Actually nice to see this kind of common-sense regulation.
The risk-reward ratio associated with retractable door handles is absurdly skewed. On the one hand, you can get locked in a burning and extremely flammable car if you're involved in any kind of traffic accident. On the other hand, you get a literally imperceptible improvement to aerodynamics and range. Retractable handles just seem extremely stupid in a trivially obvious way.
Apple is generally my goto for form over function. Or even beauty over function. Generally, I don't want regulators making design decisions, but this might be a good example where safety risk really outweighs sleekness.
The laptop and phone maker with some of the highest performance, best battery life, best screen quality and best trackpad is form over function. Of course this makes sense.
The company whose top seller is a device intended to go in your pocket and is fragile and slick as a bar of soap. So much so that there is an entire industry to build cases for it. Granted, the market has spoken and it's the best selling device of all time. But both the iphone design and Tesla's door handles demonstrate aesthetic over practicality.
If you think it's fragile, you're completely ignorant to the current state of phone durability. Literally you have zero idea what you're talking about and just commenting out of your ass based on pre-conceived bias.
Quite frankly you are part of the reason that the modern internet is garbage. You present your "alternative-facts" as if they are truth despite having zero bearing on the truth. You're just a fucking disinformation bot like the MAGA crowd with just as much supporting evidence. You should be ashamed. But you're a green account created to respond so you don't have to show your true feelings on your real account. So you have no shame. You can't even commit to your own opinions on your own account. Despicable.
The authors report that restoring NAD+ balance in the brain -- using a compound called P7C3-A20 -- completely reversed Alzheimer's pathology and recovered cognitive function in two different transgenic mouse models (one amyloid-based, one tau-based). The mice had advanced disease before treatment began.
- There's room for skepticism. As Derek Lowe once wrote: "Alzheimer's therapies have, for the most part, been a cliff over which people push bales of money. There are plenty of good reasons for this: we don't really know what the cause of Alzheimer's is, when you get down to it, and we're the only animal that we know of that gets it. Mouse models of the disease would be extremely useful – you wouldn't even have to know what the problem was to do some sort of phenotypic screen – but the transgenic mice used for these experiments clearly don't recapitulate the human disease. The hope for the last 25 years or so has been that they'd be close enough to get somewhere, but look where we are."
- If the drug's mechanism of action has been correctly assigned, it's very plausible that simply supplementing with NMN, NR, or NADH would work equally well. The authors caution against this on, IMO, extremely shaky and unjustified grounds. "Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer."
There are numerous chemical supply companies that will list chemicals like this “for sale”. They might not have it in stock but they hope they’ll get your search traffic and be able to synthesize it if you place an order.
If you look at the amounts, they’re tiny. I don’t know the doses that would be used in humans but typically ordering from chemical supply shops would be economically infeasible for just about any drug. These are meant for one-off studies and experiments, not ongoing human use.
There have been a growing number of online groups arranging to do group buys of synthesized experimental drugs based on studies. I’ve followed a few of them and the results range from people losing their money, receiving product that is too contaminated to use, or in some cases they go to great lengths to verify the chemical but then discover it doesn’t do what the original study promised it would do. In some of the more horrifying cases I’ve seen forum posts from people reporting long lasting chest pains from one chemical, and another chemical was sending people into psychosis. So if (when) these chemicals start appearing on group buy sites I suggest ignoring it until more research is done. Making yourself into a lab rat is not a good idea.
> If you look at the amounts, they’re tiny. I don’t know the doses that would be used in humans but typically ordering from chemical supply shops would be economically infeasible for just about any drug. These are meant for one-off studies and experiments, not ongoing human use
I didn't get the impression that the person above was suggesting actually buying it here, but rather just pointing out that if it does prove effective in human trials, it's going to become cheaply and easily available since it's already possible to order online for research.
There appears to be some danger in using NAD+ without the supervision of an experienced physician.
"Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer."
Depends entirely on the stage of the disease and the aggressiveness of the cancer! Getting an aggressive brain cancer when you had early stage Alzheimer’s [1] would be tragic. The tradeoff would be years of life.
For the record, I have no idea what the actual risk tradeoff is, but the point of regulation is that nobody does. You can’t have informed consent when you can’t be informed.
[1] Aside: Alzheimer’s is relatively early stage, as dementias go. It’s frequently diagnosed by onset in younger people.
The chemical the parent comment linked is different.
NAD itself isn’t usually supplemented because it’s broken down by your digestive system. So NAD precursor supplements have been available for a while: NR and NMN specifically. These are the precursors they were talking about.
The actual drug used in this study has a different mechanism of action. It’s not directly available as a supplement, but like the parent commenter discovered you could technically find a chemical supply house to synthesize a tiny quantity of it.
There have been a growing number of online groups arranging to do group buys of synthesized experimental drugs based on studies...
There's also a good number of cases of people getting exactly what they ordered. There's been a thriving market for Retatrutide, ozempic's more powerful younger brother, for years despite it not being approved yet.
Also, people with Alzheimer's don't have the luxury of being able to wait 20 years for it to be approved.
I was actually researching this yesterday for a groupbuy, the synth is chromatography-free which means gram scale production is possible with much less cost than expected .
And there's room for thinking there's water in the ocean. We have no idea whether this would work at all or how it would work at all in humans. We have one experiment in mice, which as you say can't have Alzheimer's.
This is a nice step, like developments in fusion energy. That's part of research, and let's hope and investigate it, but it's absurd to think about it as anything but a science project right now.
Sadly, it's worse. We don't have one experiment that works in mice: we have dozens, if not hundreds. We've cured "Alzheimer's in mice" many times over. The treatments never work in humans, because it's not the same disease. We don't know the root cause of the human disease and so we can't model it accurately in mice.
> We don't know the root cause of the human disease
It's increasingly likely that there is no "root cause" to find in humans, but rather, that Alzheimer's is what happens when there's enough external stressors acting on the brain.
I've seen an analogy of a leaky roof being used: the leaks are things like age, stress, heavy metals, mold, bad sleep, bad diet. Genetics defines the original building materials (resilience) of the roof. You can put buckets under a certain number of leaks but if there are too many your ability to repair gets overwhelmed and the result is diseases like dementia.
I think something similar applies to other diseases of aging like heart disease, arthritis, osteoporosis, diabetes, perhaps even cancer.
The downside of this is that's it's hard to imagine a miracle drug being the solution. But the upside is that a combination therapy that identifies the "leaks" and works on reducing or eliminating them will likely be effective against a wide range of age related diseases.
The therapy will likely consist of drugs and supplements in combination with lifestyle changes.
I totally get that people are not mice, however animals studies have been useful for all sorts of diseases. Are they really uniquely bad for Alzheimer's?
To put it simply, mice don't get Alzheimer's. We're not studying mice with Alzheimer's, we're studying mice with an mutation chosen for resembling Alzheimer's. But we don't know whether this model replicates the actual mechanisms of the disease, or if it's superficial.
Thanks for the explanation, this really clears up the concerns here. It's easy to imagine scientists attempting to model in in mice and making real progress, but it's also easy to imagine us misunderstanding the real disease well enough such that what we've modeled in mice does not produce real results.
And the author of the paper has disclosed that they have patent on the drug being tested. Let's see if the results can be reproduced by others. Then let's see how it tests with humans.
Aren't "steps" toward fusion energy a little fake though? IIUC fusion research is a front for nuclear testing, so there's a vested interest in showing "progress" to greenwash the gargantuan spend on nuclear weapons.
EDIT referring to the need for fusion and plasma research for modeling warheads in the absence of full tests.
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer.
As someone who's seen both cancer and Alzheimer's up close, that would be a very easy choice.
From multiple personal experiences, including both of my parents, dementia is a slow, horrible death where you are robbed of your dignity and end up dragging all of your relatives through a very long, very torturous hell. You will be drooling, pissing, and shitting yourself, all while slowly reverting back to a low IQ childhood mentality where you're very likely to have outbursts and verbally or physically attack the people around you. Your loved ones will be tormented, and if you don't have loved ones then if you're lucky you'll be tossed into a room and forgotten about by underpaid, overworked staff at some run-down nursing home. If you're not lucky you'll be laying in a gutter on the street until you die.
Interestingly my wife helped a friend whose father had the disease during the pandemic.
He had worked as a professor and after retirement had suffered with AD for years but had stayed "independent" because his wife was high functioning mentally but low functioning physically and formed a good team.
He'd bought long term care insurance so he had the resources to afford both a room at a care home but also personal help from home aides, including my wife. He didn't really know what was going on most of the time but he never got angry or flustered and was always pleasant to deal with.
We had trouble with certain homes having a way they want to do things or requiring things that weren't really necessary, one insisted that he get a pacemaker because he had bradycardia. When he lived with his son between homes probably the most difficult thing was that he got up in the night to use the bathroom and would end up urinating in the wrong place. He got much better care than many residents because people were always coming around to see him and the staff knew that we cared and would advocate for him.
He passed away at 92 and outlived many of the people who knew him at work so he had just a small memorial ceremony. I saw it as an example of healthy aging and talked about it a lot with my wife -- and it made me think about myself and my own fear that my ability to compensate for my schizotaxia may degrade when my brain degrades and I can picture myself becoming really nasty and it gives me all the more incentive to rewrite my habits while I still can.
Sadly, cancer isn’t one singular disease. Types of cancer can be excruciatingly painful for many years, which is also tormenting to everyone around you. I wouldn’t wish either on anyone.
Cancer. The worst types of it have the advantage of killing quickly. Alzheimer's destroys the self, and you survive a long time with it, leading to much more suffering, both to you (to the extent you continue to exist) and to your family.
I have a different perspective. The worst types of cancer kill slowly and cause agonizing suffering.
Alzheimer's leads to negative outcomes for your caregivers, but by many accounts many affected individuals do not suffer all that much, if at all, due to their lack of awareness.
If I were diagnosed with Alzheimer's, I would seek out assisted suicide. But I think it's more complicated than that: its existence incentivizes pushing people toward assisted suicide. The government finds a way to help with bloated medical care budgets; unscrupulous family members guilt trip the sick to choose the option to keep the inheritance intact.
The best solution allows it for severe cases, while still investing money in research and spending money for palliative care so it remains an option and not a demand. But that's a tricky line to maintain.
My grandmother's case ended up bankrupting my grandfather and seriously straining the rest of the family. Which ultimately put my grandfather in a pennyless position when he was in his 90's, and poor state care when he was declining - not what he or my grandmother worked their entire lives for. Our family couldn't replace what was lost in the years of care for my grandmother's body, long after she herself was gone.
Never something she would have wanted, but you don't really have a choice and dignified death is never given as an option.
Its the slippery slope proved real by places like my home country of canada keeping other people from having it. I am a huge supporter of assisted suicide but what my country has gone way too far. find a way credibly Keep it to impending death with lots of pain and alzeimers like disease and you would have strong majority acceptance.
Except that time of death comes on average many years later for Alzheimer's than cancer. In the same thought, better die from heart attack instantly but unfortunately much earlier, which would be devastating for the relatives.
Is this the same NAD+ that’s prescribed by longevity / hormone clinics?
Edit: after some googling, sounds like NAD+ (which you can get from real doctors) is the “building blocks” similar to how protein is the building blocks for muscle, while the experimental compound changes/enhances how the building blocks are used inside your cells.
So you might need some NAD+ precursor like NMN and this compound for it to work in humans because by the time you’re old it’s much harder for your body to make. Was the experiment done in older mice or younger ones that have NAD+ but artificial Alzheimer’s ?
NMN and NR are both good but NMN might not be available anymore as some company decided to repurpose it as a drug instead of supplement. Best combo nowadays looks to be liposomal NR with pterostilbene, a sirtuin activator. NR boosts NAD+ (the main electron transporter in mitochondria), pterostilbene activates sirtuin SIRT1 that regulates aging. B2/Riboflavin might be a good idea as well as it is a FADH donor, secondary electron transport carrier especially in nerves/brain. B1 to the mix as every single metabolic reaction needs it and it's depleted by consuming lots of carbs or drinking alcohol, a common western diet. Niacin is less effective in raising NAD+ but the flush can open up veins and flood hard to reach extremities of the body with blood so it's probably good from time to time. Slow B3 seems to be even worse for raising NAD+.
- you took niacin too often (best to do it once a few days as body adapts quickly)
- you have a gene mutation that prevents you from absorbing enough B3 (common in some schizophrenia cases that can be managed by huge doses of daily B3, like 4-10g)
Alzheimer's is, by definition, dementia with associated amyloid plaques in the brain. Since you can't detect the plaques without cutting into the brain, the diagnosis is normally given based on symptoms of dementia (significant loss of memory or other cognitive functions) without other clear reasons (no evidence of vascular events, head trauma, brain tumors or other neurological diseases etc).
You mentioned amyloid plaques. What about tau tangles? I thought Alzheimer's required both. If someone (or some dog, for that matter) has amyloid plaques but no tau tangles, is that Alzheimer's? If they have tau tangles but no amyloid plaques, what is it?
And what about the brains that show amyloid plaques, tau tangles, and Lewy bodies? Or plaques plus vascular lesions? At autopsy, most elderly brains show mixed pathology. Does that person have Alzheimer's plus Lewy body dementia plus vascular dementia? Three diseases? Or one brain failing in multiple correlated ways that we've artificially carved into separate categories?
It sounds like we have at least five different pathological markers that correlate with cognitive decline, often co-occurring, with inconsistent symptom mapping. What makes 'Alzheimer's' a disease rather than a region we've named in a high-dimensional space we don't really understand all that well?
> What makes 'Alzheimer's' a disease rather than a region we've named in a high-dimensional space we don't really understand all that well?
Nothing. I think it's sometimes in fact called a syndrome, not a disease per se. Since we don't really understand the mechanism of action, it remains more of a diagnosis by exclusion rather than anything else.
My understanding is that amyloid plaques can actually be seen with a specialized PET scan now, so it can be more definitively diagnosed in living people.
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer.
Does this mean that people are having to trade Alzheimer in exchange for high risk of cancer? Or does this mean that we need better precursors that don't require that trade off?
There's no good evidence that supplementation with NMN, NR, etc. increases the risk of cancer in healthy people. There's some speculation that it might be risky for people with cancer to take those supplements, but the picture is far from clear. Some papers even suggest that they can be beneficial. (e.g., https://pmc.ncbi.nlm.nih.gov/articles/PMC10177531/ )
In terms of risk-benefit analysis, if this stuff actually cures Alzheimer's, then even a 10x increased risk of cancer (all types) is acceptable, as Alzheimer's is frequently a fate worse than death whereas cancer can be managed whilst keeping your personality and sanity intact. In reality, the increased risk of cancer from something like NMN is perhaps 1.005x. To all appearances, totally negligible.
The problem, for Pieper, is that NMN/NR/NADH are ubiquitous and cost pennies per dose. So, if they work (big if), this new research is unmonetizable. The team leads would win a Nobel Prize, but Big Pharma gigabucks are out of the question. Let's see what happens.
Furthermore, we don't even know whether NAD precursor supplementation works. They raise intracellular NAD+ levels, but unclear whether they raise intercellular NAD+, which is what really matters. There are also those that say NAD+ recycling matters more than we think, and precursors don't address that.
Could explain how a compound that's already on the market and has been patented for (some) medical use at least once in 2015 (expiring 2035) might make a good case for "Big Pharma gigabucks"? I thought one reason for a lack of research into "repurposablity" of existing small molecule drugs is the fact that new applications cannot be independently patented?
You absolutely can patent existing drugs. There's a whole scummy pharma industry that takes existing drugs that are widely used off-label and patents that off-label use.
I think it’s worth addressing this with more nuance.
Companies can get a METHOD-OF-USE PATENT (MOU) on an old drug for a new INDICATION.
This gives them the exclusive right to LABEL AND MARKET that drug for that indication for a period of time.
I however, doctors can prescribe and pharmacists can substitute generics for the new indication, regardless of the MOU.
For a company to profit off an MOU, they strategically need to create a new FORMULATION. This is a new dose or delivery mechanism (extended release, topical, etc). A new formulation can be protected with conventional patents that go beyond an MOU.
With an MOU + patent on a new formulation, the company has a brand where they are the only ones allowed to make the new formulation and the only ones with a product approved to be marketed for the new indication.
Getting FDA approval for the new brand is not the main hurdle for the company. To get insurers to pay the premium they want over the cost of existing treatment options, they have to show it’s safer or more effective than those existing options. Otherwise insurance will block it.
In principle, this means that repurposing should only enable companies to profitably repurpose off patent off label applications if they can provide a real patient benefit.
Whether this is the best or most efficient way to promote this kind of innovation, or whether it works as well in practice as it would seem in theory, is a separate question.
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels.
I think it means one should read the very next sentence:
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels.
> Legit feels like Nvidia just buying out competition to maintain their position and power
Well, I mean, isn't that exactly what they should be doing? (I'm not talking about whether or not it benefits society; this is more along the lines of how they're incentivized.)
Put yourself in their shoes. If you had all that cash, and you're hearing people talk of an "AI Bubble" on a daily basis, and you want to try and ensure that you ride the wave without ever crashing... the only rational thing to do is use the money to try and cover all your bases. This means buying competitors and it also means diversifying a little bit.
Dunno thought AGI would make everything obsolete and it's just around the corner? It looks rather like it dawns on everyone that transformers won't bring salvation. It's a show of weakness.
Despite China's fertility rate plummeting to 1.09, the country has a demographic cushion that will carry it through mid-century without serious economic consequences. China's "Alpha" generation (currently ages 6-16) is a large demographic echo of its massive Baby Boom, and will stabilize the workforce through the 2020s and keep the dependency ratio favorable until at least 2030. China's dependency ratio won't surpass America's until the mid-2040s. Two straightforward policy levers -- raising the retirement age from 50-60 to 65 and dramatically increasing college enrollment (already jumped from 26.5% to 60.2% since 2010) -- will offset all effects of gradual aging over the next 25 years. Real demographic strain won't materialize until post-2050 when the large Millennial generation retires without a comparable replacement cohort. The idea that demographics will erode China's competitive position in the next two decades is overblown.
If you want to talk demographics, there are a lot of places that are way worse off than China. Obviously there are the usual suspects, S.Korea and Japan, but also Germany, Italy, and Spain. (Europe's largest economies, France aside... and I'm not so sure about France!) All of them have demographic situations that are far worse than China's, unless you genuinely subscribe to the notion that they can somehow be fixed via mass immigration from third-world countries.
>unless you genuinely subscribe to the notion that they can somehow be fixed via mass immigration from third-world countries.
There are a lot of people who do subscribe to that, mainly people who are on the left side of the political spectrum. Heck, the entire Biden administration believed that.
Oh man, Stephen Wolfram and Jürgen Schmidthuber are probably fuming at the fact that this is called a "new" mathematical framework. It's all very old, and quite conventional, even popular -- not exactly the road not taken.
What the author did was use the Physical Church-Turing thesis, and Kleene's second recursion theorem, to show that: (1) If a universe’s dynamics are computable (PCT), and (2) the universe can implement universal computation (RPCT), then (3) the universe can simulate itself, including the computer doing the simulating.
That's basically all. And thus "there would be two identical instances of us, both equally 'real'." (Two numerically distinct processes are empirically identical if they are indistinguishable. You might remember this sort of thing from late 20th c. philosophy coursework.)
He also uses Rice’s theorem (old) to show that there is no uniform measure over the set of "possible universes."
It's all very interesting, but it's more a review article than a "new mathematical framework." The notion of a mathematical/simulated universe is as old as Pythagoras (~550 BC), and Rice, Church-Turing, and Kleene are all approaching the 100-year mark.
I'm no mathematician, but doesn't this come up against Gödel's incompleteness theorem? My brain has that roughly as "If you have a system and a model of that system, but the model is also part of the same system, something something, impossible"
Isn't GIT you can have a statement that is valid in a system, but can't be proven this way or that given the systems' axioms? And this is true for all such axiom systems? In other words the axioms are an incomplete description of the system.
Maybe the problem is axiomative deduction, we need a new inference-ology?
Maybe I'm too out of this scope but if you want to simulate Universe X plus the computer Y that simulates X then you'd need at least 1 extra bit of memory (likely way more) to encompass the simulation plus the computation running the simulation (X+Y). The computer running the simulation by definition is not part of the simulation, so how can it be that it can truly simulate itself?
In Men in Black II (2002), Will Smith learned that a miniature civilization existed in a locker. Later, Will Smith’s character learned that our civilization was in a locker of a larger civilization.
By thinking of memory usage, you’re restricting yourself to our perceived physical limits withine our perceived reality.
But, what if the things running the simulation did not have those limits? E.g. maybe data could be stored in an infinite number of multiverses outside of the infinite simulations being discussed. Any of the simulations could potentially simulate universes like ours while still allowing those simulations to contain others, to be contained by others, to have references to others, to have reflective references, etc. The makes anything and everything possible while not necessarily removing limits we have in our own simulation. It just depends on what’s running the simulation.
If a compressor can compress every input of length N bits into fewer than N bits, then at least 2 of the 2^N possible inputs have the same output. Thus there cannot exist a universal compressor.
Modify as desired for fractional bits. The essential argument is the same.
Would the compressibility of the state of the universe be useful to prove whether we are in a simulation already? (i.e. it is hard to compress data that is already compressed)
Roughly speaking, Gödel encoded (or “simulated”) the formal part of mathematics within arithmetic (using operations such as addition and multiplication), and constructed a sentence that says “this sentence is unprovable” within that simulation.
Godel's incompleteness theorem is about the limits of proof / mathematical knowledge. Algebra is still useful and true, even though the proof shows it must be incomplete.
It’s also a little silly for the same reasons discussions of theoretical computability often are: time and space requirements. In practice the Universe, even if computable, is so complex that simulating it would require far more compute than physical particles and far more time than remaining until heat death.
Hehe yeah.. For me, its just inverted search for the God. There must be somethink behind it, if its not God, then it must be simulation! Kinda sad, I would expect more from scientist.
The big riddle of Universe is, how all that matter loves to organize itself, from basic particles to Atoms, basic molecues, structured molecues, things and finally live.. Probably unsolvable, but that doesnt mean we shouldnt research and ask questions...
>The big riddle of Universe is, how all that matter loves to organize itself, from basic particles to Atoms, basic molecues, structured molecues, things and finally live.. Probably unsolvable, but that doesnt mean we shouldnt research and ask questions...
Isn't that 'just' the laws of nature + the 2nd law of thermodynamics? Life is the ultimate increaser of entropy, because for all the order we create we just create more disorder.
Conway's game of life has very simple rules (laws of nature) and it ends up very complex. The universe doing the same thing with much more complicated rules seems pretty natural.
Yeah, agreed. The actual real riddle is consciousness. Why does it seems some configurations of this matter and energy zap into existence something that actually (allegedly) did not exist in its prior configuration.
I'd argue that it's not that complicated. That if something meets the below five criteria, we must accept that it is conscious:
(1) It maintains a persisting internal model of an environment, updated from ongoing input.
(2) It maintains a persisting internal model of its own body or vehicle as bounded and situated in that environment.
(3) It possesses a memory that binds past and present into a single temporally extended self-model.
(4) It uses these models with self-derived agency to generate and evaluate counterfactuals: Predictions of alternative futures under alternative actions. (i.e. a general predictive function.)
(5) It has control channels through which those evaluations shape its future trajectories in ways that are not trivially reducible to a fixed reflex table.
This would also indicate that Boltzmann Brains are not conscious -- so it's no surprise that we're not Boltzmann Brains, which would otherwise be very surprising -- and that P-Zombies are impossible by definition. I've been working on a book about this for the past three years...
If you remove the terms "self", "agency", and "trivially reducible", it seems to me that a classical robot/game AI planning algorithm, which no one thinks is conscious, matches these criteria.
How do you define these terms without begging the question?
If anything has, minimally, a robust spatiotemporal sense of itself, and can project that sense forward to evaluate future outcomes, then it has a robust "self."
What this requires is a persistent internal model of: (A) what counts as its own body/actuators/sensors (a maintained self–world boundary), (B) what counts as its history in time (a sense of temporal continuity), and (C) what actions it can take (degrees of freedom, i.e. the future branch space), all of which are continuously used to regulate behavior under genuine epistemic uncertainty. When (C) is robust, abstraction and generalization fall out naturally. This is, in essence, sapience.
By "not trivially reducible," I don't mean "not representable in principle." I mean that, at the system's own operative state/action abstraction, its behavior is not equivalent to executing a fixed policy or static lookup table. It must actually perform predictive modeling and counterfactual evaluation; collapsing it to a reflex table would destroy the very capacities above. (It's true that with an astronomically large table you can "look up" anything -- but that move makes the notion of explanation vacuous.)
Many robots and AIs implement pieces of this pipeline (state estimation, planning, world models,) but current deployed systems generally lack a robust, continuously updated self-model with temporally deep, globally integrated counterfactual control in this sense.
If you want to simplify it a bit, you could just say that you need a robust and bounded spatial-temporal sense, coupled to the ability to generalize from that sense.
The zombie intuition comes from treating qualia as an "add-on" rather than as the internal presentation of a self-model.
"P-zombie" is not a coherent leftover possibility once you fix the full physical structure. If a system has the full self-model (temporal-spatial sense) / world-model / memory binding / counterfactual evaluator / control loop, then that structure is what having experience amounts to (no extra ingredient need be added or subtracted).
I hope I don't later get accused of plagiarizing myself, but let's embark on a thought experiment. Imagine a bitter, toxic alkaloid that does not taste bitter. Suppose ingestion produces no distinctive local sensation at all – no taste, no burn, no nausea. The only "response" is some silent parameter in the nervous system adjusting itself, without crossing the threshold of conscious salience. There are such cases: Damaged nociception, anosmia, people congenitally insensitive to pain. In every such case, genetic fitness is slashed. The organism does not reliably avoid harm.
Now imagine a different design. You are a posthuman entity whose organic surface has been gradually replaced. Instead of a tongue, you carry an in‑line sensor which performs a spectral analysis of whatever you take in. When something toxic is detected, a red symbol flashes in your field of vision: “TOXIC -- DO NOT INGEST.” That visual event is a quale. It has a minimally structured phenomenal character -- colored, localized, bound to alarm -- and it stands in for what once was bitterness.
We can push this further. Instead of a visual alert, perhaps your motor system simply locks your arm; perhaps your global workspace is flooded with a gray, oppressive feeling; perhaps a sharp auditory tone sounds in your private inner ear. Each variant is still a mode of felt response to sensory information. Here's what I'm getting at with this: There is no way for a conscious creature to register and use risky input without some structure of "what it is like" coming along for the ride.
I have more or less the same views, although I can’t formulate them half as well as you do. I would have to think more in depth about those conditions that you highlighted in the GP; I’d read a book elaborating on it.
I’ve heard a similar thought experiment to your bitterness one from Keith Frankish:
You have the choice between two anesthetics. The first one suppresses your pain quale, meaning that you won’t _feel_ any pain at all. But it won’t suppress your external response: you will scream, kick, shout, and do whatever you would have done without any anesthetic. The second one is the opposite: it suppresses all the external symptoms of pain. You won’t budge, you’ll be sitting quiet and still as some hypothetical highly painful surgical procedure is performed on you. But you will feel the pain quale completely, it will all still be there.
I like it because it highlights the tension in the supposed platonic essence of qualia. We can’t possibly imagine how either of these two drugs could be manufactured, or what it would feel like.
Would you classify your view as some version of materialism? Is it reductionist? I’m still trying to grasp all the terminology, sometimes it feels there’s more labels than actual perspectives.
> The zombie intuition comes from treating qualia as an "add-on" rather than as the internal presentation of a self-model.
Haven't you sort of smuggled a divide back into the discussion? You say "internal presentation" as though an internal or external can be constructed in the first place without the presumption of a divided off world, the external world of material and the internal one of qualia. I agree with the concept of making the quale and the material event the same thing, (isn't that kinda like Nietzsche's wills to power?), but I'm not sure that's what you're trying to say because you're adding a lot of stuff on top.
That is not what a p-zombie is. The p-zombie does not have any qualia at all. If you want to deny the existence of qualia, that's one way a few philosophers have gone (Dennett), but that seems pretty ridiculous to most people.
1. Qualia exist as something separate from functional structure (so p-zombies are conceivable)
2. Qualia don't exist at all (Dennett-style eliminativism)
But I say that there is a third position: Qualia exist, but they are the internal presentation of a sufficiently complex self-model/world-model structure. They're not an additional ingredient that could be present or absent while the functional organization stays fixed.
To return to the posthuman thought experiment, I'm not saying the posthuman has no qualia, I'm saying the red "TOXIC" warning is qualia. It has phenomenal character. The point is that any system that satisfies certain criteria and registers information must do so as some phenomenal presentation or other. The structure doesn't generate qualia as a separate byproduct; the structure operating is the experience.
A p-zombie is only conceivable if qualia are ontologically detachable, but they're not. You can't have a physicalism which stands on its own two feet and have p-zombies at the same time.
Also, it's a fundamentally silly and childish notion. "What if everything behaves exactly as if conscious -- and is functionally analogous to a conscious agent -- but secretly isn't?" is hardly different from "couldn't something be H2O without being water?," "what if the universe was created last Thursday with false memories?," or "what if only I'm real?" These are dead-end questions. Like 14-year-old-stoner philosophy: "what if your red is ackshuallly my blue?!" The so-called "hard problem" either evaporates in the light of a rigorous structural physicalism, or it's just another silly dead-end.
You have first-person knowledge of qualia. I'm not really sure how you could deny that without claiming that qualia doesn't exist. You're claiming some middle ground here that I think almost all philosophers and neuroscientists would reject (on both sides).
> "couldn't something be H2O without being water?," "what if the universe was created last Thursday with false memories?," or "what if only I'm real?" These are dead-end questions. Like 14-year-old-stoner philosophy: "what if your red is ackshuallly my blue?!"
These are all legitimate philosophical problems, Kripke definitively solved the first one in the 1970s in Naming and Necessity. You should try to be more humble about subjects which you clearly haven't read enough about. Read the Mary's room argument.
> You have first-person knowledge of qualia. I’m not sure how you could deny that...
I don't deny that. I explicitly rely on it. You must have misunderstood... My claim is not:
1) "There are no qualia"
2) "Qualia are an illusion / do not exist"
My claim is: First-person acquaintance does not license treating qualia as ontologically detachable from the physical/functional. I reject the idea that experience is a free-floating metaphysical remainder that can be subtracted while everything else stays fixed. At root it's simply a necessary form of internally presented, salience-weighted feedback.
> This middle ground would be rejected by almost all philosophers and neuroscientists
I admit that it would be rejected by dualists and epiphenomenalists, but that's hardly "almost all."
As for Mary and her room: As you know, the thought experiment is about epistemology. At most it shows that knowing all third-person facts doesn’t give you first-person acquaintance. It is of little relevance, and as a "refutation" of physicalism it's very poor.
There is no objective evidence of anything at all.
It all gets filtered through consciousness.
"Objectivity" really means a collection of organisms having (mostly) the same subjective experiences, and building the same models, given the same stimuli.
Given that less intelligent organisms build simpler models with poorer abstractions and less predictive power, it's very naive to assume that our model-making systems aren't similarly crippled in ways we can't understand.
That's a hypothesis but the alternate hypothesis that consciousness is not well defined is equally valid at this point. Occam's razor suggests consciousness doesn't exist since it isn't necessary and isn't even mathematically or physically definable.
Yeah I guess... But such question is not really intereseting.. Answer is simple, there is nothing behind it.. and people arent confortable with that answer. Hence "How" is more interesting and scientific..
Yes, is that (obvious) point being addressed in the paper? At first skimming, it just says that a "sufficiently souped up laptop" could, in principle, compute the future of the universe (i.e. Laplace's daemon), but I haven't seen anything about the subsequent questions of time scales.
The real universe might be different and far more complex than our simulated reality. Maybe a species that can freely move within 4 or 5 dimensions is simulating our 3D + uni directional time reality just like we „simulate“ reality with Sim City and Sims.
You're predicating on particles, heat death, etc as you understand it being applicable to any potential universe. Such rules are only known to apply in this universe.
A universe is simply a function, and a function can be called multiple times with the same/different arguments, and there can be different functions taking the same or different arguments.
The issue with that in terms of the simulation argument, is that the simulation argument doesn't require a complete simulation in either space or time.
It also doesn't require a super-universe with identical properties and constraints.
There's no guarantee their logic is the same as our logic. It needs to be able to simulate our logic, but that doesn't mean it's defined or bound by it.
> He also uses Rice’s theorem (old) to show that there is no uniform measure over the set of "possible universes."
I assume a finite uniform measure? Presumably |set| is a uniform measure over the set of "possible universes".
Anyway if I understood that correctly, than this is not that surprising? There isn't a finite uniform measure over the real line. If you only consider the possible universes of two particles at any distance from eachother, this models the real line and therefore has no finite uniform measure.
Okay, here's the thing: this is creating revenue, this is fascinating literature for a huge class of armchair scientists that want to believe, want to play with these mental toys, and are willing to pay for the ability to fantasize with ideas they are incapable of developing on their own. This is ordinary capitalism, spinning revenues out of sellable stories.
It's ambiguous. It could go the other way. He could be referring to that oldest of science fiction tropes: The Bulterian Jihad, the human revolt against thinking machines.
It's trivially easy to improve most aluminum alloys, especially in the 7000-series, with the addition of a little bit of Zr and sometimes a bit of mischmetal or Ce/Er/whatever. We're talking on the order 0.1% Zr and 0.3% Er, so it's not expensive. You get way better strength, better fatigue performance, and at no penalty to ductility.
Why is this not more commonly done?!?!
Why does something like 7075 still exist, when 7068 is better in every way, and 7068+Er would be better still? Yet 7068 is not only uncommon, it's practically impossible to find.
It really is amazing that Jack Ripper esque "they are poisoning the water supply to reduce sperm counts" conspiracies seem to be taking hold of so many people today.
Businesses selling testosterone boosting have managed to convince men to have major body image issues that have previously been mostly only present in women so they can sell them supplements. Good job, society.
There's definitely a kind of frenetic adversity in the whole college admissions process, at least for kids who are inclined to go that route. If anything, it has gotten much worse over the past 30 years; it's much more stressful than it used to be, and it's easy for teens to imagine that every little thing carries high stakes.
If by "adversity" you mean helping the family put food on the table, I certainly agree that there's less of that. Today we have more weird, more detached, and less rational forms of adversity.
I think it’s a broader awareness of a K shaped socioeconomic trajectory, that the odds of an upward trajectory drop considerably if you don’t follow the standard path into a top 20 university, metro, etc. as economic opportunities continue to agglomerate.
What gives me pause with that take is that it only really applies to certain geographical regions of the country. I grew up in a place where today you can still get a starter home for about 100k. The nicest homes, akin to the Home Alone house, on the market are around 500k or less. You don’t need a glamorous job to be a homeowner here, to own a couple cars on the comparatively cheap insurance rates, to send your kid to the very competent in state university. It is still the same break it has always had since the region is stagnant in population. Ironically the lack of growth actually helps the people when you consider the affordability it offers. However the mass media is blind to this region, you won’t hear about it save for browbeating over 1950s population counts, missing the point entirely of what that really means in practice for the people who live there.
K shaped economy doesn’t just refer to class, but of geography. There is a hidden line out of the middle of that K going dead straight.
In general, marketing is not a thing that you can do alone. There are, I think, four primary facets:
1. Making sure that your web presence is optimized for search, AI, etc. This is not easy and best practices are constantly evolving. Just hire RankScience or a similar firm and learn from them. Mistakes here can be extremely costly, so you'll want to make sure you're properly set up.
2. Getting good press, interviews, etc. You'll want to learn how to write a press release (there's a proper format) and have them placed. You'll also want to do outreach to publications and venues that you think are favorable or a good fit. Either buy a subscription and use Opus 4.5 for planning and editing and Kimi-K2 for writing -- or just hire a firm to take care of it and learn from them. This is less expensive than you think. (My firm pays something like $500/month for PR services.)
3. Social media and Youtube. You may not need this, and in any case should not pay for social media services. (Always unreasonably expensive, sometimes sleazy.) Just do your own thing, post cool videos if you've got 'em, comment on other people's stuff, and answer questions. Do not use Reddit. I've never seen a company use Reddit and not live to regret it.
4. Advertising. Again, you may not need this. Modern web advertising can get very expensive, very quickly -- it's practically designed to spin out of control. My recommendation would be to figure out the prior items before considering any campaigns.
The risk-reward ratio associated with retractable door handles is absurdly skewed. On the one hand, you can get locked in a burning and extremely flammable car if you're involved in any kind of traffic accident. On the other hand, you get a literally imperceptible improvement to aerodynamics and range. Retractable handles just seem extremely stupid in a trivially obvious way.
reply