Utopian Surgery II

Introduction

Before the advent of anaesthesia, medical surgery was a terrifying prospect. Its victims could suffer indescribable agony. The utopian prospect of surgery without pain was a nameless fantasy — a notion as fanciful as the abolitionist project of life without suffering still seems today to many thoughtful, well-meaning people. Yet within a decade of the first successful public demonstration at Massachusetts General Hospital in October 1846, the surgical world was transformed. The "conquest of physical pain" had been achieved; or at least its conquest in the operating theatre. The ideological obstacles to anaesthesia's universal adoption in surgery, dentistry and obstetrics dissolved within a generation.

The original Utopian Surgery (2004) drew a systematic parallel between 19th-century arguments against surgical anaesthesia and early 21st-century arguments against pharmacological or genetic relief of emotional pain. That parallel has since sharpened considerably. Two decades on, the terrain has changed: psychopharmacology has undergone its most turbulent revolution since the chlorpromazine era, and a new class of objections to the abolition of suffering has crystallised — more sophisticated than the theological vitalism of the Victorians, but no less ultimately futile in its resistance to the logic of compassion. The global toll of untreated depression, anxiety, PTSD, and chronic pain remains catastrophic. Over 700,000 people die by suicide each year; tens of millions more are maimed by the subtler machinery of psychological torment that falls short of a coroner's verdict. If anything, the mental health crisis has deepened in the post-pandemic, algorithmically-mediated, ecologically-imperilled world of the 2020s. The case for urgent action is stronger than ever; and its opponents are, as ever, more numerous and more vocal than the suffering they help perpetuate.

What has changed most dramatically since 2004 is the emergence of genuinely novel treatment modalities — ketamine and its derivatives, psychedelic-assisted therapy, GLP-1 receptor agonists with unexpected mood-brightening properties, transcranial magnetic stimulation, and the early stages of gene therapy for psychiatric genetics — that have shattered the pharmacological orthodoxy of the SSRI era. Each of these innovations has encountered resistance from what we might call the Party of Pain: those who, for reasons theological, ideological or commercial, prefer to defend the status quo of human suffering against the presumptuous engineers of better minds. Their arguments echo with remarkable fidelity the objections raised against chloroform and ether in the 1840s; and they are, in the longer run, equally doomed. The second great anaesthetic revolution — the conquest of emotional pain — is now, falteringly and incompletely, underway.

A further development since 2004 demands attention: the arrival of large-scale artificial intelligences raises with fresh urgency the question of what exactly is being abolished when we speak of abolishing suffering. The binding problem of consciousness — how unified phenomenal experience arises from distributed neural activity — is not merely an academic curiosity. It bears directly on whether our current pharmacological tools truly eliminate phenomenal pain or merely suppress its behavioural and linguistic expression. This essay is accordingly revised and extended to address the deeper metaphysical challenge facing any abolitionist project grounded in a scientifically serious theory of mind.

Historical Background

The effect of inhaling ether, chloroform, nitrous oxide and similar agents was christened by the physician-poet Oliver Wendell Holmes, Sr (1809–94). In a letter to etherisation pioneer William Morton, Holmes coined "anæsthetic" and "anæsthesia" from the Greek an, "without," and esthesia, "sensibility." The concept was not entirely new — the Greeks used the term, notably the herbalist surgeon Dioscorides (c.40–c.90 AD) — but Holmes was the first to propose it for the specific state of unconsciousness induced by gas-inhalation for painless surgery. For thousands of years the reliable prospect of surgical insensibility had seemed impossibly utopian; as unrealistic as a future of lifelong bliss now seems.

The single or combined use of alcohol, mandragora, cannabis, and opium to deaden the sensibilities before surgery had been practised in classical antiquity. It was resolutely unsatisfactory. Egyptian surgeons allegedly half-asphyxiated children undergoing circumcision by strangulation. Variations on "soporific sponges" saturated with herbs circulated through medieval medicine; their typical effect still left much to be desired. Henry Hill Hickman performed allegedly painless amputations on animals in 1824 using carbon dioxide-induced asphyxiation, and was ignored. Inhaled gases were exploited principally for hilarity and profit: nitrous oxide frolics were a spectator entertainment long before they became an operating-room tool.

The breakthroughs that heralded the modern era came from a combination of chemistry, self-experimentation, and the peculiar moral pressure exerted on dentists obliged daily to inflict screaming agony on their patients. Horace Wells, that tender-hearted Connecticut dentist, recognised in 1844 that nitrous oxide — "a new era in tooth pulling" — could end this misery. His public demonstration at Massachusetts General Hospital in January 1845 failed catastrophically when his patient stirred and cried out. The medical students laughed. Wells was ruined; he became a chloroform addict, attacked a woman, and died by his own hand in 1848, insane and embittered. The era of surgical anaesthesia was inaugurated instead by his former colleague William Morton on 16 October 1846, before an amazed audience that heard Dr John Collins Warren pronounce: "Gentlemen, this is no humbug."

What is less commonly remarked is that the mechanism by which ether, and later chloroform, produced their effects remained poorly understood — indeed, substantially mysterious — for the next 150 years. The Meyer-Overton correlation (1899–1901) proposed that anaesthetic potency tracked lipid solubility, suggesting a non-specific membrane effect; but the specific molecular targets — ligand-gated ion channels, NMDA receptors, GABA-A receptors, two-pore-domain potassium channels — were only elucidated from the 1990s onward. The anaesthetic revolution was achieved without understanding its mechanism, exactly as (critics of antidepressants now note) the monoamine revolution of the 1950s was accomplished without understanding why tricyclics and MAOIs worked. The accusation of conceptual poverty has regularly been weaponised against pharmacological relief of emotional pain; it has never been, by itself, a sufficient reason not to use what manifestly helps patients.

"The escape from pain in surgical operations is a chimera... 'Knife' and 'pain' in surgery are words which are always inseparable in the minds of patients."

— Alfred-Armand-Louis-Marie Velpeau, 1839. Within eight years of this assertion, anaesthesia was in worldwide use.

The Case for Pain

Despite its obvious advantages, pain-free surgery was opposed by a vocal minority of 19th-century clergymen, physicians, and moral philosophers. Their objections clustered around several recognisable themes: theological (pain is God's punishment for sin and His instrument of spiritual purification); vitalist (pain is essential to the life-force; anaesthesia is a kind of death); diagnostic (pain guides the surgeon and signals danger; its suppression endangers the patient); and social (the stoic endurance of suffering is constitutive of admirable character; its pharmacological removal is effeminate, unmanly, or dishonourable). These objections were not, uniformly, the product of callous stupidity. Some of the early critics correctly noted real dangers: the therapeutic window of chloroform was narrow, its long-term hepatotoxicity unrecognised, and its death rate — about 1 in 2,500 — was not negligible. Their error was to mistake the flawed implementation of a principle for a refutation of the principle itself.

Contemporary opposition to the pharmacological and genetic relief of emotional pain reproduces these objections with remarkable fidelity — updated, of course, for the idiom of a secular, scientifically literate age.

The New Vitalists

The claim that pain serves an essential diagnostic or motivating function — that a life without it would be impoverished, directionless, or somehow inhuman — is the modern vitalism. It appears in popular psychology (adversity builds character), in evolutionary speculation (low mood is an adaptive recalibration strategy), and in philosophical arguments that suffering is constitutive of meaning, empathy, or authentic selfhood. The evolutionary psychologist Paul Andrews has argued that depression is an adaptation that forces prolonged analytical rumination on complex life-problems, and should not be prematurely interrupted by antidepressants. Randolph Nesse, architect of "evolutionary psychiatry," has argued that negative emotions are evolved signals and that suppressing them risks missing important information. These are not absurd positions; they deserve serious engagement. But they are vulnerable to the same response that dispatched the 19th-century vitalists: the functional role of a signal can in principle be preserved, or improved upon, even as the phenomenal suffering that currently carries that signal is abolished. The diagnostic value of nociceptive signals does not require that they be experienced as agonising; the motivating function of low mood does not require that it shade into suicidal despair.

The Chemical Imbalance Apostates

A second family of contemporary objections has emerged from within psychiatry itself. The publication in 2022 of Joanna Moncrieff and colleagues' umbrella review challenging the serotonin hypothesis of depression — widely, if misleadingly, reported as "proof that antidepressants don't work" — served as a rallying point for a diffuse anti-pharmacological movement whose intellectual ancestry includes R.D. Laing, Thomas Szasz, and Peter Breggin. The careful version of this critique is reasonable: the "chemical imbalance" narrative was a simplification, SSRIs show modest average effect sizes, and their side-effect profile (including emotional blunting in a significant minority of users) is underappreciated. The incautious version repeats, almost verbatim, the Victorian argument that pharmacological intervention in mental distress is unnatural, addictive, and liable to suppress important emotional signals. Robert Whitaker's Mad in America and Anatomy of an Epidemic are the New York Journal of Medicine of our era: they raise real problems with overprescription and under-psychotherapy while gesturing toward an anti-medicalist ideology that, if accepted wholesale, would condemn millions of suffering people to avoidable torment.

The Authenticity Objectors

Perhaps the most culturally pervasive contemporary objection is also the most philosophically ambitious: the argument from authenticity. The claim that pharmacologically enhanced well-being is somehow less "real," less deserved, or less expressive of the individual's true self than hard-won contentment is heard from bioethicists (Michael Sandel, Leon Kass), therapists, and — with particular cultural authority — from the wellness industry, which profits from selling suffering-optional practices while morally condemning the pill. President's Council on Bioethics chairman Leon Kass argued against using cognitive enhancers and mood-brighteners on grounds that their deployment represents cheating — a violation of the authentic relationship between effort and reward. This objection, transposed to the surgical domain, is precisely that which led clerics to condemn the chloroform-assisted deliveries of James Young Simpson: women were being deprived of the "salutary ordeal" through which Mother Nature (or God) intended them to earn the love of their child. We may expect it to seem, in retrospect, equally embarrassing.

The Psychedelic Threshold New 2026

The most striking development since the original Utopian Surgery is the partial, contested, and still-embattled emergence of psychedelic-assisted therapy as the most promising psychiatric innovation since the introduction of lithium. The history of this emergence is itself a mirror of the 19th-century anaesthetic revolution, compressed into a few turbulent decades — complete with missed opportunities, failed demonstrations, bitter priority disputes, and a now-familiar chorus of "humbug."

Albert Hofmann synthesised LSD-25 in 1938 and discovered its psychoactive properties in 1943; Albert Hofmann and Roger Heim isolated psilocybin in 1958; Alexander Shulgin mapped the entactogen pharmacology of MDMA through the 1970s and 80s. Each of these compounds — the ether, the nitrous oxide, the chloroform of the psychic anaesthetic revolution — was explored with promising early results in clinical settings before the passage of the Controlled Substances Act (1970) and its global analogues drove the entire field underground. This enforced fifty-year moratorium on psychedelic research is the exact inverse of the 30-year gap between Humphry Davy's recognition that nitrous oxide "appears capable of destroying physical pain" and the commercial surgery of William Morton: both represent the same grotesque waste of human life, inflicted by the collision of promising science with ideological obstruction.

The contemporary psychedelic renaissance — centred on MDMA for PTSD, psilocybin for treatment-resistant depression, and ketamine for suicidal crisis — has reproduced in miniature all the drama of the 1840s. Rick Doblin, founder of the Multidisciplinary Association for Psychedelic Studies (MAPS), spent thirty years pushing MDMA-assisted therapy through the regulatory apparatus of the FDA, accumulating clinical trial data of a quality rarely achieved in psychiatry, and watching his work be received with the same polite scepticism that greeted Horace Wells in Boston in 1845. The FDA's Psychopharmacologic Drugs Advisory Committee met in June 2024 to evaluate MDMA-assisted therapy for PTSD. The vote was 10 to 1 against recommending approval. The parallels with Wells' disastrous Massachusetts demonstration are almost uncanny: the patient (in this case, the clinical trial programme) stirred and cried out; the committee laughed (the trial design raised methodological concerns about functional unblinding); and the innovator was sent back to Hartford — or, in Doblin's case, back to Phase 3 trials. Whether MDMA-assisted therapy for PTSD will eventually find a Morton to its Wells — whether it will be rescued by a more compelling performance before a more sympathetic audience — remains to be seen. What is not in doubt is that the suffering of hundreds of thousands of PTSD patients is not waiting for the regulatory theatre to resolve itself.

Ketamine, meanwhile, has achieved the breakthrough that psilocybin and MDMA have not yet secured. Esketamine (Spravato), the S-enantiomer of ketamine administered intranasally, received FDA approval in 2019 for treatment-resistant depression — the first genuinely novel mechanism of action approved in psychiatry since the first-generation atypicals. Its mechanism is debated: rapid NMDA receptor antagonism triggers a cascade of synaptic plasticity mediated by BDNF and mTOR signalling, effects that outlast the drug's presence by days or weeks and that have no clear counterpart in classical antidepressant pharmacology. Ketamine, like ether before it, was in recreational use long before its therapeutic potential was recognised; and, like ether, its path to legitimacy was paved with scepticism, concerns about dissociative side-effects, and the inevitable charge that it merely got patients "high." That patients with treatment-resistant depression emerge from ketamine infusions reporting resolution of suicidal ideation within hours — not the four to six weeks that characterise SSRI response — is the kind of result that should, in a rational medical culture, prompt urgent scaling. Instead, it has prompted hand-wringing about the ketamine clinic industry.

An Unexpected Backdoor

An entirely unanticipated contribution to the conquest of emotional pain has come from an unlikely direction: glucagon-like peptide-1 (GLP-1) receptor agonists, originally developed for type 2 diabetes and later deployed for obesity. Semaglutide (Ozempic, Wegovy) and its successors have produced a stream of anecdotal and emerging clinical reports suggesting broad reductions in cravings, compulsive behaviours, anxiety, and anhedonia — effects that appear to extend well beyond their action on appetite and reward. The mechanism is obscure; GLP-1 receptors are expressed throughout the limbic system, and semaglutide may modulate mesolimbic dopamine dynamics in ways that are only beginning to be characterised. The surprise here is instructive: one of the most potent mood-modifying agents of the early 21st century arrived disguised as a diabetes drug. Ether arrived disguised as a party trick. The therapeutic applications of psychoactive compounds have consistently exceeded the expectations of those charged with approving them, and consistently been discovered by pathways — self-experimentation, recreational use, clinical serendipity — that the regulatory architecture was designed to suppress.

"The ketamine clinic industry is exploiting desperate patients." — A sentiment indistinguishable, mutatis mutandis, from the Victorian charge that anaesthesiologists were exploiting credulous patients' fear of surgical pain.

The Conquest of Suffering

How close are the parallels between arguments used against technologies to relieve emotional pain and those earlier deployed against somatic pain relief? And how much further does the conquest of suffering need to proceed before the analogy becomes, as one day it surely will, an object of historical curiosity rather than a live polemical tool?

The disanalogies between the two conquests are real and should be frankly acknowledged. General anaesthesia suppresses consciousness; it is a temporary, managed annihilation of the subject. Pharmacological and genetic mood-brightening, by contrast, is not suppressant but transformative: the goal is not to render the subject insensible but to deepen, enrich, and stabilise their positive engagement with life. Strong analgesics tend to narrow and constrict consciousness; the next generation of mood-brighteners — whether entactogenic derivatives of MDMA, neuroplasticity-promoting psychedelics, or genomically engineered elevations of hedonic baseline — aspire to expand it. This is a crucial difference. Critics of the abolitionist project who invoke the fear of a pharmacologically stupefied, Brave New World-style soma-civilisation are attacking the wrong target: the goal is not anaesthesia of the spirit but its unshackling.

The CRISPR revolution has transformed the longer-term landscape since 2004. Genome-wide association studies now identify hundreds of genetic variants associated with mood disorders, with polygenic risk scores explaining a modest but growing fraction of liability variance. The therapeutic window between somatic gene therapy — targeting relevant circuits in adult individuals — and germline hedonic engineering — selecting or editing embryos for elevated hedonic set-point — has narrowed conceptually even as it remains regulated as a chasm. He Jiankui's reckless 2018 germline editing of CCR5 in human embryos demonstrated both that germline CRISPR in humans was technically achievable and that the governance infrastructure for its responsible application remained pitiably underdeveloped. The response of the scientific community — correct in its censure of He Jiankui's recklessness, less defensible in its blanket opposition to germline research per se — echoes the Victorian reflex that preferred suffering to uncertainty. Within the next decade, base editing and prime editing tools will offer precision sufficient to begin serious discussion of polygenic score-guided germline selection for resilience and positive affect. Prospective parents will face choices, on behalf of children who cannot consent, that our current ethical frameworks are not equipped to handle. They are choices, however, that will be made — either thoughtfully or carelessly.

The GLP-1 Lesson

The unexpected mood effects of GLP-1 agonists illustrate a broader principle: the neurochemical architecture of wellbeing is far more interconnected than classical psychiatry assumed. Metabolic circuits, reward circuits, interoceptive circuits, and affective circuits share molecular machinery and developmental origins in ways that are only now being mapped. The implication is both cautionary and encouraging. It is cautionary because off-target effects — intended and unintended — will be ubiquitous in any serious pharmacological assault on the hedonic baseline; the long-term neurobiological consequences of sustained GLP-1 receptor agonism in the limbic system are not yet understood. It is encouraging because it suggests that the number of pharmacological entry points into the system of suffering may be considerably larger than the classical monoamine model implied. The mesolimbic dopamine system is not the only approach road to the abolition of misery; nor are the opioid and serotonin systems the only relevant substrates. The kappa-opioid system, the endocannabinoid system, the orexin system, the nociceptin/orphanin FQ system, and now GLP-1 receptors all deserve serious attention as targets for the attenuation of suffering without the collateral costs that attend classical pharmacology.

Re-engineering the architecture of the mesolimbic dopamine system remains, however, a central goal. The meso(cortico-)limbic dopamine system mediates not merely pleasure but appetitive motivation — the capacity to want as well as the capacity to like. This distinction, established by Kent Berridge and colleagues' dissection of hedonic hotspots and wanting circuits in rodents, is pharmacologically important: classical euphoriants like cocaine and amphetamine potentiate wanting without proportionately potentiate liking; anhedonic depression may involve the opposite dissociation. A pharmacology that repairs the wanting-liking relationship — and anchors both to a higher baseline — is more ambitious than merely suppressing the phenomenology of sadness, but it is the kind of tool that the abolitionist project requires.

Nociception Without Tears

Not everyone has the physiological capacity to suffer pain. Several syndromes of congenital insensitivity to pain (CIP) are known, most attributable to loss-of-function mutations in the SCN9A gene encoding the Nav1.7 voltage-gated sodium channel. Carriers of SCN9A gain-of-function mutations suffer from the opposite condition: paroxysmal extreme pain disorder, an unremitting private hell. The Nav1.7 channel has attracted intense pharmaceutical interest as an analgesic target, and small-molecule Nav1.7 inhibitors have reached clinical trials, with variable results. The challenge is selectivity: Nav1.7 is expressed in many peripheral nociceptive neurons, but achieving analgesic efficacy without cardiovascular or autonomic side-effects has proved difficult. The science is illuminating, however: it confirms that phenomenal pain can in principle be surgically excised from the nervous system at a defined molecular locus, without — so far as can be determined from CIP patients, who lead otherwise normal lives — abolishing the functional information-processing role of nociception. CIP subjects learn to avoid tissue damage through visual inspection and rational inference rather than through the tutoring of agony.

The predictive processing account of pain, developed by Karl Friston, Anil Seth, and colleagues in the first decade of the 21st century, offers a theoretically richer picture. On this account, pain is not a passive signal transmitted from the periphery to the cortex: it is an actively generated hypothesis about the state of the body, constrained by ascending nociceptive signals but substantially determined by prior expectations and descending predictions. The brain, on this view, infers that the body is in danger and generates phenomenal pain as a motivating prior to action. This reframing has radical implications for abolition: if pain is prediction-generated, then updating the generative model — altering the priors that make a signal feel agonising — is in principle achievable without abolishing nociception itself. Placebo analgesia, psychedelic disruption of the default mode network, and the pain-relieving effects of deep social connection all plausibly operate partly through this mechanism. The phenomenal intensity of pain is not fixed by the nociceptive signal; it is a function of the entire predictive hierarchy of the subject. A compassionate and scientifically serious programme for the relief of suffering must target the hierarchy, not merely its peripheral inputs.

The affective counterparts of CIP — sporadic cases of extreme constitutive hyperthymia without mania, or individuals at the very top of the distribution of trait positive affect — are exceedingly rare, presumably reflecting strong ancestral selection for anxious and pain-sensitive phenotypes. They are not, however, functionless freaks. High-functioning individuals who operate near the ceiling of positive affect, exhibiting what Martin Seligman calls "authentic happiness" in a constitutional rather than achieved sense, do not appear to be impaired sensors of danger or error. Their existence refutes the claim that phenomenal pain is causally necessary for adaptive behaviour. Whether pharmacology or genetics can reliably reproduce this phenotype at scale — and whether the phenotype can be achieved without pathological mania — are open and urgent empirical questions.

The Binding Problem New 2026

There is, lurking at the heart of the abolitionist project, a problem that the 19th-century anaesthetic revolution did not face — or faced, at least, only in the nightmarish form of curare. Curare, the South American arrow poison adopted as a surgical muscle-relaxant in the 1940s, was for a time mistaken by some anaesthetists for an anaesthetic agent. A number of patients underwent surgery while fully conscious but paralysed, unable to communicate their agony. Curare produced a perfect simulacrum of adequate anaesthesia — still body, low heart rate, no vocalisation — while leaving phenomenal suffering intact. The horror of awareness under anaesthesia is, in small measure, a permanent feature of modern surgical practice, since neuromuscular blocking agents are routinely combined with general anaesthetics, and the depth of anaesthesia is never perfectly calibrated.

The analogous risk for the psychiatric pharmacopoeia is more subtle and more philosophically profound. Many of the agents currently deployed to suppress symptoms of depression, anxiety, and pain may, to varying degrees, suppress the behavioural and linguistic expression of suffering without equivalently reducing its phenomenal intensity. The "emotional blunting" reported by a significant minority of SSRI users — a flattening of both negative and positive affect, a reduction in the felt intensity of all experience — could represent genuine phenomenal relief, but could equally represent a dissociation between reported and experienced wellbeing of the kind curare achieved in the somatic domain. Patients who report emotional blunting are not, typically, suffering less; they are feeling less. These may not be the same thing.

The binding problem — the question of how the brain produces unified phenomenal experience from distributed neural activity — bears directly on this concern. David Pearce's variant of physicalistic idealism proposes that phenomenal experience is identical with patterns of quantum-coherent neuronal activity in the CNS, and that the unity of conscious experience reflects genuine physical superposition across neuronal assemblies. If something like this is correct — and the hard problem of consciousness ensures that no account of its neural basis can be dismissed as obviously wrong — then crude monoamine modulation operates at entirely the wrong level of description to guarantee the elimination of phenomenal suffering. It may modulate the neural correlates of suffering at the level of classical synaptic chemistry while leaving the deeper quantum substrate untouched; or it may — and here the pharmacology becomes deeply speculative — interact with the relevant quantum-coherent processes in ways that genuinely abolish phenomenal pain. We do not know.

This uncertainty is not a counsel of despair. It is, rather, an argument for taking the phenomenology of suffering, and reports of emotional blunting, more seriously than clinical outcome measures typically do. A Hamilton Depression Rating Scale score of 8 ("mild depression") obtained from a patient who reports feeling phenomenally flattened is not the same outcome as a score of 8 obtained from a patient who reports feeling quietly content. The difference matters enormously — it may be the difference between an analogue of curare and an analogue of ether — and it is currently invisible to our measurement instruments.

The binding problem also motivates the longer-term project of germline hedonic engineering. If the goal is not merely to suppress the expression of suffering but to genuinely eliminate its phenomenal texture from the fabric of conscious experience, then interventions at the level of synaptic pharmacology are at best palliative. Engineering a genome that consistently produces nervous systems operating at a higher hedonic baseline — in which gradient signals analogous to pain are phenomenally less intense, or carry less distress, in the same way that the mild discomfort of stubbing a toe does not occupy the same phenomenal register as the agony of a surgical amputation without anaesthesia — requires intervening at the architectural level, not the symptomatic level. This is the long-run goal; current pharmacology is the Wells demonstration, not the Morton triumph.

"The reasons for the persistence of suffering in the world are now more ideological than scientific. Pain — and pleasure — are controllable."

— Utopian Surgery (2004). Twenty-two years later, this claim is more, not less, defensible — even as the mechanisms of control reveal themselves to be more complex than the original formulation suggested.

Crossing the Threshold

Humanity may or may not ever launch a global abolitionist project to eradicate suffering. The ethical urgency of engineering a cruelty-free world is not felt keenly by everyone, and the obstacles — ideological, political, technical, and philosophical — are formidable. But the question has subtly changed since 2004. It is no longer whether technologies capable of substantially eliminating the phenomenology of suffering will exist; the evidence from ketamine, psychedelic-assisted therapy, CRISPR, predictive-processing pharmacology, and GLP-1 agonism collectively establishes that they will. The question is now whether their development will be governed by a coherent ethical framework, or whether it will proceed through the same mixture of serendipity, commercial incentive, moral panic, and regulatory obstruction that characterised the anaesthetic revolution.

The accelerating compression of the genomic timeline is the most important new variable. Human germline editing has already been performed, recklessly and in secret; the institutional response — a moratorium backed by inadequate enforcement — is a plausible analogue to the Zurich city fathers' initial ban on anaesthesia. It will not hold. The question is not whether prospective parents will be offered the opportunity to select embryos partly on the basis of predicted hedonic set-point, but when and under what conditions. Given the near-universal preference, among people who have suffered from depression or anxiety, not to have their children inherit that suffering, the demand for such selection will be powerful once the genomic predictors reach useful accuracy. The technology will arrive; the ethics are lagging badly.

The global mental health crisis, compounded by the aftermath of the COVID-19 pandemic, the anxieties of accelerating climate change, and the cognitive and emotional hazards of algorithmically-optimised social media, has enlarged the constituency of the afflicted — and, perhaps, the political will to address them with something more ambitious than a waiting list for CBT. Depression is now among the leading causes of disability globally; anxiety disorders affect nearly a billion people; the opioid crisis has made the pharmacological management of pain a political flashpoint. Into this environment, ketamine clinics and psilocybin therapy centres and semaglutide prescriptions have arrived as imperfect, contested, commercially ambiguous, and nevertheless genuine advances. Each one has encountered a version of the case for pain; each one has survived it.

The largest analogy between the 19th-century and 21st-century conquests of suffering may be the most historically encouraging. Within living memory of the Morton demonstration, anaesthesia in surgery was universally adopted, its early opponents forgotten or mocked, and the very concept of accepting surgical agony as natural and inevitable had passed into a cultural incomprehension so complete that it required conscious historical effort to reconstruct. The arguments of the City of Zurich and Dr William Henry Atkinson ("I think anesthesia is of the devil") did not merely lose the intellectual debate; they were erased from the cultural memory of medicine. It is at least possible — and the optimist would say probable — that the arguments of the contemporary Party of Pain, whether delivered in the idiom of evolutionary psychology, authenticity ethics, or anti-psychiatry, will undergo the same fate. The suffering they defend will one day seem as alien and unnecessary as the surgical theatre of screaming before October 1846.

Timescales are uncertain; on a pessimistic analysis, generations of avoidable misery still lie ahead before any post-Darwinian transition is complete. Sceptics are right to note the distance between current pharmacological palliatives and the germline engineering of perpetual bliss. The sceptics of 1838 were right to note the distance between soporific sponges saturated with mandragora and the reliable anaesthesia that Morton would demonstrate eight years later. The gap was closed by chemistry, courage, and compassion. The gap before us is considerably larger and will require the tools of genomics, neuroscience, philosophy of mind, and global governance. But the direction of travel is not seriously in doubt. The heartbreaking suffering of the old Darwinian order is destined to pass into evolutionary history; what remains to be decided is the speed of its departure, and whether its ending will be managed with the wisdom its victims deserve.

A ghastly legacy from our Darwinian past is poised to pass into history. Whether kinder and gentler implementations of pain's functional analogues will be prudently retained, or whether sentient life will transcend the aversive dimension of experience altogether, depends on choices that the current generation is — whether it acknowledges it or not — already beginning to make.

David Pearce
2026