21 May 2019
Genome editing has featured frequently in the headlines and is a technology with the potential to revolutionise healthcare. Although a number of genome editing techniques are well established in research, the development of more advanced tools, including the CRISPR system, has brought genome editing into the spotlight.
Genome editing can be performed in germline cells (sperm, eggs or embryos) to induce heritable genetic changes or in somatic cells (other cells) to induce non-heritable changes. Somatic cell editing is much closer to clinical implementation, yet has received far less media attention. In this and related briefings we specifically consider this form of genome editing, the potential clinical impact of this technology, and the ethical and regulatory considerations surrounding current and future use in healthcare.
Genome editing involves the deliberate alteration of a cell’s genome through cutting, inserting or otherwise altering DNA. The term is often used interchangeably with ‘gene editing’; however, as editing can occur outside genes, ‘genome editing’ is the more accurate term.
Modern genome editing techniques, in use since the mid-1990s, are not the first technologies capable of altering a genome. Other less precise techniques have been available for decades, primarily as research tools. Naturally occurring phenomena, such as radiation, retroviruses (viruses that insert into host cell DNA) and transposons (mobile genetic elements), have also been used to make alterations to DNA.
Genome editing is considered by many to be part of the gene therapy toolkit. Gene therapy is a term used to refer to treatments that change the genetic content of a patient’s cells to treat disease. Technologies that introduce changes to the genetic content of cells include techniques that do not directly alter the genome, with some simply depositing new genetic material into cells. However, all these technologies raise broadly similar ethical and regulatory considerations.
Some technical features of modern genome editing techniques distinguish them from many other gene therapies; these include:
These characteristics make genome editing particularly promising for several clinical applications. The potential of modern genome editing to provide a broad range of therapeutic benefits is the foremost ethical justification for its development, but also contributes towards the hype surrounding the technology.
Ethical discussion surrounding human genome editing predominantly focuses on modifying the germline, the impact of such changes on future generations, and the implications of so-called ‘designer babies’ (the creation of genetically modified embryos). These issues, while important, have diverted attention away from the arguably more pressing issues associated with clinical applications of somatic genome editing.
There is debate surrounding whether the distinguishing features of modern genome editing create novel ethical considerations over and above those generated by other gene therapy approaches. Some argue that these technologies raise, and perhaps magnify, existing ethical concerns,1,2 including how to ascertain which conditions are sufficiently ‘serious’ enough to warrant making genetic changes, distinguishing between medical treatment and human enhancement, and the use of technologies for which the potential adverse effects are not fully understood.
Others suggest that rather than merely incrementally amplifying existing concerns, genome editing technologies pose novel ethical considerations due to the broader context and potential scale of their use. Advances in genome editing techniques have enabled applications that were once considered vague possibilities to become reasonable probabilities.
UK regulation covering gene therapies is drafted broadly, and focuses on the intended purpose rather than the specific technology used. Therefore, somatic cell genome editing is currently regulated under the same framework as existing gene therapies, as an Advanced Therapy Medicinal Product.3 ATMPs require licensing of clinical trials by the Medicines and Healthcare products Regulatory Agency, and market authorisation from the European Medicines Agency.
The Government4 (supported by other stakeholders) emphasises that at present there is no need to revise existing legislation. Whilst there seems to be very little clarity about how it might develop, critics argue that regulatory change will be necessary to ensure that existing laws and guidelines are fit for purpose for genome editing applications.
Genome editing utilises different mechanisms to traditional gene therapy, suggesting that different approaches to safety assessment may be required. Revisions might also be needed to clinical trial protocols, to the procedures for patients receiving treatment, and to limit the potential for health tourism. Even in the absence of legislative change, it is likely that regulators will still require more resources for evaluation and oversight as demand increases, costs decrease and the therapeutic potential broadens.
Modern genome editing techniques are relatively new, resulting in a limited (though rapidly expanding) evidence base for their use in medicine. Current concerns and considerations surrounding the use of genome editing techniques in a clinical setting include:
Somatic genome editing builds on many of the capabilities of technologies that have existed for some time and is part of the continuum of technological progress of genomic medicine. However, the potential impact of the widespread use of genome editing in medicine on individuals and society may justify special ethical, legal and regulatory consideration aside from other medical technologies.
Two additional policy briefings examine the unique opportunities and challenges arising from clinical application of genome editing and how far the current regulatory landscape may need to evolve in response to technical advances.