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.

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