Pandora’s Plasmid

Hubris versus humanitarianism

Introduction

Heritable human genome editing (HHGE) has advanced rapidly, enabled by CRISPR (Cas9) and derivative techniques.

Gene editing has been investigated for treating genetic illness in children and adults, but clinical use has remained limited by technical constraints and serious ethical and social concerns. 

Edits on single genes can permanently nullify transmissible genetic ailments such as muscular dystrophy, beta-thalassaemia, cystic fibrosis, and Tay-Sachs disease. However, many conditions with a genetic basis are not linked to a single gene but arise from many genes, each with a small effect. They may also need an environmental trigger on top of a genetic predisposition, and that trigger is often unknown.

Concerns

One major concern about genetic editing is the prospect of altering germline DNA, which can be passed down to future generations. Children would carry the consequences of their ancestors’ decisions, including any damage or excessive editing along the way.

In 2018, the first children reported to carry genetic enhancements were born in the People’s Republic of China. These baby girls were selected and edited as embryos and then gestated. Their edits appear to be heritable, which made the births a ‘Sputnik moment’ for HHGE, albeit one that has scientists around the world aghast at the potential implications.

Implications

There is a fear that such innovations could increase inequality in society, by enabling healthy and affluent people to further cement their advantages, potentially creating super-humans who would eclipse regular ‘kludges’.

The specialisation of labour in capitalism has enabled far greater efficiency than would otherwise be possible. Genetic specialisation might follow, with working-class people encouraged to enhance their strength or stamina. Such incentives could lead to runaway effects, or a race to the bottom.

There are also risks of a loss of genetic diversity. Many disease-causing genes are adaptive to some degree. For example, carrying a single copy of the sickle cell gene protects against malaria, which is why it was selected for through evolutionary processes. Applying HHGE to make apparent improvements therefore risks ‘ironing out’ mutations which may be beneficial in certain contexts.

Response

The World Health Organization’s Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing is deliberating on national and global governance strategies.

The International Commission on the Clinical Use of Human Germline Genome Editing, which was convened by the U.S. National Academy of Medicine, the U.S. National Academy of Sciences, and the U.K.’s Royal Society and includes members from 10 countries, was tasked with addressing the scientific considerations that would be needed to inform broader societal decision-making.

Put briefly, the Commission’s observations and recommendations are as follows:

• A moratorium on genetically enhanced pregnancies until the technology is safer and more reliable.

• Further societal dialogue required.

• Situations vary, so blanket rules are not likely to be helpful.

• Limit to monogenic diseases of a life-threatening nature, and situations of demonstrated fertility issues requiring genetic counselling.

• Only permit safe and secure techniques that don’t introduce parallel changes elsewhere in the genome (off-target edits).

• Biopsy blastocysts to ensure compliance, safety, and efficacy.

• Further work with stem cells, including induced pluripotent stem cells (iPSCs), to avoid use of embryos.

• Competent regulatory bodies are necessary, along with an international panel.

• Evaluate techniques prior to their deployment.

• Watchdogs should be established.

Challenges

In a globalised world, it is challenging to enforce a moratorium on HHGE. Jurisdictional flags of convenience will arise, with clinics opening in relatively remote parts of the world for wealthy patrons. In fact, banning such technologies outright is likely to create greater inequity in society, since only the wealthy could travel to get them. A ban would also invoke the Iron Law of Prohibition: whatever is outlawed tends to become more potent. The risk of being caught could lead to more procedures being done in one go.

Government rationing of HHGE will have similar problems. Genetic enhancement run by the public sector might be something like an East German Trabant car. Low quality, expensive, and with a multiple-year waiting list. Meanwhile those with the resources would merely travel overseas.

Even the richest person in the world probably doesn’t have a meaningfully better smartphone than a person on the Clapham Omnibus. The very latest developments in available technology are distributed in constant updates to the masses. It might therefore be most societally equitable to create incentives that make HHGE more like an iPhone than a Trabant. Politically, though, it is a harder sell.

Future Possibilities

It remains to be seen whether non-germline approaches, such as epigenetic histone methylation, will also prove feasible. There is some evidence that epigenetic transmission can occur across generations in C. elegans and Drosophila melanogaster, though it’s still debated how much this occurs in human beings. 

Some endocrine-disrupting chemicals may have effects across generations, although the human evidence remains limited. Diethylstilbestrol (DES), a synthetic oestrogen once prescribed in pregnancy, is associated with documented cancer, fertility, pregnancy, and urogenital risks in people exposed in utero; whether the effects reach later generations is still under study. 

It may be possible to ‘whisk’ the epigenome to reset such inherited effects, but science has yet to make much progress here. Such developments could eventually offer alternatives to HHGE by mitigating the expression of a gene without altering it, reducing the heritability risk.