Gene Editing

Lord Winston Excerpts

Thursday 30th January 2020 Lords Chamber

[Lord Winston (Lab)]

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.

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.

--- Later in debate ---

[Viscount Hanworth (Lab)]

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.

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 β-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.

[Lord Winston]

We have used modified sperm in pigs, as we have in mice, so it is certainly a possibility.

[Viscount Hanworth]

I have now learned something. However, we must now ask where this leaves us. The first point to be made is that the existing methods of gene editing are of insufficient accuracy to be used in human reproduction without the accompaniment of a rigorous pre-implantation genetic diagnosis. In such circumstances, they have no advantage over the existing methods of embryo cultivation and implantation, provided that there is a possibility of selecting a disease-free embryo.

A word should also be said about the eugenic fantasies that have accompanied the publicity surrounding recent advances in gene editing, notably the CRISPR technique. It has been suggested that they have created the prospect of breeding humans endowed with superior qualities of athleticism, brainpower or other desirable traits. I believe that such fantasies can be dismissed. Notwithstanding the example given to us by the noble Lord, Lord Moynihan, the human qualities in question are the consequence of multiple genetic endowments. They are also affected by environmental and epigenetic influences, and such determinants are way beyond the reach of gene-editing techniques.

Finally, one is struck by the thought that the Cas-9 enzyme could be devoted to its original purpose, which is to defeat vital infections. Also, the bacteriophages against which it is naturally directed could be employed as substitutes for the human antibiotics whose efficacy is very rapidly declining.