HPSC1000 Assignment 2
Question: Should we edit the human germline?
Source 1
[1] De Wert, G., Heindryckx, B., Pennings, G., Clarke, A., Eichenlaub-Ritter, U., van El, C. G.,
Forzano, F., Goddijn, M., Howard, H. C., Radojkovic, D., Rial-Sebbag, E., Dondorp, W., Tarlatzis, B.
C., Cornel, M. C., & European Society of Human Genetics and the European Society of Human
Reproduction and Embryology (2018). Responsible innovation in human germline gene editing:
Background document to the recommendations of ESHG and ESHRE. European journal of human
genetics : EJHG, 26(4), 450–470. doi:10.1038/s41431-017-0077-z
This paper presents information gathered by the European Society of Human Reproduction
and Embryology (ESHRE) and the European Society of Human Genetics (ESHG).
The differences between somatic gene editing and human embryo gene editing are
explained, and various technologies to achieve germline engineering are summarised. The
authors review research on both human and non-human zygotes, contrasting promising
successes with observed high rates of potentially dangerous genetic mosaicism and off-
target mutations.
The ethical advantages outlined for this kind of technology include possible multi-
generational health gains, increased respect for reproductive autonomy, and the “increasing
of equality of opportunity” by granting capability to those who may have otherwise been
adversely affected by genetic chance. Conversely, objections on the basis of disability rights,
autonomy violation of future children, disregard for the moral status of research embryos,
and the possibility for non-medical misuse are also summarised.
In summary, this paper is an important source of information as it provides a thorough
background of the technological mechanisms, current global legislation, ethical debates, and
safety concerns surrounding human germline engineering.
Source 2
[3] HARRIS, J. (2016). Germline Modification and the Burden of Human Existence. Cambridge
Quarterly of Healthcare Ethics, 25(1), 6-18. doi:10.1017/S0963180115000237
In this paper, John Harris disputes common objections to mitochondrial replacement therapy
(MRT), where a sick embryo receives healthy mitochondria from a donor. Harris quotes
research that shows 6% of babies are born with a serious birth defect of genetic or partially
genetic origin, and that between one-in-three to one-in-five deaths occur per live birth [4-9].
He uses these findings to highlight potentially unnecessary hesitancy in qualification
standards for the approval of assisted reproductive technologies (ARTs).
Resistance to MRT on the grounds of a child having three parents, as it technically involves
the addition of genetic material from a source outside either parent, is also disputed by
Harris. He says that mitochondrial DNA does not bestow any of the characteristics usually of
relevance between parents and children, and simply grants the child a life without
susceptibility to serious diseases.
Ignoring the consent of the genetically modified child is also dismissed as a non-issue. It is
argued that parents already make a plethora of decisions without the consent of their child,
including its possible genetics given the genotype of each parent, diet once born, and living
conditions.
Harris believes that it is our moral duty to “lighten the burden of human existence”, and
provides a number of justifications for how germline editing is a powerful means to achieve
this.
Source 3
[10] Campbell, J., & Stock, G. (Eds.). (2000). Ruth Hubbard: “Germline Manipulation” [E-book]. In
Engineering the Human Germline : An Exploration of the Science and Ethics of Altering the Genes
We Pass to Our Children, 109–111. Oxford University Press. https://ebookcentral-proquest-
com.ezproxy.library.sydney.edu.au/lib/usyd/detail.action?docID=271388
Ruth Hubbard’s contribution to this book summarises her strong disapproval of human
germline engineering, even if proven safe. This viewpoint is in direct contrast to the
ESHRE/ESHG recommendations (source 1) [1,2].
Investing the time, expertise, and money into advancing human germline editing technology
is argued to be an individualistic misuse of valuable resources that could be used to prevent
larger amounts of suffering. Another practical objection is given with respect to the women
who will be required to undergo potentially risky procedures to obtain the needed embryos.
A large emphasis is placed on unacceptable levels of ignorance involved in manipulating the
germline. Hubbard argues that the effects of any genetic manipulation cannot ever be
accurately predicted, as so many human genes act interdependently. Adverse effects may
also present themselves decades after the birth of the child, after which the procedure may
have already been assumed safe, and consequently widely implemented.
For parents interested in gene editing for therapeutic reasons, Hubbard advocates for other
ARTs, to use sperm/egg donors, or to adopt. For parents interested in enhancement, she
discredits their fitness to be parents, arguing that parenthood requires the flexibility to deal
with phenotypic uncertainties, and to accept who their child may be.
Hubbard’s take on germline engineering presents a number of ideas not mentioned in any of
the other presented sources, making it an important addition to the debate.
Source 4
[11] Gyngell, C., Douglas, T., & Savulescu, J. (2017). The ethics of germline gene editing. Journal of
Applied Philosophy, 34(4), 498-513.
In this paper, the authors advocate pre-implantation genetic diagnosis (PGD) over genetic
editing to select for favourable genes. They argue that a wider range of diseases are able to
be tackled than in PGD. With PGD, none of the embryos produced for screening may be a
suitable genetic match, and it is possible that the chosen healthy embryo may still be a
carrier for the disease selected against. Furthermore, the chance of being able to target
more than just a few different undesirable genes with the typically few available embryos
becomes statistically slim. These are all problems that the authors argue can be overcome
with genetic editing.
As for opposition on the basis of possible mutations or unpredictable repercussions, off-
target effects are compared to the known higher rates of gametic mutations already
expected from cancer treatments, or in aging men. Neither is used to restrict reproductive
liberty.
While enhancement is not directly advocated for, the authors note a number of existing
therapeutic procedures such as lasik eye surgery and plastic surgery that are capable of
being used for non-therapeutic purposes but are nonetheless accessible.
This paper is a useful addition to the discussion as it presents a number of points in favour of
germline editing different to those used by Harris in source 2 [3].
Source 5
[12] Lagay, F. (2001). Gene therapy or genetic enhancement: does it make a difference?. AMA
Journal of Ethics, 3(2).
While not offering any concrete solutions, Lagay shows that what can be classed as
therapeutic use can be ambiguous. One example presented is the option of immune system
fortification, whereby otherwise normal children could be made immune to sicknesses such
as the common cold or flu.
Lagay classifies possible uses of genetic intervention into the four categories of therapy,
enhancement, prevention, and remediation. She hypothesises that many people may be in
favour of all uses except for enhancement. She raises the matter of equal access to the
different categories of genetic intervention, and the possibility for the increase in inequity
between rich and poor. If an acceptable treatment is not seen to align with a medical
purpose, it may only be afforded to those who can pay for it. Finally, Lagay questions how
easy it will be for physicians to determine what the patient’s best interest is in receiving any
of these treatments.
In summary, this paper is important to consider in the context of human germline
engineering as the approval of most people in favour of its use is conditional, but when
scrutinising these conditions in detail, their arguments may be flawed. If human germline
engineering is to proceed, it is important that clear, unambiguous boundaries are set that
those administering and receiving treatment can abide by.
References (Including 5 Chosen Sources)
[1] De Wert, G., Heindryckx, B., Pennings, G., Clarke, A., Eichenlaub-Ritter, U., van El, C.
G., Forzano, F., Goddijn, M., Howard, H. C., Radojkovic, D., Rial-Sebbag, E., Dondorp, W.,
Tarlatzis, B. C., Cornel, M. C., & European Society of Human Genetics and the European
Society of Human Reproduction and Embryology (2018). Responsible innovation in human
germline gene editing: Background document to the recommendations of ESHG and
ESHRE. European journal of human genetics : EJHG, 26(4), 450–470. doi:10.1038/s41431-
017-0077-z
[2] de Wert, G., Pennings, G., Clarke, A., Eichenlaub-Ritter, U., van El, C. G., Forzano, F.,
Goddijn, M., Heindryckx, B., Howard, H. C., Radojkovic, D., Rial-Sebbag, E., Tarlatzis, B. C.,
Cornel, M. C., & European Society of Human Genetics and the European Society of Human
Reproduction and Embryology (2018). Human germline gene editing: Recommendations of
ESHG and ESHRE. European journal of human genetics : EJHG, 26(4), 445–449.
https://doi.org/10.1038/s41431-017-0076-0
[3] HARRIS, J. (2016). Germline Modification and the Burden of Human
Existence. Cambridge Quarterly of Healthcare Ethics, 25(1), 6-18.
doi:10.1017/S0963180115000237
[4] Boklage, C. E. (1990). Survival probability of human conceptions from fertilization to
term. Int J Fertil, 35(2), 75.
[5] Green, R. M. (2001). The human embryo research debates: Bioethics in the vortex of
controversy. Oxford University Press.
[6] Macklon, N. S., Geraedts, J. P., & Fauser, B. C. (2002). Conception to ongoing
pregnancy: the ‘black box’of early pregnancy loss. Human reproduction update, 8(4), 333-
343.
[7] Edmonds, D. K., Lindsay, K. S., Miller, J. F., Williamson, E., & Wood, P. J. (1982). Early
embryonic mortality in women. Fertility and sterility, 38(4), 447-453.
[8] Roberts, C. J., & Lowe, C. R. (1975). Where have all the conceptions gone?. In Problems
of birth defects (pp. 148-150). Springer, Dordrecht.
[9] Bovens, L. (2006). The rhythm method and embryonic death. Journal of Medical
Ethics, 32(6), 355-356.
[10] Campbell, J., & Stock, G. (Eds.). (2000). Ruth Hubbard: “Germline Manipulation” [E-
book]. In Engineering the Human Germline : An Exploration of the Science and Ethics of
Altering the Genes We Pass to Our Children, 109–111. Oxford University Press.
https://ebookcentral-proquest-
com.ezproxy.library.sydney.edu.au/lib/usyd/detail.action?docID=271388
[11] Gyngell, C., Douglas, T., & Savulescu, J. (2017). The ethics of germline gene
editing. Journal of Applied Philosophy, 34(4), 498-513.
[12] Lagay, F. (2001). Gene therapy or genetic enhancement: does it make a
difference?. AMA Journal of Ethics, 3(2).