumed nicotine a few hours before bed).
I had to get some surgery on my fingers, and the staff seemed relieved to learn I don't smoke. Something about narrowing blood vessels making this kind of operation less successful. Not sure if they were just trying to cheer me up or it's an actual thing :-)
Which is itself a major risk factor for dementia (and strokes)
And stomach cancer
https://www.sciencedirect.com/science/article/abs/pii/S00062...
Very interesting. Though nicotine also has a lot of potential side effects that can make it really counterproductive for the health of an elderly person.
Humans have to become mice to advance
That's a funny thought, we experiment on mice, then one day we accidentally create super mice while trying to solve diseases. From that day, it will be the mice who dominate our world.
I welcome our cute new overlords.
That's the premise of the (newer) Planet of the Apes movies
When the Yogurt Took Over…
The Secret of NIMH mentioned. Let's go!
Future mice-kind archaeologists will have a treasure trove of research to dig through