Carhart-Harris & Friston 2019 – REBUS and the Anarchic Brain

Reposted from Enthea with permission from the writer: 


Drs. Robin Carhart-Harris and Karl Friston recently published a beautiful paper – REBUS and the Anarchic Brain (a).

It’s great for two reasons:

  1. It presents a plausible unified theory of how psychedelics work.
  2. It’s a wonderful jumping-off point into the literature. Every paragraph is full of pointers to research that’s come out in the last 5 years, and boy are there a lot of rabbit holes to go down – it’s filled out my reading list for the next several months.

Carhart-Harris is the director of Imperial College London’s newly minted Centre for Psychedelic Research; Friston is a famous neuroscientist.

REBUS is a (somewhat dubious) acronym for RElaxed Beliefs Under pSychedelics. The basic idea: psychedelics reduce the weight of held beliefs and increase the weight of incoming sensory input, allowing the beliefs to be more readily changed by the new sensory information.

REBUS pulls together Carhart-Harris’ Entropic Brain theory and Friston’s Free Energy Principle, both of which relate to the hierarchical predictive coding model of cognition. There’s a lot of jargon & nuance here, but the essential idea of hierarchical predictive coding is pretty straightforward:

  • The brain generates mental models that predict upcoming sensory inputs. (The predictions are called “priors,” as in “prior beliefs.”)
  • These predictive models are layered on top of each other in a hierarchy – the higher levels send predictions down the hierarchy; the lower levels report sense data upwards.
  • In cases where the model’s top-down predictions do not match the bottom-up sensory input, the model either (a) updates its priors based on the new sense data, or (b) ignores the sense data and maintains its priors.

(Scott Alexander’s review of Surfing Uncertainty has a lot more on predictive coding.)

Carhart-Harris & Friston theorize that the main thing psychedelics are doing is relaxing the weight of the brain’s top-down prediction-making (“REBUS”) and increasing the weight of the bottom-up sense information (“the Anarchic Brain”). This allows bottom-up information to have more influence on our conscious experience, and also on the configuration of the hierarchy overall.

Carhart-Harris & Friston analogize this process to annealing – heating up a metal dissolves its crystalline structure, then a new structure recrystallizes as the metal cools:

The hypothesized flattening of the brain’s (variational free) energy landscape under psychedelics can be seen as analogous to the phenomenon of simulated annealing in computer science – which itself is analogous to annealing in metallurgy, whereby a system is heated (i.e., instantiated by increased neural excitability), such that it attains a state of heightened plasticity, in which the discovery of new energy minima (relatively stable places/trajectories for the system to visit/reside in for a period of time) is accelerated (Wang and Smith, 1998).

Subsequently, as the drug is metabolized and the system cools, its dynamics begin to stabilize – and attractor basins begin to steepen again (Carhart-Harris et al., 2017). This process may result in the emergence of a new energy landscape with revised properties.

Psychedelics “heat up” the brain, increasing plasticity and weakening the influence of prior beliefs. As the psychedelic stops being active, the brain “cools” – the hierarchy re-forms, though perhaps in a different configuration than the pre-psychedelic configuration.

This explains how psychedelic trips can cause changes that last long after the substance has exited the body – in those cases, the psychedelic facilitated a change in the organization of the brain’s cognitive hierarchy.

Psychedelic therapy is showing promise for mental disorders associated with too-rigid thought patterns – depression, anxiety, addictions, maybe OCD, maybe eating disorders. In predictive-coding lingo, “disorders that may rest on particularly rigid high-level priors that dominate cognition.”

In these disorders, new information can’t revise the existing story of how things are, because strong priors suppress the new info before it can update anything.

The REBUS model straightforwardly explains how psychedelics help with disorder like this – by relaxing the strong top-down priors and boosting the bottom-up inputs, bottom-up inputs have more ability to effect the system. Here’s an illustration from the paper:

rebus-schema

The top sketch is a brain where strong top-down priors dominate. New sensory inputs are suppressed and can’t update the hierarchy. The bottom sketch is the same brain while on a psychedelic – the top-down priors have been relaxed and bottom-up sensory information flows more freely through the system, causing a bigger impact.

Okay, nice theory, but can we observe this in the brain? Is there any evidence for it?

Carhart-Harris & Friston place the default mode network at top of the brain’s predictive hierarchy. The default mode network is the network of brain regions that’s most active when the brain isn’t engaged with any specific task. It also appears to be the seat of one’s sense of self. The default mode network is intensely relaxed by strong psychedelic experiences – this is subjectively felt as ego dissolution, and allows for the propagation of bottom-up sense data (which are also boosted by psychedelics).

Carhart-Harris & Friston identify two mechanisms by which psychedelics may relax the default mode network – activation of 5-HT2AR serotonin receptors (there are lots of these receptors in the default mode network), and disruption of α and βwave patterns, which seem to propagate top-down expectations through the brain (and are correlated with default mode network activity).

In addition to the brain-scan-style evidence they cite throughout the paper, Carhart-Harris & Friston dedicate a long section to behavioral evidence (“Behavioral Evidence of Relaxed Priors under Psychedelics”). Briefly, there are several studies showing that surprise & consistency-making responses to sensory stimuli are reduced while on psychedelics, which is what we’d expect if the influence of top-down priors was lessened.

To sum up, REBUS and the Anarchic Brain places psychedelics in a predictive coding framework to give a unified theory of what psychedelics do – they decrease the influence of top-down prediction-making and increase the influence of bottom-up sense data. The theory has the nice quality of tying many disparate psychedelic phenomena together with an underlying explanation of what’s going on. Plus, it gives a brain-based explanation for why psychedelic therapy is helpful for disorders like depression, anxiety, and addiction.



See also: Mike Johnson’s pieces A Future for Neuroscience and The Neuroscience of Meditation which summarize a lot of the research by the Qualia Research Institute (QRI) on this topic. In particular, much like this paper by Carhart-Harris and Friston, at QRI we’ve been working on integrating the neuroscientific paradigms of Entropic Brain, Connectome-Specific Harmonic Waves, Predictive Coding, and our own contribution of Neural Annealing into a unified theory of psychedelic action for a number of years.

Our first mention of Neural Annealing in relation to psychedelics was in Algorithmic Reduction of Psychedelic States in 2016, and we are pleased to see that the concept is becoming a live idea in academic neuroscience in 2019.*

From our point of view, an extremely promising area of research that mainstream neuroscience has yet to explore is the Symmetry Theory of Valence. In particular, we claim that the very reason why Neural Annealing improves not only global control, belief, and behavioral consistency, but also mood and sense of wellbeing is because it smooths and symmetrifies your neural patterns of activation. Will this turn out to become part of mainstream neuroscience in the future? Well, since QRI was calling Neural Annealing years in advance, perhaps in retrospect you’ll also see that we were on the money when it came to the mathematics of valence. Only time (and funding) will tell.


*It should be noted that unbeknownst to us Steven Lehar might be the first person to discuss neural annealing in the context of psychedelic states of consciousness. In his 2010 book “The Grand Illusion” he talks about annealing on LSD and ketamine. Here are some key articles about it: Free-Wheeling Hallucinations, The Resonance and Vibration of [Phenomenal] Objects, The Phenomenal Character of LSD + MDMA, and From Point-of-View Fragmentation to Global Visual Coherence: Harmony, Symmetry, and Resonance on LSD.


Featured image credit: Michael Aaron Coleman

Cluster Headache Frequency Follows a Long-Tail Distribution

[Warning: Disturbing content ahead. Why talk about it? This is an ethically very serious topic and it deserves more attention. But please beware that thinking about this might be bad for one’s mental health.]


One of the key insights that shows why Effective Altruism is so important is that the positive effect on the world that results from donating to various charities follows a long-tail distribution:

health interventionsCost-effectiveness of health interventions as found in the Disease Controls Priorities Project 2. See “The moral imperative towards cost-effectiveness in global health” by Toby Ord for more explanation. [Taken from: The world’s biggest problems and why they’re not what first comes to mind]

It is for this, among other, reasons why focusing on the best interventions really pays off. Where else can we expect long-tails to appear?


In Get-Out-Of-Hell-Free Necklace we discussed how introducing a new metric into the Effective Altruist ecosystem could shed light on neglected cost-effective interventions. We presented the Hell-Index:

A country’s Hell-Index could be defined as the yearly total of people-seconds in pain and suffering that are at or above 20 in the McGill Pain Index (or equivalent)*. This index captures the intuition that intense suffering can be in some ways qualitatively different and more serious than lesser suffering in a way that isn’t really captured by a linear pain scale.

In a future article we will discuss how the quality of suffering as a function of different medical and psychological conditions very likely follows a long-tail distribution. That is, some conditions such as Cluster Headaches (which affect about 1 in 1000 people worldwide) produce pain that is orders of magnitude worse than the pain experienced in other kinds of medical conditions, such as migraines (which are themselves already described as orders of magnitude worse than tension headaches). In other words, a 0-10 pain-scale is better thought of as a logarithmic compression of the true levels of pain rather than a linear scale. So concentrating on the worst conditions could really pay off for reducing suffering in bulk amounts.

Now: the long-tailed nature of suffering may extend beyond the quality of suffering, and show up also in its quantity. That is, the frequency with which people experience episodes of intense suffering, even among those who experience the same kind of suffering, is unlikely to be normally distributed.

Intuitively, one may think that how much suffering people endure on a given year follows a normal distribution. This intuition says that if the median number of hell-seconds people endure in a year is, say, 1,000, then people who are at the 90% percentile of hell-seconds experienced per year will be experiencing something like 1,500 or at most 2,000. If suffering follows a long-tail distribution, in reality the 90% percentile might be experiencing something more akin to 10,000 hell-seconds per year, the 99% percentile something akin to 100,000, and the 99.9% something akin to 1,000,000. If true, such a heavy skew of the distribution would suggest that we should concentrate our energies on addressing the problems of the people who are unlucky to be on the upper ranges, rather than be overly concerned with “the typical person”*.

Unfortunately, I come to share the bad news that suffering probably follows a very long-tail distribution:

It is generally acknowledged that Cluster Headaches are some of the most painful experiences that people endure. Having a single Cluster Headache, lasting anywhere between 15 minutes to 4 hours, is already an ethically unacceptable situation that should never happen to begin with. It is disheartening to know that 1 in 1,000 people experience such extreme pain. But the truth of the matter is yet much worse than we intuitively think…

We recently analyzed a survey** of Cluster Headache patients that was conducted with the intention of determining the reasons why sufferers do or do not use psychedelics to relieve their pain. As it turns out, LSD, psilocybin, and DMT all get rid of Cluster Headaches in a majority of sufferers. Given the safety profile of these agents, it is insane to think that there are millions of people suffering needlessly from this condition who could be nearly-instantly cured with something as simple as growing and eating some magic mushrooms.

We will get back to this in more depth in later articles, but for the time being what we want to highlight is the responses to the question “About how many cluster headaches do you get in a typical year?”.

After cleaning the data***, we end up with 270 participants. We then ranked the values from smallest to largest, and visualize them:

270_ranked

Honestly I am a bit suspicious of the very top numbers (I do not know how you can fit 25,000 Cluster Headaches in a year, so perhaps the participant interpreted the question as “lifetime number of Cluster Headaches”). So, just to be safe, we cut the top 20 highest numbers and visualize the bottom 250 values:

first_250_

This is clearly a long-tail distribution. And since many people online do claim to have 3 or more Cluster Headaches a day, I am inclined to believe this curve. To zoom in on some parts of the distribution, here are some additional histograms that focus on the lower percentiles:

If we take the logarithm of the number of yearly Cluster Headaches, the distribution looks remarkably normal:

log_of_estimated_total_half_bins_till_12

Natural log of the responses to the question “About how many cluster headaches do you get in a typical year?”

Using a Shapiro-Wilk normalcy test does not rule out a Gaussian distribution (p >0.05). Although this in no way shows that that the distribution is log-normal (which would require more specialized statistical analysis), it is at least suggestive of it.

I should also point out that the distribution is really close to the 80/20 Pareto principle – we see that the top 20% of the participants contain about 83% of the CH incidents per year. Below you will find the percent of the total number of incidents accounted for by the bottom x% of the respondents:

  1. The bottom 10% accounts for .06% of incidents
  2. The bottom 20% accounts for 0.36% of incidents
  3. The bottom 30% accounts for .95% of incidents
  4. The bottom 40% accounts for 1.82% of incidents
  5. The bottom 50% accounts for 3.17% of incidents
  6. The bottom 60% accounts for 5.54% of incidents
  7. The bottom 70% accounts for 9.56% of incidents
  8. The bottom 80% accounts for 17% of incidents
  9. The bottom 90% accounts for 30% of incidents
  10. The bottom 95% accounts for 43% of incidents

Below we also include the number of yearly Cluster Headaches experiences at different percentiles:

  1. 10% percentile experiences 5 CH/year
  2. 20% percentile experiences 17 CH/year
  3. 30% percentile experiences 30 CH/year
  4. 40% percentile experiences 45 CH/year
  5. 50% percentile experiences 70 CH/year
  6. 60% percentile experiences 105 CH/year
  7. 70% percentile experiences 200 CH/year
  8. 80% percentile experiences 365 CH/year
  9. 90% percentile experiences 730 CH/year
  10. 95% percentile experiences 1095 CH/year
  11. 98% percentile experiences 2190 CH/year

I believe that this information is crucial to consider when assessing cost-effective interventions to help people who endure intense suffering.


Here are some additional results from the survey.

cluster_headache_tryptamine_use

The following graphs are about the beliefs and attitudes of Cluster Headache sufferers who do not use tryptamines (LSD, psilocybin, DMT, etc.) to treat their condition:

 

I think it is fair to say that the survey shows that one of the biggest barriers preventing CH patients from using tryptamines to treat their condition is simply the difficulty of acquiring them. Since a number of interviews we’ve conducted have shown that even sub-hallucinogenic doses of DMT can abort cluster headaches (writeup coming soon), more education could easily address the barrier of being concerned about hallucinogenic side effects. The social stigma seems like a minor problem, and the legal implications (the hardest to change, perhaps), are a big concern to about half of the participants (ratings of 4 or 5/5). Hence the importance of passing new laws allowing people with this condition to use them without repercussions.

Do CH sufferers who do not use tryptamines think they would work?

no_use_cluster_headache_belief_in_effectiveness

And do they work? Here is what the CH sufferers who do use them say:

use_cluster_headache_effective

Effectiveness

use_cluster_headache_kind

Tryptamines used

If we interpret a 2 or 3 in the 0 to 5 scale as an equivalent to a “maybe”, and a 4 or 5 as a “yes” to the question “do they work?” we see a big difference between non-users beliefs in their effectiveness and their reported effectiveness by users. 24% of people who use tryptamines to treat their CHs report that “They have completely eliminated the cluster headaches” and in total 68% mark it as either a 4 or a 5 in the scale (which we can interpret as “working” even if not “completely eliminating them”). This is compared to only 30% of non-users who believe the tryptamines would work. This large discrepancy also suggests that outreach and education could help sufferers give this approach a try.

Finally, we also looked at whether the users and non-users had different number of incidents per year (reasoning that perhaps those who experience more incidents would be more desperate to try legally and socially risky treatments). We notices that there is a very slight difference in the mean (and mean-log) for the number of CH incidents a year between the 20% of sufferers who treat their CHs with tryptamines and those who don’t. I won’t report the difference in the mean because the skew of the distribution makes such a metric deceptive, but the log-mean of yearly incidents of tryptamine users is 4.73 whereas for all the rest it is 4.10 (which reaches statistical significance of p < 0.05 based on a t-test). That said, we don’t think this is a very practically relevant difference. The distributions look roughly the same:

tryptamine_vs_non_tryptamine_users

The similarity between these two distributions also suggests that there is a long way to go to make sure that those who are the worse off get prompt access to tryptamines.

The End.


See also https://clusterbusters.org/, which is an organization that aims to make psychedelics legally available to people who suffer from this condition. Please consider donating to them to help this very important cause. Also consider donating to MAPS which is championing the use of psychedelics for mental health applications. Finally, consider also donating to organizations that care and strategize about how to reduce intense suffering, such as: QRI, FRIOPIS, and The Neuroethics Foundation.


*There are instrumental considerations here – if experiencing more than, say, 5,000 hell-seconds in a year is very likely to make you depressed and ineffective, then it might pay-off to also spend resources on keeping as many people as possible below that level. In particular, to be an effective Effective Altruist it pays off not to be heavily depressed and nihilistic.

**Thanks to Harlan Stewart for taking the initiative to conduct this survey. He advertised it on the Facebook groups and subreddits of Cluster Headache sufferers and got 371 responses.

***Some people provided numerical answers, which we used directly. Some other people provided ranges, in which case we used the middle point between the values provided (e.g. “200 to 300” was coded as “250”). Some people provided lower bounds, in which case we simply used such lower bound (e.g. “500+” was coded as “500”). We discarded the data of people who didn’t provide an answer in any of those formats – which left 270 participants. A more strict analysis that uses *only* the numerical responses results in the same observations listed above (e.g. the distribution is equally long-tailed and it appears to be log-normal).


[Cross-posted in Effective Altruism Forum]

Frequency Specific Microcurrent for Kidney-Stone Pain

Excerpt from The Resonance Effect: How Frequency Specific Microcurrent is Changing Medicine (2017) by Carolyn McMakin 

Kidney Stone Pain

Everyone who has ever had a kidney stone will tell you that the kidney-stone pain is the worst. Emergency rooms treat it with morphine, and nothing else seems to touch it.

The phone rang on a summer Sunday morning and I hardly recognized the friend who grunted through gritted teeth to ask if “my machine” could treat kidney-stone pain. I told him that I’d never treated it before, but I’d be willing to try if he could make it to my house. He shuffled from the front door to the couch bent forward at the waist, sweating in pain. I put one wet graphite glove under his back and the other glove on his abdomen. He tried hard not to moan as I covered him with a soft blanket and placed my hand on top of the glove on his abdomen.

Education said that kidney-stone pain had to be about spasm in the ureter, the tube that carries the stone from the kidney to the bladder. The frequency for spasm was 29 hertz on channel A. The frequency for the ureter was 60 hertz on channel B. It did absolutely nothing: no warmth, no relaxation or softening, nothing. Maybe there was bleeding caused by the rough stone shredding the ureter as it traveled? I tried 18 hertz to stop bleeding on channel A. The glove didn’t get warm, and the pain didn’t change.

I really didn’t want my gray-faced friend to be my first failure. Reaching for inspiration, I tried the always-reliable 40 hertz to reduce inflammation. Nothing changed. Desperation amplified the small murmur of my intuition in my head, “Don’t get sloppy! Be thorough.”

There is a sequence of frequencies leading up to inflammation. The sequence was 20 hertz for “pressure or pain reaction,” 30 hertz for irritation, 40 hertz for inflammation. I never ran the whole sequence because 40 hertz always worked and I had no idea what a “pressure or pain reaction” might be. The buttons clicked down from 40 hertz to 20 hertz on channel A, and two things happened in seconds. The glove resting on his abdomen got hot — not just warm, it was hot. His abdomen started to soften. The feeling is hard to describe. It feels like a balloon feels when it has been sitting on the floor overnight. The tissue softens and stays soft while the correct frequency is working, and it returns to normal when the frequency is finished.

His voice was a little slurred when he fell asleep a few minutes later as he said, “Is that supposed to make me feel woozy?” His deep relaxed breathing said he was out of pain.

There are frequencies for the stone, so I tried those after twenty quiet minutes of watching him doze. The glove got hot, the abdomen softened, and ten minutes later he bolted awake and yelped, “The stone’s moving.” True to its promise, 20 hertz on A and 60 hertz on B reduced the pain again and put him back to sleep. Forty minutes later he left, pain-free, and passed the stone that night with no increase in pain.

I told this story at the Advanced Course in Australia a few weeks later, and one of the Australian practitioners reported that she treated her husband for kidney stone pain with 20 hertz on A and 60 hertz on B. He was out of pain in an hour and passed the stone uneventfully.

Every case of kidney stones treated since then has responded exactly the same way. When the patient has gripping lower back pain from lifting suitcases during a long dehydrating flight but treating the muscles doesn’t help, experience finally admits it’s not the muscle. Intuition says, “I wonder if it’s a kidney stone?” The learning curve is very steep and short when the glove gets hot, the muscles begin to relax, the pain goes down in minutes, and the patient falls asleep.

When one specific frequency combination, and only one, works every time anyone uses it, and when it does something that is otherwise impossible, then it can’t be impossible. It’s got to be resonance.

Every Child is a Genetic Experiment: FAAH Clinical Trials for Hedonic Recalibration as Educated Guesses Rather than Reckless Experimentation

by David Pearce, in response to Quora question: How do you break the hedonic treadmill?

 

The easiest pain to bear is someone else’s.
(François de La Rochefoucauld)

Could two small genetic tweaks get rid of most of the world’s mental and physical pain?
A tentative answer is: just conceivably. More cautiously, the problem of suffering should be genetically soluble this century. Before launching into a long list of caveats and complications – and outright scepticism – it’s worth considering a case study. The subject has waived anonymity.

Jo Cameron is a retired Scottish schoolteacher, a socially responsible vegan and pillar of the local community. Jo has gone though life in a perpetual state of “mild euphoria”. She has unusually high levels of anandamide (from the Sanskrit for “bliss”) and is never anxious, though her serenity may vary. Jo doesn’t feel pain, or at least not in any sense most of us would recognise: childbirth felt like “a tickle”. She is hyperthymic, but not manic. Unlike previously reported cases of congenital analgesia, Jo didn’t die young or find the need to adopt a “cotton-wool” existence to avoid bodily trauma. She came to the attention of medical researchers only when her disdain of painkillers for what “ought” to have been an excruciating medical procedure – a trapeziectomy on her right thumb – intrigued her doctor. “I had no idea until a few years ago there was anything that unusual about how little pain I feel – I just thought it was normal.
With CRISPR genome-editing, lifelong bliss could be normal.

Jo Cameron is first known case of someone with mutations in both the FAAH gene and its newly-discovered sister gene, FAAH-OUT, which modulates the FAAH gene. The FAAH gene (short for Fatty Acid Amide Hydrolase) is a protein-coding gene responsible for degrading bioactive fatty amides, most notably the endogenous cannabinoid anandamide. Previous mutations of FAAH are known, but the FAAH-OUT gene was previously reckoned a pseudogene. Single FAAH mutations are associated with high pain-tolerance, reduced anxiety and a sunny outlook without Jo’s “extreme” syndrome of well-being. Jo’s son has the single mutation.

Other case studies may be cited. I often use (again with prior consent) the example of my transhumanist colleague Anders Sandberg (“I do have a ridiculously high hedonic set-point”) – although Anders’ pain-sensitivity lies within the normal range. The pain-modulating SCN9A gene, which has dozens of alleles conferring varying pain (in)tolerance, is much better studied (cfHow much do our pain thresholds differ?).

What biologists call the Environment of Evolutionary Adaptation (EEA) ensures such outliers are rare. Although Jo Cameron shows accelerated wound-healing, not being a “normal”, neurotic mother on the African savannah would have carried a fitness-cost. Predators are unforgiving of relaxed moms. Our sugary “wildlife documentaries” barely hint at the cruelties of Nature. Pain, fear and anxiety are intimately linked. “Only the paranoid survive”, said Intel boss Andy Grove; and this bleak diagnosis can be true of market capitalism to this day. But we are not living on the African savannah – or even in a world of unfettered free markets. Looking ahead, all kinds of risks can be offloaded to artificial intelligence. AI and smart prostheses can potentially manage risks moreeffectively than bias-ridden humans. Intuitively, for sure, tampering with our reward circuitry will be hazardous. Genetically modifying or creating superhappy organisms with relative pain-insensitivity and enhanced zest for life will lead to increased personal risk-taking. Yet the story is more complicated. A great deal of risky and self-destructive behaviour in today’s world involves not happy, pain-free people, but the pain-ridden, depressive and psychologically disturbed. Life-loving optimists typically value life more – and seek to preserve and protect it. Anecdotally, I don’t think it’s a coincidence that some of the happiest people I know dedicate their lives to the study and prevention of existential risk.

So a practical question arises.
Should a large, well-controlled clinical trial of CRISPR babies be launched, with some babies carrying Jo’s two mutations, others a single FAAH mutation like her son, and controls?
If the trial is successful, then the controls and (in due course) the wider human population could enjoy remedial gene-therapy to share the benefits.

One of the few publications to recognise the far-reaching significance of Jo’s case is the magazine Wired (cfCrispr Gene Editing Could One Day Cut Away Human Pain). Instead of the double mutation promising “only” better drugs to treat pain, humanity can now tackle the problem of suffering at its source.

Bioconservative critics will be appalled at the idea: “Doctor Mengele!” “Eugenics!” “Designer babies!” “Gattaca!” “Brave New World!” Being malaise-ridden is normal and natural. Creating superbabies would be hubris. Where will it lead? How do we know gene-editing won’t be used by despots to create a race of fearless superwarriors?
In more measured language, how can experimentation with the lives of sentient beings without prior informed consent be ethically justified?

Indeed. Yet all babies born today are unique and untested genetic experiments. All baby-making entails creating involuntary suffering. None of our genetic experiments first passed muster with a medical ethics committee. Any proposal to create transhuman superbabies will probably strike our descendants as genetic remediation, not enhancement. If we reject the arguments of anti-natalists, who view Darwinian life as malware, then all prospective parents are committed to practising genetic experimentation – just not under that inflammatory label. So what’s at issue is not the principle of genetic innovation, only whether we should harness the new tools of CRISPR-Cas9 genome-editing to conduct our experiments more responsibly. If aspiring writers can benefit from proofreaders and editors, why not aspiring parents too – where the stakes are higher?

Your question asks about breaking the hedonic treadmill (cfWhat would people who never suffered be like?). Breaking or otherwise dismantling the hedonic treadmill is worth distinguishing from recalibration of its dial-settings. Hedonic adaptation can be broken in human and non-human animals by experimentally inducing “learned helplessness” and behavioural despair in response to chronic, uncontrollable stress. Hedonic adaptation can be broken at the other extreme by using intracranial self-stimulation of the mesolimbic dopamine system. “Wireheading” shows virtually no tolerance. Pathological cases of a broken hedonic treadmill occur “naturally” in chronic unipolar depression and, much more rarely, in euphoric unipolar mania. Attempts to cheat the hedonic treadmill via drugs are fraught with pitfalls. The most powerful mood-brighteners, namely the opioids, activate the hedonic treadmill rather than mitigate it. Some opioid users end up with a habit hundreds of times their starting dose. Natural selection did not design living organisms to be happy.

Functionally, therefore, genetic recalibration is a more fruitful strategy than abolishing the hedonic treadmill, both for the individual and society at large. For what it’s worth, I personally think we should aim for a hyperthymic civilisation built on a biology of invincible well-being. Future sentience will be underpinned by gradients of bliss. However, nothing so grandiose need be envisaged in order to warrant human CRISPR trials of happy babies. Grant some fairly modest ethical assumptions, e.g. other things being equal, intelligent moral agents should act so as to reduce the burden of suffering, or at least not wantonly add to it. For any genetic intervention that alters default hedonic tone, conserving information-sensitivity to “good” and “bad” stimuli is critical. In other words, we should aim to retain the hedonic treadmill but transform its negative feedback-mechanisms into a hedonistic treadmill – where “hedonism” is understood not in the amoral popular sense of a life of drink, drugs and debauchery, but as embracing Mill’s “higher pleasures”. Hence the hedonistic imperative. If clinical trials of superbabies go well, prospective parents world-wide could be offered the opportunity to have happy, heathy babies via CRISPR genome-editing, preimplantation genetic screening and counselling.

A biohappiness revolution would be extremely cost-effective. Depression, anxiety disorders and chronic pain-syndromes significantly reduce economic growth worldwide. By conserving hedonic adaptation, but ratcheting up hedonic range and hedonic set-points, humanity can conserve and enhance empathetic understanding, social responsibility and critical insight while enriching default quality of life. By conserving hedonic adaptation, we can also conserve cherished traditional values, if so desired. Yesterday’s utopias involved overriding the preferences of others, whether for their own notional good or in pursuit of some higher cause. By contrast, elevating your pain-tolerance and raising your hedonic set-point would radically enrich your life but wouldn’t challenge your values and preferences – unless one of your core values is preserving the genetic status quo.

What could go wrong with a biohappiness revolution?
Cue for vast treatises and a sci-fi movie.
However, as well as seriously – indeed exhaustively – researching everything that could conceivably go wrong, I think we should also invesigate what could goright. The world is racked by suffering. The hedonic treadmill might more aptly be called a dolorous treadmill. Hundreds of millions of people are currently depressed, pain-ridden or both. Hundreds of billions of non-human animals are suffering too. If we weren’t so inured to a world of pain and misery, then the biosphere would be reckoned in the throes of a global medical emergency. Thanks to breakthroughs in biotechnology, pain-thresholds, default anxiety levels, hedonic range and hedonic set-points are all now adjustable parameters in human and non-human animals alike. We are living in the final century of life on Earth in which suffering is biologically inevitable. As a society, we need an ethical debate about how much pain and misery we want to preserve and create.

Investing Time and Resources in Happiness

As a function of time and resources, what is the optimal way to reduce suffering and maximize happiness?

You have 1 minute and no money: Try to calm down and distract yourself with music.

You have 1 hour and 1 dollar: Ignore the dollar, just make a playlist of songs you really enjoyed in your life and play it as you dance.

You have 1 day and 50 dollars: Go get yourself some hard drugs.

You have 3 months and 1,000 dollars: Get some gym equipment, establish a workout routine, hangout with friends as much as possible, get laid, go to see movies, go to a beach.

You have 3 years and 3,000 dollars: Learn about Buddhist meditation, get fit, and then focus on achieving the Jhanas states. Stay in them for as long as you can.

You have 10 years and 10,000 dollars: Investigate charities that minimize suffering, or make your own. Fund-raise in order to eliminate suffering in people who have cluster-headaches by giving them access to tryptamine vape-pens, help the spread of pain-killers for people dying in hospitals in third-world countries, etc.

You have 50 years and 10,000,000 dollars: You found a research institute devoted to identifying the biochemical, functional, or behavioral causes of suffering, identify promising large-effect-size genetic modification technologies in order to enable sustainable hedonic-tone enhancement. You build a company that sells permanent hedonic tone amplification. With the money you get rid of factory farming and implement a wild-animal welfare system. Then you get rid of game-theoretical impasses using ultra-bliss technology.

Do you think that some psychedelic drugs, such as DMT, can help mathematicians visualize the hyperbolic geometry of space? Or could mathematicians glean other interesting insights through the experience?

[From Quora]

The answer is yes (though I am the writer of the piece that is linked, so take my answer with a grain of salt).

The number of novel mathematical objects encoded in the structure of one’s experience when under the influence of DMT is huge. Most mathematicians who try it will come out feeling that they “don’t even know where to start”.

So let’s start simple.

Consider the “Chrysanthemum” level of DMT intoxication (which is the 2nd of 6 levels). Anybody who has read “The Symmetry of Things” by John H. Conway, Heidi Burgiel, and Chaim Goodman-Strauss (or who has a deep acquaintance with symmetry groups by other means) will *readily recognize* the fact that the symmetry groups that appear on such DMT visuals are *not Euclidean*.

At that level they would see rapidly-flickering superpositions of hyperbolic symmetry groups like *2 3 11, *2 3 7, 2 4 5, 2 3 9 (the picture below), etc. Together with the fact that these visuals are completely “flat-looking” rather than curved, this is the smoking gun that what you are looking at/experiencing is a hyperbolic phenomenal space.

2 3 9 Hyperbolic Symmetry Group

And this is not even discussing the 3D hyperbolic space that becomes apparent (if you know what to look for) on higher levels of DMT. For instance, on level 3 you can experience 3D Euclidean symmetry groups tesselate your visual field, on level 4 you can experience 3D hyperbolic space and “prime” objects that belong to that geometry (which are impossible to reproduce faithfully in Euclidean space). Level 5 leads to global topological bifurcations of the phenomenal space, which gives rise to even more exotic objects with hard-to-grasp mathematics. And level 6… well, there IS a level 6, and that’s as much as I’m willing to say for the time being.

In future, I believe that mathematicians who care to *look closely* will see the signature of exotic mathematical spaces on the “DMT Realms” everywhere. This will become common knowledge in both neuroscience and mathematical circles.

As David Pearce likes to say: “Some people think we are reaching the age where fundamental knowledge has been achieved… I think the enterprise of knowledge has scarcely begun.” Studying exotic states of consciousness is not even at a pre-Galilean stage, it perhaps is even at a pre-Socratic stage. Alas, if more people pay attention and document their experiences carefully, such that a critical mass of rational brilliant psychonauts is reached, there will be a “knowledge explosion”.


For more see: The Hyperbolic Geometry of DMT Experiences: Symmetries, Sheets, and Saddled Scenes (cf. Explain Like I’m 5 version), and How do you conceptualize the entities many individuals describe encountering when they’ve consumed DMT?

On Hitting the Actual Target of Hedonic Tone

Practically speaking, I think that our single best psychopharmacological bet for tackling depression, anxiety, and above all chronic pain worldwide in the next decade is to:

1) Identify great, non-toxic, partial mu-opioid agonists with extremely high therapeutic index (e.g. tianepetine, 7-hydroxymitragynine, etc.), and

2) Prescribe them in conjunction with anti-tolerance drugs (such as proglumide, agmatine, black seed oil, small dose ibogaine, etc.).

I think that whomever manages to patent a mixture of partial opioid agonist + anti-tolerance drug that works in the long term will be a multi-billionaire within a couple of years while actually reducing/preventing massive amounts of untold suffering.

imgsrv

Proglumide: A Promising Anti-Tolerance Agent (proof of concept of what is to come)


Ps. My core research at QRI is not pharmacological but rather phenomenological and “patternceutical“. So I am not pursuing the above line of research myself as the core objective of the next few years. But if I was looking into pharmacological options, that’s where I’d shine some light on. If you are in the field, I urge you to look into this option. For more info: “Anti-Tolerance Drugs“.

“Letter from Utopia” and Other Triple-S Transhumanist Media

by Nick Bostrom (2010)

Dear Human,

Greetings, and may this letter find you at peace and in prosperity! Forgive
my writing to you out of the blue. Though you and I have never met, we are
not strangers. We are, in a certain sense, the closest of kin. I am one of your
possible futures.

I hope you will become me. Should fortune grant this wish, then I am not
just a possible future of yours, but your actual future: a coming phase of you,
like the full moon that follows a waxing crescent, or like the flower that
follows a seed.

I am writing to tell you about my life – how good it is – that you may choose
it for yourself.

Although this letter uses the singular, I am really writing on behalf of all
my contemporaries, and we are addressing ourselves to all of your
contemporaries. Amongst us are many who are possible futures of your
people. Some of us are possible futures of children you have not yet given
birth to. Still others are possible artificial persons that you might one day
create. What unites us is that we are all dependent on you to make us real.
You can think of this note as if it were an invitation to a ball that will take
place only if folks turn up.

We call the lives we lead here “Utopia”.

*

How can I tell you about Utopia and not leave you mystified? What words
could convey the wonder? What inflections express our happiness? What
points overcome your skepticism? My pen, I fear, is as unequal to the task as
if I had tried to use it against a charging elephant.

But the matter is so important that we must try even against long odds.
Maybe you will see through the inadequacies of my exposition.

Have you ever known a moment of bliss? On the rapids of inspiration,
maybe, where your hands were guided by a greater force to trace the shapes
of truth and beauty? Or perhaps you found such a moment in the ecstasy of
love? Or in a glorious success achieved with good friends? Or in splendid
conversation on a vine-overhung terrace one star-appointed night? Or
perhaps there was a song or a melody that smuggled itself into your heart,
setting it alight with kaleidoscopic emotion? Or during worship?

If you have experienced such a moment, experienced the best type of such a
moment, then a certain idle but sincere thought may have presented itself to
you: “Oh Heaven! I didn’t realize it could feel like this. This is on a
different level, so very much more real and worthwhile. Why can’t it be like
this always? Why must good times end? I was sleeping; now I am awake.”

Yet behold, only a little later, scarcely an hour gone by, and the softly-falling
soot of ordinary life is already piling up. The silver and gold of exuberance
lose their shine. The marble becomes dirty.

Every way you turn it’s the same: soot, casting its veil over all glamours and
revelries, despoiling your epiphany, sodding up your white pressed collar and
shirt. And once again that familiar beat is audible, the beat of numbing
routine rolling along its tracks. The commuter trains loading and unloading
their passengers… sleepwalkers, shoppers, solicitors, the ambitious and the
hopeless, the contented and the wretched… like human electrons shuffling
through the circuitry of civilization.

We do so easily forget how good life can be at its best – and how bad at its
worst. The most outstanding occasion: barely is it over before the sweepers
move in to clean up the rice. Yellowing photos remain.

And this is as it should be. We are in the business of living, and life must go
on. Special moments are out-of-equilibrium experiences in which our
puddles are stirred up and splashed about; yet when normalcy returns we are
usually relieved. We are built for mundane functionality, not lasting bliss.

So the door that was ajar begins to close, disappearing hope’s sliver behind
an insensate scab.

Quick, stop that door! Look again at your yellowing photos, search for a
clue. Do you not see it? Do you not feel it, the touch of the possible? You
have witnessed the potential for a higher life, and you hold the fading proof
in your hands. Don’t throw it away. In the attic of your mind, reserve a
drawer for the notion of a higher state of being. In the furnace of your heart,
keep an aspiring ember alive.

I am summoning this memory of your best experience – to what end? In the
hope of kindling in you a desire to share my happiness.

And yet, what you had in your best moment is not close to what I have now
– a beckoning scintilla at most. If the distance between base and apex for
you is eight kilometers, then to reach my dwellings requires a million lightyear ascent. The altitude is outside moon and planets and all the stars your
eyes can see. Beyond dreams. Beyond imagination.

My consciousness is wide and deep, my life long. I have read all your
authors – and much more. I have experienced life in many forms and from
many angles: jungle and desert, gutter and palace, heath and suburban creek
and city back alley. I have sailed the high seas of cultures, and swum, and
dived. Quite some marvelous edifice builds up over a million years by the
efforts of homunculi, just as the humble polyps amass a reef in time. And
I’ve seen the shoals of colored biography fishes, each one a life story,
scintillate under heaving ocean waters.

The whole exceeds the sum of its parts. What I have is not merely more of
what is available to you now. It isn’t just the particular things, the paintings
and toothpaste-tube designs, the record covers and books, the epochs, lives,
leaves, rivers, and random encounters, the satellite images and the hadron
collider data – it is also the complex relationships between these particulars
that make up my mind. There are ideas that can be formed only on top of
such a wide experience base. There are depths that can be fathomed only
with such ideas.

You could say I am happy, that I feel good. You could say that I feel
surpassing bliss. But these are words invented to describe human
experience. What I feel is as far beyond human feeling as my thoughts are
beyond human thought. I wish I could show you what I have in mind. If
only I could share one second of my conscious life with you!

But you don’t have to understand what I think and feel. If only you bear in
mind what is possible within the present human realm, you will have enough
to get started in the right direction, one step at a time. At no point will you
encounter a wall of blinding light. At no point will you have to jettison
yourself over an end-of-the-world precipice. As you advance, the horizon
will recede. The transformation is profound, but it can be as gradual as the
growth that made the baby you were into the adult you think you are.

You will not achieve this through any magic trick or hokum, nor by the
power of wishful thinking, nor by semantic acrobatics, meditation,
affirmation, or incantation. And I do not presume to advise you on matters
theological. I urge on you nothing more, nothing less, than reconfigured
physical situation.

*

The challenge before you: to become fully what you are now only in hope
and potential. New capacities are needed if you wish to live and play on my
level.

To reach Utopia, you must first discover the means to three fundamental
transformations.

The First Transformation: Secure life!

Your body is a deathtrap. This vital machine and mortal vehicle, unless it
jams first or crashes, is sure to rust anon. You are lucky to get seven decades
of mobility; eight if you be Fortuna’s darling. That is not sufficient to get
started in a serious way, much less to complete the journey. Maturity of the
soul takes longer. Why, even a tree-life takes longer!

Death is not one but a multitude of assassins. Do you not see them? They
are coming at you from every angle. Take aim at the causes of early death –
infection, violence, malnutrition, heart attack, cancer. Turn your biggest
gun on aging, and fire. You must seize control of the biochemical processes
in your body in order to vanquish, by and by, illness and senescence. In
time, you will discover ways to move your mind to more durable media.
Then continue to improve the system, so that the risk of death and disease
continues to decline. Any death prior to the heat death of the universe is
premature if your life is good.

Oh, it is not well to live in a self-combusting paper hut! Keep the flames at
bay and be prepared with liquid nitrogen, while you construct yourself a
better habitation. One day you or your children should have a secure home.
Research, build, redouble your effort!

The Second Transformation: Upgrade cognition!

Your brain’s special faculties: music, humor, spirituality, mathematics,
eroticism, art, nurturing, narration, gossip! These are fine spirits to pour
into the cup of life. Blessed you are if you have a vintage bottle of any of
these. Better yet, a cask! Better yet, a vineyard!

Be not afraid to grow. The mind’s cellars have no ceilings!

What other capacities are possible? Imagine a world with all the music dried
up: what poverty, what loss. Give your thanks, not to the lyre, but to your
ears for the music. And ask yourself, what other harmonies are there in the
air, that you lack the ears to hear? What vaults of value are you witlessly
debarred from, lacking the key sensibility?

Had you but an inkling, your nails would be clawing at the padlock in sacred
frenzy.

Your brain must grow beyond the bounds of any genius of humankind, in its
special faculties as well as its general intelligence, so that you may better
learn, remember, and understand, and so that you may apprehend your own
beatitude.

Mind is a means: for without insight you will get bogged down or lose your
way, and your journey will fail.

Mind is also an end: for it is in the spacetime of awareness that Utopia will
exist. May the measure of your mind be vast and expanding.

Oh, stupidity is a loathsome corral! Gnaw and tug at the posts, and you will
slowly loosen them up. One day you’ll break the fence that held your
forebears captive. Gnaw and tug, redouble your effort!

The Third Transformation: Elevate well-being!

What is the difference between indifference and interest, boredom and thrill,
despair and bliss?

Pleasure! A few grains of this magic ingredient are dearer than a king’s
treasure, and we have it aplenty here in Utopia. It pervades into everything
we do and everything we experience. We sprinkle it in our tea.

The universe is cold. Fun is the fire that melts the blocks of hardship and
creates a bubbling celebration of life.

It is the birth right of every creature, a right no less sacred for having been
trampled upon since the beginning of time.

There is a beauty and joy here that you cannot fathom. It feels so good that
if the sensation were translated into tears of gratitude, rivers would overflow.

I reach in vain for words to convey to you what it all amounts to… It’s like a
rain of the most wonderful feeling, where every raindrop has its own unique
and indescribable meaning – or rather a scent or essence that evokes a whole
world… And each such evoked world is subtler, richer, deeper, more
palpable than the totality of what you have experienced in your entire life.

I will not speak of the worst pain and misery that is to be got rid of; it is too
horrible to dwell upon, and you are already aware of the urgency of
palliation. My point is that in addition to the removal of the negative, there
is also an upside imperative: to enable the full flourishing of enjoyments that
are currently out of reach.

The roots of suffering are planted deep in your brain. Weeding them out
and replacing them with nutritious crops of well-being will require advanced
skills and instruments for the cultivation of your neuronal soil. But take
heed, the problem is multiplex! All emotions have a natural function. Prune
carefully lest you reduce the fertility of your plot.

Sustainable yields are possible. Yet fools will build fools’ paradises. I
recommend you go easy on your paradise-engineering until you have the
wisdom to do it right.

Oh, what a gruesome knot suffering is! Pull and tug on those loops, and you
will gradually loosen them up. One day the coils will fall, and you will
stretch out in delight. Pull and tug, and be patient in your effort!

May there come a time when rising suns are greeted with joy by all the living
creatures they shine upon.

*

How do you find this place? How long will it take to get here?

I can pass you no blueprint for Utopia, no timetable, no roadmap. All I can
give you is my assurance that there is something here, the potential for a
better life.

If you could visit me here for but a day, you would henceforth call this place
your home. This is the place where you belong. Ever since one hairy
creature picked up two flints and began knocking them together to make a
tool, this has been the direction of your unknown aspiration. Like Odysseus
you must journey, and never cease journeying, until you arrive upon this
shore.

“Arrive?” you say; “But isn’t the journey the destination? Isn’t Utopia a
place that doesn’t exist? And isn’t the quest for Utopia, as witnessed
historically, a dangerous folly and an incitement to mischief?”

Friend, that is not such a bad way for you to think about it. To be sure,
Utopia is not a location or a form of social organization.

The blush of health on a convalescent’s cheek. The twinkling of the eye in a
moment of wit. The smile of a loving thought… Utopia is the hope that the
scattered fragments of good that we come across from time to time in our
lives can be put together, one day, to reveal the shape of a new kind of life.
The kind of life that yours should have been.

I fear that the pursuit of Utopia will bring out the worst in you. Many a
moth has been incinerated in its pursuit of a brighter future.

Seek the light! But approach with care – swerve if you smell your wingtips
singeing. Light is for seeing, not dying.

When you embark on this quest, you will encounter rough seas and hard
problems. To prevail will take your best science, your best technology, and
your best politics. Yet each problem has a solution. My existence breaks no
law of nature. The materials are all there. Your people must become
master builders, and then you must use these skills to build yourselves up
without crushing your cores.

*

What is Suffering in Utopia? Suffering is the salt trace left on the cheeks of those
who were around before.

What is Tragedy in Utopia? There is tragedy in Snowman’s melting. Mass
murders are not required.

What is Imperfection in Utopia? Imperfection is the measure of our respect for
things as they are and for their history.

What is Body in Utopia? Body is a pair of legs, a pair of arms, a trunk and a
head, all made of flesh. Or not, as the case may be.

What is Society in Utopia? Society is a never-finished tapestry, its weavers equal
to its threads – the parts and patterns an inexhaustible bourne of beauty.

What is Death in Utopia? Death is the darkness that ultimately surrounds all
life.

What is Guilt in Utopia? Guilt is our knowledge that we could have created
Utopia sooner.

*

We love life here every instant. Every second is so good that it would blow
our minds had their amperage not been previously increased. My
contemporaries and I bear witness, and we request your aid. Please, help us
come into existence! Please, join us! Whether this tremendous possibility
becomes reality depends on your actions. If your empathy can perceive at
least the outlines of the vision I am describing, then your ingenuity will find a
way to make it real.

Human life, at its best, is fantastic. I’m asking you to create something even
greater. Life that is truly humane.

Yours sincerely,
Your Possible Future Self


See also a musicalized video rendition of this piece by Mario Montano: Letter From Utopia


Analysis

Nick Bostrom is a prominent transhumanist philosopher and academic who works at Oxford’s Future of Humanity Institute. An incredibly prolific writer, Nick has a very wide and comprehensive worldview. I find his work extremely valuable and worth diving into. Letter From Utopia is one of my favorite works of his, as it encompasses what David Pearce called “The Three Supers of Transhumanism“: Super-Intelligence, Super-Longevity, and Super-Happiness (cf. Triple-S Genetic Counseling). Bostrom also has other amazing stories and essays (such as The Fable of the Dragon-Tyrant, cf. story video rendition by CGP Grey: video), but Letter From Utopia takes the cake for not leaving behind anything of crucial importance.

Alas, despite Bostrom’s far-reaching contributions, many argue that Nick’s most important impact has been in the field of AI Alignment (cf. Superintelligence: Paths, Dangers, Strategies). In 2009 AI safety research was perceived to be a fringe concern of sci-fi aficionados and weirdos. Today, partly thanks to Bostrom (along with Yudkowsky, Chalmers, and others), many top journals publish serious work in this area.

I worry that this is not as good as it may seem. Nick Bostrom’s name is first and foremost associated with AI safety, followed by the Simulation Argument and Existential Risk, and only later by his extensive work on all other areas of transhumanism. For example, if you search Youtube for his name, you will see that of the top 20 results, 15 concern AI safety/digital superintelligence. Of the remaining 5, 3 are about the Simulation Argument, 1 is about agnosticism, and 1 is CGP Grey’s Dragon-Tyrant video. Where are the Triple-S videos?

nick_bostrom_top_results

I remembered that I encountered the work of both David and Nick when I was 16, googling terms like consciousness, AI, psychedelics, and far future. I was drawn to both of them, though I particularly liked David’s focus on ending suffering as a priority and his acknowledgment of the scientific significance of altered states of consciousness. I thought that their work was complementary rather than redundant. Alas, Bostrom is far more well known than Pearce, perhaps due to his success as both a fringe philosopher and a mainstream academic. In contrast, David dropped out of Oxford out of frustration with the academic community; the analytic philosophy of the time was not empirical, and it focused on language use rather than real philosophical questions, including the nature of suffering, psychedelics, and physical causality (e.g. “Philosophy may in no way interfere with the actual use of language, it can in the end only describe it. For it cannot give it any foundation either. It leaves everything as it is. It also leaves mathematics as it is, and no mathematical discovery can advance it.” – Wittgenstein). Bostrom, unlike Pearce, has the blessing of Ra, the God of optionality, superlativity, status legibility, and groundless prestige. And yet, it was David’s conversation with Nick that gave rise to the creation of the World Transhumanist Association, and provided one of the most important memetic Schelling points of the early 2000s. Alas, David is not focused on AI Safety. Why?

People in the transhumanist community accuse David of not getting it. David, after all, is not a mathematician, computer scientist, or physicist; he is merely a philosopher. I must confess that the very first time I met David Pearce in person I got the sense that (1) he was an incredibly well-read and creative genius in most areas of philosophy, and yet (2) naïve and unenlightened in the field of AI. As a fan of his work, and having co-founded the Stanford Transhumanist Association a couple of months earlier, I thought to invite him to give a talk at Stanford (see: David Pearce at Stanford – 2011).

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David Pearce and the officers of the Stanford Transhumanist Association (December 1st 2011) at Palo Alto’s Chinese Vegan restaurant Garden Fresh, before David’s talk.

We had a lively conversation while eating dinner at a Chinese vegan restaurant before the event along with other members of the Association. I recall that he checked all of the right boxes when it came to personal identity (Open/Empty Individualism), ethics (consequentialism), physics (Everettian multiverse), psychedelia (they disclose new varieties of qualia), evolution (modern synthesis; selfish gene), social signaling theory (Mating Mind and sexual selection theory), and more (see his Reddit AMA). And yet, how could he dare to say that a digital computer would never be conscious? Meeting a brilliant thinker who had a better grasp of my favorite topics than I did and yet would try to hit on one of my core load-bearing beliefs was uncomfortable and unexpected. I dismissed his take on AI as that of a fuzzy thinker (at least in this area); I reassured myself by recalling that it was me who was studying AI academically at a top US institution and not him. Little did I know that over the next few years, and after hanging out with him in person for over 20 cumulative hours, he would finally change my mind- and worldview- concerning this whole field. If it wasn’t for him, I suspect I would have jumped on the bandwagon of AI-as-the-top-priority (cf. Altruists Should Prioritize Artificial Intelligence). Thankfully, I was already extremely interested in consciousness and didn’t have it in me to dismiss it. Additionally, my interest in personal identity reduced my (relative) interest in longevity research (at least as the top priority), for if we are all one consciousness, dying is more akin to forgetting a timeline than a true ontological death. The instrumental value of intelligence, however, ought not to be taken for granted, which is why I now advocate for a twin approach of improving subjective wellbeing while retaining critical insight. Figuring out that consciousness required more than digital computation utterly transformed my approach to transhumanism, and I largely credit this change to my conversations with David.

 

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Later on I met Mike Johnson, Romeo Stevens, and a number of other top thinkers in the field of consciousness who could both understand the genuine problems consciousness poses and at the same time grasp the broader transhumanist meme-plex, transcend it, and include it (cf. Why I think the Foundational Research Institute should rethink its approach). Thus we founded the Qualia Research Institute, in order to bring a new full-stack meme-plex where consciousness – and valence – are front and center. Alas, we have experienced some resistance…

AI safety is sexy. If you are a smart, industrious, open-minded, and systematizing undergraduate, studying AI gives you access to a wide circle of really fun people to hang out in. It also signals intelligence, sober-mindedness, and stoicism. It gives you both an in into smart cool kid circles, and a profitable career in Silicon Valley. It allows you to straddle the world of normies and cutting-edge thinkers.

But, crucially, you have to consider the opportunity cost that comes from directing such a large fraction of hyper-intelligent young altruistic systematizers to this problem. The field is plagued with misconceptions about pleasure and value; Eliezer Yudkowsky’s Fun Theory suffers from the severe delusion that value comes from the intentional object of experience, rather than from its phenomenal character. Brian Tomasik’s (admittedly tongue-in-cheek) People for the Ethical Treatment of Reinforcement Learners is seemingly unaware of the fact that neuroscience has found that pleasure/suffering and reinforcement learning are doubly dissociated. Pleasure is not reinforcement, and until you grasp this, your ethical models will output nonsense.

Tongue-in-cheek, perhaps AI risk is a real threat. Not because of the usual reasons, but because it siphons out top brain power into a relatively sterile field, leaving vast amounts of unclaimed marginal value in the fields of rejuvenation research and valence technologies by the wayside.

In light of all of this, I would want to advocate for the reinvigoration of the broader transhumanist meme-plex, now updated with a post-Galilean understanding of consciousness. Writers, animators, Youtubers, and philosophers ought to collaborate in creating more balanced Triple-S Transhumanist outreach in the form of widely consumable media. This, I think, is the path forward.

Triple S Genetic Counseling: Predicting Hedonic-Set Point with Commercial-Grade DNA Testing as an Effective Altruist Project

The term “Transhumanism” has many senses. It is a social movement, a philosophy, a set of technologies, and a conceptual rallying flag. David Pearce pins down the core sentiment behind the term like this:

If we get things right, the future of life in the universe can be wonderful beyond the bounds of human imagination: a “triple S” civilisation of superlongevity, superintelligence and superhappiness.

– David Pearce, in The 3 Supers

The concept of a “triple S” civilization is very widely applicable. For example, one can imagine future smart homes designed with it in mind. Such smart homes would have features to increase your longevity (HEPA filters, humidity control, mold detectors, etc.), increase your intelligence (adaptive noise-canceling, optimal lighting, smart foods), and happiness (mood-congruent lighting, music, aromas, etc.). Since there are trade-offs between these dimensions, one could specify how much one values each of them in advance, and the smart home would be tasked with maximizing a utility function based on a weighted average between the three S’s.

Likewise, one could apply the “triple S” concept to medical care, lifestyle choices, career development, governance, education, etc. In particular, one could argue that a key driver for the realization of a triple S civilization would be what I’d like to call “triple S genetic counseling.” In brief, this is counseling for prospective parents in order to minimize the risks of harming one’s children by being oblivious to the possible genetic risk for having a reduced longevity, intelligence, or happiness. Likewise, in the more forward-looking transhumanist side of the equation, triple S genetic counseling would allow parents to load the genetic dice in their kid’s favor in order to make them as happy, long-lived, and smart as possible.

Genetic counseling, as an industry, is indeed about to explode (cf. Nature’s recent article: Prospective parents should be prepared for a surge in genetic data). Predictably, there will be a significant fraction of society that will question the ethics of e.g. preimplantation genetic diagnosis for psychological traits. In practice, parents who are able to afford it will power ahead, for few prospective parents truly don’t care about the (probabilistic) well-being of their future offspring. My personal worry is not so much that this won’t happen, but that the emphasis will be narrow and misguided. In particular, both predicting health and intelligence based on sequenced genomes are very active areas of research. I worry that happiness will be (relatively) neglected. Hence the importance of emphasizing all three S’s.

In truth, I think that predicting the hedonic set-point of one’s potential future kids (i.e. the average level of genetically-determined happiness) is a relatively more important project than predicting IQ (cf. A genome-wide association study for extremely high intelligenceBGI). In addition, I anticipate that genetic-based models that predict a person’s hedonic set-point will be much more accurate than those that predict IQ. As it turns out, IQ is extremely polygenetic, with predictors diffused across the entire genome, and it is a very evolutionary recent axis of variance across the population. Predictors of hedonic-set point (such as the “pain-knob gene” SCN9A and it’s variants), on the other hand, are ancient and evolutionarily preserved across the phylogenetic tree. This makes baseline happiness a likely candidate for having a straight-forward universal physiological implementation throughout the human population. Hence my prediction that polygenetic scores of hedonic-set point will be much more precise than those for IQ (or even longevity).

Given all of the above, I would posit that a great place to start would be to develop a model that predicts hedonic set-point using all of the relevant SNPs offered by 23andMe*.  Not only would this be “low-hanging fruit” in the field of genetic counseling, it may also be a project that is way up there, close to the top of the “to do” list in Effective Altruism (cf. Cause X; Google Hedonics).

I thought about this because I saw that 23andMe reports on health predispositions based on single SNPs. From a utilitarian point of view, of particular interest are SNPs related to the SCN9A gene. For example, I found that 23andMe has the rs6746030 SNP, which some studies show can account for a percentage of the variance associated with pain in Parkinson’s and other degenerative diseases. The allele combination A/A is bad, making you more prone to experience pain intensely. This is just one SNP, though, and there ought to be a lot of other relevant SNPs, not only of the SCN9A gene but elsewhere too (e.g. involved in MAO enzymes, neuroplasticity, and pleasure centers innervation).

Concretely, the task would involve making two models and then combining them:

The first model uses people’s responses to 23andMe surveys to come up with a good estimate of a person’s hedonic set-point. Looking at some of the questions they ask, I would argue that there are more than enough dimensions to model how people vary in their hedonic set-point. They ask about things such as perception of pain, perception of spiciness, difficulty sleeping, stress levels, whether exercise is pleasant, etc. From a data science point of view, the challenge here is that number of responses provided by each participant is very variable; some power users respond to every question (and there are hundreds and hundreds), while most people respond to a few questions only, and a substantial minority respond to no questions at all. Most likely, the distribution of responses per participant follows a power law. So the model to build here has to be resilient against absent data. This is not an insurmountable problem, though, considering the existence of Bayesian Networks, PGMs, and statistical paradigms like Item Response Theory. For this reason, the model would need to both predict the most likely hedonic set-point of each participant, and provide confidence intervals specific to the participant based on the quality and relevance of the questions answered.

The second model would involve clustering and dimensionality reduction applied to the SNPs that are likely to be relevant for hedonic set-point. For example, one dimension would likely be a cluster of SNPs that are associated with “maximum intensity of pain”, another might be “how quickly pain subsides once it’s stimulated”, another “how much does pleasure counter-balance pain”, and so on. Each of these dimensions is likely to be determined by different neural circuits, and interact in non-linear ways, so they deserve their own separate dimension.

And finally, one would make a third model that combines the two models above, which predicts the hedonic set-point of a person derived from the first model using the genetic dimensions found by the second model. If you are an up-and-coming geneticist, I would like to nudge you in the direction of looking into this. As a side effect, you might as well get filthy rich in the process, as the genetic counseling field explodes in the next decade.


Bonus Content: What About Us?

Admittedly, many people will note that predicting a fraction of the variance of people’s hedonic set point with commercial DNA testing products will only really alleviate suffering in the medium to long term. The people who will benefit from this technology haven’t been born yet. In the meantime, what do we do about the people who currently have low hedonic set-points? Here is a creative, politically incorrect, and enticing idea:

Let’s predict which recreational drugs have the best cost-benefit profile for individuals based on their genetic makeup.

It is no secret that people react differently to drugs. 23andMe, among others, is currently doing research to predict your particular reaction to a drug based on your genetic makeup (cf. 23andMe can now tell you how you’ll react to 50+ common drugs). Unfortunately for people with anxiety, depression, chronic pain, and other hedonic tone illnesses, most psychiatric drugs are rather subtle and relatively ineffective. No wonder, compared to heroin, an SSRI is not likely to make you feel particularly great. As David Pearce argued in his essay Future Opioids, there is substantial evidence that many people who become addicts are driven to take recreational substances due to the fact that their endogenous opioid system is dysfunctional (e.g. they may have bad variants of opioid receptors, too many endorphin-degrading enzymes, etc.). The problem with giving people hard drugs is not that they don’t work in the short term; it is that they tend to backfire in the long-term and have cumulative negative health effects. As an aside, from the pharmaceutical angle, my main interest is the development of Anti-tolerance Drugs, which would allow hard drugs to work as mood-enhancers indefinitely.

This is not to say that there aren’t lucky people for whom the cost-benefit ratio of taking hard drugs is, in fact, rather beneficial. In what admittedly must have been a tongue-in-cheek marketing move, in the year 2010 the genetic interpretation company Knome (now part of Tute Genomics) studied Ozzy Osbourne‘s entire genome in order to determine how on earth he has been able to stay alive despite the gobs and gobs of drugs he’s taken throughout his life. Ozzy himself:

“I was curious, [g]iven the swimming pools of booze I’ve guzzled over the years—not to mention all of the cocaine, morphine, sleeping pills, cough syrup, LSD, Rohypnol…you name it—there’s really no plausible medical reason why I should still be alive. Maybe my DNA could say why.”

Ozzy Osbourne’s Genome (Scientific American, 2010)

Tentatively, Knome scientists said, Ozzy’s capacity to drink entire bottles of Whisky and Gin combined with bowlfuls of cocaine and multiple packs of cigarettes over the course of… breakfast… without ending up in the hospital may be due to novel mutations in his alcohol dehydrogenase gene (ADH4), as well as, potentially, the gene that codes for CLTCL1, a protein responsible for the intake of extra-cellular material into the cell’s inside. These are wild speculations, to be clear, but the general idea is brilliant.

Indeed, not everyone reacts in the same way to recreational drugs. A recent massive study on the health effects of alcohol funded by the Bill and Melinda Gates Foundation (cf. No amount of alcohol is good for your overall health) suggests that alcohol is bad for one’s health at every dosage. This goes against the common wisdom backed up with numerous studies that light-drinkers (~1 alcohol unit a day) live longer and healthier lives than teetotalers. The new study suggests that this is not a causal effect of alcohol. Rather, it so happens that a large fraction of teetotalers are precisely the kind of people who react very badly to alcohol as a matter of poor metabolism. Hence, teetotalers are not unhealthy because they avoid alcohol; they avoid alcohol because they are unhealthy, which explains their shorter life expectancy on average. That said, the study did show that 1 alcohol unit a day is, although damaging, very minimally so:

Anyhow, the world’s cultural fascination with alcohol is bizarre to me, considering the existence of drugs that have a much better hedonic and cost-benefit profile (cf. State-Space of Drug Effects). Perhaps finding out with genetic testing that you are likely to be an above-average alcohol metabolizer might be good to lessen your worry about having a couple of drinks now and then. But the much bigger opportunity here would be to allow you to find drugs that you are particularly compatible with. For example, a genetic test might determine based on a polygenetic score that you might benefit a whole lot from taking small amounts of e.g. Khat  (or some such obscure and relatively benign euphoriant). That is, that your genetic make-up is such that Khat will be motivation enhancing, empathy-increasing, good for your heart and lungs, reduce the rate of dopamine neuron death, etc. while at the same time producing little to no hangovers, no irritability, no sleep issues, or social dysfunction. Even though you may have thought that you are “not an uppers person”, perhaps that’s because, genetically, every other upper you have ever tried is objectively terrible for your health. But Khat wouldn’t be. Wouldn’t this information be useful? Indeed, I would posit, this might be a great step in the right direction in order to achieve the goal of  Wireheading Done Right.


*23andMe is here used as a shorthand for services in general like this (including Ancestry, Counsyl, Natera, etc.)

Featured image credit: source.

A Non-Circular Solution to the Measurement Problem: If the Superposition Principle is the Bedrock of Quantum Mechanics Why Do We Experience Definite Outcomes?

Source: Quora question – “Scientifically speaking, how serious is the measurement problem concerning the validity of the various interpretations in quantum mechanics?


David Pearce responds [emphasis mine]:

It’s serious. Science should be empirically adequate. Quantum mechanics is the bedrock of science. The superposition principle is the bedrock of quantum mechanics. So why don’t we ever experience superpositions? Why do experiments have definite outcomes? “Schrödinger’s cat” isn’t just a thought-experiment. The experiment can be done today. If quantum mechanics is complete, then microscopic superpositions should rapidly be amplified via quantum entanglement into the macroscopic realm of everyday life.

Copenhagenists are explicit. The lesson of quantum mechanics is that we must abandon realism about the micro-world. But Schrödinger’s cat can’t be quarantined. The regress spirals without end. If quantum mechanics is complete, the lesson of Schrödinger’s cat is that if one abandons realism about a micro-world, then one must abandon realism about a macro-world too. The existence of an objective physical realm independent of one’s mind is certainly a useful calculational tool. Yet if all that matters is empirical adequacy, then why invoke such superfluous metaphysical baggage? The upshot of Copenhagen isn’t science, but solipsism.

There are realist alternatives to quantum solipsism. Some physicists propose that we modify the unitary dynamics to prevent macroscopic superpositions. Roger Penrose, for instance, believes that a non-linear correction to the unitary evolution should be introduced to prevent superpositions of macroscopically distinguishable gravitational fields. Experiments to (dis)confirm the Penrose-Hameroff Orch-OR conjecture should be feasible later this century. But if dynamical collapse theories are wrong, and if quantum mechanics is complete (as most physicists believe), then “cat states” should be ubiquitous. This doesn’t seem to be what we experience.

Everettians are realists, in a sense. Unitary-only QM says that there are quasi-classical branches of the universal wavefunction where you open an infernal chamber and see a live cat, other decohered branches where you see a dead cat; branches where you perceive the detection of a spin-up electron that has passed through a Stern–Gerlach device, other branches where you perceive the detector recording a spin-down electron; and so forth. I’ve long been haunted by a horrible suspicion that unitary-only QM is right, though Everettian QM boggles the mind (cfUniverseSplitter). Yet the heart of the measurement problem from the perspective of empirical science is that one doesn’t ever see superpositions of live-and-dead cats, or detect superpositions of spin-up-and-spin-down electrons, but only definite outcomes. So the conjecture that there are other, madly proliferating decohered branches of the universal wavefunction where different versions of you record different definite outcomes doesn’t solve the mystery of why anything anywhere ever seems definite to anyone at all. Therefore, the problem of definite outcomes in QM isn’t “just” a philosophical or interpretational issue, but an empirical challenge for even the most hard-nosed scientific positivist. “Science” that isn’t empirically adequate isn’t science: it’s metaphysics. Some deeply-buried background assumption(s) or presupposition(s) that working physicists are making must be mistaken. But which? To quote the 2016 International Workshop on Quantum Observers organized by the IJQF,

“…the measurement problem in quantum mechanics is essentially the determinate-experience problem. The problem is to explain how the linear quantum dynamics can be compatible with the existence of our definite experience. This means that in order to finally solve the measurement problem it is necessary to analyze the observer who is physically in a superposition of brain states with definite measurement records. Indeed, such quantum observers exist in all main realistic solutions to the measurement problem, including Bohm’s theory, Everett’s theory, and even the dynamical collapse theories. Then, what does it feel like to be a quantum observer?

Indeed. Here I’ll just state rather than argue my tentative analysis.
Monistic physicalism is true. Quantum mechanics is formally complete. There is no consciousness-induced collapse the wave function, no “hidden variables”, nor any other modification or supplementation of the unitary Schrödinger dynamics. The wavefunction evolves deterministically according to the Schrödinger equation as a linear superposition of different states. Yet what seems empirically self-evident, namely that measurements always find a physical system in a definite state, is false(!) The received wisdom, repeated in countless textbooks, that measurements always find a physical system in a definite state reflects an erroneous theory of perception, namely perceptual direct realism. As philosophers (e.g. the “two worlds” reading of Kant) and even poets (“The brain is wider than the sky…”) have long realised, the conceptual framework of perceptual direct realism is untenable. Only inferential realism about mind-independent reality is scientifically viable. Rather than assuming that superpositions are never experienced, suspend disbelief and consider the opposite possibility. Only superpositions are ever experienced. “Observations” are superpositions, exactly as unmodified and unsupplemented quantum mechanics says they should be: the wavefunction is a complete representation of the physical state of a system, including biological minds and the pseudo-classical world-simulations they run. Not merely “It is the theory that decides what can be observed” (Einstein); quantum theory decides the very nature of “observation” itself. If so, then the superposition principle underpins one’s subjective experience of definite, well-defined classical outcomes (“observations”), whether, say, a phenomenally-bound live cat, or the detection of a spin-up electron that has passed through a Stern–Gerlach device, or any other subjectively determinate outcome. If one isn’t dreaming, tripping or psychotic, then within one’s phenomenal world-simulation, the apparent collapse of a quantum state (into one of the eigenstates of the Hermitian operator associated with the relevant observable in accordance with a probability calculated as the squared absolute value of a complex probability amplitude) consists of fleeting uncollapsed neuronal superpositions within one’s CNS. To solve the measurement problem, the neuronal vehicle of observation and its subjective content must be distinguished. The universality of the superposition principle – not its unexplained breakdown upon “observation” – underpins one’s classical-seeming world-simulation. What naïvely seems to be the external world, i.e. one’s egocentric world-simulation, is what linear superpositions of different states feel like “from the inside”: the intrinsic nature of the physical. The otherwise insoluble binding problem in neuroscience and the problem of definite outcomes in QM share a solution.

Absurd?
Yes, for sure: this minimum requirement for a successful resolution of the mystery is satisfied (“If at first the idea is not absurd, then there is no hope for it”– Einstein, again). The raw power of environmentally-induced decoherence in a warm environment like the CNS makes the conjecture intuitively flaky. Assuming unitary-only QM, the effective theoretical lifetime of neuronal “cat states” in the CNS is less than femtoseconds. Neuronal superpositions of distributed feature-processors are intuitively just “noise”, not phenomenally-bound perceptual objects. At best, the idea that sub-femtosecond neuronal superpositions could underpin our experience of law-like classicality is implausible. Yet we’re not looking for plausible theories but testable theories. Every second of selection pressure in Zurek’s sense (cf. “Quantum Darwinism”) sculpting one’s neocortical world-simulation is more intense and unremitting than four billion years of evolution as conceived by Darwin. My best guess is that interferometry will disclose a perfect structural match. If the non-classical interference signature doesn’t yield a perfect structural match, then dualism is true.

Is the quantum-theoretic version of the intrinsic nature argument for non-materialist physicalism – more snappily, “Schrödinger’s neurons” – a potential solution to the measurement problem? Or a variant of the “word salad” interpretation of quantum mechanics?
Sadly, I can guess.
But if there were one experiment that I could do, one loophole I’d like to see closed via interferometry, then this would be it.