Should we make attempts to change the human genome? - Shaz Raja

Should we make attempts to change the human genome?

Shaz Raja

During a pandemic, it has been asserted that we, as a species, have encountered many hurdles – as well as overcome just as many difficulties. Thus, as we enter a new a recuperating age with vaccine distributions beginning, we must reflect on what has enabled us to come this far. Since the era of the plague, society has made many scientific advancements in technology and medicine, and had it not been for such developments, it is unlikely that any of us would even be reading this article. Hence, I pose a question, the next logical step in human advancement and one that has seen reluctance and scepticism: “Should we make attempts to change the human genome?” .

The notion of “making attempts to change the human genome” leeches onto the fundamental doctrine of recommendation and/or obligation such that an action ‘should’ be done if there is a perceived benefit, whereas it ‘should’ not be done in the reverse scenario. The answer, therefore, lies in the evaluation of ‘benefit’ and ‘disadvantage’ –corresponding to a ‘good’ and ‘bad’ . As this scenario exists in the realm of biological advancement and medical applications, the foundational pillars underpinning evaluation will be that of bioethics: beneficence, nonmaleficence, justice, and autonomy; upon which further considerations may be noted. The motivations for changing the human genome fall broadly into two categories: gene therapy, and gene enhancement. Whereby gene therapy constitutes an “introduction of exogenous genes into cells with the goal of ameliorating a disease condition" (with some adding the prospects of prevention) gene enhancement may be inclusive of that which “improves bodily condition or function beyond what is needed to restore or sustain health”

However, with these distinctions, there remains room for discourse on what constitutes a “disease condition” , or “function beyond what is needed to restore or sustain health” . For the sake of this piece, however, these nuances as well as those on ‘normality ’ and ‘disability ’ cannot be covered. Furthermore, the means of changing the human genome can take place in two strata of cells: somatic cells (nonheritable) and germline (heritable) cells. In contrast to germline cells, changing the human genome in somatic cells creates effects biologically constrained to the individual in which such edits take place and this is already being clinically trialled. However, changing the human genome in germline cells carries on such changes in the progeny of such individuals – requiring greater consideration.

Therefore, in the case of genomic modification in somatic cells (SCGM), it may be argued that gene therapy in these cells is comparable to any other type of medication or treatment. Offering treatment that may reverse a harmful genetic allele to one that is not, gene therapy, under the ethical pillar of beneficence could even be seen as an obligation to provide gene therapy to persons for whom it is the best, or only, course of treatment – persons who would otherwise have their health compromised.

However, such a procedure may not conform to the remaining pillars such as in the premise of autonomy and SCGM in foetuses. The debate of ‘personhood’ (when a foetus is considered to have rights) is outside the scope of this piece and thus, following the English law, one can state that a foetus, is not considered a ‘person’ prior to 24 weeks, and thus, the issue of autonomy and informed consent is waived (as SCGM in foetuses would take place in the earlier stages of development). To follow, even if the foetus were to be considered a ‘person’ , a foetus cannot be considered Gillick competent and so treatment, assessed under beneficence and non-maleficence, merely requires maternal consent (as in the case of foetal surgery).

Furthermore, when approaching germline cell genomic modification (GCGM), it may be used to prevent the transmission of inherited genetic diseases; however, an immediate objection to this is that alternatives exist e.g. not having children, adoption and using donated germ cells. Nonetheless, this does not satisfy some parents’ desires to have genetically related children where IVF (in vitro fertilisation) with PGD (preimplantation genetic diagnosis) may be utilised instead. However, some object to the discarding of unused embryos (as done in PGD) and PGD is not a viable option where all or a majority of embryos will be affected (e.g. Huntington’s disease); in such situations, GCGM may offer an alternative. Likewise, GCGM is merely an extension of SCGM that allows the prevention of hereditary diseases that cannot be treated by SCGM (e.g. those prevalent multiple tissues like cystic fibrosis). In some cases, for genetic disorders that are fatal, it allows birthing children with longer predicted lifespans. Thus, under the pillar of beneficence, GCGM should take place if such a condition can be resolved and it is in interest of the foetus. Despite the pillar of beneficence in SCGM and GCGM, conflict arises considering the ethical requirement of non-maleficence: SCGM has not been proven to be entirely safe accurate nor effective, and there has been associated deaths. In addition, for GCGM, it cannot be said to be able to effectively treat conditions due to issues such as mosaicism. Hence, on one hand one can suggest that the human genome should not be edited, as it’s efficacy or toxicity cannot be proved; on the other hand, it can be asserted that further genome editing should occur in laboratories on human tissues and embryos to advance understanding. Despite so, although SCGM has not been proven to be entirely safe due to the prospects of off-target effects and side-effects resulting from limited accuracy –such errors in DNA replication occur naturally (e.g. the reason for many genetic conditions in the beginning) and it has been suggested that since the rise of CRISPR-Cas9 genome editing technology, it offers accuracy that is increasingly similar to, or more accurate, than natural replication. Mosaicism, on the other hand, may be overcome by carrying out such genome editing in the genomes of gametes directly before fertilisation.

Moreover, although GCGM may alleviate potential financial/emotional burdens on individual families (an incentive under the pillar of beneficence), a continuation of a lack of research (as identified above) leads to possible effects on the human gene pool if certain alleles are removed which may be a factor in natural selection (e.g. positive selection of sickle-cell anaemia and protection). However, were GCGM carried out, it would only be for the treatment of a few diseases such as Tay-Sachs as not enough genes have been directly identified as disease-inducing: thus, not having an effect on the human gene pool.

Correspondingly, it may even be considered unjust to reject GCGM under parental autonomy as they already determine the genetic makeup of the child (by selecting mates). However, socially it may present risks of alienation and anguish as children are seen as ‘constructed products’ that are naturally ‘not enough’ – possibly even leading to a greater compromise in psychological and social health (e.g. depression, anxiety). Another thought exists that GCGM may be utilised under the pillar of justice to provide equality to those whose ascendent traits put their progeny at a disadvantage.

Furthermore, objections to gene therapy exist due to the probability of leading to gene enhancement; occurring as such editing could be considered ‘ unnatural’; however, this argues on the fallacy that natural is superior (e.g. diseases themselves are natural). In fact, some transhumanists hold it to be an extension of evolution such that humans are defective in their requirements and cognitive ability – it is ‘natural’ to improve them (e.g. caffeine). Likewise, objections to gene enhancement suggest the demarcation of social advantages (e.g. plastic surgery) as it may start to be considered ‘ unfair’ to those without such modification. Further objections relay the prospects of eugenics and an intolerance of disability; however, these are probabilistic thoughts and ignore the precedence that strict regulations and sanctions in place may prevent such results.

Be that as it may, the concept of ‘engineering’ children is distasteful and as political theorist Michael Sandel once wrote, “to appreciate children as gifts is to accept them as they come, not as objects of our design or products of our will or instruments of our ambition. Parental love is not contingent on the talents and attributes a child happens to have” . Thus. this concurs that although such potentials exist, parents should still limit modifications to that which is ‘therapy ’ , and not ‘enhancement’ – as doing so may lead to a cumulative culture that views humans differently.

In conclusion, one cannot deny the notion that we should make attempts to change the genome, however, there may objections in how we change the genome. Attempts to change the human genome in laboratory settings should be allowed as it may increase the efficacy and toxicity of treatments of disease that may benefit the population. However, the question of modifying the genome in clinical settings rests on identifying at which point the maleficence outweighs the beneficence and how carefully it may monitored for its intended purposes under the ethical consideration of justice (e.g. therapy).