Aiming for Adaption – an essay on germline gene-editing

Every year the Oxford Uehiro Center for Practical Ethics has an essay competition for students. I submitted the essay below, which didn’t get selected, but having spent some time on it, I am sharing it here, in the hopes that somebody will find it interesting.

Aiming for Adaption

Abstract

In an increasingly interconnected and complex world, how should we make decisions?

I will explore this question in the context of the debate surrounding germ-line engineering of the human genome, as the deliberate enhancement of humans is becoming increasingly feasible. When re-imagining the human species, what values should guide our actions and laws?

Given our increasing ability to change lives, societies and our planet in extreme and lasting ways, the choices we make today will have a greater impact on future lives than those made by previous generations. It is critical that we get them right. I will argue that we need to incorporate more diverse solutions into our scope of thinking about genome engineering. Unfortunately, in both the medical sciences and elsewhere, there is an increasing tendency to apply methods that lead to the illusion that only one solution exists to any given problem. When designing human genomes, this approach might bring short-term gains, but I will make the case that when facing a complex problem, such as inferring which traits will give coming generations the highest welfare, we need to aim for adaption, not perfection.

Invitation to the GP-write: genome-project write, a meeting for scientists in May 2017 on how to "print" or write, a whole human genome.
Invitation to the GP-write: genome-project write, a meeting for scientists in May 2017 on how to “print” or write, a whole human genome. From http://engineeringbiologycenter.org/may-2017-meeting

Introduction

While we might have stumbled into the Anthropocene by chance, we are now approaching a time where we can apply our power in a more deliberate manner (1). Editing the human genome is in many ways the ultimate test for the Anthropocene man and woman, and due to technical advances, it is one that we will likely face very soon. Gene editing techniques will permeate and become standard in reproductive medicine, for example, when correcting debilitating genetic diseases in embryos used for in vitro fertilization. The relevant question concerning our children’s genetic design will shift from “should we do it?” to “how do we do it right?”. It will be hard to argue against these treatments. The physician will have prevented a disease before it arises, the parents will have given their child a better chance in life, and a healthy child will now be allowed to develop (2). Yet if we accept changes to some genes, why not change them all? The question of how to do it, and to what degree, is what our generation needs to contemplate. In this essay, for the sake of argument, I will assume that it is possible to engineer the human germ-line and that this can be done in a safe manner with little inconvenience for the parents (3). Fully capable then, how should we proceed?

It is tempting to relegate the question to one best made by the parents and leave it at that. Parents roughly know which environment their child will grow up in, and might reasonably be able to pick traits that will be important for a good life. This seems insufficient though; traits selected for, while beneficial for the child, might be in conflict with other ethical considerations valued in society (Savulescu and Kahane, 2009). Even if some axiom could be formulated which rational parents would follow, it underestimates the scope of our power. We are no longer in an era where mistakes affect us only in one time period or in one locality. If the Anthropocene parents unwillingly make a bad decision, it will not only affect the child or family; that decision will perfuse through the genes of generations. Decisions become intertwined and far-reaching, and it therefore seems fair to suggest that the surrounding community ought to have some say in those decisions.

Unfortunately, even what constitutes “bad” decisions might not be immediately clear. Historically, when we have modified other animals or plants, we have bred towards idealized versions of these species, aiming for largest utility (in say crop return) or elegance (in say beauty of an animal). Medical decision-making is no different. Once an approach has been shown to work, it is considered unethical not to apply the same treatment to everyone. Indeed, once gene signatures have been identified and successfully incorporated into a child’s genome, such as for increased intelligence or happiness, it is unlikely that a parent, doctor or local authority would allow further changes to that signature. This approach naturally leads to a more uniform genetic makeup, which would improve the individual, but could leave our race as a whole susceptible to sudden shifts in our environment, the same way our homogenous food supply is now vulnerable to climate change (4). This generates an obvious dilemma: how do we conserve the biological resilience we have paid for throughout millennia, while improving the health and welfare of our children?

There is another complication, which is one that is far more difficult to approach. The human genome is not deterministic. While we might be built from a script, we are, in the words of Siddhartha Mukherjee, “built to go off-script” (Mukherjee, 2016). The human genome is not only complicated, as for example an airplane engine is, where if we only understood each component, we could anticipate its function. It is also complex in the sense that the mixing of genes leads to emergent properties that did not exist before. Changes to already existing genes or introduction of completely novel functions would not be isolated from these interactions. Indeed, they would be an active part of them. The prediction of large-scale changes might be possible for immediate generations, but would become impossible when considering longer time scales, with the slight, but real possibility of catastrophic failure in welfare or genetic fitness.

Starlings swarming before migrating south: even though we know how the individual components in a system works, it can be impossible to predict how they will behave in groups; emergent behaviors might arise, that are never seen when looking at just one bird - or gene - alone.
Starlings swarming before migrating south: even though we know how the individual components in a system works, it can be impossible to predict how they will behave in groups; emergent behaviors might arise, that are never seen when looking at just one bird – or gene – alone.

Aiming for Adaption

These considerations profoundly affect how we should approach engineering the human genome, or other complex systems. They hint that neither universal maxims nor predictions of future welfare can be expected to fully address dilemmas arising from our newfound abilities. Instead I propose a soft principle on which we can stand: rather than aiming for perfection, we must aim for adaption.

This entails not setting rigid objectives, but fluid ones. When confronted with an unpredictable system, the best approach is not one of uniformity, but one of variation. Instead of aiming for one idealized image of man, freed from all genetic faults, we must imagine something much more muddied: versions of ourselves that are variable, perhaps even more so than we are naturally today, in the hopes that some of these will flourish. We must accept change, errors and blunders to a higher degree, and if we do want to edit our genes, blind ourselves to a certain extent. We should not pursue the “best” gene signature, but “incomplete” ones that include some diversity. The experiment of the Anthropocene should not be to excel in some specific traits, a Sisyphean task that will fail, but instead to identify broad environments within which our genes can evolve, and to identify many of them.

What could these environments be? Other have suggested that when enhancing humans we should perfect our intelligence, creativity or our morals (Savulescu et al., 2011). These traits could well be defined as part of the core constituents of that which makes us human. If these were to be the domains we engineered, we should be ready to accept that they will change considerably, possibly in detrimental ways. Perhaps a better environment would simply be the general health of humans, with the understanding that this is the best soil in which core constituents could thrive and leave it to the individual to excel beyond that.

This seems a miserable conclusion: as we approach the peak of our omnipotence, we are tied down by our knowledge that either we will fail in our goal of perfection or, if we accept the aim of adaptability, that our work will often be in vain. Perhaps there is some solace in the fact that there might be normative claims to support this aim. A number of people have defended both diversity (Aurenque, 2015) and disabilities (Garland-Thomson, 2012) as qualities that are intrinsically good. Or perhaps we will come to understand our blinding as a form of a self-imposed veil of ignorance, ensuring a just society (5). Personally, I find it valuable to live in world that is quirky and strange. This is not because it is necessarily a better place, but because it does provide the variation from which novel possibilities arise, something that a perfect world would not.

Conclusion

It is easy to attack what I am suggesting here: for one, many of the problems I have highlighted could easily be solved simply by ensuring that every human in every generation were genetically designed. Alternatively, we could reintroduce imperfect genomes, if things start to go wrong. Another obvious problem is the sacrifice of our children’s excellence for inferiority. Finally, it has been suggested that we can get around the complexity of nature by applying certain heuristics to our engineering (Sandberg, 2009).

All these are important interjections. I would be a very poor proponent of my own aim, if I did not at least give them room to be considered or tried out. It is worth noting though, that most of these objections would not be this generous in return. This seems to me a general trend: whether solutions are proposed by algorithms, doctors or politicians, they are increasingly monocultural, to the detriment of diversity and hence emergent ways of living. This is a great shame, not least because solutions that are adaptable are showing their force in many other domains; counterintuitively, error-prone and messy solutions outperform optimal ones when approaching problems in economics (Arthur, 1992), conflict-zones (Sagarin et al., 2010), climate change (Verweij et al., 2006) and even general decision-making (Johnson et al., 2013), most likely because all these domains can be considered complex systems as well. It seems that the possibilities inherent to variation somehow bring out the best in humans, a good we should be careful not to throw away. As we begin to engineer humans, it will be important that we retain this gift.

Notes

(1) Here I will use the word Anthropocene to define the era in which human activities significantly impacts biological systems.

(2) That is not to say that you could not argue against this. I merely do not think these arguments will be successful in practical political terms.

(3) A number of techniques are good candidates for allowing this level of control. Here I will suggest just one: it is technically feasible to precisely synthesize (i.e. write) DNA in large amounts and paste them together. It was recently proposed to use these methods to print a human genome (Boeke et al., 2016). The genomes of both parents can easily be sequenced (i.e. read), and thus a genome from both parent’s genomes could be inferred in which one could correct mutations or insert novel functions, before it being synthesized and inserted into an egg.

(4) It’s worth noting that any trait that gives even a slight survival advantage will quickly permeate through the genetic makeup of a population, whether or not we actively introduce it in an individual.

(5) Luciano Floridi has suggested that John Rawls’ ’veil of ignorance’ is actually a veil of uncertainty (Floridi, 2015).

References

Arthur, W. B. (1992). On Learning and Adaptation in the Economy. Santa Fe Institute, 1–31.

Aurenque, D. (2015). Genetic diversity as a value: imposing fairness. Am J Bioeth 15, 18–20.

Boeke, J. D., et al. (2016). The Genome Project-Write. Science.

Floridi, L. (2015). The Politics of Uncertainty. Philos Technol.

Garland-Thomson, R. (2012). The case for conserving disability. J Bioeth Inq.

Johnson, D. D. P., et al (2013). The evolution of error: error management, cognitive constraints, and adaptive decision-making biases. Trends in Ecology & Evolution.

Mukherjee, S. (2016). The Gene. Penguin Random House.

Sagarin, R. D., et al. (2010). Decentralize, adapt and cooperate. Nature.

Sandberg, A and Bostrom, N. (2009). The Wisdom of Nature: An Evolutionary Heuristic for Human Enhancement.

Savulescu, J., and Kahane, G. (2009). The Moral Obligation To Create Children With The Best Chance Of The Best Life. Bioethics.

Savulescu, J., et al. (2011). Enhancing Human Capacities. Wiley-Blackwell.

Verweij, M., et al. (2006). Clumsy solutions for a complex world: the case of climate change. Public Administration.

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