The ethics of gene editing

Gene editing technologies hold great promise for advancing medicine and should be embraced

Go to the profile of Chris Gyngell
Jan 20, 2016
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Rapidly developing gene editing (GE) technologies are revolutionising biotechnology and hold great promise for advancing medicine. Despite the fact GE has only been widely used for the last few years, it has already helped create malaria-fighting mosquitoes, drought resistant wheat, hornless cows and cancer killing immune cells. The potential applications of GE in the next decade are difficult to imagine.

GE is a major improvement from earlier genetic engineering technologies. Early techniques relied on viruses to deliver novel genetic material to cells. This method was ineffective and imprecise, resulting in unintended changes to large segments of the genome. In contrast gene editing techniques use enzymes to alter DNA. They are precise, effective and the first technology that has serious potential as a clinically useful modifying of human DNA.

It is this potential application of GE – making alterations to the human germline that could potentially be transmitted to the next generation – which has marred them in controversy. Earlier this year, a lab based in China caused a massive uproar when it was the first to use GE on human embryos. Two of the world’s most prestigious scientific journals, Nature and Science published commentaries calling for such research to be banned or strongly discouraged. The US based National Institutes of Health, said that such research, “was a line that should not be crossed”.

It is clear that germline GE holds tremendous potential in the fight against disease. 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.

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 a steroid injection was developed that if taken by a woman while pregnant would change 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 a wondrous medical breakthrough, which should be provided to all. Gene editing may make such an intervention a reality one day.

None the less there remains strong opposition to the clinical use of germline GE. Three arguments are commonly used against germline editing. 1) The use of such technologies will eventually lead to “designer babies”, by enabling parents to pick non-disease related genes for their children. 2) It will lead to deepening social inequalities, as the rich will have access to gene editing technologies which are denied to the poor; and 3) It will have unpredictable effects on future generations.

When scrutinized, I don’t believe these arguments support placing broad restrictions on germline GE. If we are worried about designer babies, we could limit GE for the purpose of avoiding disease, just like we currently do with PGD. Similarly, while many medical goods are expensive, and are therefore more readily available to the rich, state sponsored health systems often subside these goods and promote equal access. There is no reason to think that GE would be unlike other medical goods in this regard; if expensive it could still become widely available with state subsidisation. Finally, many technologies have unpredictable effects on future generations. Who can predict the effect of information technologies like smart phones on future generations? Unpredictability alone is not a good reason to ban something.

Furthermore, it is important to note that most arguments against germline GE only apply to its use for reproductive purposes. Even for those who think that GE should never be used to create a live baby, it is undeniable that GE in human embryos has enormous potential in basic research.

The use of germline GE in research is valuable for at least three reasons. 1) It allows researchers to investigate the role of genetics 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 cells lines can be used in medical research. This includes the creation of improved cellular models of diseases like Parkinson 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 can be used directly in therapies. For example, gene edited embryonic cells could be used to create blood cells that target leukaemia. These cells could then be used as part standard cancer treatment treatments.

Such research is legal in certain parts of the world. For instance, in the UK, gene editing research on human embryos is legal if the embryos are not implanted into a woman, and are destroyed after 14 days of development. It is important to distinguish this research from the reproductive application of GE. The use of GE in a pure research capacity is no more ethically problematic that other research involving human embryos. There is no reason to ban it, even for those even for those who are fundamentally opposed to the creation of genetically modified people.

We should support the use germline GE in research even if we are opposed to its reproductive applications.

Go to the profile of Chris Gyngell

Chris Gyngell

Marie Skłodowska-Curie Fellow , Uehiro Centre for Practical Ethics

Chris Gyngell is a Marie Skłodowska-Curie Fellow with the Uehiro Centre for Practical Ethics. His research interests lie primarily in bioethics, moral theory, and the ethical and legal implications of new reproductive technologies, such as the gene editing

2 Comments

Go to the profile of James L. Sherley, M.D., Ph.D.

Dear RegMedNet Members:

"It is clear that germline GE holds tremendous potential in the fight against disease."

While the use of "potential" keeps the posted pronouncement "true," at the same time, it also leads to the actual paucity of knowledge and predictability being altogether obscured. This is called misleading, which this article certainly does.

For example, how many cells are required to achieve a given GE change? Thousands of cells are employed currently in laboratory experiments. Could we get it down to 100's? Probably. Down to one or two? So, how many human embryos (which are also living human beings) will be needed for the research and the final therapies, if embryo GE (i.e., "germline GE" by the author) therapy did in fact prove successful? As the author notes, there are ethical considerations that preempt germline transmission concerns, which are a very important topic for discussion in their own right. It is important to recognize that although many governments allow and support research that destroys human embryos, many of their citizens still find the research objectionable.

A related technical concern are the well known, but often understated or omitted as here, off-target effects of GE. While this adverse effect rate is decreasing, no one can yet say that it poses no concern for embryo GE.

The author presents an imaginative panacea view of "potential" fruits of embryo GE. At our current state of knowledge, both individuals and society on the whole are better served by scientifically informed caution. If embryo GE could somehow prove beneficial altogether, it will be because non-embryo GE succeeded first. The embryo chasers need to give the public a chance to first learn about and embrace the possibilities that ethical, non-embryo GE presents. Companies and research laboratories are already gearing up to attempt new gene editing therapeutics for diseases for which the causative genetic defect and the disease natural history are well-known. Rushing ahead to poorly informed embryo GE is likely to precipitate the same fallout that hESC research dumped onto non-embryonic stem cell research. Confusion, misinformation, fear, and reduced support. Good science is also prudent.

James Sherley, M.D., Ph.D.
Director
Asymmetrex LLC
Boston, MA, USA
http://asymmetrex.com/
jsherley@asymmetrex.com

Go to the profile of Chris Gyngell
Chris Gyngell over 2 years ago

Thanks for your comment James.

We obviously disagree on the future clinical benefits of germline GE. I will note that in their joint statement on gene editing, the US National Academy of Sciences, the U.K.'s Royal Society, and the Chinese Academy of Sciences state that a potential application of germline GE is to avoid severe inherited diseases. Given that genes play a role in many disease, I fail to see how the claim these technologies have enormous potential in medicine is misleading. Maybe it's just a matter of semantics.

Regardless of the future clinical benefits of GE; the most immediate use of embryonic GE will be in furthering our understanding of human development. Scientists have already applied to use germline GE in studies looking at human development. One reason such studies are useful is because they allow us to better understand the phenomenon of natural embryo loss. Every year around 200 million embryos are lost in pregnancy. For those, like you, who think that each embryo is a living human life, this is the greatest cause of human death each year. Hence we would have very good moral reasons to proceed with such research.

I agree though that GE has more potential clinical benefit in somatic cells. I also agree with you that we need to exercise scientific caution. I just believe germline GE it is a road we should proceed down cautiously, not one we should be too scared to walk down at all.