92.Genomic sequencing provides information that can help us understand patients’ diseases and determine the treatments that might be most effective for them. Genome editing might be one of the ‘personalised’ treatments opened up by sequencing. Technological advances are providing an increasing capability to precisely edit, delete or insert genetic material at specific points in genomic sequences. However, as a treatment still in its infancy, genome editing raises different technological and ethical issues to genomics.
93.Research Councils UK outlined to our predecessor Committee the relationship between genomics and genome editing, and the potential applications of each:
Genomics allows us to pinpoint genes important to animal, plant and human health, farming and species’ diversity in the wider environment, and to understand how genes are inherited and how they change across generations. Genome editing allows scientists to precisely modify genes to study their role in biology and disease, to synthesise useful gene products, modify cells for therapeutic purposes, and improve crops or farmed animals.
The Wellcome Sanger Institute explained that:
Although genomics and genome editing have scientific and technological overlap they represent two distinct areas of research and technology and each have their own distinct regulatory and ethical challenges that do not easily lend themselves to consideration as one entity.
94.Dr Magdalini Papadaki, of the Association of the British Pharmaceutical Industry (ABPI), told us that genome editing is one form of a “very promising” group of therapies known as cell and gene therapies. She explained that genome editing for therapeutic use is still at an early stage of development:
We are just starting to see the first clinical successes of cell and gene therapies. We have only eight cell and gene therapies approved in the whole of Europe […] Gene editing is already in clinical trials as a subset of gene therapies, but it came out of the academic pipeline a maximum of one and a half to two years ago. Although we are starting to see some clinical trials, just think of it as the next wave of gene therapy, so it is a bit more distant.
The ABPI told our predecessor Committee that:
The UK is a world leader in the research and development of [advanced therapy medicinal products], but as other countries continue to invest heavily in this industry it is important that the UK continues to build on this base to secure its position as a global hub for researching, developing, manufacturing and adopting advanced treatments.
Professor Bell warned that “the UK does not want to miss out on [genome editing]. In a way, we missed out on antibodies; let’s not miss out on this, because we think it is going to be quite big”.
95.One of the UK’s ten Catapult Centres focuses on ‘cell and gene therapies’, and has been supporting the industry since 2012. Its budget from Innovate UK in 2016–17 was £14m. Professor Waseem Qasim, of the Institute of Child Health, told our predecessor Committee, however, that:
The UK has set up various programmes to develop cell and gene therapy—the Catapult and so on—but the amount of spend is nowhere near as high as other countries are putting in.
Professor Qasim also highlighted that the development of genome editing was being constrained by the NHS’s capacity to deliver new therapies, including limited “bed space, specialist nursing staff [and] laboratory processing capacity”, as well as insufficient infrastructure for manufacturing necessary biological products:
One of the critical things we deal with is that we have to make disabled viruses—we call them vectors—to deliver some of the reagents. The capacity to do that is saturated in the UK; there is a waiting list to try to get into the laboratories to manufacture those types of goods. That needs addressing; it is a bottleneck.
96.Since Professor Qasim gave evidence to our predecessor Committee, the Life Sciences Sector Deal has announced that the Industrial Strategy Challenge Fund will support advanced therapies, including genome editing. Professor Bell told us that measures have been taken to support viral vector manufacturing, but that more still needs to be done:
One thing that came out of the tranche of money that appeared with the launch of the [Life Sciences Industrial Strategy] is that we are going to create a manufacturing facility for early phase and mid-phase viral vectors, which I think will be really welcome. Will it satiate the need? It will not for sure; there will still be a substantial demand, and I think we need to think about how we can encourage companies in that space to place their manufacturing capabilities here as well.
Dr Papadaki told us that the ABPI welcomed Innovate UK’s open competition to build viral vector manufacturing infrastructure, but warned that “incentives, other than just Innovate UK funding for these companies to expand, are also an important approach to it”.
97.Dr Papadaki believed that genome editing was one of a number of new technologies that were challenging the traditional approach to research and development:
We need to have a greater level of co-ordination between the different stakeholders—NHS, NICE and MHRA—new collaborative schemes and almost a new pathway for decision-making where all those players share the same evidence or are part of a continuous decision process. This was the basic premise [that the Accelerated Access Review] put into the picture.
Professor Bell told us that the NHS had in essence applied the approach of the Accelerated Access Review to genome sequencing, and that he wanted that approach to also be applied for gene and cell therapies and for genome editing:
These are transformational therapies. We do not want to wait four or five years before they get adopted; we want to make sure they are adopted quickly and efficiently.
98.Technological progress will depend, however, on the further evolution of the regulatory regime for genome editing, and the ethical debate that will underpin that. There are different ethical factors involved in the different types of therapeutic applications of genome editing:
The Wellcome Trust, the Association of Medical Research Charities and Cancer Research UK believed that “the differences between somatic and germline research, and the differences between research and clinical applications, need to be carefully distinguished in ethical discourse about the benefits and risks of genome editing technologies”.
99.The Wellcome Sanger Institute highlighted areas with fewer potential ethical issues:
Genome editing is an immensely powerful research tool, and not all uses of genome editing are ethically contentious or require any additional regulation. The use of genome editing to create cell-lines that better mimic human disease or allow high-throughput screening of drugs against cancer causing mutations are examples where genome editing is providing highly impactful research but has no direct consequences for human health or reproduction.
Similarly, for somatic genome editing, provided efficacy and safety can be established, there seems to be a near-consensus that it poses fewer ethical issues. The Nuffield Council on Bioethics reviewed the ethics of genome editing in 2016, and concluded that although “there is always some risk attached to the introduction of a new therapeutic product […] it is unlikely that, for the most part, therapies based on genome editing will raise distinctive issues for the handling of safety and efficacy considerations”. The Christian Medical Fellowship agreed:
If gene editing tools are used with the aim of addressing a genetic disorder and saving the lives of an existing mature embryo, foetus or post-natal individual, without any intention to change the germline, it is a positive therapeutic development that does not raise many new significant ethical problems, other than safety.
The Nuffield Council on Bioethics told our predecessor Committee that “given concerns over the uncertainty of outcomes, a relevant consideration will be whether alterations to the genome in patients’ tissues can be neutralised or reversed”.
100.In contrast, there is significant debate around the ethics of editing germ cells or human embryo cells. The Nuffield Council on Bioethics told our predecessor Committee that “of all the potential applications of genome editing that have been discussed, the genetic alteration of human embryos in vitro has consistently generated the most controversy”. The evidence we have received has described a variety of important ethical considerations, and our predecessor Committee examined many of these, including:
101.UK research organisations published a joint statement on genome editing in 2015, acknowledging that genome editing of human germ cells or embryos “raises important ethical and regulatory questions, which need to be anticipated and explored in a timely and inclusive manner as the basic research proceeds, and prior to any decisions about clinical application”. Nevertheless, they argued that “genome editing technologies may hold significant potential for clinical application in the future”. The Academy of Medical Sciences told our predecessor Committee that “in some cases, the ability to edit the genome of a germ cell or embryo may be the only means by which parents are able to have a biologically related child unaffected by a hereditary disease”. Genetic Alliance UK, representing patients affected by genetic conditions, wanted to see potential applications of genome-editing as a reproductive treatment examined further. The 2015 joint statement by UK research organisations concluded that:
Research using genome editing tools holds the potential to significantly progress our understanding of many key processes in biology, health and disease and for this reason we believe that responsibly conducted research of this type, which is scientifically and ethically rigorous and in line with current legal and regulatory frameworks, should be allowed to proceed.
The US National Academies concluded in 2017 that:
Heritable genome-editing trials must be approached with caution, but caution does not mean they must be prohibited. If the technical challenges were overcome and potential benefits were reasonable in light of the risks, clinical trials could be initiated.
Professor Chris Whitty, the then Interim Government Chief Scientific Adviser, told us that genome editing is an “area where science cannot stray beyond what the public, as represented by Parliament, are comfortable with”.
102.A range of regulators currently oversee different aspects of genome editing in research and clinical application, including the Human Tissue Authority, the Medicines and Healthcare products Regulatory Agency and the Human Fertilisation and Embryology Authority. Therapies involving somatic genome editing are regulated similarly to other gene therapies, and clinical trials of such therapies have already started. The implantation of a genetically altered embryo into a woman is currently prohibited under the Human Fertilisation and Embryology Act 2008, other than under certain conditions to prevent the transmission of serious mitochondrial disease. Research involving human embryos, up to 14 days old, is permitted subject to the conditions of the Act.
103.Many stakeholders supportive of continued research into genome editing told our predecessor Committee that the existing regulations in this area are adequate for the moment. The Wellcome Trust, the Association of Medical Research Charities and Cancer Research UK believed that “the UK currently strikes a good balance with the regulation of genomic and genome editing technologies”. The Association of the British Pharmaceutical Industry thought that “the UK is a leading location for robust and proportionate regulatory thinking”. The Academy of Medical Sciences stated:
We support the continued use of genome-editing in pre-clinical biomedical research, provided that the work is scientifically and ethically rigorous, and is in line with the relevant regulatory and legal frameworks […] The Academy recognises that the [Human Fertilisation and Embryology Act] provides a robust and sufficiently flexible architecture to govern the ethically sound use of embryos in such a way, and believes that these regulations are also adequate.
104.The Department of Health and Social Care told us that “the Government has no plans to amend the [Human Fertilisation and Embryology] Act to permit germline modifications”. The CMO did not want a review of the 14-day rule, because “there is an ethical debate that will take another five to ten years, but there are risks in opening up that Act, because it is not about mitochondria and gene editing; it is about a lot of women’s health”.
105.Mitochondrial donation is a technique that allows women whose mitochondria (structures found in the fluid inside cells) carry serious inherited disease to give birth to children free from mitochondrial disease, by transferring ‘packets’ of the mother’s nuclear DNA to a donor cell containing healthy mitochondria. Since mitochondria contain small sequences of DNA, children born following mitochondrial donation inherit DNA from the donor as well as from their mother and father. In 2015, the UK Parliament became the first in the world to make such treatments lawful. The British Medical Association told our predecessor Committee that:
Should a time arise in the future such that it would be appropriate to consider a specific reproductive application of genome editing, we believe the process of parliamentary and public engagement which preceded the mitochondrial donation regulations would be a good model for policy-makers in the UK to follow.
The process that accompanied the legislative change to allow mitochondrial donation was also raised by others as a good example to follow if germline editing were to be permitted.
106.Genome editing is a rapidly developing technology that is already a powerful tool for research, and which has significant promise for therapeutic use. Different applications of the technology entail different ethical considerations, with ‘germline’ editing being the subject of particular debate. The UK currently has a strong regulatory environment in this area, striking a balance between enabling important research and providing public confidence that ethical and other considerations are given appropriate oversight.
107.We recommend that the Government specifically require UK Research and Innovation to closely monitor the development of genome editing for potential obstacles to innovation in this area. If it becomes appropriate to review or amend the current regulations in light of technological developments, the Government should use a similar process as the one that accompanied legislative changes to allow mitochondrial donation.
260 ‘’, POSTnote 541, Parliamentary Office of Science and Technology (2016)
261 Research Councils UK ()
262 Wellcome Trust Sanger Institute ()
265 The Association of the British Pharmaceutical Industry ()
267 ‘ ’ (2017)
268 ‘ ’ (2017)
269 taken on 29 March 2017, HC (2016–17) 854, Q201
270 taken on 29 March 2017, HC (2016–17) 854, Q215
271 taken on 29 March 2017, HC (2016–17) 854, Q215
272 ‘’, HM Government (2017)
275 ‘’ (2016)
278 The Royal Society of Biology ()
279 Wellcome Trust, Association of Medical Research Charities and Cancer Research UK ()
280 Wellcome Trust Sanger Institute ()
281 ‘’, Nuffield Council on Bioethics (2016)
282 Christian Medical Fellowship ()
283 Nuffield Council on Bioethics ()
284 Nuffield Council on Bioethics ()
285 For example, see the Academy of Medical Sciences (), Genetic Alliance UK (), the Christian Medical Fellowship (), the Center for Genetics and Society () and Human Genetics Alert ()
286 taken on 29 March 2017, HC (2016–17) 854
287 ‘’, The Academy of Medical Sciences, The Association of Medical Research Charities, the Biotechnology and Biological Sciences Research Council, the Medical Research Council and the Wellcome Trust (2015)
288 The Academy of Medical Sciences ()
289 Genetic Alliance UK ()
290 ‘’, The Academy of Medical Sciences, The Association of Medical Research Charities, the Biotechnology and Biological Sciences Research Council, the Medical Research Council and the Wellcome Trust (2015)
291 ‘’, The National Academies of Sciences, Engineering and Medicine (2017)
292 taken on 17 October 2017, HC (2017–19) 437, Q60
293 ‘’, POSTnote 541, Parliamentary Office of Science and Technology (2016)
294 Human Fertilisation and Embryology Act 2008
295 The Wellcome Trust, Association of Medical Research Charities and Cancer Research UK ()
296 Association of the British Pharmaceutical Industry ()
297 The Academy of Medical Sciences ()
298 Department of Health ()
301 ‘’, POSTnote 431 (2014)
302 Human Fertilisation and Embryology Authority ()
303 British Medical Association ()
304 For example, the Wellcome Trust, the Association of Medical Research Charities and Cancer Research UK ()
Published: 20 April 2018