I. Jo Cameron, Bio-Arhat

Suffering is part of the human condition, except when it isn't.

I met a man at an ACX meetup once who claimed he has never felt anxiety, not even the littlest bit. His father was the same way, so maybe it's genetic.

Some people feel more pain than others. The “more pain” category includes some big demographic groups like redheads, who seem to feel some types of pain more intensely and may need up to 20% more anaesthetic, though their exact processing differences are complicated. But there are also various lesser-known genetic conditions that can make bizarre things - water, light touch, mild temperature changes - excruciatingly painful. The most exotic cause of this syndrome has to be platypus venom, which is both painful in and of itself and also seems to increase the body’s overall capacity to feel pain; for years after a platypus scratch, every tiny scrape will hurt worse than usual.

The “less pain” category includes people who say they've never felt pain at all. There's a genetic condition called congenital insensitivity to pain; patients are incapable of hurting. Most of the “purest” cases die tragically during childhood; in a typical story, they rest their hand on a hot stove, fail to notice, and burn to death. The ones who survive usually turn out to have something in between pain insensitivity and pain asymbolia, where they can notice pain but it doesn’t feel particularly unpleasant. This can still be dangerous - imagine having to argue a young child out of putting her hands on stoves - but it’s a bit more survivable, and there are some weird genetic clusters of it here and there. An Italian family with a mutation in ZFHX2 are immune to pain; so are a Pakistani family with a mutation in SCN9A. Some of these syndromes have other weird side effects; the Italian family doesn’t sweat, and the Pakistani family can’t smell.

Our physical differences are easy to notice. Everyone knows that some people are black, some white, some Asian or Hispanic. Everyone knows that some babies are born with one arm, or three eyes, or webbed fingers. But nobody knows how many mental mutants walk among us. Here’s a Reddit post by a guy who says spicy food has no effect on him, complete with a video of him eating Carolina Reaper peppers and looking kind of bored. Here are some pictures by a woman who can see 100x more colors than normal.

People talk a lot about “neurodiversity”, but they mostly just mean that some people are autistic or whatever. The true extent of neurodiversity - like 99% of the colors that one woman can see - remains invisible to most of us.

My other disagreement with neurodiversity advocates is that they insist no neurotype is better than any other. This is, as they say, a postmodernist lie. The best neurotype belongs to a 76 year old Scottish woman named Jo Cameron.

Cameron’s condition was discovered ten years ago, when her anaesthesiologist noticed she needed no pain medication after a difficult surgery. He checked her records and found she had never asked for pain medication, and moreover, that she described giving birth as basically painless. He got intrigued and recommended she talk to a team at University College London researching pain-related disorders.

The London team interviewed her and (let’s be frank) tortured her for several days, then reported their results. Cameron appeared to be incapable of any form of suffering. She could not feel pain. She had never been anxious or depressed. She described her feelings after her first husband’s suicide (from bipolar disorder) as:

“I looked at the state he was in, and I thought, Maybe it’s good,” she said. Cameron was back at work the day after the funeral. “It sounds cold. But you say to people, ‘I’m not being cold! Look, horrible things happen.’ I’m not in airy-fairy land. Horrible things are going to happen. You have to cope with it. You have to say to yourself, ‘I can’t help that person.’ You help them as much as you can, but when you can’t help them anymore, then you have to help everyone else.”

The most interesting feature of Cameron’s condition is her total normality. One might worry that a person who couldn’t suffer would be cold and psychopathic, but in fact Cameron was a special education teacher known for her kindness and patient with extremely tough students. One might worry that she might lack the righteous anger necessary to fuel political engagement, but in fact she has strong political opinions (she doesn’t like Boris Johnson) and attends protests. One might worry that she would be unable to relate to regular humans, but she’s been married twice and has two children, who she’s on great terms with. One might worry that she would lack the full range of artistic appreciation, but she reports crying at sad movies just like everyone else.

Cameron seems to be somewhere between pain insensitivity and asymbolia; she’s had some very mild stove-related accidents, but always seems to figure out the situation in time. She hasn’t lost the ability to sweat. She hasn’t lost the ability to smell. The only Special Bonus Side Effect the London team was able to find is that apparently her wounds heal perfectly cleanly, without scars.

She is, as far as anyone can tell, totally fine and normal. She just doesn’t suffer.

For centuries, philosophers have praised suffering as a necessary part of the human condition. Without suffering, we couldn’t learn, couldn’t empathize, couldn’t be fully human. Jo Cameron forces us to ask: is that just cope?

II. David Pearce, Suffering Abolitionist

For centuries, philosophers have praised suffering as a necessary part of the human condition. For decades, David Pearce has told those other philosophers that they are bad and wrong.

Turn-of-the-21st-century Oxford was an exciting place. Derek Parfit was leading a renaissance in utilitarian thought. New technologies like the personal computer, the Internet, and the Human Genome Project were inspiring a new generation of transhumanists. Out of this milieu, philosophers like Nick Bostrom, Will MacAskill, and Toby Ord were laying the groundwork for what would become the rationalist and effective altruist movements. Utilitarians, they argued, were charged with relieving the suffering of the world as quickly and effectively as possible. Technology offered new opportunities to do this at scale. This could be ending poverty and curing diseases (if you were well-grounded in the present moment) or creating a superintelligence to lead us to a post-scarcity future (if you were feeling more ambitious).

But there’s always been a sort of split in philosophy. On one side, you have people like Plato and Marx, thinking about how to improve the world. On the other, you have people like Epictetus and the Buddha. Even if you improved the world, they say, you would never be happy. If you want happiness, you have to look within.

If the effective altruists are firmly on the Plato/Marx side of the divide, developing the Buddhist/Stoic version of transhumanist utilitarianism fell to David Pearce.

Pearce isn’t a philosophy professor. He dropped out of Oxford partway through undergrad - you can read more about why in his What Is It Like To Be A Philosopher interview. In the tradition of Diogenes, he’s never held a formal academic job or really any job at all; he says he supports himself primarily through buying and selling domain names.

(being a combination philosopher/domain-name-monger has its advantages; along with his main site, you can find his arguments scattered across pages like utilitarianism.com, biopsychiatry.com, and superhappiness.com)

Pearce says: solving poverty and curing disease is very hard. And even if we did, it wouldn’t end human suffering. And even if we did, it wouldn’t end animal suffering. Suffering is a fundamentally biological process which requires a biological solution. Pearce himself found a biological solution to his own suffering; he alleviated his severe depression with the antidepressant selegiline. Selegiline isn’t for everybody; it can take the edge off negative experience, but it hardly makes you perfectly happy forever. To make people perfectly happy forever, we need to take this principle and build on it.

A partial near-term victory would look something like a universally available drug that could make people happy and pain-free with no side effects (so, for example, it wouldn’t turn you into a lotus-eater who sat blissed out on the couch your whole life, any more than seligiline did to Pearce himself). Total victory would require some kind of long-term change to the brain/body system that let it do all its normal work - growing, learning, working, changing - without pain, suffering, or any other negative emotion.

For a philosopher, Pearce is very practical. Sure, he has dozens of essays on why it’s morally correct to end suffering. But he also wants to start the project himself. You can read his analysis of dozens of drugs and how they might contribute to some kind of hypothetical future “make everyone happy all the time” cocktail. Early on, he rejects the obvious choices - heroin, cocaine, SSRIs - for the obvious reasons. By the end, he’s investigating weird drugs that even I - who have kind of made a career knowing about weird drugs - have never heard of. Apimostinel originally looked promising, but failed Phase 3 trials. Nomifensine seemed promising but was later found to cause a serious blood disorder. His most promising lead is LIH383, a chemical which seems to increase the brain’s natural opiate tone, potentially producing the effect of a small, dose of opiate without any negative effects or addiction potential. But this is way past his ability to test, and so far he hasn’t been able to interest any pharma companies.

(I tried a distant LIH383 relative once, for Science, but didn’t notice any effect)

The counterarguments write themselves. Brave New World, drain all meaning from life, live in pods, eat bugs, that kind of thing. Pearce has counter-counter-arguments to all of them (you can see his answers to 500 common questions here). He thinks that if the normal human emotional range is 100 points centered on 0 (let’s say from tortured despair at -50 to ecstasy at +50) then it would be just as meaningful to live in the 100 point range centered at +100 (from ecstasy at +50 to ultra-ecstasy at +150).

(yes, obviously there’s a hedonic treadmill - Pearce’s goal is to find some biotech intervention that works prior to the hedonic treadmill, giving you a hedonic treadmill around a different set point)

All of these debates are pretty theoretical, though. Most people either take immediately to Pearce’s position or are violently repelled. I don’t know how much any argument can do to change that. To me, you either start with a deep hatred for the suffering of your fellow beings, and all of this makes sense to you - or you start from some other moral foundation and it seems to miss the point. Are any of these intuitions communicable?

Maybe you could try eating a couple of Carolina Reaper peppers - the ones from that YouTube video earlier. Maybe eat a whole handful at once. Maybe rub them in your eyes for good measure. Then, when you’re rolling on the floor screaming and cursing your past self for making this decision, think of the people who live with chronic pain conditions and feel this way every day. Think of the wounded soldiers who lie on the battlefield screaming for water until they finally expire, or the animals who get eaten from the inside by parasites, or the mentally ill people stuck in padded rooms so they don’t try to kill themselves to escape the pain, or the chickens in factory farms that have their beaks cut off and can never move and are starved for weeks at a time and sometimes drown in their own waste. Can you get have a mystical conversion experience from eating enough peppers? I don’t know, but I feel like this is the kind of vision that could make someone a Pearcian.

There’s more to life than just not being in pain. There’s love, family, beauty, knowledge, community, etc. But there’s also more to life than having money. And most of us realize that very poor people struggling to put food in their mouths can’t fully enjoy love, family, beauty, etc. The world is on fire, and although some of us live on nice little islands of bearability, it’s hard to enjoy them when you can look just off your island and see everyone else on fire. If the fires got put out, maybe we could enjoy the other stuff more whole-heartedly instead of always looking over our shoulder at a world full of endless misery.

This is Pearce’s thesis. It’s not as popular as the normal effective altruism that just tries to help solve poverty and cure diseases. While Ord and Bostrom and MacAskill got followers and press coverage and friendly billionaires, Pearce and his movement (“suffering abolitionism”) got a few very devoted email correspondents.

This started to change around the turn of the decade. In 2017, Pearce came out with a new book, Can Biotechnology Abolish Suffering? In 2018, a group of psychonauts founded Qualia Research Institute, which among its many other projects wants to mainstream Pearcian ideas. According to rumor, someone gave Pearce a big grant. And finally, the news about FAAH-OUT convinced the small circle of people around Pearce to to stop speculating and try to put some of their ideas into action.

III. Marcin Kowrygo, Far Out CEO

In this year’s list of ACX Grantees, one got outsized attention:

Several people asked me to write more this - hence this post.

I interviewed Marcin to learn more about his project. He was extremely gracious about the conditions (over a buggy video link, at 3 AM, with me mostly too sick to speak), and did his best to decipher my half-grunted, half-coughed questions and hold up most of the conversation.

In early 2023, suffering abolitionist Michael Sparks founded the Far Out Initiative to further explore FAAH-OUT and its implications. He collected a team of polymath philosophers and biohackers, and recruited Marcin, a neurobiologist and veteran EA, to lead their group.

Marcin is the first to admit he’s not a typical CEO. He works part-time, on a volunteer basis (he has other jobs that help him support himself, but they’re also with weird charities). His ten-person team (nine of whom are also unpaid volunteers) is heavy on enthusiastic philosophers, low on people with corporate experience. His available funds are somewhere in the very low six figures.

His team had originally been looking into minicircles, tiny pieces of DNA related to bacterial plasmids. In theory, you can put the gene you want on a minicircle, deliver it via IV into your patient, let it seep into cells, and get them to express the gene for a few months until the minicircles degrade - no scary permanent genetic engineering required. With the right combination of minicircles, you might be able to get cells to mimic Cameron’s FAAH-OUT mutation. There was even an experimental clinic in the libertarian charter city of Prospera that seemed willing to handle the logistics once they designed the gene. After treating a few people, maybe some pharma company or government would take notice.

But by the time of our interview, this plan was falling apart. Minicircles are hard to make. They can’t get inside cells efficiently enough to do much. Even if they could get into peripheral cells, they’d have trouble crossing the blood-brain barrier and getting into brain cells. The clinic in Prospera claimed to have solved some of these problems, but it seems to be either confused or fraudulent.

That leaves good old CRISPR. It’s illegal to CRISPR humans, and you’d have to do it at the embryo stage anyway. But it’s legal and practical to CRISPR animals. If you could CRISPR something like FAAH-OUT into cows, chickens, etc, you could create breeds of animal that don’t suffer. They think farms would go for it - non-suffering livestock isn’t just good press, it’s also healthier and (potentially) produces tastier meat. Then vegans could continue fighting for factory farming abolition as usual. But it wouldn’t be quite as desperate, and there wouldn’t be as many casualties along the way.

So Marcin’s current plan is to investigate CRISPR and suffering-free animals. Then, once his team has done something about animal welfare, he’ll circle back to humans with more resources and try to figure something out.

Let’s back up and talk about some of the challenges they face:

Is FAAH-OUT even responsible for Jo Cameron’s condition? When I first wrote about FAAH-OUT, Twitter user @the_megabase got interested and ran some analyses. They were able to find a few other people in the UK Biobank with Cameron’s pattern of FAAH and FAAH-OUT mutations, none of whom had any unusual pain resistance. They point out that over the past twenty years, the vast majority of associations between single genes and exciting phenotypes (“candidate genes”) have failed, proving in the end to be only statistical noise. Will that happen here too?

Marcin said he’s pretty concerned about this. He thinks there’s some supplementary evidence that FAAH-OUT is involved - in animal studies, mice without the FAAH gene, mice without the FAAH gene did seem to experience less pain (not zero) than control mice, and mice given FAAH inhibitors showed less anxiety. He’s currently talking to the University College London team that did the original Cameron studies to see what they think of this, and whether they have any good explanation. If UCL eventually decides they messed up, Marcin has some backup low-suffering genotypes he can use instead, and is willing to look for more - hopefully not the ones that lose the sense of smell or the ability to sweat.

What’s the patent situation? Far Out Initiative really wants this therapy to be available cheaply to everybody, not controlled by some specific pharma company. This might involve patenting it themselves, so that nobody else can patent it; after doing this, they would give the patent away freely. They’re waiting until they have something patentable before thinking too hard about this.

How safe will it be? In 2016, a Portuguese pharma company tested a FAAH inhibitor, BIA 10–2474, as a potential new painkiller. The trial was a disaster - out of 90 patients, one died and five were hospitalized. This almost never happens in clinical trials - pharma companies are usually good at eliminating potentially dangerous candidate drugs in vitro or in animal studies - so it was one of the biggest medical news stories of the year, and it chilled further research into FAAH.

I can’t find anyone claiming to know exactly what went wrong with BIA 10-2474 (see here for what we do know). But the FDA released a statement a few months later saying they were confident that it was a particular feature of BIA 10-2474 and not a problem with FAAH inhibition in general. I don’t know their exact reasoning, but it might have to do with many other pharma companies trying different FAAH inhibitors with no problem. Far Out adds that the FAAH knockout mice also seem to do fine.

Neither the minicircles nor CRISPR are drugs, so they wouldn’t be expected to have any similar problems.

IV.

What happens after suffering-free livestock and minicircles? Now we’re getting Now we’re getting too far out for even the Far Out Initiative to have many opinions. But David Pearce is very clear on what he wants for humanity’ future.

Pearce writes:

The hypothetical shift to life lived entirely above Sidgwick's "hedonic zero" will mark a momentous evolutionary transition. What lies beyond? There is no reason to believe that hedonic ascent will halt in the wake of the world's last aversive experience in our forward light-cone. Admittedly, the self-intimating urgency of eradicating suffering is lacking in any further hedonic transitions, i.e. a transition from the biology of happiness to a biology of superhappiness; and then beyond. Yet why "lock in" mediocrity if intelligent life can lock in sublimity instead?

Naturally, superhappiness scenarios could be misconceived. Long-range prediction is normally a fool's game. But it's worth noting that future life based on gradients of intelligent bliss isn't tied to any particular ethical theory: its assumptions are quite weak. Radical recalibration of the hedonic treadmill is consistent not just with classical or negative utilitarianism, but also with preference utilitarianism, Aristotelian virtue theory, a deontological or a pluralist ethic, Buddhism, and many other value systems besides.

Recalibrating our hedonic set-point doesn't - or at least needn't - undermine critical discernment. All that's needed for the abolitionist project and its hedonistic extensions to succeed is that our ethic isn't committed to perpetuating the biology of involuntary suffering. Likewise, only a watered-down version of psychological hedonism is needed to lend the scenario sociological credibility. We can retain as much - or as little - of our existing preference architecture as we please. You can continue to prefer Shakespeare to Mills-and-Boon, Mozart to Morrissey, Picasso to Jackson Pollock while living perpetually in Seventh Heaven or beyond.

Nonetheless an exalted hedonic baseline will revolutionise our conception of life. The world of the happy is quite different from the world of the unhappy, says Wittgenstein; but the world of the superhappy will feel unimaginably different from the human, Darwinian world. Talk of preference conservation may reassure bioconservatives that nothing worthwhile will be lost in the post-Darwinian transition. Yet life based on information-sensitive gradients of superhappiness will most likely be "encephalised" in state-spaces of experience alien beyond human comprehension. Humanly comprehensible or otherwise, enriched hedonic tone can make all experience generically hypervaluable in an empirical sense - its lows surpassing today's peak experiences. Will such experience be hypervaluable in a metaphysical sense too? Is this question cognitively meaningful?

Pearce’s old friend Nick Bostrom imagines a future of superintelligence. But Pearce will count his own contribution complete if he gives us superhappiness, supermeaning, superbeauty, and superspirituality. And why shouldn’t he? People on LSD and MDMA have all of these things. All we need to do is figure out how to do it without the trippy hallucinations, urge to go to raves, and occasional neurotoxicity. Don’t say it’s impossible! All you need to do is find the right Scottish person!