Heritable Human Genome Editing Can Cure or Prevent Diseases

By César Palacios-González

@CPalaciosG 

More than a year after the fallout from He Jiankui’s announcement to the world that he had edited human embryos in order to made them resistant to HIV, the debate on whether we should move ahead with heritable human genome editing has given no signs of slowing down. For example, just a couple of days ago the UK House of Lords was debating this issue, and the WHO’s advisory committee on genome editing is running a consultation on the governance framework that should rule over human genome editing. While there are many ethical questions surrounding human genome editing, there is a question that recently has gained prominence: is heritable human genome editing therapeutic?

Human Genome Editing Does Not Cure

Some academics have recently argued that heritable human genome editing is not therapeutic. For example, the authors of the recently published Geneva Statement on Heritable Human Genome Editing hold that “Perhaps the most fundamental and widespread misrepresentation is that heritable human genome editing is needed to treat or prevent serious genetic diseases”. And Tina Rulli, from the University of California Davis, maintains that “rCRISPR [reproductive CRISPR] does not save lives or cure diseases that would otherwise exist”. According to all of them what heritable human genome editing actually achieves is to create an individual without a specific deleterious gene or genes. The question that comes to mind here is: why is this difference between curing someone and creating someone relevant for the genome editing debate? One answer to this question, very roughly, is that we have weighty moral reasons to cure, treat, or prevent disease in existing humans, whereas we do not have the same reasons to create particular kinds of human individuals. Even when this second question is very interesting, here I will focus on the first one, this is: is heritable human genome editing therapeutic?

The Importance of Nuance

The genome modifications that can be passed down to future generations are those carried out in early embryos, gametes, and gamete precursor cells. This means that if, in an early embryo, we replace a section of the genome that causes disease, then when this embryo develops and its gametes are produced such gametes will not have that section of the genome that causes disease; they will instead have a new section which does not cause disease. Of course, the previous is predicated on the genome editing intervention working as planned. What I just said about early embryos also applies to gametes and gamete precursor cells. We edit their genomes and the edited-out section will not be passed down to future generations, whereas the section that replaced it can be passed down to future generations.

Critics of the thesis that heritable human genome editing interventions are therapeutic are right in that the in vitro editing of gametes, or gamete precursor cells, would not be therapeutic for an existing human. They are right for the simple reason that gametes and gamete precursor cells are not human beings. However, this does not apply to early embryos. Since human embryos are human beings, genome editing carried out in them could treat, cure, or prevent disease for the being that is edited. This is true even if we accept that human embryos are not human persons. For example, Huntington’s disease is a neuro-degenerative disease of genetic origin. For those who have it, parts of the brain stop carrying out their functions properly over time, and the symptoms of this disease usually appear in the third decade of life. If, through genome editing of an early embryo, we were to edit out the defective gene that causes this disease then it would be right to say that we have prevented the appearance of a disease in an existing individual. Here we have to be attentive to the fact that the intervention is preventive for the embryo that we are modifying, I am silent in regards to future generations.

What Happens First Is Important

You might have noticed that Tina Rulli’s claim and that of the authors of the Geneva Statement differ in an important way. Rulli’s claim is about individuals who would otherwise exist. In order to make her case, Rulli asks the reader to image a couple who knows that they are at a high risk of begetting a child with a serious genetic condition. According to her, the couple has three options: i) have sex and beget a child who will be at high risk of having the disease, ii) create a child using a genome editing technology who will have a low risk of having the disease, and iii) do not have any children at all. Rulli concludes that because the option of not having any children is available to the parents, option (iii), then this undermines the claim that heritable human genome editing is lifesaving or curative. In her own words “rCRISPR [reproductive CRISPR] is not morally urgent because it does not involve a child whose existence, or illness, is inevitable”.

In order to understand why Rulli is mistaken let us pay attention, again, to early embryos. Rulli maintains that a “clinician first creates an embryo with genetic defects, and then ‘rescues’ it using rCRISPR”. Now, it is true that a genome edited child’s existence might causally depend on the clinical decision to employ a genome editing technique. For example, a couple who knows that they are at high risk of creating a child with a genetic disease go to their healthcare providers seeking to avoid this. The healthcare providers make a plan with them: they will resort to IVF, then they will scan the embryos, and after that they will carry out genome editing in those embryos who have the deleterious genes. Now, any embryo created following this plan most probably would not have existed if the couple had not decided to resort to the genome editing technique. Why? Because the timing of conception, and thus the gamete that fused and created such individuals, would have changed.

However, it is also true that a genome edited child’s existence might not be causally dependant on the clinical decision to employ a genome editing technique. For example, suppose that a couple decide to have a child through IVF because of past fertility problems (without ever considering genome editing). After the embryos have been created the doctor offers the couple to scan the embryos. The doctor comes back and tells them that all three embryos have the gene for Huntington’s disease, but that they can employ a genome editing technique to replace the gene. The couple accepts the offer and the embryos are edited. In this second case the existence of the embryos is not causally related to the decision of carrying out the genome editing, showing that Rulli is mistaken. This being the case we have to conclude that heritable genome editing interventions can indeed cure, treat or prevent diseases in individuals that would otherwise exist.

At this point we can conclude two things. First, diseases in human early embryos (i.e. human beings) can be cured, treated and prevented via genome editing. Second, in vitro genome editing of gametes, and gamete precursor cells, does not cure, treat or prevent disease in existing human beings. It is important to have this in mind when discussing the ethics of heritable human genome editing. Otherwise, we might fail to properly appreciate who could be benefited from such biotechnologies.