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.

Google Hedonics

 

Happy_Holi

Holi Doodle. It would also be a good Google Hedonics Logo 🙂

Hello my children!
Hello my sons!
Hello my daughters!
Hello my brothers and sisters!

I’m here to tell you that the world’s last unpleasant experience…
Will be a precisely dateable event!

Yes! It will happen in our lifetimes if we commit all of our energy today…

To the task of Paradise Engineering!

– Yacht, Paradise Engineering

(referencing David Pearce’s Hedonistic Imperative)

Google is an amazing company. Not only is the code infrastructure that they use stunning in power and elegance, but the culture they foster is fun-loving, humanistic, and promoting of employees’ creativity. According to many vocal Googlers, the motto “don’t be evil” is not just empty rhetoric. It is an ideal people share and attempt to uphold. Better yet, Google may even be reducing the number of people doing outright evil things, although indirectly.*

Google’s publicly stated mission is to “organize the world’s information and make it universally accessible and useful.” This goal will be accomplished with a combination of intensive and extensive approaches, ranging from making the world’s information infrastructure more robust to enabling cheap, widely accessible Internet worldwide.

But Google’s actual technological investments go much further, and there are not only a few, but multiple genuinely futuristic research projects on the table. Among them, most notably, is Calico, a company with the explicit mission to “harness advanced technologies to increase our understanding of the biology that controls lifespan” with the aim of delaying, preventing and ultimately reversing aging altogether.

Now, all of this is not only futuristic. Anyone who is aware of the general ideas pursued in transhumanism will realize that Google is more than futurist: It fosters transhumanist goals.

The three Ss of Transhumanism

Although a precise definition of transhumanism is beyond the scope of this (and any) article, for the time being it will suffice to mention three of its main goals. As seen in this video produced by the British Institute of Posthuman Studies (BIOPS for short), these goals are: Super Intelligence, Super Longevity and Super Happiness.

Using that broad outline of transhumanism, can we say that Google is a transhumanist company?

Super Intelligence

Google is certainly furthering the goal of understanding and engineering Super Intelligence. It is doing so by funding and implementing Artificial Intelligence research projects that aim to make AI tools universally useful and available to everyone. Although this is not the same as understanding conscious intelligence (a controversial topic)**, it is inarguably a huge step forward. By producing high-performing, universally available digital AIs, Google and other AI-focused companies will help us offload a large amount of mental menial work into wearable computers. Indeed, the era of the cyborg is upon us. Embedded neural networks are likely to help us achieve better sensory-processing speeds and raw memory capacities, not to mention instant thought-controlled access to the world’s reserves of knowledge.

Super Longevity

As mentioned earlier, Google is already helping the cause of Super Longevity with Calico and a host of other projects. In particular, Google is accelerating worldwide genetic research with its Google Genomics platform, which presumably will also help fight disease and cause people to live longer.

Super Happiness

What is missing, though, is the use of this genius-level talent, amazing infrastructure, and public-good-oriented culture for the furthering of the goal of Super Happiness.

I propose that Google start a research project called Google Hedonics. Its goal would be to develop a fundamental understanding of the functional, biomolecular, and quantum signatures of pure bliss, and the know-how for instantiating it sustainably in all living organisms (if they so desire). Of course, a grandiose goal like that is not a requirement for a happiness-oriented project: It would suffice if they were to simply focus on reducing, as fast as possible, the incidence of extremely negative experiences.

The hedonic treadmill guarantees that no amount of social reform, universal welfare, access to health care or widespread participation in a culture of art will achieve long-term wellbeing for everyone in society. Depression, anxiety, anhedonia and boredom are bound to stay put unless we tackle the underlying genetic and biochemical causes of negative hedonic tone.

Google Hedonics’ goal would be to sabotage the hedonic treadmill. It would thus combine a variety of psychological, biochemical, psychophysical and genetic research projects to the effect of figuring out how to sustainably raise anyone’s hedonic set point. Google Hedonics would not be pursuing quick shortcuts to happiness, but rather, a deep understanding of the roots of bliss and suffering.

Some people argue that this is the most important task of all. For if we manage to prevent experiences below hedonic zero, nothing will ever quite “go wrong” in the same way it has before.

If we have our way, at any rate, we may someday read “H is for Hedonics” in the Alphabet listing of projects.

Utopian Pharmacology

Contrary to popular opinion, a world in which life-long super bliss is the universal norm is not nearly as bad as it sounds. As discussed in the State-Space of Drug Effects article, human euphoria is not adequately captured by a unidimensional metric. Arguably, the hedonic quality of a given experience is multifaceted and full of complexities. When people imagine widespread happiness, it is common for them to simultaneously project a feeling of shallowness and vanity into such an imagined world. This need not be the case: Surely fast and slow euphoria are not conducive to much depth of feeling and thought, but spiritual and philosophical euphoria is anything but. Empathogens like MDMA and 2C-B often (but not necessarily) produce experiences of great complexity, depth and unfathomable beauty. Likewise, people who have experienced deeply blissful mystical experiences attest that pleasure and the sublime can happily coexist.

Google Hedonics would certainly not limit its scope of research to understanding shallow and vain varieties of happiness. On the contrary, it would place a great deal of resources into understanding what brings wondrous depth to the human experience.

What Google Hedonics is Not

  • Finding quick and dirty shortcuts to euphoria, in a way similar to today’s acute euphoriants (alcohol, cocaine, morphine, etc.)
  • Research limited to bodily euphoria: Although feeling well and healthy is a precondition to fulfilling happiness, it is not enough. Spiritual and philosophical bliss are probably a requirement for satisfactory paradise engineering.
  • An ideology-driven project to impose a belief in a particular philosophy of mind, such as functionalism. It is not possible to successfully tackle the problem of suffering if one’s background assumptions about consciousness are incorrect. Google Hedonics would experimentally investigate various theories of consciousness without a preconceived notion of which one is true (functionalism, panpsychism, dualism, etc.)
  • And, importantly, it would not just be an economics startup! That is to say, its goal would not be to help people find what they want for cheap as informed by hedonic regressions, or even an AI-powered dating website. None of those things would sabotage the hedonic treadmill, and thus are irrelevant for its goal.

What are some example projects Google Hedonics could do?

These are just a few ideas to get your imagination started. They are unlikely to do the trick of instantiating lifelong bliss, but at least they don’t fail by design:

  • Combining ultrasound neurostimulation and neuroplasticity-enhancing drugs on depressed people to induce long-term potentiation in their nucleus accumbens (the so-called “pleasure center”).
  • Studying fMRI activity patterns of hyperthymics (generally happy people) using Google’s cutting-edge machine learning technology. Are there surprising symmetries in their distribution of voxel activation?
  • Using NLP technology to cheaply diagnose depression throughout the world, and identifying activities, substances and environments that would sustainably raise people’s hedonic set point.
  • Measuring the epigenetic changes of people who undergo hedonic tone-enhancing spiritual training (such as metta) to identify the genetic markers of sustainable spiritual bliss.
  • Enhancing and extending healthy loving relationships with oxytocin spray and other empathogenic technology (chemical or not).

Personally, I don’t think any of the above would deliver miraculous therapies that prevent anxiety and depression altogether, but they would each deliver hints of tremendous importance. I trust that at a place like Google a thorough probabilistic cost-benefit analysis of the expected hedonic return of each possible research project would be conducted in earnest.

Effective Altruism

Google recently hosted EA Global. The very thought of this occurring is a great source of hope for me. Finally, altruism and rationality are meeting, and very smart people are spearheading it. The missing piece, as far as I can see, is a theoretically-sound utility function to maximize. The (attempted) use of QALYs in utilitarian calculations is a huge improvement upon hand-wavy head-counting. But hedonic tone is not yet in the picture, much less a truly sound way of measuring it, let alone optimizing for it. Google Hedonics would provide this missing piece and more: An actual solution for not having to ration bliss, by disconnecting it from the limited resources it has, as of now, always been limited by.


*Mary “Missy” Cummings , a roboticist from Duke University, has stated in several interviews that if it wasn’t for Google and other similar companies, organizations like the Department of Defense and military contractors would have and attract top technical talent. Instead, at least in the US, real top technical talent in the area of computing technologies is concentrated in large companies like Google, research universities, and even startups. Thankfully, fewer and fewer bright kids grow up looking at the Defense Department as a great place to build a career. Google’s “don’t be evil” may already be vindicated: There aren’t any more geniuses working for militaristic aims; they now work on futuristic projects that aim to improve the lives of everyone in the world (rather than to merely guarantee brute-force supremacy of one country over another).

**Qualia Computing argues that consciousness can accomplish certain computational tasks that digital computers cannot, even in principle, realize. Phenomenal binding is the key step in the information processing pipeline that distinguishes conscious systems from merely information-processing systems. This, however, is controversial, and I tend to assume that decades will elapse before neuroscientists and AI researchers alike come to a consensus on this matter. If phenomenal binding is indeed necessary for some computational tasks we usually ascribe to intelligence, let alone super-intelligence, we will need more than a revolution in machine learning algorithms to achieve this particular goal of transhumanism. We will need to investigate the quantum substrate of our wetware, our very mind/brains.