Research proposed by Dr Kathy Niakan of the Francis Crick Institute in London, in which human embryos are to be genetically modified, has received approval from the HFEA, the UK fertility regulator. However, implanting of embryos is still illegal, and the embryos used are to be destroyed after 7 days.
A group in China, lead by Juinjiu Huang at Sun Yat-sen University, carried out genetic modification of ‘non-viable’ human embryos last year, which cannot result in a live birth. They attempted to modify the gene responsible for β-thalassemia, a disorder in which haemoglobin is mutated and anaemia develops. The group found a number of serious obstacles, including low levels of splicing and uptake of the DNA insert. The paper from this group was rejected by the journals Science and Nature on ethical grounds according to Huang. However, Dr Niakan’s proposal is the first instance of gene editing in human embryos being approved by a regulatory system.
Gene editing is a technique in which the DNA is altered using engineered nucleases – proteins which ‘cut’ DNA at specific sites. The ends at the site of the break are then joined to a DNA insert to produce a specific, targeted mutation.
"The paper from this group was rejected by the journals Science and Nature on ethical grounds"
Genetic modification of embryos has long been a controversial topic within the scientific community. Some argue in favour of the technique, due to the potential removal of potentially crippling genetic diseases before birth. However, changes made through modification can be inherited further down the blood line, prompting others to advise the technique not be used, as effects on future generations cannot be predicted.
Ethical factors would also need to be considered – to what sort of level should we make changes? There is potential for a ‘slippery slope’, where we move from using the technique as a method to treat disease to other unsafe or unethical uses, such as controversial ‘designer babies’.
The recent development of a new gene editing technique called CRISPR resulted in an international summit last December, in which the potential uses and ethics of gene editing in human embryos were discussed. This is because CRISPR is much cheaper and more easily carried out than previous techniques.
“The overriding question is when, if ever, we will want to use gene editing to change human inheritance,” said summit chair David Baltimore.
Over the course of the summit, a range of positions on human germline gene editing were presented. The summit declared it would be “irresponsible to proceed with any clinical use of germline editing” until we better understand the risks involved, though did not move to ban such editing.
Dr Niakan’s research is intended to find out which genes are required during development to produce a healthy baby, and will investigate processes occurring in the first seven days following fertilization. During this period, we develop from a single cell to a group of 200 to 300 cells known as a blastocyst. At the blastocyst stage, cell differentiation has begun to take place, with cells becoming organised for specific roles.
"The summit declared it would be “irresponsible to proceed with any clinical use of germline editing” until we better understand the risks involved"
“Miscarriages and infertility are extremely common, but they're not very well understood” says Dr Niakan. Of fertilised eggs, less than 50% reach the early blastocyst stage, around 25% implant into the womb and only 13% develop beyond 3 months.
There are areas of DNA which are highly active during development, many of which are unique to humans and so cannot be studied using animal models. The roles of these genes are not currently understood. Developing our understanding of how these genes may direct development could improve our understanding of why infertility occurs and improve fertility treatments such as IVF.