November 26, 2018

expert reaction to reports of the first genome edited babies

Reactions to reports that a Chinese researcher has created the first genome edited babies.

Nuffield Council statement on reports of first gene-edited babies born in China:

“Today, the media has reported that gene-edited babies have been born in China. If these reports are true, this is deeply concerning. The possibilities raised by heritable genome editing could have significant implications for individuals and for all of society. Furthermore, we do not know enough about the safety of these procedures or welfare implications. It’s crucial that action is taken now to support research on safety, facilitate public debate, and put in place appropriate governance.

“In July, the Nuffield Council on Bioethics published a report on the ethical and social issues raised by heritable genome editing interventions. We concluded that their use could be morally permissible in some circumstances. These circumstances do not, however, exist at present, anywhere. In our report we have discussed what these circumstances might be, but it is now for the wider society to agree them, and to define what governance measures should apply.

“We recommended that any use of genome editing interventions should be guided by two overarching principles: they must be intended to secure, and be consistent with, the welfare of the future person; and they should not increase disadvantage, discrimination or division in society. More work needs to be done to establish whether these principles can be met.

Pete Mills, Assistant Director, Nuffield Council, added:

“Coming on the eve of the second international summit on genome editing, this announcement looks like a cynical attempt to seize headlines. If the claims are true, it is a premature, inexplicable and possibly reckless intervention that may threaten the responsible development of future applications of genome editing.”

Dr Kathy Niakan, Group Leader, Francis Crick Institute, said:

“If true, the report is very concerning. This would be a highly irresponsible, unethical and dangerous use of genome editing technology. In the UK, it is rightly illegal to establish a pregnancy from a genome-edited embryo. Given the significant doubts about safety, including the potential for unintended harmful side-effects, it is simply far too premature to attempt this. We need much more research to understand the fundamental biology before we even consider applying such techniques clinically.

“This worrying report highlights the urgent need for public consultation and international regulation to protect the public from potential harm. Such premature application of an emerging technology could be highly damaging in so many ways. As well as the very real risks posed to the individuals involved, this approach threatens to undermine support for ethical, well-regulated research. Trying to rush the technology forwards, skipping vital scientific and ethical steps, could end up setting us all back.”

Prof Sarah Fidler, Professor of HIV and Communicable Diseases at Imperial College London, said:

“The technology of editing genes to confer cells that become resistant to HIV is not new, but has not been done in embryos. It is unclear yet whether this news has been substantiated in a scientific publication. Media reports so far suggest that the father of these two children had HIV. If this is correct, this would not be considered an indication to look for genetic reasons to prevent transmission of HIV to the infants. If the mother is HIV negative, or has HIV but is on effective antiretroviral therapy (ART), there is no risk of transmission of HIV to her babies. If the father is HIV positive but on effective ART there is zero risk of onward viral transmission to his partner, as shown in previous studies (PARTNER and HPTN 052 studies) and no risk of HIV transmission to his children through this route.”

Prof Darren Griffin, Professor of Genetics, University of Kent, said:

 “Not good, not good, not good.  In a world where scientists, by and large, try to be aware of ethical and social issues surrounding the work that we do, this report takes us back to the Stone Age.

“Scientists cannot be seen to be trying to forge ahead in the absence of ethical constraint. An international treaty on embryo research is now an absolute priority to prevent this happening again.

“Everything about this report is wrong: It is not a peer reviewed article, the findings are not corroborated by the scientific community.  There has been no efficacy and safety testing of the procedure e.g. for off-target effects, nor has it been established that all the cells in the embryo were likely to have been successfully edited.

“Gene editing of embryos holds great promise for a range of issues, if dealt with in a responsible manner, and within an appropriate ethical framework. This report drives a huge scythe through a lot of efforts of responsible to proceed with caution.”

Prof Robert Winston, Emeritus Professor of Fertility Studies / Professor of Science and Society, Imperial College London, said: 

“If this is a false report, it is scientific misconduct and deeply irresponsible.

“If true, it is still scientific misconduct.

“A basic ethical principle is the autonomy of individuals we treat and the need for informed consent for any experiment.

“The foetus cannot give informed consent.  Moreover this is an experiment likely to go wrong as CRISPR/Cas9 is not totally reliable and there may be all kinds’ effects, physical and mental, which could be devastating.

“Worse still this opens the way to genetic enhancement for desirable characteristics.

“It should be condemned.”

Sarah Norcross, Director of the Progress Educational Trust said:

‘This news is shocking on many levels. First, we would have expected to see a lot more research into the safety and efficacy of genome editing in human embryos, before attempting to achieve a pregnancy. Second, we would have expected the first such application of genome editing to be on an embryo which had a serious genetic condition with life-limiting consequences. Given our current level of knowledge, editing the genome of healthy embryos to attempt to confer resistance to HIV is completely unethical.”

Prof Daniel Brison, Honorary Professor of Clinical Embryology and Stem Cell Biology; Scientific Director of the Department of Reproductive Medicine, University of Manchester, said:

“We should not be fanning the flames of publicity for a totally unverified claim.  The last line of the Telegraph piece says it all, the scientist involved ‘also has two genetics companies’…!”

Prof Shirley Hodgson, Professor of Cancer Genetics, St George’s, University of London (SGUL), said:

“This report is of a partially successful gene editing process resulting in the birth of babies with a genetically engineered gene which should reduce the likelihood of that child becoming infected with HIV. However, the scientists performing the editing procedure only obtained ethical approval after they had started the experiment, and there are many potential harms from the procedure. The editing was incomplete and did not affect all the cells of the embryo, the potential for off target mutations in other genes was not investigated as far as I can see….as the work has not been published in peer reviewed journals…..and the other effects of the edited gene such as increased susceptibility to other viral infections could be disadvantageous have not been sufficiently considered. Although this technique has the potential for benefit, such research without sufficient regulatory oversight and peer review is very worrying and could potentially bring the whole field in to disrepute.”

Dr Nathan Treff, Cofounder, Chief Science Officer, and Clinical Laboratory Director, Genomic Prediction Inc., said:

“While it is difficult to fully assess the validity of claims made without having access to peer reviewed data, the work reported thus far represents a significant milestone in the application of gene editing to prevent disease.  The scientific community has assumed the first application would be to edit out Mendelian diseases such as cystic fibrosis. Preventing HIV infection may therefore not be an ideal first, but it will be important to evaluate the genetic analyses performed prior to embryo transfer and following delivery, to confirm the validity and efficiency of editing performed, as well as the claim that “off-target” effects are indeed absent.”

Julian Hitchcock, Partner, Marriot Harrison LLP, said:

“It is illegal to implant genome edited human embryos or human embryos made using edited precursors, in the UK.  However, the Nuffield Council on Bioethics’ Report on ‘Human Genome Editing and Human Reproduction’ (published in July 2018) found no categorical moral objection to such editing, and set out principles upon which it might be permitted in some circumstances.  The news from China highlights the urgency of following up the 15 Nuffield recommendations, and of reviewing the UK’s regulatory framework so that, should Parliament agree to permit limited gene editing of human gametes, precursors or embryos for implantation, the UK is able to set and maintain the highest standards of clinical safety.

“The editing of human embryos for research purposes is lawful in the UK, subject to a licence from the HFEA and to meeting the standard conditions required for any other research project involving human embryos.”

Dr Yalda Jamshidi, Reader in Genomic Medicine, St George’s, University of London (SGUL), said:

“Gene editing tools are fantastic for research but we are still not able to control them well enough to ensure they are safe and efficient for use in humans. The scientists who carried out these studies chose to focus on a gene associated with risk of HIV, however we already have ways to prevent HIV infection and available treatments should it occur. We also do not need gene editing to ensure it isn’t passed on to offspring. We know very little about the long term effects, and most people would agree that experimentation on humans for an avoidable condition just to improve our knowledge is morally and ethically unacceptable. Whether the results stand up to scrutiny or not we need as a society to think hard and fast about when and where we are willing to take the risks that come with any new therapeutic treatment, particularly ones that could affect future generations.”

Dr Christophe Galichet, Senior Laboratory Research Scientist, The Francis Crick Institute, said:

“A Chinese researcher, Dr He Jiankui of Shenzhen, has claimed to have performed genome editing in human embryos leading to the birth of twin girls.  However, this claim has not been supported by any evidence as the research has not been published and thus has not been peer-reviewed.

“While the new genome editing tool, CRISPR/Cas9, is very powerful, it also has its setbacks.  CRISPR/Cas9 uses a type of navigation system in order to find which part of the genome to cut and edit.  This molecular “navigation system” is based on DNA sequence complementarity and it might happen that an extremely similar DNA sequence fools the navigation system to edit the genome in the wrong place; called off-target effect.

“Furthermore, when genome editing is done in early developing embryos (one cell stage), the editing might not happen straight away, meaning that the one cell embryo would have moved on to become a two or four cells embryo. Each cell of the embryo will have the editing tools and will edit the genome independently of its neighbours. In this situation, the embryo is growing from a mix population of edited cells generating a chimeric individual; not all cells of the body have the same genome.

“As no evidence has been given, it is difficult to determine whether these crucial parameters have been assessed by Dr Jiankui.

“Within the UK, genome editing in human embryo is very regulated and only for research purposes.”

Dr Channa Jayasena, Clinical Senior Lecturer in Reproductive Endocrinology, Imperial College London, said:

“It was always inevitable that genetic modification of humans would begin. My fear is that this has been rushed through without due consideration of the consequences, both for human health and for society. Making mistakes during gene editing may create new genetic diseases, despite the noble intention of preventing genetic disease by cutting out the ‘bad DNA’. Will this open the door for ‘designer babies’ who have been selected for specific physical and behavioural traits? We urgently need an international treaty to regulate gene editing of humans, so that we can decide if and when it is safe to use.”

Prof Paul Freemont, Co-Director of the Centre for Synthetic Biology and Innovation, Imperial College London, said:

“I am shocked and disappointed about this work as it is absolutely not clear as to who benefits from this research. Genome editing is a powerful technology with huge benefits – however if this research is proven then it has resulted from no consultation with broader stakeholders and is merely showing technically what might be possible. Everyone in the field already knows what is possible and proving that one can do something technically does not make it acceptable. With the dawn of a new era of genetic technologies it is absolutely essential that the application of such technologies has societal and broader stakeholder approval and this work clearly goes beyond this.”

Prof Peter Braude, Emeritus Professor of Obstetrics and Gynaecology, Division of Women’s Health, King’s College London, said:

“It was inevitable that someone trying to reach the limelight would likely try this. However it is often better to be safe than to be first. Hence the holding of the Second International Summit on Genome Editing starting in Hong Kong tomorrow where just such issues will be discussed.

“At present there are sufficient concerns over off target effects of CRIPSR/cas9 genome editing to be cautious, and to ensure that appropriate experiments on embryos in vitro have been undertaken before moving on to first in wo(man). This is especially the case when any changes made in the genome will be trans-generational – the changes, whether good or bad, will be passed on down from the altered child to their children and so on.

“It is also strange that Dr He has picked CCR5 as his target, citing the huge problem of HIV internationally and particularly from his point of view, in China. Gene editing is a labour intensive single individual technique that requires the use of IVF. If he really believes in this challenge, surely HIV vaccination would reach many more people effectively, and would not require any risky alteration of genes.

“If gene editing is to be used after appropriate safety testing, then surely it would be prudent to use it first for serious genetic diseases for which no safe alternative exists or where other proven technologies, such as preimplantation genetic diagnosis, might be ineffective or inappropriate.

“His own website has some important tenants which he seems to be ignoring himself – ‘Respect a child’s autonomy: Everyone deserves freedom from genetic disease: but only for serious disease, never vanity”.”

Prof. Joyce Harper, Professor in Genetics and Human Embryology, Institute for Women’s Health, UCL, said:

“Today’s report of genome editing human embryos for resistance to HIV is premature, dangerous and irresponsible. I was part of the Nuffield Council on Bioethics working group – we spent 20 months examining all aspects of genome editing. Our conclusion was that we need a public debate as this procedure is taking reproduction to a different level than ever before. And we need legislation. But before this procedure comes anywhere near clinical practice, we need years of work to show that meddling with the genome of the embryo is not going to cause harm to the future person. And are we going to see fertile couples going through these procedures so they can edit their embryos? I call this the reproductive and genetic rich – those who have funds may pay for this unnecessary treatment. We are very lucky in the UK to have the Human Fertilisation and Embryology Authority who will sensibly legislate any future ART procedures. But countries such as China really concern me.”

Dr Dusko Ilic, Reader in Stem Cell Science, King’s College London Faculty of Life Sciences and Medicine, said:

“The genome of the twin girls born this month in city of Shenzhen has been edited to delete the functional gene C-C motif chemokine receptor 5 (CCR5). CCR5 gene is expressed ubiquitously and it has a role in immune system activation. Mutations in the CCR5 gene are linked to resistance to HIV virus infection. Today, symptoms of HIV infection can be kept under control and millions of HIV-positive people worldwide live a normal life. If the titre of HIV virus is undetectable, the risk of transmission of HIV infection to babies is minimal, especially in case of HIV-positive men and HIV-negative mothers. Furthermore, CCR5-linked resistance seems not to be absolute – isolated cases of HIV-positive patients that lack CCR5 have been reported. In one of twins only one copy of the gene was deleted, which does not protect the baby from HIV infection, it might result only in slower progress of the disease. Then, why He Jianhui has done this? The first thing that comes in mind is to claim fame of being the first.

“According to the Associated Press report, the couples were recruited through Baihualin, a Beijing-based AIDS advocacy group, in exchange for a free IVF treatment. In all couples, the men have been HIV-positive, whereas the women were not. All men had the infection kept under control and the titre of HIV virus was undetectable, which means that risk of transmission of HIV infection to babies was neglectable. He Jianhui and a Head of the Ethics Committee who approved the study said that they helped families and their children and that this is ethical – medical staff handling the HIV-positive samples were aware of potential risk of being infected.

“Although He Jianhui claims that the couples fully understood the risk and they were offered a choice between non-manipulated or manipulated embryos, it does not make sense that they really have comprehended the risks to which they were exposing their babies and themselves. The consent forms called the project an “AIDS vaccine development” program.

“If this can be called ethical, then their perception of ethics is very different of the rest of the world.” 

Dr Sarah Chan, Chancellor’s Fellow at Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, said:

“The announcement made today, that the world’s first genome-edited babies have been born in China, is of grave ethical concern.

“In evaluating this news, we should first remember that these claims have not yet been scientifically validated through peer reviewed publication and independent scientific review. Yet whether or not the veracity of these reports is eventually borne out, making such claims, in a way that seems deliberately designed to provoke maximum controversy and shock value, is irresponsible and unethical.

“Human genome editing is a highly contested, still emerging technology. While it holds tremendous potential for benefit, its development must be carefully governed via a process of inclusive global discussion amongst all those concerned. Instead, the covert application of human genome editing followed by this cavalier announcement of the work as a fait accompli puts at risk the entire future of this crucial technology. It threatens to jeopardise the relationship between science and society as well as causing damage to China’s international scientific reputation, and might potentially set the global development of valuable therapies back by years. Good science is not just about generating knowledge in a vacuum; context and consequences are vitally important, and the consequences of this irresponsible action may be dire indeed.

“Furthermore, leaving aside the wider scientific and social consequences, the research is itself is deeply ethically problematic. Every scientific statement issued to date has emphasized the need for further research before genome editing is ready for clinical application to human embryos. The premature application of this experimental procedure involved exposing the children to as-yet uncharacterised, poorly understood risks. This might be justifiable where there are huge benefits to be gained, as for example where children would otherwise suffer a life-threatening, otherwise incurable disease. The claim made by those responsible for the research, however, is that the babies have been genome-edited in an attempt to make them immune to HIV. The lifetime risk of contracting HIV is extremely low in the first place; there are other means of prevention; and it is no longer an incurable, inevitably terminal disease. Putting these children at such drastic risk for such a marginal gain is unjustifiable. And playing with children’s health and families’ hopes in order to use them as a means for a cheap publicity stunt is nothing short of despicable.”

Prof Julian Savulescu, Director Oxford Uehiro Centre for Practical Ethics, University of Oxford, said

“Chinese researcher He Jiankui of Shenzhen claims to have gene edited two healthy embryos, resulting in the birth of baby girls born this month, Lulu and Nana. He edited a gene to make the babies resistant to HIV. One girl has both copies of the gene modified while the other has only one (making her still susceptible to HIV).

“If true, this experiment is monstrous. The embryos were healthy. No known diseases. Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer. There are many effective ways to prevent HIV in healthy individuals: for example, protected sex. And there are effective treatments if one does contract it.

“This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit.

“It contravenes decades on ethical consensus and guidelines on the protection of human participants in research.

“In many other places in the world, this would be illegal punishable by imprisonment.

“Could gene editing ever be ethical? If the science progressed in the future and off target mutations reduced to acceptable and accurately measurable level, it might be reasonable to consider first-in-human trials (with appropriate safeguards and thorough ethics review) in one category of embryos: those with otherwise lethal catastrophic genetic mutations who are certain to die. Gene editing for this group might be life-saving; for these current babies, it is only life-risking.

“These healthy babies are being used as genetic guinea pigs. This is genetic Russian Roulette.”

Declared interests

Prof Sarah Fidler: Professor Fidler’s work includes involvement with the HIV Prevention Trials Network (HPTN)

 Prof Darren Griffin: “No COI.”

Julian Hitchcock: “I was a member of the Nuffield working party and am also a Trustee of the SMC.” 

Dr Christophe Galichet:  “I declare no conflict of interest.”

Dr Dusko Illic:  “I declare no conflict of interests”

Dr Channa Jayasena: “No Conflicts”

No others received.