Engineering a Consensus:   Edit Embryos for Research, Not Reproduction

Written by Dr Chris Gyngell, Dr Tom Douglas and Professor Julian Savulescu

A crucial international summit on gene editing continues today in Washington DC. Organised by the US National Academy of Sciences, National Academy of Medicine, the Chinese Academy of Sciences, and the U.K.’s Royal Society, the summit promises to be a pivotal point in the history of the gene editing technologies.

Gene editing (GE) is a truly revolutionary technology, potentially allowing the genetic bases of life to be manipulated at will. It has already been used to create malaria-fighting mosquitoes, drought resistant wheat, hornless cows and cancer killing immune cells. All this despite the fact GE only become widely used in the past few years. The potential applications of GE in a decade are difficult to imagine. It may transform the food we eat, the animals we farm, and the way we battle disease.

Despite these far-reaching implications, public debate has been focused on a very specific sort of gene editing. Earlier this year, a lab based in China caused a massive uproar when it was the first to use GE on human embryos. Scientists and public interest groups in the USA called for an international ban on any similar research. A leading scientific journal published a commentary calling for such research to be strongly discouraged. The US based National Institutes of Health, said that such research, “was a line that should not be crossed”.

Many arguments have been offered against GE in human embryos. These have adverted, among other things, to the possibility that GE might be used to create designer babies, deepen social inequalities or cause heritable genetic defects. There is disagreement (and confusion) about these concerns. However, this disagreement need not prevent a consensus on other, more pressing, practical matters.

In some countries, such as the UK, certain forms of gene editing research on human embryos are legal if the embryos are not implanted into a woman, and are destroyed after 14 days of development. An application has already been lodged with the Human Fertilisation and Embryology Authority (HFEA) to perform gene editing in compliance with these standards. The pioneering Chinese study was performed under similar conditions – it could never have resulted in a live birth.  A vital question is whether we should allow this type of research – the editing of human embryos that will never be implanted into a woman; or indeed leave a petri-dish.

Some may fear that it will be impossible to pursue this research without also opening the door to objectionable reproductive uses of GE. But this is not the case.

This debate is in many ways similar to the debate around cloning. Many people feared that allowing research on cloning techniques would lead to the creation of cloned babies. In that debate, it was helpful to draw a clear distinction between reproductive cloning and therapeutic cloning. Reproductive cloning is cloning to produce a live born baby. Therapeutic cloning is utilising cloning for the understanding and treatment of human disease. Importantly, therapeutic cloning research continued and ultimately contributed to the development of a new technology –Induced pluripotent stem cell (iPS) technology—that holds out immense promise as a way of developing stem cell treatments that are ‘customised’ to an individual patient and can be created without the destruction of human embryos. Meanwhile, reproductive cloning has become virtually a non-issue, with few seriously suggesting that we should be striving to create clones of existing people.

In cloning, a distinction between reproductive applications and research enabled clearly beneficial research to proceed while controversial applications were set aside. We propose that the parallel distinction should be drawn, and emphasised, in discussions of GE: we should distinguish between the gene editing of embryos for research purposes, and for reproductive purposes. While there is widespread agreement that GE should not be used for reproductive purposes, its use in research should be encouraged.

Using GE on human embryos would be valuable in medical research for at least three reasons. 1) It allows researchers to investigate the role of particular genes play in early human development. This could lead to non-GE treatments that reduce embryo loss in pregnancy and improve fertility. 2) It will allow the creation of new stem cell lines that can be used in medical research. This includes the creation of improved cellular models of diseases like Parkinson’s disease. These modified cell lines could be used test the efficiency of particular drugs, and could therefore lead to improved pharmaceutical treatments. 3) It may one day lead to the creation of modified stem cell lines which could be used directly in therapies. For example, gene edited embryonic cells could be used to create blood cells that kill leukaemia. These cells could then be used as part of cancer treatments.

The use of GE in this research would be no more ethically problematic than other research involving human embryos. It should not be banned, even if the creation of genetically modified people is wrong.

The summit in Washington is an important opportunity to build an international consensus on this point. A positive outcome would be widespread agreement that GE research in human embryos is ethical for research purposes, provided strong research guidelines are followed; however reproductive uses should be banned until such time that there is further consensus.  Attention should now turn to ensuring any agreed international standards can be implemented and monitored worldwide.

In the future there may be good reasons for us to consider using GE for reproductive proposes. Most immediately, GE could be used to correct mutations which cause simple genetic diseases, such as cystic fibrosis, muscular dystrophy and Tay-Sachs disease. Such diseases can already largely be prevented through genetic selection technologies such as preimplantation genetic diagnosis (PGD). However, PGD has significant limitations. Its ability to avoid disease is directly related to the number of embryos that can be created through IVF. Sometimes couples will produce only one or two embryos, in which case PGD will not be effective to avoid even simple genetic diseases. GE can be used to make multiple changes to a single embryo. It is free of PGDs limitations and would be a more efficient way of preventing simple genetic diseases. Moreover, genetic selection it is not a cure for disease. It merely stops a person who would have had a disease from coming into existence; and allows a different disease free person to be born. GE doesn’t change who exists but prevents a particular person from developing a disease. In this way it is similar to a vaccine, except that its effects are heritable (which might reasonably be thought an advantage).

More significantly, GE’s ability to make multiple changes to a single embryo means that, in the long term, it could be used to prevent a far greater range of disease than PGD.  Cancer, diabetes, and heart disease all have significant genetic components. It is at least conceivable that we could use GE to make us resistant to these diseases – which are among the leading cause of mortality worldwide. Imagine an injection was developed that if taken by a woman while pregnant would change in the in-uterine environment in such a way that the embryo become resistant to cancer and cardiovascular disease.  Most would consider such an intervention to be an important medical breakthrough, which should be provided to all. Gene editing may make such an intervention a reality one day.

Many will disagree with us about the great potential of GE to prevent disease, and the ethics of using it on embryos to achieve this goal.  Drawing a distinction between the gene editing of embryos for research purposes, and for reproductive purposes, will allows us to debate such issues without impeding research in the meantime.  Much important gene editing research can take place entirely in petri dishes, and this should not be compromised due to concerns about reproductive applications.  Indeed a more informed discussion about the benefits and risks of reproductive gene editing can place after the technique has been employed in basic research.

For now we should only edit embryos for research, not reproduction.

 

This article is a cross post with the Oxford Martin School

 

 

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3 Responses to Engineering a Consensus:   Edit Embryos for Research, Not Reproduction

  • Caroline says:

    I’m for designer babies.

    We already force all kinds of risks on babies just by having them, we allow them to die by the thousands in developing countries, and we will likely continue doing both.

    The good that could come from designer babies is considerable and will probably outweigh the harms.

  • Owen Schaefer says:

    Looks like the actual recommendations just released by the summit are in line with what y’all propose! (not linking to avoid spam filter, but Google “”On Human Gene Editing: international summit statement”). Non-reproductive research given the green light, clinical germline suggested moratorium until better evidence and more debate. (given there are no current trials on reproductive germline therapies, this won’t actually change practice in the near term, I think)

    Unsurprisingly, they also OK’d clinical somatic cell gene therapy, which is a much more established approach than germline editing. Though I always approving of somatic gene therapy while disapproving of germline therapy a little puzzling, with the air of inconsistency. In theory, somatic cell therapy could also be used by parents to ‘engineer’ positive traits in fetuses. While there’s no chance of the alterations being passed on to future generations in somatic therapy, this always struck me as a less important feature of germline editing. Objections typically center on mucking around with a given individual’s nature, not as much with the down-the-line reproductive consequences. After all, the reproductive risks would only arise after at least a decade and a half had passed, with plenty of time to study effects and develop further therapeutic techniques to mitigate intergenerational harms. To the extent that long-term harms are adverted to in objections to genetic engineering, it is usually by appeal to a dystopia where genetic modifications are routinely enforced at each generation – not situations where earlier generations did germline modification, then stopped. The most plausible objections to germline modification center on the wrongs of genetic modification itself and its immediate social consequences, which will be much more near-term and potentially insoluble if something goes wrong. But then, the same thing is true of somatic cell therapy on fetuses.

    Maybe because somatic cell therapy has to target particular cells/cell types, the individual risks are smaller. And fetal somatic therapies haven’t to date (that I know of) been used for the creation of ‘designer babies’. Still, the objection to tinkering with human nature (which plays a large role in objections to germline engineering) seems to apply similarly to the case of somatic cell therapy. Or am I missing something?

  • Chris Gyngell says:

    Hi Owen, I think you’re exactly right. It’s inconsistent to level “desinger baby” objections just at germline interventions and not somatic interventions. The only thing I can think of is that it will often be harder to do effective somatic modifications. To make somatic changes to muscles or hearts, for example, you may have to edit millions of cells to make sure each had the desired change. Much easier to edit one embryonic cell. Still that’s merely a technical difference

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