This post was written by Andrés Constantin and Patricio López Turconi.
Genome editing and CRISPR
CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats) is a new technique of genome editing that offers the possibility of inserting, removing and correcting DNA with relative simplicity and efficiency. Scientists had already developed the ability to edit the genome by altering its DNA, but the CRISPR method has gained attention for being a cheaper, faster and more precise gene editing tool.
CRISPR are short RNA sequences used with Cas9 (CRISPR-associated protein 9) or similar exogenous nucleases that, when delivered to a cell, can cut the genome to excise DNA sequences or insert new ones. The change is achieved by going in while the cells are still dividing to remove a portion of the DNA sequence and replace it with another different, pre-selected and pre-created sequence.
CRISPR can target two types of cells: somatic (body) or germ (egg and sperm) cells. In somatic gene modification the recipient’s genome is changed, but the change is not passed on to the next generation. In germline gene modification, the parents’ egg and sperm cells are changed with the goal of passing on the changes to their offspring.
Germline gene modification can, in turn, be separated into two distinct processes: germline treatment or transfer, and germline enhancement. The first one replaces damaged or harmful traits to prevent or treat genetic diseases. The second one aims to crate or enhance a particular capability or trait, ultimately giving parents the ability to select, modify and create exact genetic traits.
Social Justice, Legal and Ethical considerations
Recently, Chinese researcher and scientist He Jiankui claimed to have engineered the birth of healthy twin girls through altered embryos to ensure they would not contract HIV, through the use of the CRISPR technology. This case of germline gene modification generated serious concerns relating to scientific ethics and the law. According to the Chinese Academy of Engineering (CAE), researcher He Jiankui violated China’s policies and regulations on gene-related research since it carried out an explicitly prohibited clinical operation without scientific validation and full consideration of the unpredictable safety risks. As a matter of law, the Chinese government prohibits the genetic manipulation of human gametes, zygotes and embryos for reproductive purposes and, according to the Chinese Academy of Medical Sciences, ethics calls for scientists to obtain sufficient evidence for the safety and effectiveness of CRISPR technology before the implementation of such high-risk research.
The ethical considerations differ depending on the type of cells targeted by CRISPR technology. In the case of somatic cells, the research involves a voluntary trial participant, and the risks and ethical concerns are confined to that individual. However, germline cells modification procedures principally involve a future person for whom the adverse outcomes may be difficult to redress. In this sense, procedures that target reproductive cells open up the discussion on the following ethical issues.
Safety – It is impossible to know all the ways in which viable offspring may be affected. This is contrary to the ethical principle of due care, that requires research studies to proceed cautiously and only when supported by sufficient and robust evidence.
In order to assess all the possible risks, and in view of the limitations of current technologies, it is possible that scientists and researchers will need to discard embryos when the editing has not been successful. The destruction of embryos implied in these techniques would revive the well-known controversy on the principle of respect for human life and the related issue of the status of zygotes, embryos and fetuses.
Human dignity – The ethical principle of respect for persons requires recognition of the personal dignity of all individuals, acknowledgement of the centrality of personal choice, and respect for individual decisions. It implies that all people have equal moral value, regardless of their genetic qualities.
The modification or enhancement of genetic traits of reproductive cells that have no therapeutic value can be considered to violate human dignity, since it may undermine the offspring’s personhood and uniqueness in the following ways:
Choosing someone else’s genetic endowment can be considered a means of making the offspring a mere instrument for the fulfillment of the wishes and preferences of others;
It has been argued that choosing someone else’s genetic endowment might be analogous to enslavement, except that the limitations on their freedom take the form of a biological characteristic rather than a physical constraint or psychological oppression. Under this logic, the intervention offends the essential dignity and nature of the person as a free and independent human being. It is important to note that a person’s genome, as it relates to the form and experience of their unique embodiment, can be constitutive for aspects of their psychosocial identity.
Choosing someone else’s genetic endowment can bring about concerns with regards to eugenics.
Autonomy and consent –All individual’s genetic data is considered personal data. Autonomy in genetics should take into account the person being tested. In order to decide autonomously, the person has to get reliable information and proper genetic counseling.
In that sense, prior voluntary informed consent without due inducement should be obtained before conducting any human research or testing. For research involving those lacking mental capacity, consent should be obtained from a legal representative. This can be easily achieved in cases of genetic modification of somatic cells.
However, in cases of germline treatment or enhancement, it is apparent that an embryo is unable to give informed consent. The need for informed consent intensifies in these cases, taking into account that the procedure can be constitutive for certain aspects of the offspring’s identity
Social solidarity– Both germline treatment and enhancement procedures may have an impact on the perception of disability and on societal solidarity with disabled people. Having the ability to eradicate the transmission of genetic diseases will probably foster discrimination or stigmatization of certain populations and communities (in particular, to parents that choose not to undergo CRISPR treatments or to already existing people with disabilities).
Bioethicists also believe that genetic determinism may lead to an underestimation of other determinants of health, in particular, of other biological, behavioral, psychosocial and environmental factors. This would result in a failure to identify the real causes of some diseases, affecting scientific and technological progress.
Social justice– Genetic techniques still require a lot of resources that are difficult to afford by some health systems, fostering health barriers related to inequalities in the distribution of wealth. It is possible that the use of genome modification techniques will compound existing inequalities or entrench advantages. This would be the case if, for example, the service were only available at a cost that would be prohibitive to some who might wish or need to use it.
These new developments and breakthroughs in gene editing, with their multiple and controversial applications, are raising serious concerns regarding the appropriate way to address its impact and implications. The health, ethics and human rights communities must work together in examining the risks, challenges and threats that these technologies pose and envision a way forward that ensures the full respect for human dignity.
The views reflected in this expert column are those of the individual authors and do not necessarily represent those of the O’Neill Institute for National and Global Health Law or Georgetown University. This blog is solely informational in nature, and not intended as a substitute for competent legal advice from a licensed and retained attorney in your state or country.