Gene Editing

Viscount Hanworth Excerpts

Thursday 30th January 2020 Lords Chamber

[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.