Australasian Science: Australia's authority on science since 1938

Human Embryos Edited


Scientists have used CRISPR to edit human embryos, removing a mutation linked to a heritable heart condition.

CRISPR is surprisingly easy to use, and what was stopping us from editing human embryos wasn’t really any technical limitation; it was more ethical barriers, concerns for safety, and lack of pressing medical need.

This study by Ma et al. ( is more about testing the boundaries of our society vs any real technical advance. In fact, most of the “editing” observed was actually not what the researchers intended. For example, the changes induced were not precisely controlled “editing”, as healthy DNA from the embryo actually guided the correction. So while technically a success, the researchers did not really do what they meant to do, and this highlights how things could go wrong if we rush into editing human embryos without really understanding how the process works.

If, as a society, we were going to develop these approaches to genetically modify embryos to cleanse genetic mutations, there will inevitably be some mistakes and we need to consider that carefully.

CRISPR genome editing will eventually revolutionise medicine, and in the near future could be particularly useful for therapies to repair inherited mutations such as those causing cystic fibrosis, sickle cell anaemia, immune deficiencies, or common diseases including HIV or various cancers.

On the other hand, talk of designer babies and genome editing for traits like intelligence or beauty is still very much science fiction, as we don’t really even know how to control these traits genetically. In most cases genetic mutations act in complicated ways, and can have different effects in different people. Basically recreational hacking of the human genome is still very much science fiction, so now is a good time for us as a society to discuss what we are OK with and what should be illegal.

A/Prof Greg Neely is the Head of the Dr John and Anne Chong Lab for Functional Genomics at The University of Sydney.

This is a big leap forward and quite a remarkable study which has really addressed the issues previously seen with gene editing whereby off-target (unwanted) effects were always a by-product of the technology. Previously the problems with a genetic mistake were fixed, but not without also causing unwanted changes to other genes.

This is a real breakthrough in that the researchers have shown they can repair their target gene within the embryo, which causes heart disease, without producing any off-target effects.

It is obvious that CRISPR technology has the ability to alleviate the suffering that is caused with many genetic conditions (e.g. cystic fibrosis). However, it could also allow for the manipulation of human traits such as height, eye colour etc., as well as many other applications such as crop and animal production.

This technology currently remains in the testing stage, and these latest developments raise further ethical questions for society to consider, much like IVF treatment was up for debate 40 or 50 years ago.

Prof Nigel McMillan is a cancer biologist working in the field of gene editing at Griffith University’s Menzies Health Institute Queensland, and President of The Australasian Virology Society.

From a purely research perspective, this is an exciting advancement, improving our understanding of how the embryo behaves during the first 5 days of life, and showing improved promise as a research tool. Clinically, the DNA editing incorporated small mistakes into the DNA, meaning these embryos would never be suitable to transfer to a patient. Genetically, understanding whether we can repair both copies of a faulty gene – the ultimate goal, and where this technology would likely be of use clinically – is no clearer.

As a biologist, understanding if this technology is safe, and whether a healthy human baby can be born from a genetically modified human embryo seems unanswerable right now. Seeing more experiments being performed in larger animal models (agricultural species like cow and pig) and in non-human primates will be essential, and should, in my opinion, be a research priority before more healthy human embryos are used for research purposes.

But it’s not as simple as just being able to perform a biological technique successfully in a laboratory setting. Research needs to proceed only with extreme caution. Concurrent with the advances in the bench biology, multidisciplinary teams of biologists, IVF specialists, psychologists, bioethicists, social scientists, policy-makers and advisors, and most importantly consumers (as well as many others), must work together to ensure that if one day scientists are positioned to perform the genome editing safely in humans, that globally it is considered useful, appropriate and desirable.

Dr Hannah Brown is a Research Fellow at The University of Adelaide’s Robinson Research Institute.

My reading of the report in Nature is that an already existing strategy of simply testing embryos produced by artificial insemination, and selecting embryos for implantation that have inherited two intact copies of the gene in question, remains an alternative approach...

Accordingly, for the foreseeable future human germ line modification, if it occurs at all, will be extremely rare. It may be considered in cases where both parents are affected by a serious genetic disease and thus only capable of producing offspring carrying “homozygous”’ mutations. But from this work we don’t know if that will even be possible.

I doubt it will be used in any other situations, such as genetic enhancement, for the simple reason that the risks and benefits are not clearly defined. We do not yet know enough about the risk of off-target effects, nor do we generally know which genes would provide enhancements.

The fact that the procedure can be done in the lab doesn’t mean that the very few potential parents who might benefit will move to rapidly adopting it. The process of modifying an embryo in a test-tube is one thing, but successfully carrying that embryo to term is obviously a much more significant undertaking.

Prof Merlin Crossley is a molecular biologist and the Dean of Science at The University of New South Wales.

The two major technical concerns with gene editing in human embryos are the creation of mosaic embryos which have a mixture of edited and unedited copies of a gene, and the introduction of unintended mutations in the genome, known as off target effects. This new study thoroughly investigates these potential issues and remarkably the efficiency of gene editing was very high, there was effectively no mosaicism and no off-target mutations were detected.

Importantly, the study showed that mutation repair in embryos appears to preferentially occur using the mother’s gene copy rather than the introduced DNA template. The one embryo with mosaicism (out of 42 embryos) had all cells edited/repaired, but some cells had used the mother’s normal sequence and others had used the DNA template normal sequence. This would be avoided by changing the design of the template DNA.

A/Prof Leanne Dibbens is NHMRC Senior Research Fellow and Head of the Epilepsy Genetics Research Group at The University of South Australia.

This is a promising beginning to what is going to have to be a prolonged investigation into the safety and efficacy of gene editing. It is a technique that offers a great deal in terms of treating devastating conditions, but there’s also considerable concern about potential risks.

If it’s to be allowed here, there are also some legal hurdles to be overcome. In New Zealand at present, the legal status of this sort of research is somewhat in limbo. Human embryo research is only allowed on “non-viable” embryos, but there are difficulties around determining precisely what that means.

The UK and Australia both research on surplus embryos: those created during IVF treatment, but which have no prospect of ever being used to create a pregnancy. Proposals have been made to allow this in New Zealand, but for now it couldn’t be done.

In terms of using this technique for reproductive purposes, again the legal status isn’t exactly certain. The Human Assisted Reproductive Technology Act 2004 [NZ] makes it illegal to “implant into a human being a genetically modified gamete, human embryo” but there’s no definition within the Act of “genetically modified”. Assuming it mirrors the definition in the Hazardous Substances and New Organisms Act 1996 [NZ], Parliament would need to make changes to the law before this technique could be used to create an embryo for reproductive purposes.

In short, we’re quite some way – legally as much as technologically – from seeing gene editing in living humans, at least in New Zealand.

A/Prof Colin Gavaghan is Director of the Centre for Law and Policy in Emerging Technologies at The University of Otago, New Zealand.

The research in the US by Ma et al., using CRISPR in human embryos at the stage of fertilisation to edit out a gene associated with a significant form of heart disease, is an important advance in our understanding of genome editing.

Injecting the genome editing components into the egg before fertilisation seemed to enable the genome editing to be targeted more precisely than in previous studies, and appeared to minimise the likelihood of genetic disorders in resulting embryos. Such improvements in genome editing processes are particularly significant, as these alterations would be passed on to any offspring of the resulting embryo. Also, minimising the chances of an embryo developing with the gene associated with this form of heart disease is likely to benefit those using pre-implantation genetic diagnosis as part of assisted reproductive techniques.

However, genome editing research with human gametes and embryos is still at an early stage. In editing out a gene associated with a significant heart disease in the resulting embryos, it is important to avoid the creation of other embryos which then have a different genetic disorder.

A/Prof Justin Oakley is Deputy Director of the Monash Bioethics Centre.

For many decades we have been using technology to prevent transmission of inherited diseases. IVF clinics around the globe routinely screen for embryos that are free of genetic mutation where couples carry a risk of passing on a genetic condition to their children. The discovery by Ma and colleagues describes how it may be possible to correct the mutation in an IVF embryo, effectively rescuing the embryo which would otherwise be discarded.

While their proof-of-principle paper describes how they have improved the efficiency of the technology used to correct the defect, more research is required to optimise the approach to ensure that the correction does not inadvertently cause further harm. Given existing methods employed by IVF clinics enable parents to have children free of genetic disease, the adoption of new technology to correct genetic defects in human embryos requires careful consideration.

A/Prof Megan Munsie is Deputy Director in the Centre for Stem Cell Systems at The University of Melbourne, and Head of the Education, Ethics, Law & Community Awareness Unit at Stem Cells Australia.