February 2019 Pulse

On 25 November 2018, the MIT Technology Review reported that a Chinese scientist, He Jiankui, claimed to have created the first CRISPR-edited babies. In the first of five YouTube videos posted on the same day, He announced that ‘Two beautiful little Chinese girls, Lulu and Nana, came crying into the world as healthy as any other babies a few weeks ago’.

This landmark case has profound ramifications for the ongoing debate among scientists, ethicists and theologians surrounding the ethics of human gene editing.

He and his team worked with couples where the fathers are HIV-positive. Employing a relatively new technology called CRISPR/Cas 9 they deactivated a single gene called CCR5 in the embryos created through in-vitro fertilisation and then implanted them in the mothers. CCR5 is the protein that the HIV viruses use to gain entry into human cells. Its deactivation would therefore theoretically prevent or reduce the risk of infection.

He and his team were not the first scientists to use CRISPR on human embryos. In 2015, Chinese scientists Canquan Zhou and Junjiu Huang used CRISPR to remove the gene that causes the blood disorder known as β-thalassema when it is mutated. And in 2017, Shoukhrat Mitalipov and his team at the Oregon Health and Science University used the same technology to successfully extract a genetic variant from embryos that causes a deadly heart condition called hypertrophic cardiomyopathy.

The difference between the earlier studies and the one conducted by He and his team is that the latter has disabled a normal gene to reduce the risk of a child from getting an infection – they did not remove a defective gene that predisposes an individual to a particular disease. In addition, the infection in question can be prevented by other means, such as safe sex-education or the use of anti-viral drugs.

Scientists have found He’s editing to be incomplete because some cells have silenced copies of CCR5 while others do not. They have also pointed out that CCR5 is not the only protein that transports HIV and that some strains of the virus can enter the cell through another protein called CXCR4. Deactivating CCR5 therefore does not guarantee immunity.

He’s work has resulted in a furore in the scientific community. Ethicists and biomedical watchdogs have condemned the work as ‘monstrous’, ‘unconscionable’ and ‘a grave abuse of human rights’. The Southern University of Science and Technology, where He and his team worked, claimed that it was unaware of the project and immediately launched an investigation. Its preliminary statement described the work as a ‘serious violation of academic ethics and standards’.

This case has once again brought to the surface the serious ethical questions related to genetic research in general and genetic engineering (in this case, gene editing) in particular. It is impossible to address all these issues in the brief compass of this article. I can only provide here a very brief sketch of the moral and ethical issues related to gene editing in a human embryo.

Moral Status of the Embryo

First and foremost, we must clarify the moral status of the human embryo. According to the Christian faith, the human being is a creature made in the image and likeness of his Creator (Genesis 1:26-28) and therefore possesses inviolable dignity and value from its conception. This means that the human embryo must be regarded as a person worthy of our respect and protection. The human embryo therefore must never be treated merely as human tissue that is created in the laboratory, experimented upon and then discarded.

To cause the death of a human embryo in the name of science is to violate the Nuremberg Code (1948), which states that ‘No experiment should be conducted, where there is an a priori reason to believe that death or disabling injury will occur’. Those who are of the view that gene editing does not violate human dignity fail to take into consideration the fact that in perfecting the technology and technique, thousands of human embryos are routinely subjected to research and subsequently destroyed in laboratories across the world.

Off-Target Results

Gene editing, whether conducted in an adult subject or an embryo, is often accompanied by significant risks, some of which scientists are unable to fully anticipate at this point. For example, there is always the potential of error in editing the gene of an early embryo, which some scientists have described as off-target genetic effects.

As the term suggests, off-target genetic mutations occur when the technology employed hits a DNA sequence that is not its intended target. Because of the nature of gene editing, even minor off-target hits may have major consequences. This is especially the case when the subject is a developing embryo. Such mistakes could result in genetic abnormalities or the onset of disease in the foetus as it develops or during adulthood.

Another possible risk of gene editing in embryos is mosaicism. As a result of the intervention, the embryo may come to possess two different populations of cells (a mosaic of edited and unedited genes) with two distinct genotypes.

Several studies have shown that mosaicism is especially common when the CRISPR/Cas 9 system is used on embryos. Studies have also indicated that mosaicism can result in major phenotypic changes that can adversely affect the health of the child. Some known genetic disorders that are directly attributed to mosaicism include: Down syndrome, Klinefelter syndrome and Turner syndrome.

Epigenetics

Scientists and ethicists are also concerned about the way in which gene editing in embryos may affect the epigenetic code that controls the thousands of genes within each cell and determines whether they are switched on or off. They believe that editing the gene of an early embryo could result in changes in the epigenetic information that may have adverse consequences on the health and wellbeing of the offspring.

While we have certainly made great strides in bio-medicine and technology, the fact remains that we are only beginning to understand the genetic factors that regulate embryological and foetal development. That is why leading biologists like Jennifer A. Doudna of the University of California and David Baltimore, the former president of the California Institute of Technology, are calling for a worldwide moratorium on human genome editing.

Future Generations

Besides inflicting possible harms to the embryo, scientists are also concerned that genome editing in embryos could have adverse consequences for future generations that are difficult to predict at this point in time. This is because the genetic modifications made to a developing embryo can potentially be irreversibly transmitted down the line.

Scientists working on the human genome must take seriously their responsibility for future generations. Mark Frankel and Audrey Chapman have rightly cautioned the scientific community, which often displays ‘too great a readiness to attempt to control the genetic inheritance of our offspring’, to carefully consider the consequences that their work might have on their children’s children.

The theologian Donald Mac-Kay has argued that Jesus’ command to love one’s neighbour (Luke 10) extends even to future generations. And in the context of the present discussion, that love is expressed in the careful evaluation of how our current scientific interventions might benefit or harm our children.

In its instruction on bioethical issues, Dignitatis Personae, the Congregation for Doctrine of the Faith of the Roman Catholic Church provides some clear perspectives on the issues we are considering. Dignitatis Personae is clearly in favour of certain forms of gene therapy. For example, it explicitly states that ‘Procedures used in somatic cells for strictly therapeutic purposes are in principle morally licit’.

But a bright line is drawn when it comes to genetic modifications on the germline or the early embryo that may have unpredictable consequences for the future generation.

The moral evaluation of germ line cell therapy is different. Whatever genetic modifications are effected on the germ cells of a person will be transmitted to any personal offspring. Because the risks connected to any genetic manipulation are considerable and yet not fully controllable, in the present state of research, it is not morally permissible to act in a way that may cause possible harm to the resulting progeny (emphasis on original).

Much more can be said about this important and complex issue. But I hope that this brief discussion has sufficiently shown that there are profound theological and moral reasons why gene editing in human embryos should not be permitted.



Dr Roland Chia is Chew Hock Hin Professor of Christian Doctrine at Trinity Theological College and Theological and Research Advisor for the Ethos Institute for Public Christianity.