My Lords, I open this debate in a spirit of inquiry and concern rather than as an expert with well-established views. I do so because I am a journalist, not a scientist. The field of gene editing is developing so widely across the planet and so deeply in the range of applications that it is time to back the calls of many scientific institutions to extend the debate beyond the medical and scientific fields, where, until recently, any degree of concern has been concentrated. It is time for everyone to know what is going on.
Before I get to the meat of the matter, here for a start is an issue raised by two charities, Genetic Alliance UK and the Progress Educational Trust, once they knew about this debate. In the interests of clarity, they have asked for the phrase “genome editing” to be used consistently in this debate, rather than simply “gene editing”. They warn against too often using the term “CRISPR”, a process of genome editing pioneered since 2012, as if it were the synonym for gene editing in general when there are several other techniques. Having explained that to your Lordships, for the purposes of this debate, and because it was used in its title, I shall refer to gene editing.
Last December, a Chinese scientist was convicted of practising a medical procedure without a licence to do so. He was sentenced to three years in prison and fined 3 million yuan. He is He Jiankui, a name now familiar throughout the world of gene editing. He had researched and produced, through the use of CRISPR, the genomes of what have since become two little girls. What is more, he declared that he had done so at an international genome editing conference in 2018. The world of biogenetics was appalled and flew into an explosion of panic and outrage. The welfare of the little girls is not a matter of public record—not yet.
Last November, I was invited by the Royal Society to chair a debate called “The Quest for the Perfect Human”. Its four panellists were people steeped in the science and application of gene editing and each was familiar with CRISPR. One, Dr Rodger Novak, was co-founder in 2013 of CRISPR Therapeutics. Another was Professor Robin Lovell-Badge of the Crick Institute, where many of its 110 labs are allowing scientists to analyse gene function and disease processes. Professor Lovell-Badge is also a member of the World Health Organization Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. More of that later.
Intervention in a person’s genes for the sake of medical benefits is a technique that was always on the cards once the human genome project was declared complete in 2003. However, science is a constantly flowing river and, before then, interventions such as IV fertilisation had resulted in the first IVF baby, Louise Brown, being born as long ago as 1978. From the late 1980s, scientists in the UK were developing pre-implementation genetic diagnosis—PGD—a process whereby parents with a serious inherited disease in their family can avoid passing it on to their children. This technique is approved in the UK by the Human Fertilisation and Embryology Authority.
My Lords, I thank the noble Baroness for initiating this debate. Although I agree with much of what she has said, I have a different viewpoint of how the science might develop. It is right and proper that society decides what science output to control and whether it is right for society to benefit from it if it harms society.
Perhaps I may start from a different angle. This is a story of another time—of a plausible future 20 or 30 years from now—in which the human experience of life and health, and perhaps even who we are, will unfold unlike anything we have known hitherto. In future, citizens will learn early in life, through a combination of intelligence gathered from their smart accessories, embedded devices and more accurate information from genetic testing, their predisposition to disease—whether they are heading towards disease, depression, dementia or any other condition.
More importantly, they will have a choice of an exit strategy. They will be able to choose a familiar route of medication, behavioural change or lifestyle change, or they might choose novel treatment paths. Those predisposed to disease will be able to have their risky DNA removed or altered. Those with neurological conditions might be treated with brain implants, and even cognitive function might be restored by a cling-film-like membrane or hair-like wires inserted into the brain to restore neuronal connections.
Brain implants are already in use in tens of thousands of patients with epilepsy, tremors, seizures, Parkinson’s disease and even some conditions related to mental health. If such treatments were effective and safe, who would not choose them to divert the course of their illness? Yet our genes and neurons are more than origins of our illness; they are also part of our substrate, our being, our humanity. Would manipulating them risk altering who we are?
Yet we cannot stop science and scientific developments that may make people’s lives better. As humans, we have been shaped by our discoveries: stone tools, fire and its control, eye glasses, electricity, antibiotics, nuclear physics, organ transplants, in vitro fertilisation and the internet, to name but a few.
My Lords, I warmly congratulate the noble Baroness on introducing this debate of great importance. I admired her for suggesting that it was in the spirit of inquiry and concern, not as an expert; I echo her comment. The joy of this place is that we have many distinguished scientists and clinicians as well as many distinguished ethicists among the Lords Spiritual and many others, so this is the right place to discuss this critical subject.
I shall quickly declare an interest as a member of the international advisory council of Chugai, a research-intensive Japanese pharmaceutical company involved in a pioneering genomics analysis programme. I have not discussed this debate with the company, incidentally.
All are aware that nearly every human ailment has some basis in our genes. The recent advancements in genomics are among the most impactful and exciting developments in medical research. Research using genome editing is enabling significantly improved diagnostics and treatment of a range of diseases including cancers, diabetes and cardiovascular disease.
I want to go back 40 years to when I published a paper in the Journal of Child Psychology and Psychiatry on the management of families with Huntington’s Chorea— now called Huntington’s disease—an incurable inherited neurological disorder that severely damages co-ordination and mental abilities, often resulting in psychosis. At that time there was no way to predict who carried the gene until it was manifest in deteriorating symptoms and, inevitably, a prolonged and deeply distressing death. It was a family secret, a taboo subject. However, as life-changing genetic medicine has developed, remarkable progress has been made, as has just been suggested, such that we can now perform genetic testing on high-risk individuals before the onset of symptoms. Pre-implementation genetic diagnosis now allows us to test embryos produced using IVF in order to prevent those with HD genes being implanted and, consequently, prevent the offspring inheriting the disease. Just last year uniQure announced a clinical trial for a gene therapy solution, AMT-130, which aims to utilise a harmless virus to add extra genetic code to patients’ neurons to make them produce a chemical that lowers the mutant Huntington protein. This is the first AAV to enter clinical testing for the treatment of Huntington’s disease—a wonderful example, but just one of many, of the benefit that genome editing may bring.
12:33 pm
The Lord Bishop of Carlisle
My Lords, I add my own congratulations and gratitude to the noble Baroness, Lady Bakewell, on securing this timely and important debate. Unlike my noble friend Lord Patel and other noble Lords yet to speak, I am not a scientist. However, I have vivid memories of following the Human Genome Project with a mixture of excitement and awe as I realised its huge potential for good. I have been equally impressed by the many recent developments in gene editing, including the 100,000 Genomes Project and CRISPR-Cas9, which we have heard about, and their implications for the prevention or treatment of diseases such as cystic fibrosis, muscular dystrophy and cancer.
As our Library briefing makes clear, the benefits for personalised, precision human healthcare in particular could be enormous. The Church of England is supportive of what is going on, especially in the UK, which is leading the way. But, as always with progress of this kind, as we have already been reminded several times, several ethical considerations need to be taken very seriously and have already been mentioned. It is to those that I will now refer, given the generally accepted need of an ethical framework for all this work.
First, there is clearly a need to distinguish between research and its clinical application. Just because we have discovered that we can do something does not necessarily mean that we should do it, for a variety of reasons. In both research and application, it is essential to establish margins of risk for the participants. In the case of research the participants are of course embryos which, according to the HFEA code of practice, need to be granted “proper respect”. That respect is not easy to define but it means that they should never be viewed simply as commodities for experimentation or a means to an end. The 14-day limit for research on early embryos plays an important role here, since that is when the so-called primitive streak begins to appear.
Where clinical procedures are concerned, the participants will include donors, prospective parents and, above all, prospective children, as well as their eventual offspring. We need to consider every aspect of their well-being, including the psychological and social. At the moment, it really is not possible to know how subsequent generations of children might be affected by gene editing in their parents and grandparents. Interactions between genes might not come to light for several generations, so we need further research into the interrelatedness of genes before the clinical application of genome editing is likely to prove universally efficacious or safe.
Also, as we were reminded by the noble Lord, Lord Patel, there is a further distinction to be drawn between somatic or non-reproductive cells and germ or reproductive cells, as the Medical Research Council and others have made clear in the past. Human somatic gene editing does not present any novel ethical dilemmas but human germline genome editing has been aptly described as the bioethical equivalent of splitting the atom. This means its clinical application requires a very nuanced ethical approach. In particular, we need to be aware of unexpected outcomes and unintended consequences, such as deleterious changes in social attitudes; for instance, in our approach to disability and the stigmatisation of individuals.
My Lords, I declare an interest as a founder president of Progress. I take some objection to its attempts to change the nomenclature, as it did at the time of embryo research when it called the embryo the pre-embryo. I do not think that is particularly helpful; it will not really make much difference to how we handle the actual biology and the science.
I am an unashamed gene editor. I have been involved with gene editing in embryos for nearly 30 years and have a company, Atazoa, which has looked at different methods of modifying embryos. We have done that both in mice and in pigs, and not only in embryos but in sperm, so I feel that I have something worth contributing to this debate.
I am grateful to so many people for mentioning preimplantation genetic diagnosis, or PGD, which was invented in my own laboratory. Alan Handyside and I published that first paper, and the first patients are now aged 30, so there is already a technique for preventing genetic disease that has been pretty reliable. It is not absolutely reliable—mistakes have occasionally been made—but the advantage of embryo biopsy is that one is not fundamentally changing the embryo and any risk taken is therefore simply a failure of that patient to get pregnant. As far as we know, there are no epigenetic consequences; we do not think that it causes long-term ill-health.
As the Human Fertilisation and Embryology Authority has been mentioned, I should say that it admitted this week in answer to a Written Question that it has no follow-up on any of the issues currently important in embryology in IVF. So we do not know what happens to babies in the long term after egg freezing, and we have no follow-up on PGD or on a whole range of issues. Such issues are far more important than regulation of IVF, which is done quite inaccurately much of the time. Due to the finances, many private clinics are doing things that most of us in this House would regard as utterly disreputable, such as selling research treatments that have no basis. It is clear that there will always be that risk, just as there was with He Jiankui in Shenzhen University. We also have to say that any medical procedure can be misused; I do not think in vitro fertilisation, or even gene editing, are any worse. Of course, it is terrible for the child born irreparably damaged, who carries that gene editing through their lifetime and passes it on to the next generation—of course, it cannot be controlled in the future. The risk of gene editing in the embryo is of massive importance and it is therefore extremely valuable that we have this debate at least to put this online today.
My Lords, it is impossible to follow that outstanding speech by the noble Lord, Lord Winston. I hope the House will forgive me if I focus on this subject as it applies to international sport.
It is interesting to reflect that 100 years ago in competitive sport the distinction was between the amateur and professional ranks. Today the focus is on the drug cheats who knowingly take banned performance-enhancing drugs to gain a competitive advantage. London was supposed to be the cleanest Games in history; statistically, they turned into the dirtiest. There were 116 failed tests at the London Olympics in 2012, beating the mark of 86 set in Beijing. Of those 116 athletes, 69 have subsequently been disqualified—more than triple the number caught doping at the 2004 Athens Olympics and, as your Lordships will know, only the dopey dopers are foolish enough to get caught during the height of the competitive season.
Thanks to the noble Baroness, Lady Bakewell, we have the opportunity in this debate to look to the future and focus on the next major challenge to clean competitive sport. The outlook is bleak, for the battle between sports cheats and testers is poised to enter a whole new era. The consequences of gene editing for performance enhancement in sport are real. That is why the World Anti-Doping Agency has extended its 2003 ban on gene doping to include all forms of gene editing. It already bans the use of genetically modified cells and gene therapy if they have
“the potential to enhance sport performance”.
The list also includes
“gene editing agents designed to alter genome sequences and/or the transcriptional or epigenetic regulation of gene expression”,
although, interestingly, the responsibility lies with the athlete, which is impossible if their gene editing eventually one day becomes somatic.
The field is advancing incredibly fast, in part due to the discovery in the Olympic year of London 2012 of an easier editing method, CRISPR, which has been referred to, and its subsequent sons and daughters. The challenge in global sport for the remaining years of the 21st century will move on to the consequences of fast-moving developments derived from gene editing, where genetically engineered athletes will be set against the untainted natural skills of the fastest, highest and strongest competitors on earth. At the heart of the debate will be therapeutic use, as opposed to performance enhancement, among athletes, as rightly referred to by the right reverend Prelate.
My Lords, the whole House will want to thank the noble Baroness, Lady Bakewell, for giving us the opportunity to discuss this hugely important topical but also morally important question, which raises grave issues regarding the science and ethics of what we might do, especially regarding eugenics, to which the noble Baroness referred. I particularly endorse the remarks that were made by the right reverend Prelate the Bishop of Carlisle and the noble Lord, Lord Winston, who made an incredibly important speech in our debate today, asking us to consider the wider issues that are at stake here.
The noble Baroness will have seen the response of the British Society for Genetic Medicine to Matt Hancock and his ambition to conduct genomic sequencing of healthy newborns. It says that that could be “problematic”, because the genetic code of a healthy newborn
“will only rarely predict future disease accurately”—
a point the noble Lord, Lord Winston, reminded us about. The society says that it is important that
“children are not tested for adult onset conditions if there is no effective preventative intervention or treatment in childhood. Issues such as sample and data storage, access and retrieval also require detailed scrutiny”.
It says:
“Such a venture therefore needs to be carefully researched, and the ethical and societal aspects require careful consideration before roll-out to the general population.”
However, other forces are at work. This morning, I sent a letter to the Minister, the noble Lord, Lord Bethell, from the Royal Academy of Engineering, as well as my response. I was dismayed to see the phraseology it used in talking about gene editing, citing factors such as
“economic activity and sustainable and resource-efficient solutions to the societal challenges faced in food, chemicals, materials, water, energy … and environmental protection.”
My Lords, like other noble Lords, I will talk mainly about gene editing as it relates to human reproduction, which is a highly contentious issue at present.
The UK recently completed a project to map the genomes of 100,000 individuals. When an individual’s genome has been mapped, therapies can be tailored to address their personal ailments, including cancers. An individual’s genetic information can serve to identify the precise nature of the cancer, then the cancer can be treated by means that are more subtle and less invasive than the surgery, chemotherapy and radiotherapy on which we have depended hitherto. In mapping an individual genome, one can also discover whether an individual is a carrier of a pathological recessive gene, such as those that give rise to cystic fibrosis, muscular dystrophy or sickle cell anaemia.
There is detailed genetic knowledge of many monogenic disorders. In such cases, gene editing might serve to alleviate the disease and prevent it being transmitted to future generations. Genetic editing, which is the topic of this debate, denotes the introduction of new genetic elements into organisms. It has been pursued in the laboratory since the 1970s, with plants and animals as the subjects. Hitherto, the major drawback of this technology has been the random way in which the DNA is inserted into the host’s genome. This can impair or alter other genes within the organism, which has disbarred its widespread use in humans.
Recent advances have meant that gene therapy can now be targeted more precisely. Among the novel techniques is CRISPR gene editing, which is based on a modified version of a bacterial antiviral defence system. This method allows DNA to be cut at a specific location, which is identified by the code incorporated in the Cas9 enzyme, which does the cutting. Then, the repair mechanisms of the cell can be relied on to mend the break and, at the same time, incorporate a DNA snippet or plasmid that has been introduced in the company of the Cas9 enzyme.
We have used modified sperm in pigs, as we have in mice, so it is certainly a possibility.
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As our Library briefing points out, there is also the danger—the noble Baroness, Lady Bakewell, referred to this—of facilitating eugenics or designer babies. The current consensus is clearly that such practices are ethically unacceptable. This raises the further ethical issue of human enhancement. The borders between treating illness, enhancing health and enhancing human performance and attractiveness are fairly porous, as we already know from periodic scandals in the world of sport. That needs more exploration before genome editing becomes a widespread clinical reality. So too does the question of social disparity, especially if clinical genome editing is to become primarily available through the private sector, as with IVF. This certainly needs to be adequately analysed and addressed. It was of course one of the two principles which the Nuffield Council on Bioethics insisted upon when commenting on the ethical acceptability of gene editing.
I remarked in opening on the huge potential for good that gene editing has, especially in the early prediction and diagnosis of certain diseases. I certainly believe that to be the case despite the ethical whirlpools which need to be negotiated along the way. Perhaps we also need to be wary of exaggeration and its attendant danger, genetic determinism. For instance, it has recently been proposed that all newborn children should be offered genomic testing. That in itself is fraught with ethical difficulties, from consent—who gives it?—through to subsequent applications for life insurance, although there is a current agreement on that.
Even more perplexing is the fact that many illnesses, such as cancer, dementia and heart disease, are not due to just one factor. As a recent article by Dr Phil Whitaker in the New Statesman points out:
“Numerous genes contribute to susceptibility and all interact in fiendishly complex ways with environmental and lifestyle factors. The risk estimates achieved by commercial genomics tests are no better (and may even be worse) than our current clinical judgements.”
That has been stated also by the British Society for Genetic Medicine. Even if the predictions are accurate, there may not be a lot that we can do about them apart from feel anxious, and we have more than enough anxiety around already.
We are asked in this debate to take note of recent developments in the field of gene editing. I for one am glad to do exactly that, with admiration for all the work that is going on, and enthusiasm, but not entirely without some ethical reservation.
A recent headline in the Times suggested that we can now eliminate genetic disease by gene editing. That is complete nonsense. We cannot eliminate hereditary disease because so many of these genetic defects will not be expressed in the genome of the parents being screened. In fact, many of these defects occur between the generations, at the time when the egg or the sperm is formed, during meiosis or at other times. The idea that we can eliminate hereditary disease is rather like the Tower of Babel: it is trying to be so ambitious that we lose sense of what our humanity is. That is really important and I will come back to it.
I have to say that we were criticised, in this House as well as elsewhere, when we produced the first pre-implantation genetic diagnosis and it was said that we were undertaking eugenics. If you go to YouTube, you can hear a recording of Anne Sofie von Otter singing “Wiegala”, a lullaby that includes the words “Schlaf mein Kindelein”—sleep, my child. It was sung by its composer, Ilse Weber, as she entered the gas chamber at Auschwitz carrying her child. She wanted to comfort the child, who was frightened, and she died in that gas chamber. We know that this happened, because there were eyewitnesses, and we have the score of the poem she wrote. That is eugenics, because her only fault was that she was Jewish—a 41 year-old woman with two children. There was nothing else and the science was misused. Science is always capable of being misused: it is not just Nazis, anyone can do it. This was done in China and it can be done in this country, as it can in Europe. Let us not forget that.
Regulation is not really the answer here. I shall come back to that, if I may. We have to differentiate between eugenics and reasonable medical intervention. It seems to me that eugenics is where you involve a population. When you are dealing with an individual, you think of the best solution for that family; therefore, sometimes you decide to put back an embryo that has had some mitochondrial change—which, incidentally, is not gene editing, but simply changing the spindle, and therefore rather a different process. Gene editing has not been done in this country. We gave approval for that, but gene editing is banned and should remain banned, in my view, because the risks are appalling.
CRISPR is not an accurate technique. It is the best technique we have yet devised, and far better than the techniques we were using, introducing viruses into embryonic cells, but it carries the risks of off-target mutations, of epigenetic effects, of possibly producing cancer, of misdiagnoses and of producing, as the right reverend Prelate pointed out, completely unpredictable effects. I greatly valued and admired his speech, which was an important intervention in this debate.
One of the concerns we must understand has to do with our humanity. If we went through enhancement, we might end up with the basic principle of ethics being completely confounded. We believe in ethics because, whether we are religious, scientific or humanist, we believe in the notion of the sanctity of human life. If we make a superhuman, what value has human life? Playing God is something we should do; it is not wrong to do that. Imitating God, making use of our intelligence to provide the best solution to things, is what we are empowered to do and should be doing. However, to try to imitate God in the way they did, for example, at the Tower of Babel, if that parable or lesson is right, is utterly inappropriate, in my view.
We have to recognise that regulation will not work; it did not work in China and it would not work in this country. You could not prevent somebody doing this out of hand. We must recognise that we have to collaborate. International law will not work, but having more scientists working together and understanding the ethical issues will. I bet that if Dr He had worked in our laboratory, he would not have done that experiment in China. He worked somewhere in the United States. He was not an embryologist, which was not very helpful, because he did not understand the ethical issues raised. That understanding is something we have to grasp more and more.
There will always be huge ethical hurdles to consider, as evidenced by the rogue Chinese scientist Dr He Jiankui, but for sure there will be others seeking to fill his research shoes and the possibility of hidden funding to attempt to create the perfect athlete, which, as the noble Lord, Lord Winston, noted, will be impossible. However, it will not be impossible to create enhanced athletic performance.
My call for an outright ban on the application of this science in the world of competitive sport does not mean that I am blind to the potential of gene editing outside sport. However, I caution on the reality of further laboratory work in this context. Genes have a significant role to play in sporting performance, but they will never deliver sporting glory on their own. Without the balance of genetic advantage, environment, coaching and training, there will never be gold medal outcomes.
Take the example of the benefit of altitude training. As elite athletes acclimatise to high altitude, they acquire more red blood cells, which allow them to carry more oxygen. When they compete at lower altitudes, they get a natural boost to the muscles when additional oxygen is available. This blood-expanding effect can enhance performance by up to 2%. While that sounds like a tiny improvement, it can be the difference between missing selection and a gold-medal performance.
As evidenced by David Epstein in his seminal book The Sports Gene, the celebrated Mäntyranta—the multi-gold medallist in cross-country skiing in Finland—had a genetic trait which led to an extraordinary blood cell count, measured at up to 65% higher than that of the average man. It demonstrated that even trace quantities of EPO could bring major performance advantages. Subsequently, in all, 97 members of his family were examined, 29 of whom had remarkably high haemoglobin —many were champions in cross-country skiing. The geneticist Albert de la Chapelle discovered that, of the 7,138 pairs of bases that make up the EPO receptor gene, a single base was different in the 29 family members who had unusually high levels of haemoglobin. Each family member, like all human beings, had two copies of the EPOR gene. But at position 6,002 in only one copy of each affected family member’s two EPOR genes, there was an adenine molecule instead of a genuine molecule—a minuscule alteration, but the impact was immense. The production of red blood cells ran amok. Here was a mutation beneficial for an athlete, but otherwise of little consequence.
Of course, natural examples such as this are extremely rare, and applying that science in the laboratory and finding the athleticism genes is extraordinarily complex and difficult. However, it is attractive to those who wish to cheat in international sport to achieve glory. This is the road that will be travelled by rogue sports geneticists to cheat the system, which we must block through effective regulation and legislation, both domestically and through international co-operation, however great the challenge. David Epstein went on to say:
“A persistent inability to pinpoint most sports genes doesn’t mean they don’t exist, and scientists will, slowly, find more of them.”
One conclusion we can all reach is that, despite the uncertainty surrounding the potential application of gene editing to competitive sport, its potential is real. It should have no place in competitive sport. As I have made clear, in the 21st century, cheating by means of performance-enhancing drugs is an issue of today, and it is an issue of tomorrow for those geneticists who will go to any lengths to corrupt the athlete, and, sadly, many nation states in search of glory, in one of the few sectors where some countries can gain national pride. Gene editing clearly has huge benefits, such as relieving the burden of heritable diseases. However, it has no place in the sports arms race if we are to protect the integrity of competitive sport between clean athletes and rejoice in fair competition between young sports men and women worldwide.
If applied to humans—which has yet to be excluded—I admit that the language employed in the academy’s letter sounds rather disturbing. For example, it uses words such as “exploiting”, “explosive”, “market pull” and “technology push” and “commercialisation and industrialisation”. The Royal Academy of Engineering’s report also focuses on commercialisation to the apparent exclusion of ethical discussion, apart from a glancing reference to consumer choices in clothing.
Reference has been made in your Lordships’ House to earlier debates on the 1990 legislation, the establishment of the Human Fertilisation and Embryology Authority and the use of mitochondria. It is important to say in the context of such debates that we should not tantalise or raise expectations unduly. During our debates in your Lordships’ House on mitochondrial replacement, we were told that there would be cures and that they would be imminent. What progress has been made on clinical use since the licences were granted by the HFEA? It is an interesting precedent in the context of today’s debate.
One of my last contributions as a Member in another place before standing down was in a debate on genetics and embryology. I said:
“Legislation cannot be value-free or ethically neutral. A dirigiste or disinterested approach—marketplace genetics—simply would not do.”—[Official Report, Commons, 19/7/1996; col. 1444.]
So I cheered when, in December 2018, the World Health Organization established an expert panel to develop global standards for the governance and oversight of human genome editing. Its consultation closes on 7 February.
A year ago, in an article in Nature magazine, 18 scientists and ethicists from seven different countries called for
“a global moratorium on all clinical uses of human germline editing—that is, changing heritable DNA (in sperm, eggs or embryos) to make genetically modified children.”
My noble friend Lord Patel referred to this point earlier; I endorse entirely his call for a global moratorium for at least a five-year period. The scientists warned against using tantalising arguments to justify the risks and pointed to unknown dangers, including attempts to correct or modify susceptibility to one disease and unwittingly opening the way to another. They said:
“It will be much harder to predict the effects of completely new genetic instructions—let alone how multiple modifications will interact when they co-occur in future generations. Attempting to reshape the species on the basis of our current state of knowledge would be hubris.”
They warned of
“marketing pressure to enhance their children.”
They warned:
“Genetic enhancement could even divide humans into subspecies.”
They said that implications for
“future generations could have permanent and possibly harmful effects on the species.”
Very significantly, Jennifer Doudna, one of the two scientists jointly responsible for CRISPR-Cas9 gene editing technology, is cautious about its use in humans and calls for prudence. Her co-discoverer and co-inventor, Emmanuelle Charpentier, has far stronger reservations. She urges us to look for alternative approaches and, along with her colleagues, says that
“germline editing is not yet safe or effective enough to justify any use in the clinic.”
She says that, even with experience, study and future research,
“substantial uncertainty would probably remain.”
Against this background, around 30 countries currently have legislation that directly or indirectly bars all clinical uses of germline editing. Although a regulatory approach, which has been referred to, and an international treaty—perhaps mirroring those on chemical and biological weapons—is what I prefer, I recognise the challenge of securing such international agreement. Of course, UNESCO signally failed to create a legally binding convention outlawing human cloning.
However, we should at least attempt to secure voluntary pledges to prohibit the clinical use of human germline editing while a moratorium is in place. I like others’ suggestion of a global genome editing observatory to track developments and foster widespread debate. I welcome the Minister’s response to that proposal.
The urgency of tackling the wild west of marketplace genetics was illustrated by the way in which, in late 2018, the Chinese biophysicist. He Jiankui ignored ethical and scientific norms in creating the twins Lulu and Nana, who were referred to earlier. His use of gene editing on embryos was not a correction of any existing disorder but an attempt to immunise the twins against HIV—an attempt at enhancement that appears to have introduced novel mutations. On 4 December, the Guardian warned:
“China gene-edited baby experiment ‘may have created unintended mutations’.”
Initial approbation turned to condemnation; as we know, He Jiankui is now in jail.
The Chinese Academy of Sciences is to be commended for its robust and unequivocal condemnation of He’s activities, which, it said, represent
“a gross violation of both the Chinese regulations and the consensus reached by the international science community. We strongly condemn their actions as extremely irresponsible, both scientifically and ethically.”
I hope that the logic of that argument will be extended when we look at issues such as DNA profiling and, although it is wider than today’s debate, when we think about the million Uighurs incarcerated in Xinjiang, all of whom have had their DNA profiled. I wrote to the Minister about this; although it is outside the scope of today’s debate, I hope that he will reply to my points and place a copy of that correspondence in the Library.
As the noble Lord, Lord Winston, reminded us, this is a week in which we commemorate terrible events. In December 1946, the so-called Doctors Trial opened the eyes of the world to the way in which medics and scientists had committed appalling and vile crimes against humanity. It must always be our objective to ensure that good science and good ethics march hand in hand and always go together.
As we have heard, there are two types of gene therapy. In somatic cell gene therapy, the therapeutic genes are transferred into any cell other than a germ cell, which excludes sperm and egg cells. Such modifications affect the individual patient only, and are not inherited by offspring. In germline gene therapy, germ cells are modified by introducing functional genes into their DNA. The change will be passed on to subsequent generations.
Australia, Canada, Germany, Israel, Switzerland and the Netherlands prohibit human germline gene therapy. The techniques are regarded as unsafe and it is maintained that there is insufficient knowledge of the risks to future generations. The US, by contrast, has no controls regarding human genetic modification beyond the regulations that apply to therapies in general.
We need to consider whether the denial of germline therapy is a significant impediment to the application of genetic technology for the betterment of human welfare. For this, we need to look at some examples. We may begin by considering the case of a recessive gene such as sickle cell anaemia. Genetic editing might be used to eliminate the genes from the germline of a procreating couple, each of which contains a single copy of the gene. In normal circumstances, there would be a one in four chance that any offspring would inherit two copies of the faulty gene from the parents. This is a consideration that might encourage the couple to remain childless. However, there are several other recourses that are more obvious and familiar than gene therapy.
The parents might, for example, use in vitro fertilization to produce several embryos. After a few rounds of cell division, the cells of the embryos could be subjected to a biopsy. If any of them were found to be free of the faulty gene, it could be implanted in the mother. This recourse is described, as we have heard, as pre-implantation genetic diagnosis. Another recourse would be to use the sperm of a donor who has been shown to be free of the pathological gene. This would ensure that the offspring could not be afflicted by the disease, and that at most, they would inherit only a single copy of the recessive gene. Another possibility is an embryo donation to the mother using the ovum of a third party. The final recourse, which seems eminently practical and desirable, would be the adoption of a child.
Gene editing could in principle be used to the same end as pre-implantation genetic diagnosis. It would be possible to use techniques to correct, within the human embryos, the mutant beta-globin gene associated with sickle cell anaemia. The treated embryos would be grown in vitro and subjected to genetic sequencing to allow the selection of those in which the desired modification had been achieved, and one or more of them could be implanted. However, there seems to be no advantage in such a rigmarole in the case that we are considering.
A stronger case could be made for gene-edited conception where both parents have two copies of the recessive mutant gene. Another instance in which gene editing might be justifiable is where one of the parents contains two copies of a dominant pathological gene which is bound to be inherited, with ill effects, by any offspring. Sometimes, the affliction will be so severe that the individual is unlikely to procreate. However, some genetic diseases such as Huntington’s disease are not manifested soon enough to become obstacles to procreation.
Another theoretical possibility is to apply gene-editing techniques to the gametes—that is, the egg and sperm cells—instead of to the already-formed embryos. To my uncertain knowledge, albeit that I have been informed by the noble Viscount, Lord Ridley, on this matter, this is not part of the current repertory. However, there could be no avoidance of the need for a biopsy of the resulting embryos.
Time moves on, and in June 2013 the UK Government agreed to develop legislation that would legalise three-person IVF as a treatment to eliminate mitochondrial diseases that pass from mother to child—it is called MRT—and the 2015 mitochondrial donation regulations, allowed under the Human Fertilisation and Embryology Act 1990, made this possible with parliamentary consent.
I mention this background to indicate how genetic procedures are becoming more and more common in modern medicine and to place gene editing and its direction in that context. As one of the panellists said at the Royal Society debate, a line drawn in the sand gets washed away by the tide of change. Perhaps prompted by Mr He Jiankui’s extraordinary announcement, in 2018 the UK Nuffield Council on Bioethics published a report which concluded that
“though there may be many individual objections, there exists no categorical ethical objection to planting genome-edited human embryos.”
Given that, as I have outlined, existing UK law already allows limited editing of genomes in human reproduction, the eventual wide acceptability of editing to prevent the transmission of serious diseases and to eliminate them from the germline appears likely in the near future.
That being so, a number of ethical and social issues need to be considered. Before setting them out, let me summarise the present state of law around the world concerning gene editing. No country explicitly allows human germline genome editing, but many have no prohibition on it either. In the UK these matters are, as I have indicated, the concern of the HFEA, which requires all such matters to be done under licence. The August 2017 issue of Nature first reported on the American use of gene editing in humans. In response, George Annas, director of the Center for Health Law, Ethics and Human Rights at Boston University School of Public Health declared that
“the scientists are out of control.”
What makes a big difference to all this is the speed of scientific developments and the availability of editing techniques that are precise, affordable and easy to apply. We know that many are being used successfully under licence in the treatment of rare diseases. Their availability around the world makes their use, official or unofficial, likely to spread. CRISPR is the most well known. When CRISPR was first announced, the acronym received 19 million hits on Google, 5,000 articles were written, 28,000 patents were taken out and, as we know, two babies were born. The prospects for the future of medicine and the human race are huge: 8 million babies are born each year with genetic defects and most will die quite soon. The potential for doing good is enormous. There is talk, for example, of being able to eliminate sickle cell disease entirely, and families blighted by the possible inheritance of Huntington’s can look to gene editing permanently to delete the aberrant gene from their germline. Work is also being done on type 1 diabetes.
In this country, the Government set up the national genomic healthcare strategy last February to improve existing services for those with rare diseases, with the NHS offering genome sequencing as part of its service. One in 17 people in this country—6% of the population —will be affected by a rare disease at some point in their lives. That is 3.5 million people in the UK and 30 million across Europe. It is because so many new techniques are in use or imminent that it is important to confront the broader ethical and social dilemmas.
Is it ethical to change for ever a human germline to eliminate from human history certain patterns of inheritance? There have been calls for a moratorium, or at least a pause. How can and should the world control this? In the wake of Mr He Jiankui’s announcement, the World Health Organization has set up a committee of experts to look at the governance of the process and to create a framework that will consider the risks, benefits and various models of regulation—hard laws, soft laws and so on. How can any regulation be policed? With the techniques cheap and available, who is to stop rogue operators, or even biohackers, seeking to make such changes? How might a political tyrant one day make it serve his or her interests? The WHO report is expected this spring.
Another major consideration arises: what is to be considered an illness and who decides? Is deafness an illness? Should we be seeking to wipe it out? Is autism an illness? Many of those who belong to such communities would not think so. The offspring who result from gene editing have no say in the matter, and the consent of the patient is one of the major principles of medical practice. Who has the authority to rule on such a matter, and what form would any such ruling take? Would it be a total ban or would there be conditional permissions? Who is to write the framework, and should it be universal or local?
Another matter is social justice. To whom will this new facility be made available? Will it be acceptable for rich countries to forge ahead, leaving behind poorer countries that cannot afford such developments? Will rich individuals be able to benefit while the poor cannot? Who will have the right to refuse such treatment and to whom? The project risks widening, in an ever new and devastating way, the differences between rich and poor, and dividing the human race into subsections worthy of some futuristic science fiction. Indeed, such fictions have already been written—Huxley’s Brave New World, Kazuo Ishiguro’s Never Let Me Go and plenty of others. The imagination of our novelists is running ahead of the science.
The debate that I chaired at the Royal Society was called “The Quest for the Perfect Human”. In the course of that evening, the word “eugenics” came up—the science of perfecting the human race. It was used merely as a touchstone of the worst that could be imagined, but it is why I initiated this debate.
I have spoken of what I know and what I have heard. The first is very little; the second I may have oversimplified—I stand to be corrected by experts. However, as these techniques become more widespread, what has emerged—from the considerations of the World Health Organization to those involved in this work at the Francis Crick Institute and in university research institutions across the world—is the belief that the public must be brought on board. I hope that the Government are taking to heart the concerns that exist about this exciting but fundamental change in how science is about to shape, irreversibly, the human race. I beg to move.
Yet there is something different—some may say exciting—about gaining mastery over our DNA and brains. Our complete set of DNA, its molecular code and how it is expressed give rise in each and every one of us to a singular life. In modifying DNA in human cells, we turn them into living drugs. Since 2003, over a dozen gene therapy treatments have been approved to treat cancers and other disorders, of the eyes, blood and neuromuscular systems. The technology holds promise for countless cures.
Jennifer Doudna, who is known for her work on CRISPR-Cas9, says that, in less than 30 years,
“it will … be possible to make … any kind of change to any kind of genome”.
Because of the power of the technology, she and many others have called for a moratorium on germline editing of the human genome.
Developments in somatic editing of the human genome are quite different. This is not germline editing. Genome editing and somatic editing hold out great promise for the treatment of diseases caused by genetic mutations. There are over 75,000 genetic mutations that cause inherited diseases. Unlike in germline editing, the changes made in somatic editing are not passed on to future generations.
Several CRISPR-related therapies are in early phase trials for somatic genomic editing: editing patients’ T cells for treating cancers; boosting foetal haemoglobin in sickle cell disease; editing donor cells to treat non-Hodgkin’s lymphoma; editing photoreceptor cells to treat inherited blindness. Even in the UK, there are trials related to somatic genome editing; the CRUK-AstraZeneca Functional Genomics Centre does much of the work. The UK was the first in Europe to make CAR-T therapy, as it is today, available to cancer patients.
There is still a lot of science to be done to make these treatments safer and more effective. This will happen as more new technologies develop. CRISPR-Cas9 is not now likely to be used; it will be replaced by more accurate baseline and intermediate editing, which target a single nucleotide. ACGT nucleotides make up the amino acids of DNA. The transfer of one A instead of a C may cause a mutation and a disease; editing that into a normal sequence would cure the disease permanently.
Newer technology for base editing and prime editing, as I mentioned, holds much more promise. Germline genome editing in embryos to create genetically modified people is different, and ethically fraught. In my view, there should be a global moratorium on this for at least five years; it would not include a moratorium on research, because we can learn a lot of science from research into germline editing which may help in other areas.
There is a need for better regulation. We are lucky in the United Kingdom that we have a regulatory authority that can exercise this function to regulate practices that might be unethical, including research on embryos. The authority has granted one licence for research on genetically modified embryos. It may grant others if it is satisfied that they are necessary. But there are gaps that need to be filled. Hence, I ask the Minister to address this.
When the Human Fertilisation and Embryology Act was enacted, it was in the context of the science then, but now things have changed because the technology and the science have advanced to a point where it is not just human embryos that we can modify. It could be done on gametes produced outside the body or in vivo to gametes, so there is a need to change the Act so that it meets those changed circumstances. The definition of a woman has also changed, with trans women and other issues, so we need to look at the legislation so that it meets the current status.
The second aspect is that, as the noble Baroness has already mentioned, we need to have a wider consultation with the public such as the Government had before mitochondrial transfer was legalised. That took three years of experts and patients’ panels looking at the evidence. I hope the Government will do that with genomic editing.
My second phase in this topic was as a member of the Medical Research Council under the distinguished leadership of a former Leader of this place, Earl Jellicoe. Some 35 years ago there was great excitement about the work at Cambridge—involving Sir Keith Peters, the Regis Professor at Cambridge, a man who I have recommended for a place in this House more times than I have had lunch but, I am afraid, without success—that led to the establishment of the Sanger centre, which in 1992 became the Wellcome Sanger Institute. Those were early days. Never then did I anticipate the phenomenal scientific progress that the next 30 years would bring.
Part of my purpose, and a prime concern during my National Health Service work, was to bring our great research universities together with the great teaching hospitals to protect, enhance and develop our scientific and medical research—a great strength in the UK where we see ourselves as a global leader. As we leave the EU, it is all the more important that we protect and enhance our competitive strength, in which biomedical sciences are a leader.
There has been great leadership at the Department of Health and Social Care. Jeremy Hunt launched Genomics England. Given its vast potential, it is vital to see the UK in a leadership position. I pay great tribute to Sir John Chisholm, Jon Symonds and many others who have served there. The House will be aware of the excellent work the organisation has undertaken through the landmark 100,000 Genomes Project since the organisation was launched in 2013. The project, which saw the full genome sequencing of 100,000 patients with cancer or rare, infectious diseases, places the UK at the cutting edge of genomic science.
Similarly, I pay tribute to the last Chief Medical Officer, Dame Sally Davies, a wonderful woman who I know really well. I am delighted to say that she is now the first female master of Trinity College, Cambridge. She worked on many causes—antimicrobial resistance, obesity and much else—but showed real leadership on genome sequencing. She has earned vast admiration. One of her research areas was sickle cell disease, so she really knew the patient cost of that. As CMO, she called for a gene-testing revolution in the hope that whole genome sequencing would become as common as blood tests and biopsies. It may cost around £700 a patient, but it can improve diagnosis and care for a majority of patients, allowing doctors to tailor treatments to each patient’s needs.
While the patients who participated in the 100,000 Genomes Project all gave full consent for their biological data to be sequenced, there are still some who are troubled by the implications of this technology for their privacy. Dame Sally has always said that the data can be stored securely and anonymised, but I well appreciate this point. One of my greatest battles in my health role was a fight with the insurance industry, which would weight clients, if they had an HIV test, as though they were HIV positive. I felt passionately that this was so counter to public health, and I am pleased to say that it changed its policy in the end. However, anxiety about what will become of patient information is real and genuine.
The NHS Genomic Medicine Service continues to develop. The leadership shown by Jeremy Hunt has been taken up by Matt Hancock and there is a great deal of potential. Like others, my concern is regulation. The first Bill that I took through the House of Commons in my own right when I became Minister of Health was what became the Human Fertilisation and Embryology Act. Coming back to the points made by the noble Baroness, Lady Bakewell, public debate on that was so important. Hysteria and misinformation are quite different from rational, evidence-based logic and the problem is always how to communicate that, so I was delighted to hear about her recent conference. At that stage, we were trying to spread information. The noble Lord, Lord Winston, who is in his place, was very much part of the campaign at that time, as were many others.
There was a real danger that we would not get the Bill through the House of Commons. I think the noble Lord, Lord Alton, was also there at that time. The Bill got a bit hijacked by the abortion debate. As ever, debates in the Lords were critically helpful and important. I remember drawing frequently on many of the Lords’ comments to take the work forward. Subsequently, I invited the noble Baroness, Lady Deech, to chair the Human Fertilisation and Embryology Authority, which she did magnificently. It has been said by the noble Lord, Lord Patel, and others that there have been light years of change since then, including MRT and much else.
The difficulties that we now need to consider are profound. I ask the Minister: how will we show leadership in regulation, nationally and internationally? It is complex and confused. It was 12 years from Louise Brown to the Human Fertilisation and Embryology Authority. How does he see the future?