Has the gene genie now left the bottle and entered the clinic?

It has been said that after the discovery of the double-helix structure of DNA and the mapping of the human genome, DNA editing technology constitutes the dawn of a new genetic era. In 2015 the technique known as CRISPR, lauded for democratising gene editing thanks to its in-expense and ease-of-use, was named the ‘Science’ journal’s breakthrough of the year.

Earlier this month a study published in ‘Nature’ detailed how a US-South Korean research team were able to use CRISPR technology to eliminate a genetic mutation from embryos that cause heart walls to thicken, often leading to sudden heart failure. The disease, called hypertrophic cardiomyopathy (HCM), affects one in 500 people and has been linked to the sudden death of otherwise healthy young people, including some high profile athletes. HCM is caused by an error in a single gene and anyone who is a carrier has a 50 % chance of passing it on to their children. Significantly, this new technique holds out the prospect of stopping the disease being passed down the generations.

To demonstrate proof of principle, the research team used sperm from a volunteer carrier of the genetic mutation to fertilise donated egg cells. Ceasing the experiment after five days of embryonic development, 72 % of embryos were found to be free from disease-causing mutations.

One of the chief innovations of the technique was the timing of the intervention. The team injected CRISPR-Cas9 gene-editing machinery into the eggs while they were being fertilised, overcoming two hurdles which had thwarted previous efforts. Firstly, so-called ‘mosaicism’ whereby the problematic genetic mutation is not corrected in all embryonic cells and so remains intact in some. Secondly, the creation of ‘off-target’ or unintended mutations causing new problems, such as increasing cancer risk.

Just because we can, does it mean we should?

Human embryo genomes were actually already modified in China a few years ago, where researchers succeeded with only a small number of their 86 non-viable embryos. This latest announcement is the first time success with the technique has been reported outside China. While it is still currently illegal in many countries to implant a genetically modified embryo, some argue that this milestone brings human trials unavoidably closer.

However, detractors of this kind of germ line editing have pointed out that genes usually perform more than one task in the body, so a tweak here, could have unintended consequences there. Furthermore, these impacts might not get picked up as the affected genes may fall outside the scope of testing.

Indeed, there is not consensus within the wider genetic community itself that benefits outweigh safety concerns. Writing in ‘Nature’ in 2015, a group of researchers called for a moratorium on human germ line modification. They argued that as well as having ‘unpredictable effects on future generations’, current technologies could provoke a public backlash stalling the development of therapeutic genetic changes not intended to be inheritable.

Along with ethical debates about the scope of permissible disease correction, come concerns for a future where the technology is also pursued for human enhancement. Perhaps inevitably, the recent announcement has renewed claims in the media that this research takes us further on a trajectory towards the creation of ‘designer babies’, with the world divided into genetic haves and have-nots.

Perhaps the best rebuke to the extremes of both camps comes from the study itself which introduces an intriguing twist to the intertwined strands of science-fiction and fact. Surprisingly, the test genome did not – as had been expected - treat the new piece of CRISPR engineered DNA as a template for integration into its code, to replace the faulty gene. Rather, the technique damaged the mutated gene in the father''s sperm, prompting a healthy version to be copied over from the mother''s egg.
Consequently, the technique only currently works when one parent already has a healthy version of the gene, complicating the notion of simple selection from a genetic menu.

Perhaps alongside the eradication of heart-stopping disease, we should also decrease the spread of heart-stopping headlines.