5. Development and Ethics
© 2022 Kristien Hens, CC BY-NC-ND 4.0 https://doi.org/10.11647/OBP.0320.05
Development and Environment
In the previous chapter, we have seen how epigenetics is a term with different connotations. It bears a family resemblance to the much older term epigenesis, which denotes a way of looking at how organisms acquire a specific form. Adherents of the theory of epigenesis believe that an organism develops its form during development in interaction with the environment. Preformationists, on the contrary, believe that the form of an organism is already defined from its conception. The environment can either be the milieu inside or outside of an organism. The more recent term epigenetics refers to contemporary research in molecular biology that studies the intracellular mechanisms of gene expressions. These mechanisms can be controlled by genes or the environment and work throughout an organism’s lifetime. I have also discussed the concept of the epigenetic landscape as Conrad Waddington devised it. He described a network of genes that we could consider a landscape which guides the development of a particular cell towards a specific endpoint (Creighton and Waddington, 1958). Important concepts here were canalization (the mechanism that causes the development of a cell to take a specific path, a particular ‘valley’ in the landscape) and plasticity, which introduces the possibility of adapting to changes.
The different meanings of epigenetics have at least two aspects in common. First, there is the idea of development. The emphasis is on how organisms develop and interact throughout a lifetime. They ‘lay down a path in walking’, to quote the late cognitive scientist and enactivist thinker Francisco Varela (Varela, Rosch and Thompson, 1992).1 Development is not confined to what happens in the womb or the first phases of an organism’s development but continues from conception to death. Secondly, there is an emphasis on the environment. Epigenetic changes occur under environmental control. We have seen that whether something is ‘caused’ by genes or environmental factors stresses a false dichotomy. It suggests that these are two well-defined spheres on equal footing when explaining the causality of traits, behaviours, and pathologies. We have seen that the concept of ‘gene’ is far from straightforward. Even more complex is the idea of the environment. The environment can denote behavioural factors, such as lifestyle and nutrition, and factors in the physical environment, such as pollution. There can be psychological factors such as stress and trauma. Moreover, our culture could also be considered a factor contributing to gene expression. And besides cultural influences on gene expression, we can also look at culture itself in terms of development and epigenetics.
Quite a few scholars have theorised the relationship between genes and culture. Think about the seminal work by Richerson and Boyd, Not by Genes Alone (Richerson and Boyd, 2006), in which they describe how culture changes the nature of human evolution and, at the same time, how human beings change a culture. Hence, culture and human biology evolve together. Iddo Tavory, Eva Jablonka, and Simona Ginsburg elaborate on cultural epigenetics (Tavory, Jablonka and Ginsburg, 2014; Jablonka, 2016). They build on Waddington’s epigenetic landscape. They write about how a cultural system is a dynamic entity into which individuals are introduced, in which they develop, and to which they contribute. Groups of individuals become socialized into a culture. Culture can be considered a social landscape comparable to Waddington’s original ‘epigenetic landscape’ compiled from genes. Each social community is a niche construction with particular dynamics and life patterns that evolve and develop. The inhabitants maintain these customs and practices over time for these customs to become canalized. Each community has its own culture. Concurrently, these smaller communities are part of bigger social landscapes, so more complex regulatory structures are required to help maintain or canalize each of them.
Tavory, Jablonka and Ginsburg illustrate this using two examples. First, there is the example of the Orthodox Jewish society in LA’s Beverly-LaBrea neighbourhood. This culture is thriving amid a transgressive, secular youth culture. Several factors help to maintain the religious tradition. There are well-established geographical limits: community members attend the same places and schools. Every person has multiple obligations in the community, and people do not have much time for anything else. They wear particular clothes and thus distinguish themselves from others outside their community. In this way, the specific tradition has become canalized. To a large extent, the culture is resilient against external pressures. Tavory and colleagues also give another example: urban poverty in the USA (Tavory, Jablonka and Ginsburg, 2014). They describe a cycle of poverty: people born into urban poverty tend to be poor themselves, and it is tough to break this cycle. We can ask ourselves why this is the case. There seem to be many social-cultural factors that lead to this situation. They include the structure of the state and the schooling system, and to some extent, biological and epigenetic factors such as alcohol and drug consumption. Moreover, when someone succeeds in escaping this vicious circle of poverty, they usually disappear from this society, leaving no positive influence. There is also a geographical factor. A poor neighbourhood has certain geographical boundaries, and there may be attractors such as cheap housing or the availability of drugs that make it hard to break through these boundaries. The cycle of poverty is canalized.
These two examples suggest that a cultural epigenetic approach offers little hope of improving suboptimal situations, such as urban poverty. Epigenetics does not automatically lead to less deterministic conceptions than a purely genetic view of the world. However, the Waddingtonian network approach to culture and biology describes how certain traits and behaviours have become canalized dynamically. The ideas of canalization and plasticity leave an opening for change. Indeed, Waddingtonian networks are not set in stone. They can change and reshuffle. Understanding canalization and plasticity can help us intervene and reshuffle the valleys into desirable paths. In what follows, I shall return to the challenges and opportunities of epigenetics for ethics.
Development and Ethics
What is so special about the ethics of epigenetics that differentiates it from the ethics of genetics? We have already discussed that epigenetic changes can be transgenerational, maybe even heritable. This extended timeframe poses some extra challenges when we think about responsibility. We can assume that pregnant mothers have some responsibility for the unborn child. Many would consider a pregnant woman engaging in binge drinking irresponsible if she knows the dangers to the future child’s health. However, if epigenetic findings suggest an influence by the behaviour of men long before they even consider siring children, how should we, for example, evaluate the responsibility of teenage boys who smoke if we know that this may affect the health of potential future children? Surely, fifteen-year-old boys should preferably not smoke for their health, but it would be strange to claim they are responsible for future children they might never have (Hens, 02/2017). Another relevant aspect when discussing the ethics of epigenetics is that epigenetic markers may be more readily reversible than genetics. It may be easier to wipe out or induce a methyl mark than alter a gene (Nakamura et al., 2021). This reversibility offers many opportunities for therapy, but it also raises some interesting ethical questions. The idea of precision medicine suggests a shift towards more preventive rather than curative medicine and entrenches the idea of taking responsibility for one’s health. However, if epigenetic markers can more readily be changed, this may suggest a move back to more curative medicine. Consider the scenario of the smoking fifteen-year-old boys. We should perhaps not bother telling them to stop smoking, as we will be able to wipe out the deleterious influence this has on their future offspring. Undoubtedly, the fact that something can be cured does not relieve us of the responsibility of preventing harm from happening in the first place. The same goes for systemic responsibilities such as pollution. The idea that we may eradicate the nefarious epigenetic effects of pollution in the future is comforting. However, it feels wrong to allow harm to occur because we can fix the consequences later. At the same time, we cannot count on the fact that this biomedical knowledge will ever be available. Perhaps the most important new aspect that epigenetics brings is that of unpredictability. Epigenetics is about interaction with the milieu. It positions organisms as fundamentally open to their environment. We must factor in an amount of chance. I shall discuss chance, indeterminacy and creativity more in Part Two. For now, suffice it to say that keeping in mind both the reversibility and indeterminacy of epigenetics can function as a shield against deterministic interpretations of epigenetics and eugenic interpretations.
Authors have warned that epigenetics, and focusing on the environment, does not automatically imply more plasticity and malleability. The idea that we are defined not only by our circumstances and lifestyle but also by the experiences of our ancestors may suggest that we are determined by more than merely our genes. Indeed, epigenetics determinism, being determined by both genes and environment, may even be worse than genetic determinism. It suggests that there is no relief from the traumas of our grandparents or great-grandparents. Contrarily, the idea that the epigenetic layer is malleable also opens the way to what Eric Juengst and colleagues have called ‘epi-eugenics’ (Juengst et al., 2014). If the aim is to create better people, the idea that we can tinker with environments and their molecular effects opens up more possibilities. Developmental Origins of Health and Disease (DOHaD) research stresses the importance of environmental influences at the earliest points in life, at conception and in utero. It thus raises questions about the responsibilities or even duties of pregnant people towards the health of their offspring. Popular media has already translated specific findings regarding a mother’s duties, for example, the claim that eating bacon and eggs during pregnancy will make your child smarter. In their book Blinded by Science, David Wastell and Susan White point out the consequences of neuroscientific and epigenetic research (Wastell and White, 2017). They describe the possible implications of focusing on the first three years of development. Parents may feel pressure to do everything right and make no mistakes when it comes to parenting their young children. Stressing this ‘window of opportunity’, in which children’s brains are flexible, has spawned a whole industry of tools, toys and techniques to ‘improve’ your child. In Part Three, I shall question the idea of improvement itself. For now, I believe that these presumptions make the same mistake: they assume, just as people did before about genetics, that epigenetic knowledge will lead to more control over who we are and who we can become. A developmental approach, with epigenetics as one of its molecular proofs, may ultimately show that the desire for control is misguided. As I shall argue in Part Two, we need a kind of ethics that engages with unpredictability, chance, and lack of control.
I shall not go into more detail regarding the ethics and consequences of epigenetics. Bioethicists, sociologists, and lawyers have already written about this extensively. For an overview of the discussion from the last decades, the reader can consult the excellent literature review by Charles Dupras, Katie Michelle Saulnier and Yann Joly (Dupras, Saulnier and Joly, 2019). Instead, I shall give one example of how a more developmental view of organisms can shed new light on the assumptions we have taken for granted, specifically reproductive ethics.
Certain concepts of development are thoroughly influencing how we approach bioethical issues. This influence becomes apparent when we think about specific discussions in reproductive ethics. A common assumption is that at least our (numerical) identity is fixed at conception. This assumption is linked to the conception of personhood in certain religions: think about the Catholic church and its absolute prohibition of abortion. They argue that personhood starts at conception. Conception is defined as the merging of genes from the sperm and the ovum. When considering reproductive ethics, the idea that identity is created at the point of conception carries much normative weight in secular bioethics too. This idea is related to the relevance that the (non-)identity problem seems to have for reproductive ethics. Derek Parfit has described the non-identity problem in his seminal book Reasons and Persons (Parfit, 1984). He asks us to imagine a fourteen-year-old girl who wants to become pregnant. We would probably advise her to wait until she is older and/or has more stability in life. Postponing would give the hypothetical child a better chance in life. However, Parfit asks us to consider for whom this would be better. It may be better for the girl herself to focus on her studies first before engaging in the demands of parenthood. But we cannot say that it would be better for ‘the child’, as the child she conceives in her late twenties will be a different child than the one she might give birth to if she became pregnant now. After all, in theory, a different sperm and ovum will produce a different child in the future. So, leaving aside the potential harm to the girl herself, can we say that the child that would be conceived now is harmed? Moreover, the environment may be very different for the girl and the child 10 or 15 years in the future, making predictions about well-being nearly impossible. The background to this thought experiment is whether harms are always personal, affecting a specific someone, or whether situations themselves can also be harmful, even if it is difficult to pinpoint precisely for whom it is harmful. This example is classified as a non-identity problem and has had a significant impact on authors’ discussions in papers on both reproductive and environmental ethics (Del Savio, Loi and Stupka, 2015). For example, William P. Kabasenche and Michael K. Skinner describe the potential transgenerational harm of the pesticide DDT (dichlorodiphenyltrichloroethane). The use of DDT as a pesticide has been banned for decades. However, recently it has been used to control malaria in some regions of Africa. Its use is linked to the transgenerational inheritance of kidney, testis and ovary disease. Hence, the use of DDT to protect the current generation’s health will affect future generations’ health. This idea raises an ethical dilemma, which is made even more complex if we factor in the non-identity problem. Presumably, using DDT to prevent malaria will affect who is conceived at what time. If we stop using DDT, the future generation will be different from those born if we use it. This creates a paradox. The very people we are trying to save in the future will potentially never exist in the first place. To whom do we have a responsibility, then? M. C. Roy, Charles Dupras and Vardit Ravitsky have discussed the implications of the non-identity problem to reproductive technologies (Roy, Dupras and Ravitsky, 2017). The non-identity problem is relevant if the technologies affect which child will be born, not if we affect a child or embryo already in existence. Hence, epigenetic harms that occur before conception, through manipulation before fertilization, will affect identity (and bump up against the non-identity problem). However, epigenetic harms or influences, such as the culture medium, that affect the embryo in vitro will not be identity affecting, as the embryo will be the same.
In what follows, I shall investigate how a developmental view of life can challenge the importance we attribute to numerical (‘genetic’) identity. It is by no means my intention to solve the non-identity problem, just to demonstrate how different ways of looking at identity can shed a different light on decades-old discussions. In 2020, two months before the COVID-19 crisis broke out, I was at a workshop near beautiful Lake Geneva hosted by the Brocher Foundation. It would be my last ‘IRL’ conference for a long time. The workshop organizers invited scholars (sociologists, bioethicists, etc.) to reflect on the ethical implications of using CRISPR/Cas9, a procedure for altering and editing genes, on human embryos. The occasion was that a Chinese researcher, He Jankui, had used this technique on human embryos to ‘give’ them the genetic variant associated with HIV immunity.2 Several talks at the workshop engaged with whether embryo editing, using CRISPR/Cas9, was less ethical than embryo selection.
Embryo selection, or preimplantation genetic testing, has existed for decades. It means creating several embryos in vitro and performing genetic testing on them. Prospective parents can opt for this procedure if they risk transmitting a genetic mutation to their offspring. The embryos that are found to carry the genetic mutation are discarded. Only embryo(s) free of the mutation are transferred to the prospective mother’s uterus. In the case of embryo editing, which CRISPR/Cas9 has made feasible, it could, in principle, be possible to create one embryo and ‘fix’ the genetic mutation in that embryo. Each approach has its benefits. Embryo selection is a tried technique and is less invasive as it does not require changing the genetic code. However, at least one of the embryos must be free of the mutation, which is sometimes impossible. It is also impossible to insert new genes into the embryo: you must work with the genetic material of the persons from whom the sperm or egg originated. CRISPR/Cas9 could, in principle, be used to ‘fix’ genetic material that is not already available in one of the embryos. Hence, new genetic material can be added to the embryo.
From a conceptual point of view, there may be another difference between the two techniques that some presenters deemed relevant. First, in the case of embryo selection, the embryos that do have the mutation associated with the disease will be discarded. Throwing away embryos may be unacceptable for people who believe that embryos are potential or actual human persons. In the case of CRISPR, in principle, only one embryo is created, which is then ‘fixed’. So theoretically, no embryos would have to be discarded. I say ‘theoretically’ because the fact remains that embryos may perish spontaneously in vitro, so the procedure could have to be repeated several times. Moreover, many embryos will have been discarded during the experimental phase to develop both techniques. Nevertheless, when in 2016, the first so-called three-parent baby was born, it was rumoured that the prospective parents chose nuclear transfer (‘three-parent baby’ technique) rather than embryo selection to avoid the destruction of multiple embryos. The ‘three-parent baby’ technique can be used when the prospective mother risks transferring a mitochondrial disease to the child. The technique implies that the nucleus of the prospective mother’s egg is inserted in an enucleated oocyte from a donor. Thus, the mitochondria from the donor are used. For this technique, embryo selection is, in many cases, possible. The first baby conceived in this way was born in 2016 in Mexico. The story goes that the (presumably Catholic) prospective parents chose this method so that no embryos would be discarded.
As I have stated before, the distinction between choosing an embryo with ‘better’ genes or changing an embryo so that it has other genes seems relevant. This distinction is relevant regardless of the opinion of ethicists about the embryo’s status and whether they can accept that some embryos might be discarded. In the case of embryo selection, so the argument goes, you are choosing one future person over another. Even if we do not consider an in vitro embryo a person, the hope is that it will eventually become one. In the case of embryo editing, we are not choosing one future person over another. However, we are changing their genetic makeup so they will not develop a specific condition. Suppose we accept that genetic modification will give the future person a better life because they will be free of a debilitating condition. There may even be a moral duty to do so in that case. Therein, some people argue, lies the difference with embryo selection. In the latter case, we do not only increase the likelihood of a future person leading a life free of a known condition, but we are also choosing which embryo to apply this to and, in doing so, choose one future person over another. Chance is replaced by choice. Some ethicists, such as Julian Savulescu, argue that if we can select one future person over another and this one person has less chance of developing a disorder, we have a moral duty to do so (Savulescu, 2001; Savulescu and Kahane, 2009). However, if we consider Parfit’s remarks, we may also wonder for whom this action would be better. After all, the embryos that were not chosen had nothing to lose in the first place. We do not decide whether the embryos will have a specific disorder. The discarded embryos will merely not be born. If you consider being born better than not being born,3 there is no reason why picking the embryo without the mutation is better for the embryo not picked. The notable exception would be if the disorder selected against would result in life below the threshold of what is worth living. Such a threshold is difficult to define, as this may imply predicting what might be, by definition, unpredictable. However, it is difficult to say that not picking an embryo without the mutation harms the embryo with the mutation: the former future human would not come into existence. For the latter embryo, in an embryo selection procedure, the life with the mutation is simply the only one available, and such a life may be preferable to no life at all. In the case of embryo editing, the situation is different. Here, the argument goes, we are changing the person the embryo will become. Here the choice is between having a life without the disease-causing mutation or a life with the disease-causing mutation. If we consider the question of whether happiness or well-being depends upon whether someone is susceptible to a genetic disease or not, this seems relevant. If we do not remove the genetic mutation, provided that we can do this safely and efficiently, we may be negligent and cause this future person unnecessary harm.
The non-identity problem has puzzled reproductive ethicists for decades, to the extent that some people just choose to ignore it. After all, many of us would like to argue that if it is indeed possible to pick a ‘better’ embryo, or at least an embryo that will be spared a devastating genetic disease, then we must do so. However, in this workshop on the borders of Lake Geneva, the non-identity problem was used in several talks to argue for or against embryo selection or embryo editing. It is not my aim here to comment on the ethical conclusions or even to question the use of the non-identity problem in reproductive ethics. There may very well be good reasons why non-identity matters. Instead, I would like to reflect on which basis the identity problem occurs. It seems that, like Derek Parfit, many ethicists thought that what happens at conception is indeed unique (Parfit, 1984). It is where an individual starts existing. Even secular ethicists, regardless of their opinion on the status of the embryo, think that causing potential harm or benefit to one embryo and not to another is relevant, as it is this embryo that eventually becomes a person. There is a period after conception when the embryo could still split into monozygous twins. This time frame ends around the fourteenth day post-conception, when something called the primitive streak forms. For some, this moment also has moral significance, as it is deemed to be the moment when the embryo is considered an individual (Steinbock, 1992). Interestingly, the discussions about the embryo’s moral status centre around the embryo’s characteristics. Some would argue that, as it has all the potential to develop into a human being, it already has dignity and should be treated with respect. Others state that such an early embryo is just a bunch of cells and, therefore, cannot have dignity or moral standing. However, most reproductive ethicists do not deny that an in vitro embryo has an identity. Granted, everyone alive today originated from a specific embryo. What is less clear is that this type of numerical identity matters morally.
I can think of two reasons why this would be the case. First, it is possible that what counts is the numerical identity. So regardless of whether we can imagine that a given embryo can develop into different people with different personalities if it were to grow up in other circumstances in parallel universes, it is trivial that one embryo will be one person in the same universe. It is strange, though, that this merely numerical fact carries so much normative weight in discussions about harm to persons or non-persons, and it may be worth reflecting somewhat longer on why this is so. Scholars probably consider it relevant here that this embryo has a unique combination of genes that will remain the same during its lifespan. Even if the embryo in vitro per se is nothing but a bunch of cells, it already contains its essence, the (nuclear) DNA. Therefore, we may think that if we pick embryo A over embryo B, these will have different identities, even if they were raised in the same circumstances. Furthermore, what we think is essential for normative conclusions here is the unique genetic combination of each embryo. However, if that is the case, it complicates the discussion of CRISPR even further, even without considering epigenetics. If we edit an embryo to avoid a particular congenital disorder, we, in fact, also change its genetic makeup. Rather than ‘curing’ an embryo, we create a different person. If genetics is the decisive factor in identity, this may also be ethically relevant.
With these reflections, it is not my aim to draw a specific conclusion or argue one way or another. Ethical arguments for and against particular techniques that refer to the non-identity problem are often relatively dry and technical and have ideas that are hard to waylay. It is important to keep questioning the basis on which these arguments rest and which we often take for granted. What is an identity, and why would numerical identity matter so much? Maybe the importance we attributed to genetic identity suggests a preformationist view on identity and personhood at its heart. If we think about our identity, we think about something that is both stable and develops over time. Perhaps a Waddingtonian landscape is a good metaphor with stability and plasticity to adapt. This means that what is relevant in discussions about future well-being and responsibility in reproductive ethics should not only hinge on genes remaining the same but also consider the entire development of an organism, from conception until death, and encompass all its experiences and chance encounters. When we think about embryos, the future child we feel responsible for is not available yet. Interventions that change a person’s possible experiences may be more identity-affecting than a combination of genes.
Perhaps a truly developmental perspective on identity would allow us to forego these technical discussions on numerical identities and focus on other things, such as the importance of experience and context for identity. Maybe it is time for reproductive ethics to question its reliance on the primacy of genes for arguments. My gut feeling is that this would open up new perspectives beyond focusing on what happens in vitro. Nevertheless, I will leave this discussion and its potential implications for now. To fully appreciate the importance of chance and experiences, an epigenetic or developmental view of life may not yield the entire picture. The environment itself may still be a deterministic prison. As I have already hinted, epigenetics may demonstrate that we are open systems all the way into our molecules. This realisation opens up possibilities to see life differently.
In the last chapter of the 2003 collection Cycles of Contingency, Cor van der Weele states that ’DST (Developmental Systems Theory) and ethics in their present forms are clearly distinguished as normative enterprises, or, if you prefer, are worlds apart’ (Oyama, Griffiths and Gray, 2003). As I aim to bring bioethics and systems thinking in biology together, I dedicated this first part to describing the relationship between science and philosophy and ethics. I used the case of Macchiarini to argue that philosophers and ethicists should be included in scientific research projects from their inception onwards. They can function as benevolent gadflies. As gadflies, their task is to demand conceptual clarity and explanations of ideas that scientists may take for granted. In the final two chapters of Part One, I described how ethicists sometimes take concepts, such as identity, for granted. Given the sizeable existing corpus in bioethics on the ethics of genes, I spent some time explaining some of the concepts and ideas that permeate the discussion. Starting from the original meaning of ‘epigenesis’ and tracking this through Waddington’s epigenetic landscape, I described how these findings suggest a dynamic view of biology that we do not always acknowledge in current bioethical discussions on genes and genetic technologies. In the next part of the book, I will describe a view of life that stresses historicity, indeterminacy, and chance encounters. I will argue that, given the entanglement of organism and milieu, to understand and appreciate the phenomena of life, how life is experienced may be as important as understanding its mechanisms.
1 Varela was inspired by the poem Traveler, There Is No Path by the Spanish writer Antonio Machado.
2 Although this is not entirely what happened. He introduced a change in the DNA that he hoped emulated the behaviour of the gene that is responsible for HIV resistance in some people.
3 Of course, we should not take for granted the fact that being born is actually better than not being born, as is argued by David Benatar in Better Never to Have Been (Benatar, 2008).
4 In the period 2016–2018, at various public events visitors were invited to place a broken EMOTIV Epoc device on their head, with a thin sheet of paper in between. Another visitor traced the outlines of the device with a pen. At each event a set of drawings or ‘hidden designs’ was generated. These were transformed into 3D ceramic sculptural pieces using varying techniques and matter. See the chapter ‘Synaptic Morphing’ in Vandeput, B (Bartaku) 2021, Baroa belaobara: berryapple (diss.), pp. 167–197, Aalto University, Espoo, https://research.aalto.fi/en/publications/baroa-belaobara-berryapple