The downside of gene editing

Chinese researcher He Jiankui’s use of CRISPR-Cas9 technology to edit a human embryo has sparked international condemnation. The editing, aimed at disabling a gene to increase resistance to diseases like AIDS, raises ethical concerns, risks unforeseen consequences, and highlights the need for a formal global treaty on gene editing.

This article was first published in The Mint. You can read the original at this link.

Last week, the scientific press was filled with reports that He Jiankui, a Chinese researcher, had managed to successfully use CRISPR-Cas9 technology to edit a human embryo and effectively disable a gene (called CCR5) that is responsible for creating the protein pathways through which various viruses infect human cells. Embryos created using this method will, if brought to full term, result in babies that are highly resistant to diseases such as AIDS, cholera and smallpox.

The announcement has, predictably, given rise to widespread international opprobrium from biologists, ethicists and social scientists who have united in their condemnation of this latest attempt by man to tinker with nature. By editing the germ line, He Jiankui seems to have stepped over the line that no-one was supposed to cross—creating inheritable genetic traits that are capable of affecting future generations.

What’s worse, the genes that have been edited out in this case do not, themselves, cause any disease or disorder in the embryo. They merely offer a health advantage that gives those with the edited genes a better chance of not contracting certain diseases. Had the mutation been the direct cause for a genetic disease, editing out that mutation from the genome of the embryo in question could perhaps be justified. However, when the manipulation was merely to offer a greater resistance to an anticipated infection, the justification carries less weight.

To the contrary, it takes the whole issue into uncomfortable territory—not dissimilar to the realm of designer babies, a future that researchers have long attempted to avoid. While the Chinese team has been at pains to say that they will not use this technique to change physical features or intelligence, there is a fine line between providing a health advantage and improving features such as looks and IQ.

Irresponsible gene editing carries the additional risk of generating off-target consequences. It is possible and, in many cases likely, that the genetic outcome of disabling a specific protein will result in unforeseen consequences that might outweigh the advantage provided by the mutation.

In this specific instance, it has been observed that children born without the CCR5 protein pathway are highly susceptible to the West Nile virus. Thus, while genetically editing out this protein might improve the resistance of these children to diseases like AIDS, it will increase their susceptibility to other equally harmful illnesses.

Herein lies one of the more potent arguments against gene editing. The complexity of the human genome means that no edit can be entirely without consequence. Every time we change the genome hoping to offer some sort of benefit, our actions will likely result in some sort of harm as well. The exact nature of these trade-offs are often only evident after the fact, often when it is too late to do anything about it.

It is because of this uncertainty that the global medical community seems to want to err on the side of caution and has arrived at an informal consensus to refrain from experimenting with germ-line gene editing. This approach will ensure that the harmful effects, if any, remain contained to a particular individual so that they do not have a ripple effect through the blood line.

The fact that, despite the informal commitment of scientists around the world to refrain from germ-line gene editing, the Chinese scientists could still go ahead and flout that broad global understanding is an indication of how futile it is to attempt to use an informal moral consensus as a mechanism to regulate science. Once a given technology has become viable and so long as there is sufficient demand for the benefits it provides, there will always be renegade operations that are willing to defy the moral consensus and supply services to meet that demand. If we are to deal with manipulation of the human genome with any of the seriousness that the issue deserves, we will need to work towards agreeing on a formal global treaty that binds all signatory nations to a common set of commitments with regard to gene editing.

Even if we do manage to sign such a global treaty, the sovereignty of individual nation states and the fact that the coercive force of public international law depends on the submission of member states to global consensus makes the enforcement of these principles deeply challenging. In the first place, any treaty that we eventually pass will only be binding on countries that ratify it. With a few exceptions, most international treaties have only been ratified by a sub-set of the countries in the world. This means that even if the vast majority of nations prohibit genetic manipulation, there is likely to always be some place on the planet where you will be able to legally manipulate your embryos to serve some dubious objective.

As it happens, the Chinese ministry of science has reacted to the widespread consternation about this announcement by ordering everyone involved in the baby gene-editing experiment to halt their activities. The fact that they did so on the basis of nothing more than global public opinion is heartening.

However, we should not expect all countries to be so mindful of their international reputation. We would do well to arrive at a formal global consensus with regard to genetic modifications before rogue nations use these technologies to boost inbound medical tourism.