Genetic Modification of Human Beings Research Paper

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Abstract

Although genetically modified human beings have been a staple of science fiction for a long time, recent technological developments make human genetic modification plausible. It is true that some genetic modifications such as enhancement of cognitive capacities or of physical appearance are still speculative, but some others such as the modification of the mitochondrial content of the egg in order to avoid certain types of mitochondrial diseases might soon be used in human beings. This research paper describes recent advances in genetic engineering technologies that can plausibly be used to genetically modify human beings at the level of the germline. On this note, it presents some of the ethical arguments for and against such genetic modifications.

Introduction

Recent advances in biotechnologies make plausible the genetic modification of human beings. Such modifications can occur at the somatic level, changing only specific physiological functions or body parts of individuals and lasting throughout their lifetime only. They can also occur at the level of the germline, both lasting throughput the lifetime of the given individuals and being transmissible via the genome to future generations. This type of genetic modifications can be aimed at correcting genetic mutations implicated in the development of various human diseases or at improving on the human genome, i.e., genetic enhancement. There is a significant acceptance of the use of genetic technologies at the somatic level to cure or correct genetic mutations involved in disease development. However, human germline genetic modification, be it to correct certain mutations or to enhance the human genome, is considered morally contentious. Indeed, many countries have laws or guidelines that prohibit germline genetic modifications (Ishii 2014). Nonetheless, those who defend the genetic modification of human beings contend that germline genetic modifications can be of great benefit to human beings by eradicating certain diseases and reducing the burden of disease and disability and by conferring benefits such as longer and healthier lives or increased intellectual capacities. Critics, on the other hand, counter that the use of these technologies presents significant safety concerns, raises eugenic worries, is likely to increase unjust inequalities, can result in serious health risks to future generations, and could take resources away from basic health care provisions or other social programs. Because other entries, i.e., Gene Therapy, already address issues related to human genetic modifications of somatic cells, such modification will not be discussed here.

Conceptual Clarification

This research paper is concerned with germline genetic modifications of human beings rather than with somatic genetic modifications. Thus, the term “genetic modification” refers, unless otherwise stated, to germline genetic modifications. The paper therefore focuses on the development of technologies that are aimed at modifying genes in human gametes (sperms or eggs), zygotes, or early-stage embryos. Both germline and somatic modifications raise some common ethical issues. However, germline genetic modifications, unlike somatic cell genetic modifications, can be transmitted to future generations and thus raise additional ethical concerns that are absent in somatic cell genetic modifications.

History And Development

Germline genetic modifications of the mammalian genome date back to the 1980s. Indeed, the use of genetically modified animals has become an essential feature of current biomedical research. Technological developments used for the genetic modification of other animals can in principle be used in human beings. Many of these technologies, however, are still unreliable and are quite inefficient in part because of the difficulty of ensuring accurate additions or deletions of candidate genes. Nonetheless, advances in genomics, assisted reproductive technologies, and stem cell science make the possibility of genetically modifying human beings feasible today. Current genome editing technologies such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas systems have been shown to be significantly more efficient and precise than older technologies and have the potential to dramatically increase researchers’ power to manipulate genomes (Cai and Yang 2014). They allow scientists not just to introduce new genetic material at random places – as older technologies did – but to delete and edit specific parts of DNA accurately and easily. CRISPR, for instance, has reportedly been used already to create genetically modified macaque monkeys (Niu et al. 2014). Similarly, recent advances in assisted reproductive technologies open the possibility of germline modification in human beings. Groups in the USA and the UK have recently shown the feasibility of replacing mutant mitochondrial DNA (mtDNA) in unfertilized oocytes or zygotes with normal donor mitochondria, (Tachibana et al. 2009; Craven et al. 2010). Researchers believe that this technology can allow women carrying mtDNA mutations to have genetically related offspring without transmitting the condition to their children. The UK has just approved the use of this technology, becoming the first country to explicitly approve human germline modifications (Ishii 2014). Relevant authorities in the USA are also in the process of evaluating whether to allow researchers to begin clinical trials in humans.

Ethical Dimensions

The development and implementation of technologies aimed at modifying the germline raise a number of significant ethical and social concerns. For some, such concerns are serious enough to merit a moratorium or a ban in the development and use of these technologies. For others, however, the promise of these technologies calls for their development and use accompanied by careful attention to ethical aspects and appropriate regulatory mechanisms. This section discusses some of the main ethical arguments that have been proposed for and against the genetic modification of human beings.

Arguments In Favor Of Human Genetic Modification

Two prominent arguments have been presented to defend the use of genetic and reproductive technologies aimed at genetically modifying humans: the argument for reproductive freedom and the fighting genetic disease argument.

Reproductive Freedom

Some proponents of germline genetic modification base their defense on the importance of reproductive freedom and take such freedom to involve not only the right not to have children but also the right to reproduce (Robertson 1994). The right to reproduce includes the freedom to reproduce both by coital means and by noncoital ones such as the use of reproductive technologies (Robertson 1994). People who are carriers of genetic mutations and want to have children who are genetically related to them but avoid passing harmful mutations to their offspring are said to have a legitimate claim to use germline modifications. Moreover, if having children with particular traits is essential to people’s reproductive decisions, procreative freedom also protects prospective parents’ rights to seek genetic enhancement. Childbearing and rearing are normally seen by most people as experiences of great significance that are tied to conceptions of a meaningful life. To the extent that reproductive liberty is thought to be a basic right, interference with reproductive decisions is seen as morally and legally legitimate only when they clearly and seriously harm others (Robertson 1994).

Nonetheless, prospective parents wishing to have children free of particular genetic mutations can avail themselves of other currently available technologies that do not modify the germline. For instance, prospective parents can decide to use sperm or egg donors to have offspring that do not have the genetic mutation in question. These methods, however, might be unappealing to those who value a genetic connection to their children. But other methods also exist, such as preimplantation genetic diagnosis (PGD) in combination with in vitro fertilization (IVF) that would allow prospective parents to have genetically related offspring without particular mutations by selecting only unaffected embryos. It is true that IVF and PGD are expensive and of limited efficacy and involve risks to the woman, but at present there is no reason to believe that germline modification techniques would be less expensive or more efficient. Besides, they would also require the use of IVF.

The argument for reproductive liberty appears less compelling when used to defend germline modifications aimed at enhancing particular genetic traits in offspring. Whatever the right to reproduce entails, it is not at all obvious that it involves a right to have a particular kind of child, that is, one with enhanced traits.

Fighting Genetic Disease

Germline genetic modifications are thought to be an effective way to reduce the burden of certain genetic diseases or conditions. Proponents contend that given that many accept the use of somatic genetic modifications for these purposes and that such a goal is consistent with the aims of medicine, then germline genetic modifications should also be permissible (Harris 2007). Indeed, insofar as germline modifications affect the genomes of future generations, they would presumably be more efficient and beneficial, as they would eliminate the need for other individuals in the future to have to be subjected to somatic cell modifications and to suffer because of their inherited diseases. In fact, because genetic modifications could either correct certain mutations or enhance certain desired traits that are seen as beneficial to human beings, some have argued that prospective parents should not just be permitted to use germline genetic modifications but that they are obliged to do so (Harris 2007). According to these proponents, it is wrong to choose lives for future people that make them much worse off than they otherwise could have been. Insofar as technologies exist that allow prospective parents to improve the genetic makeup of future generations, there is an obligation to do so.

Even when genetic modifications can in principle prevent prospective parents from passing on certain genetic diseases to their offspring, such is likely to be the case only for relatively simple genetic mutations. Most diseases affecting human beings are far from simple. They result from interactions among multiple gene variants as well as a variety of environmental and epigenetic factors. Indeed, the sciences underlying this biological process as well as the complex process of genetic turning on and off are not fully clarified. Thus, although proponents of genetic modification hail these technologies as a way to rid human beings of the burden of disease, it is not clear how effective these technologies would be in accomplishing that goal.

Arguments Against Human Genetic Modifications

A variety of arguments have been offered against the use of technologies aimed at the genetic modification of human beings: arguments about safety, harms to society, and deontological arguments. This section presents and evaluates some of these arguments.

Safety

The most significant argument against human genetic modification involves safety concerns. It is not simply that at this stage of technological development it would be irresponsible to use these technologies in human beings. The argument is that the complexity of human biology makes it difficult to determine the risks involved in tampering with the human genome. Procedures such as mitochondrial replacement, for instance, can involve epigenetic harms or damaging effects because of the mismatch between nuclear and mitochondrial DNA. Moreover, given the uncertainty about safety and efficacy that would exist at least for the initial first-in-human trials, it would be difficult for prospective parents to give informed consent, as relevant information to make autonomous decisions would be lacking.

This concern, however, is not limited to germline modifications. Our knowledge is always limited when we use new medical technologies in human beings. Although appropriate animal research might give us some information about risks and potential benefits, such information will always be limited because of the differences between humans and other animals. Moreover, problems with the animal models used in research, the poor methodological quality of many animal studies, and publication bias all make it difficult to determine the reliability of current scientific evidence about the risks and potential benefits of most medical technologies. But in spite of this, many do not think that the uncertainty is sufficient to prevent research on new technological advances from being conducted. If so, safety concerns by themselves appear insufficient to prohibit research aimed at genetically modifying human beings. At most, these concerns call for requirements that adequate animal research, particularly with other primates, be conducted. Furthermore, even if one agrees that limited information about risks and benefits can render a choice imprudent initially, at some point in time, when more information with a variety of animal models becomes available, it might be reasonable to assume that there will be appropriate information to make a better and evidence-based choice.

Safety concerns in the case of germline modifications, however, are particularly salient because they involve not only risks to the children born through these technologies but also to future generations. Because negative health effects of genetic modifications might affect the offspring of the initially modified children without necessarily affecting the first generation, and because it would be difficult to produce research that attempts to assess such risks – as it would require significant amount of time and costs – critics of genetic modifications can argue that this research is qualitatively different from other types of research.

Concerns about safety also appear in relation to women who provide the eggs needed in order to do the required research to carry out genetic modifications. Research to ensure safety and efficacy of mitochondrial transfer, for instance, requires significant numbers of eggs. The initial studies with human embryos done by Tachibana and his group in Oregon, for example, involved the use of 106 eggs from seven women, with one of them donating 28 eggs (Tachibana et al. 2013). Similarly, nuclear genome transfer research and stem cell research, also possible techniques for human genetic modification, have already required hundreds of eggs from women. Egg extraction involves risks to women, including serious ones such as ovarian hyper stimulation syndrome. Often, however, such risks are understudied with little research being done on the long-term health effects of the drugs used for ovarian stimulation. Moreover, in countries or states where paying women for providing eggs for research purposes is permitted, economically disadvantaged women might be particularly targeted as potential egg donors. This raises concerns that the great need for eggs in order to do appropriate research will lead to increased exploitation of egg donors (Dickenson 2013).

Harms To Society

The genetic modification of human beings may be held to be morally impermissible because of possible egregious social harms. One such harm is that attempts to genetically modify our offspring are likely to diminish our respect for human life with the potential negative consequences that such would bring. Tampering with the human genome, mainly following parental desires, might lead us to see human beings as made to order – in other words, as some kind of biological factory goods, albeit special ones. This can reduce our concerns with respecting human rights and can increase discrimination and oppression of certain groups. Questions about human dignity may likewise arise.

Another possible harm to society derives from the fact that these technologies will be implemented in societies that are far from just. At least initially, these technologies will be expensive, and thus access to them is likely to be limited to those who can afford them. If genetic technologies allow some prospective parents to either correct certain diseases or to enhance particular traits that are thought valuable in our societies, an unequal access to the use of these technologies could increase the social and economic disparities between privileged elites and the great majority of others. The genetic modification of human beings thus could lead to the emergence of genetic castes for haves and have-nots (Stock 2002). By implication, this will foist another problematic dimension to the already worrisome global and local inequalities. Moreover, the use of germline modifications even for therapeutic purposes would open the door to engineering the human genome for eugenic purposes. The elimination of particular human traits that are thought to be undesirable can lead to human rights abuses and increase discrimination against those who have the undesirable traits such as those with certain diseases and disabilities. Given our recent past history, eugenic concerns seem legitimate.

Those who support genetic modification, however, argue that many other technologies that are thought to be permissible already increase inequalities in our society because only some people are able to afford them and take advantage of the benefits that they offer. The possibility that inequalities might increase is thus not a sufficient concern to ban genetic modification even if it is one that requires attention (Harris 2007). Hence, proponents contend that although increased inequality could indeed result from the use of these technologies, other strategies and not their prohibition is the answer. Inequalities created by genetic modifications could be redressed by redistribution of resources. Similarly, such inequalities could be prevented by making genetic modification technologies available to all people. Yet, how to ensure that this genetic resource will be available for all in a context where millions still lack basic health care and other needs is usually ignored.

Similarly, although worries about the eugenic use of genetic modification might seem reasonable, proponents of these technologies argue that the negative effects of eugenic programs in the past resulted from the fact that such programs were state sponsored. The use of genetic modifications should be left to parents acting as consumers, and thus such choices are unlikely to have the negative consequences of state mandate eugenics (Agar 2004). This response, however, neglects that fact that individual choices are influenced by social norms. For instance, in a society where strength is considered desirable, parents are likely to choose such a trait for their children. Individual choices can therefore have eugenic effects similar to those produced by state-sponsored programs.

Critics of genetic modification of human beings have also argued that the use of these technologies for therapeutic purposes is only the beginning of the slippery slope toward enhancement. Even if initially used to ensure that some genetic diseases are not passed onto offspring, it is unlikely that once available these technologies will not be used to modify traits that have nothing to do with diseases such as intelligence, hair or skin color, physical appearance, and so on. Usually, proponents of these technologies contend that appropriate regulations can be set so as to ensure an appropriate use. Nonetheless, what types of regulations should be proposed and how they should be enforced is not discussed.

Deontological Arguments

Various arguments against the genetic modification of human beings involve concerns not about the consequences of such modifications but focus on intrinsic aspects of the use of these technologies that make their use impermissible in human beings. For some, the practice is impermissible because it treats children merely as means to their parents’ ends (Kass 2002). This is particularly the case when genetic modifications are aimed at enhancing human traits and not just at correcting genetic mutations involved in some diseases. Advocates of genetic modification however tend to dismiss these arguments because they reject the claim that creation of genetically modified children involves impermissibly treating children as means to the parents’ ends (Harris 2007). Even if it is the case that children born as a result of genetic modifications might indeed be used as means to their parents’ ends, those children need not be used as mere means. These may not be adequate reasons to believe that parents will not love and cherish those children or that they will not treat them with respect and promote their flourishing (Harris 2007).

Critics of genetic modification also contend that such modifications threaten people’s ethical self-understanding and ability to experience themselves as free and equal individuals (Habermas 2003). Children born through these technologies will regard themselves as at least in part someone else’s project. Their freedom will be undermined by the fact that their abilities have been chosen for them by others. Rather than being responsible for their own project and for choosing their own life plans, genetically modified children will share the authorship of their life with others. An individual so created could never be truly and fully him or herself.

Moreover, some critics contend that at least some types of genetic modifications will prevent human beings from truly regarding themselves as unconditionally equal-born persons in relation to previous generations. This will result in a loss of contingency that will affect the inalienable normative foundations of society. In altering the contingency of one’s life, genetic modifications, particularly when such modifications involve the enhancement of some traits, thus threaten a necessary condition for moral equality (Habermas 2003).

Proponents of human genetic modifications have dismissed these concerns arguing that they presuppose an implausible essentialist conception of human nature (Harris 2007). They also claim that whether children who are genetically modified will see themselves as not the authors of their own lives is an empirical issue for which little evidence can be provided. Proponents of genetic modifications also argue that the necessity of symmetrical relations for equality is questionable as other human individuals, such as individuals with severe cognitive impairments, find themselves engaged in asymmetrical relations with other moral agents and their interest continue nonetheless to be weighted equally (Harris 2007).

Others have called into question the moral permissibility of human genetic modifications, again, particularly of those directed to enhance offspring, because the use of these technologies involves an impermissibly hubristic disposition (Sandel 2007). The fact that parents cannot control all aspects of their children’s lives teaches people a needed humility. Caring deeply about our children and yet not being able to choose particular traits in them teaches parents to be open to the unbidden. For critics of genetic modifications, such openness, which invites us to rein the impulse to control, is a disposition worth affirming in a society like ours that prizes mastery and control. In a world in which parents became accustomed to specifying and choosing the genetic traits of their children, this welcoming openness to the unbidden would disappear thus further promoting the hubris of human beings.

Others, however, have countered that attending to people’s dispositions alone is insufficient when evaluating the permissibility of genetic modifications (Kamm 2005). Arguably, one should also consider the good ends to be brought about by genetic modifications and the bad effects that might also occur. If the good outweighs the bad, then it is not clear that an agent’s hubristic disposition, rather than the evaluation of objective goods and bads, would make the act seeking to genetically modify our offspring morally impermissible.

Conclusion

The possibility of germline genetic modifications of human beings is now within reach. Because such modifications will have effects not just for current generations but also for future ones, we should reflect carefully about both risks and benefits before genetic modification technologies are made available to the public. But any assessment of these technologies that fails to also attend to the ways in which the use of these technologies can either challenge or reinforce values that might be appropriate or inappropriate is likely to be ethically insufficient.

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