I was wondering what your take is on the opioid crisis. Were not all concerned hedonistic pleasure seekers? — counterpunch

The underlying cause of the opioid crisis is that we are all born endogenous opioid addicts. The neurotransmitter system most directly involved in hedonic tone is the opioid system. Human and nonhuman animals are engineered by natural selection with no durable way to satisfy our cravings. Most exogenous opioid users are ineffectively self-medicating. Exogenous opioids just activate the negative-feedback mechanisms of the CNS. A solution to the opioid crisis is going to be complicated, long-drawn-out and messy. But ACKR3 receptor blockade potentially offers the prospect of hedonic uplift for all (cf. https://www.azolifesciences.com/news/20200622/New-LI383-molecule-can-help-treat-opioid-related-disorders.aspx). More research is urgently needed. Note I'm not (yet) urging everyone to get hold of ACKR3 receptor blockers. There are too many pitfalls and unknowns.

Have you seen that experiment where the orgasm centre of a rat's brain was plugged into a lever the rat could press, and it pressed the lever repeatedly until it starved to death? I was speaking more to the point that the unrestrained, hedonistic pursuit of pleasure has produced terrible consequences. And your answer is, they're seeking pleasure wrong? So, what's the right way?

Yes, humans are "playing god". Good. We should aim to be benevolent gods. — David Pearce

If we manage to survive the storm that's coming, that is.

the parasitic worm Onchocerca volvulus that causes onchocerciasis aka river blindness? — David Pearce

While it is possible to eliminate viruses or parasites that play no ecological role, to try and change a whole ecosystem is very risky. Perhaps you can understand why with a metaphor. Darwinian life is akin to capitalism. It's ugly, but it works. It works without anyone telling the system how to work, it self regulates. Your imagined life would be akin to centrally planned economy: it's nicer in theory but it doesn't work very well in practice because it relies on a few people at the top making the right decisions at all times, and they sometimes do mistakes, or just abuse of their position.

A decentralized, self-regulated system is more resilient than a centrally regulated system. And that's a dimension on which Darwinian life will always trump engineered life.

I hope I’m not too late to the party but I’ll start by asking a question relating to the debate between what I heard get called "Agent Neutral”and “Agent Relative” forms of Utilitarianism . Do you think we have any extra non-instrumental reason to minimize our own suffering or the suffering of our loved ones relative to the reason that we have to minimize the suffering of a complete stranger? Also, do you think that we have less non-instrumental reason to minimize the suffering of our enemies and people that we despise?

It's a question of timescales. Classical utilitarianism is often held to be agent‐neutral. But in the long run, it's unclear whether classical utilitarianism is consistent with a world of agents. For the classical utilitarian should be working towards an apocalyptic, AI-assisted utilitronium shockwave – some kind of all-consuming cosmic orgasm that maximises the abundance of bliss within our Hubble volume. Compare the homely dilemmas of the trolley problem. Intuitively, this kind of technological enterprise is centuries or millennia distant, so irrelevant to our lives. Yet temporal discounting is not an option for the strict classical utilitarian. Note that negative utilitarianism doesn’t entail this apocalyptic outcome. For the negative utilitarian, a transhuman civilisation based entirely on information-sensitive gradients of bliss will be ideal.

In the short-term, the practical implications of a classical utilitarian ethic are less dramatic. Given human nature, agent‐neutrality is psychologically impossible. Any attempt by legislators to enforce agent-neutrality would probably lead to worse consequences, i.e. more unhappy people. Likewise, if one is an aspiring effective altruist who gives, say, 10% of one's income to charity, then beating oneself up about not charitably giving away 90% of one's income is counterproductive. Most likely, heroic self-sacrifice will lead to "burn out" - an un-utilitarian outcome. So in practice, being a (classical or negative) utilitarian involves all sorts of messy compromises. But then real life is messy – no news here.

Should one aspire to minimise the suffering of the people we despise as much as loved ones? Yes. In practice, such impartial benevolence is impossible. But getting our theory of personal identity right can help:
https://www.hedweb.com/quora/2015.html#individualism

Have you seen that experiment where the orgasm centre of a rat's brain was plugged into a lever the rat could press, and it pressed the lever repeatedly until it starved to death? — counterpunch

Yes:
https://www.wireheading.com/hypermotivation.html
Wireheading is not a viable solution to the problem of suffering.

the unrestrained, hedonistic pursuit of pleasure has produced terrible consequences. And your answer is, they're seeking pleasure wrong? So, what's the right way? — counterpunch

In my view, the right way to seek pleasure is through genetic recalibration of the negative-feedback mechanisms of the hedonic treadmill:
https://www.gradients.com

In my view, the right way to seek pleasure is through genetic recalibration of the negative-feedback mechanisms of the hedonic treadmill: — David Pearce

Good answer. Design happier healthier babies! But where to stop?

Good answer. Design happier healthier babies! But where to stop? — counterpunch

We could engineer a world with hedonic range of 0 to +10 as distinct from our -10 to 0 to +10. But we could also engineer a civilisation of (schematically) +10 to +20 or (eventually) +90 to +100. Critics protest that a notional civilisation with a hedonic range of +90 to +100 would "lack contrast" compared to the rich tapestry of Darwinian life. But a hedonic range of, say, +70 to +100 will be feasible too.

A decentralized, self-regulated system is more resilient than a centrally regulated system. And that's a dimension on which Darwinian life will always trump engineered life. — Olivier5

If a global consensus emerges for compassionate stewardship of the living world, then the problem of suffering is tractable. We're not going to run out of computer power. Every cubic metre of the planet will shortly be accessible to surveillance and micromanagement – although synthetic gene drives allow the ecological option of remote management too.

On the one hand, we can imagine dystopian Orwellian scenarios – some kind of totalitarian global panopticon. But biotech also gives us the tools to create a world based on genetically preprogrammed gradients of bliss. In a world animated by information-sensitive gradients of well-being, there are no "losers" in the Darwinian sense of the term. Members of today's predatory species can benefit no less than their victims:
https://www.hedweb.com/quora/2015.html#stopkilling

Critics protest that a notional civilisation with a hedonic range of +90 to +100 would "lack contrast" compared to the rich tapestry of Darwinian life. — David Pearce

I suspect that, were we to live in such a civilisation, our mean hedonistic expectation will simply adjust to somewhere around 95. Anything below 95 will be deemed a disappointment if not a "micro-agression", and anything above 95 will get recorded as satisfying and truly a pleasure. In short, I suspect the gradient is relative, not absolute.

I think it is feasible. Horrible, that everyone would go around grinning all day, but feasible to genetically engineer humans to be healthier, happier. We could have wings! But if people weren't prone to chronic depression half the time where would the philosophers come from? For me, happiness is transitory, and arises from positive contrasts. I think that's why people like shopping. They buy something new and it cheers them for a while, and then fades into the background of 'stuff I've got.' I find it very difficult to conceive of happiness as a constant state, and perhaps self referentially, believe there's something worthwhile about my misery. That said, I would like wings. That would be cool!

My point was rather that no centralized decision making system can be perfect in its implementation (although they tend to look perfect on paper, but that's often due to their naivety) and that such systems tend to fossilize or at least age poorly over time. Too conservative, not addaptative enough. Darwinian systems are better from this point of view, more evolutionary and more creative.

because I lean toward idealism — Metaphysician Undercover

The only kind of idealism I take seriously just transposes the entire mathematical apparatus of modern physics onto an experientialist ontology: non-materialist physicalism (cf. https://www.physicalism.com). I used to assume the conjecture that the mathematical formalism of quantum field theory describes fields of sentience was untestable. How could we ever know what (if anything!) it's like to be, say, superfluid helium?
I now reckon such pessimism is premature:
https://www.hedweb.com/quora/2015.html#conpredicts

At the risk of stating the obvious, no one sympathetic to the abolitionist project need buy into my idiosyncratic speculations on quantum mind and the intrinsic nature of the physical.

I find it very difficult to conceive of happiness as a constant state — counterpunch

As a temperamentally depressive negative utilitarian, I find lifelong happiness hard to conceive too. But a civilisation based on gradients of superhuman bliss is technically feasible. IMO, our impending mastery of the pleasure-pain axis makes such a future civilisation likely, too, though I vacillate on credible timescales.

"Information-sensitive gradients of well-being" is more of a mouthful than "constant happiness". Nonetheless the distinction is practically important. Despite my normal British prudery, I sometimes give the example of making love. Lovemaking has peaks and troughs. But done properly, lovemaking is generically enjoyable for both parties throughout. The challenge is to elevate our hedonic range and default hedonic tone so that life is generically enjoyable – despite the dips.

I suspect that, were we to live in such a civilisation, our mean hedonistic expectation will simply adjust to somewhere around 95. Anything below 95 will be deemed a disappointment if not a "micro-agression", and anything above 95 will get recorded as satisfying and truly a pleasure. In short, I suspect the gradient is relative, not absolute. — Olivier5

The misconception that pain and pleasure are relative is tenacious. But we need only consider the plight of severe chronic depressives to recognise that it's false. Chronic depressives never cease to suffer even though some of their days are less dreadful than others. Hyperthymics lie at the opposite extreme.

My point was rather that no centralized decision making system can be perfect in its implementation — Olivier5

Phasing out the biology of suffering in favour of life based on information-sensitive gradients of well-being can be "perfect" in its implementation in the same sense that getting rid of Variola major and Variola minor was "perfect" in its implementation. Without Variola major and Variola minor, there is no more smallpox. Without the molecular signature of experience below hedonic zero, there can be no more suffering. It's hard to imagine, I know.

So a higher average of happiness. Okay, but how close is genetic science to identifying the specific genes and/or areas of the brain they want alter? I'm not the 'playing God' hysterical type, but a procedure performed on me, with my informed consent would be one thing, but on an individual as yet unborn, and not only that, but to wrest the entire genetic future of humanity from biology? To alter his children's and his children's children's genetics forever after? That's a lot to take on, and morally difficult to justify. That said, I would like wings! That would put me way out front in the intergenerational genetic arms race that would surely ensue!!

Okay, but how close is genetic science to identifying the specific genes and/or areas of the brain they want alter? — counterpunch

It's complicated: https://www.hedweb.com/quora/2015.html#devote
But which version of the ADA2b deletion variant, COMT gene, serotonin transporter gene, FAAH & FAAH OUT gene (cf. https://www.irishtimes.com/life-and-style/health-family/the-intriguing-link-between-sensitivity-to-physical-and-psychological-pain-1.3846825) and SCN9A gene (cf. https://www.wired.com/2017/04/the-cure-for-pain/) would you want for your future children?
As somatic gene therapy matures for existing humans, which allelic combinations would you choose for yourself?

Of course, bioconservatives would maintain that the genetic crapshoot of traditional sexual reproduction is best. If they prevail, then a Darwinian biology of misery and malaise will persist indefinitely.

Hi David, gene editing to the degree you are proposing has not been done to a real human (except perhaps one in China). What if it's the case that the way the phenotype and epigenetic results of gene editing work, it creates less happy humans, who suffer more? We are betting that the practical application will somehow prove out the theories. What if it doesn't and gene editing too has become a dead end?

Preimplantation genetic diagnosis and screening is worth distinguishing from gene-editing. Ratcheting up hedonic range, hedonic set-points and pain thresholds in human and nonhuman animal populations would certainly be feasible using nothing but preimplantation genetic screening alone; but germline gene-editing will be quicker.

The rogue He Jiankui case was indeed unfortunate. Well-controlled prospective trials will take time. So will preparing the ethical-ideological groundwork. Most people are accepting (if uncomfortable) with the idea of genetic interventions to prevent, say, Huntingdon's, Tay-Sachs or sickle cell disease, but not yet receptive to the prospect of selecting higher pain-thresholds or hedonic set-points.

I'm sceptical gene-editing could prove to be a dead-end. Modulating even a handful of genes such as the half-dozen I mentioned in my reply to counterpunch above could create radical hedonic uplift across the biosphere. Rather, I'm glossing over all sorts of risks, complications and unknowns – permissible in a philosophy forum when we are discussing the fundamental principles of a biohappiness revolution, but not if-and-when real-world trials begin.

It's hard to imagine, I know. — David Pearce

It's also very hard to do, I know.

It's also very hard to do, I know. — Olivier5

Indeed. At times, my heart sinks at the challenges. But if we don't upgrade our legacy code, then pain and suffering will continue indefinitely.

We could start with something easier, like improve human and animal welfare and combat climate change.

Without the molecular signature of experience below hedonic zero, there can be no more suffering. It's hard to imagine, I know. — David Pearce

What of the quote "Some of the worst things in my life never even happened" by Mark Twain. The mind is more than malleable enough to deliver levels and depths of suffering on par with physical torture. How will gene editing make us feel toward tragedy, such as death, etc? If we no longer even have the ability to be distraught at that which is tragic.. is this really progress toward humanity? If you're ill or injured, pain can sometimes be the only thing to inform you something's not quite right. If it becomes merely a vague "numbness" of no severity or actual discomfort, especially if it doesn't scale up like biological pain does.. well, is that really safe?

I've heard testimonies of people who became addicted to strong opiate painkillers, some by major surgery, some out of recreation. The pleasure rewired their body so greatly that when they had to come off of them cold turkey it was described as "the worse pain imaginable" as if "[one's] bones were being crushed into dust" throughout the entirety of their body. What if gene-editing doesn't remove suffering but simply re-calibrates it in an unfavorable way?

As you may have gathered, I'm a "better the devil you know" kind of guy when it comes to these matters.. a keeper of Pandora's Box, if you will.

If you're ill or injured, pain can sometimes be the only thing to inform you something's not quite right. If it becomes merely a vague "numbness" of no severity or actual discomfort, especially if it doesn't scale up like biological pain does.. well, is that really safe? — Outlander

You can't "edit out" human nature, without resulting in either a passive animal or monotonous robot. Do you really think, if this results in the success you envision, those rich and often less-inclined toward human well being will let it continue toward the masses? Why would they? You would simply usher in an age of Greek Mythology and "gods" ("Any sufficiently advanced technology is indistinguishable from magic").

Researchers call for greater awareness of unintended consequences of CRISPR gene editing
9 APRIL 2021
by The Francis Crick Institute

Researchers at the Francis Crick Institute have revealed that CRISPR-Cas9 genome editing can lead to unintended mutations at the targeted section of DNA in early human embryos. The work highlights the need for greater awareness of and further research into the effects of CRISPR-Cas9 genome editing, especially when used to edit human DNA in laboratory research.

https://www.crick.ac.uk/news/2021-04-09_researchers-call-for-greater-awareness-of-unintended-consequences-of-crispr-gene-editing

Dan Simmons has a pair of sci-fi books on just this topic. It imagined a transhumanist society on Earth, filled with plenty, as well as an even more evolved "posthuman" society of God-like humans recreating the Trojan War on Mars, with themselves as Greek gods. Kind of a techno-Illiad.

I don't know if I'd really recommend it. Hyperion, his sci-fi take on the Canterbury Tales is a lot better, but it has a ton of interesting ideas, it just doesn't come together, even with like 1,400 pages to do so.


---

Anyhow, thank you David for the thread. This is a very interesting topic. I don't have too much to add of my own. As a leader in local government I have to constantly balance murky utilitarian calculations with political feasibility. The transhumanist project has to work on a scale an order of magnitude greater.

I have my doubts. I'm just finishing up Will Durant's excellent history of classical Greece, and it's remarkable how similar their political problems are to those of modern Western democracies. It seems like there has been nothing new under the sun despite all the "progress."

It might just be that the idea offends me on a psychological level. The transhumanist project is like a reverse Tower of Babel, bringing heaven down to Earth. It reminds me of Dostoevsky's Grand Inquisitor or the Buddha's life before seeing death.

It seems to me that you are an agent neutral utilitarian because you seem to believe that there are only instrumental reasons to prioritize the welfare of others. An agent relative utilitarian thinks that the extent to which a given episode of suffering is intrinsically bad is relative to whom the suffering belongs to. I consider myself to be a pretty strong agent relative utilitarian because I’m mostly an ethical egoist. I believe that you have much more reason to focus on minimizing your own suffering instead of minimizing the suffering of others(if we set instrumental considerations aside).

The argument that I use to support this position relates to how I feel that hedonism is strongly compatible with egoism. Hedonism seems to go hand in hand with egoism because suffering seems to be bad by virtue of how it feels. Because of this, it seems to matter a lot who exactly has to endure that episode of suffering. Suffering doesn’t seem to be just some weird abstract concept that exists in some platonic realm like say the concept of preference satisfaction. It seems to be an actual felt experience. Because of this, I don’t think it makes sense to take some kind of a weird third person “perspective of the universe” when evaluating the extent to which the episode of suffering is bad. I think this sort of thing would actually take away the argumentative strength of the hedonistic viewpoint. What makes hedonism so compelling to me is how real I feel that the badness of my own suffering is and how hard it is for me to be skeptical of the badness of my own suffering. By contrast, I don’t even know if other people are capable of suffering let alone that I have some kind of weird abstract reason to care about it. It seems to me that the reasons that we might have to minimize the suffering of others are almost just as speculative as the reasons given by objective list accounts of welfare as to why you should think that something like knowledge can be intrinsically good. I’d be interested if you have a critique for this sort of reasoning or a different argument that you think helps reject egoism. I can also clarify the argument more but I’m trying to be brief.

What I'm really worried about is a transhumanistic approach to the human situation that is not based on an accurate understanding of that human situation; an approach that assumes too much and introspects about ourselves far too little. — Noble Dust

I share your reservations about gung-ho enthusiasm for technology. But transhumanism is a recipe for deeper self-understanding. The only way to develop a scientific knowledge of consciousness is to adopt the experimental method. Alas, a post-Galilean science of mind faces immense obstacles: https://www.hedweb.com/quora/2015.html#psychedelics
Not least, it's hard responsibly to urge the use of psychedelics to explore different state-spaces of consciousness until our reward circuitry is ungraded to ensure invincible well-being.

Somewhat related; how does transhumanism address addiction? — Noble Dust

If I might quote Pascal,
“All men seek happiness. This is without exception. Whatever different means they employ, they all tend to this end. The cause of some going to war, and of others avoiding it, is the same desire in both, attended with different views. The will never takes the least step but to this object. This is the motive of every action of every man, even of those who hang themselves.”

Transhumanism can treat our endogenous opioid addiction by ensuring that gradients of lifelong bliss are genetically hardwired.