Our research interests at the BHRC cover many aspects of early brain development and as a result we are also very interested in new technologies which have the potential to impact on developmental processes. Many of our researchers are working toward understanding the genetic basis of specific neurological diseases and disorders. Some of these disorders develop later in life but are actually the result of genetic dysfunction during early development. For this reason we are interested in technologies that have the potential to alter harmful genes.
On February 1st 2016, the UK's Human Fertilisation and Embryology Authority (HFEA) granted permission for researchers to edit the genomes of human embryos. This decision arrived in the wake of massive controversy over a new gene editing technique called CRISPR-Cas9, which allows scientists to easily and cheaply alter the genome of target cells and could potentially allow for inheritable genetic changes.
CRISPR-Cas9 is named after the technique's two main components: an enzyme that cuts DNA, called Cas9, and a gene library where Cas9 gets its instructions, called CRISPR. The technique itself was discovered accidentally while its developer, Dr Emmanuelle Charpentier, was trying to develop ways to make yogurt bacteria more resistant to viruses. Charpentier quickly saw the importance of the technique however, stating that, “people had been a bit desperate for an easy-to-use-tool [for genetic engineering].” CRISPR-Cas9 has opened the door for researchers with little or no background in genetics to alter, insert, or delete genes from the animals they were working on.
DNA is made up of patterns of molecules called nucleotides, and these patterns determine the products of a piece of DNA. Gene editing allows scientists to cut out a specific pattern of DNA in order to change how a target gene works. If, for instance, a particular pattern of nucleotides is stopping a gene from working and causing problems then this piece of the DNA could be removed and replaced. This means that those disorders which are caused by genetic malfunctions can potentially be corrected using a therapy based around CRISPR-Cas9. However, most genetic issues can't be treated at the later stages of life and have to be identified and changed before the body and the brain have finished forming. The easiest way to combat this is to perform these genetic alterations in embryos, which would change not only just that individual's genes but also the genes of any children they might have.
Genetic engineering for the purpose of treating human disease has previously been debated, usually with a focus on the risk of medical inequality and designer babies. The discovery of CRISPR-Cas9, with its ease of use and remarkably low cost, has brought that discussion into focus again, sparked off by an article by researchers from Sun Yat-Sen University in Guangzhou, China. The research described the limited effectiveness of CRISPR-Cas9 in altering the DNA of non-viable human embryos, a scientific first. These embryos would not have survived implantation even if they had somehow made their way to an IVF clinic, nonetheless this research was controversial.
Since this initial study others have come out demonstrating greater and greater accuracy with the technique, which has put pressure on the scientific community to answer the question: Should research into CRISPR-Cas9 techniques be conducted on humans? Should we be looking to genetic engineering as the future of disease prevention?
An emergency summit was called in December of 2015. Over three days, scientists, legal experts and bioethicists from all over the world discussed the state of human gene editing and its place in our collective future. “Control with respect to making babies is feasible in a country that wants to do it,” Stanford Law Professor Hank Greely asserted to the summit on its final day, “that still raises the question of countries that may not want to do it, or countries that don't have the capacity to control IVF clinics or physicians within their own borders and that is a genuine problem.” He stressed that control would be more difficult to achieve in research, especially research conducted on animals since it is much easier to hide a garage lab than an IVF clinic.
The summit dealt with the inevitability of progress in this field, and reaffirmed that the decisions surrounding human genome editing must be made by society at large not by scientists alone. In granting permission for researchers to conduct genome editing on human embryos the HFEA have taken the first regulatory step into the future. The research itself, conducted by Dr Kathy Niakan, will aim to determine what makes early embryos viable, information which could dramatically increase the success rate of IVF. After seven days, however, the embryos must be destroyed. The HFEA have outlawed the use of gene editing in embryos that will be implanted or will continue development past the first 14 days of growth. Whether this restriction will be maintained in the future is up for debate, but currently there are laws in place around the world to prevent the emergence of 'designer babies'. These laws, which prevent prospective parents from being selective about traits unrelated to the health of their potential children, would extend to this new technique. Legal reform would be necessary before genetic modification could be available to prospective parents, and even further reform would be required if those parents wanted to do anything more than 'fix' genetic health risks.
For the moment, human gene editing is heavily restricted but the question remains, for how long? How do we control a future we don't fully understand? Professor David Baltimore stated in his opening address to the gene editing summit: “Although gene editing is in its infancy today it is likely that the pressure to use gene editing will increase with time and the actions we take now will guide us into the future.”
The possibility of 'correcting' genetic alterations that produce neurodevelopmental disease is obviously exciting, however the ethical considerations are huge and far reaching. The implications of this kind of research need to be understood not just by researchers but also by society at large, so that we as a collective can decide how to approach these kinds of technologies. Is an end to genetic disease worth the potential risks of genetic editing in humans? Here at the BHRC we are striving to identify the genetic causes of many developmental disorders, but at the same time engaging with these questions. We hope that this work will help all of us to make these decisions.