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Summit agrees genome editing to proceed, with caution

07 December 2015

By Dr Jane Currie

Appeared in BioNews 831

An international summit has agreed conditions under which human genome editing, using techniques like CRISPR, should proceed.

The International Summit on Gene Editing, held in Washington, was a collaboration between the US National Academies of Sciences and Medicine, the UK Royal Society, and the Chinese Academy of Sciences. The Summit Organising Committee called the meeting in response to rapidly increasing research using genome-editing techniques, such as CRISPR.

CRISPR allows quicker, cheaper and more accurate genome editing than previously possible, but its sudden prominence has raised important ethical and societal questions.

'The overriding question is when, if ever, we will want to use gene editing to change human inheritance,' said Professor David Baltimore, leader of the Summit Organising Committee, at the opening of the summit.

Scientists, clinicians, patients and ethicists spent three days discussing the pros and cons of genome editing, which led to an agreed statement from the Organising Committee about how to go forward.

First, they said that basic and preclinical research 'should proceed', particularly to improve genome-editing technology or to understand its benefits and risks. However, they emphasised that any early human embryos or germline cells that have been edited should not be used to establish a pregnancy.

Second, they support the editing of somatic cells (that is, cells that cannot be transmitted to the next generation). They explained that such research may help treat genetic conditions and would be regulated using the existing clinical research frameworks in place for gene therapy.

Third, they said that the clinical use of germline cell editing, which could potentially be used to avoid severe inherited diseases or 'enhance' human capabilities, would currently be 'irresponsible'. They added that the ethical and societal issues of germline editing have not been sufficiently explored, and the risk of possible harm to future generations is too great.

Finally, they recommended setting up an international forum to lead on further work in this area: 'The international community should strive to establish norms concerning acceptable uses of human germline editing and to harmonize regulations, in order to discourage unacceptable activities while advancing human health and welfare.'

However, not all scientists are satisfied with the outcome of the summit. 'I'm disappointed that the organisers did not propose at least a temporary moratorium on germline human genetic modification,' Dr Paul Knoepfler, a cell biologist at the University of California, told the Guardian.

'It's not clear to me what the downside of a temporary moratorium would have been. Several of the organisers clearly and in some cases strongly advocated for a "pause" in germline editing in the last few months. What changed?'

Before the summit, CRISPR pioneer Professor Jennifer Doudna, another member of the Organising Committee, wrote in Nature:

'In my view, a complete ban might prevent research that could lead to future therapies, and it is also impractical given the widespread accessibility and ease of use of CRISPR/Cas9. Instead, solid agreement on an appropriate middle ground is desirable.

'In addition, future discussions that build on this December's meeting should address other potentially harmful applications of genome editing in non-human systems, such as the alteration of insect DNA to "drive" certain genes into a population.'

The Progress Educational Trust's public conference 'From Three-Person IVF to Genome Editing: The Science and Ethics of Engineering the Embryo' is taking place in central London on Wednesday 9 December 2015. Find out more here.


Scientists improve CRISPR accuracy

Although CRISPR/Cas9 has been a major step forward in the accuracy of genome editing, it still frequently leads to modifications at sites in the genome other than that intended. This is a major cause for concern regarding potential future applications in humans.

The Broad Institute team involved in developing CRISPR/Cas9 have now modified the genome-editing technique to significantly reduce the numbers of off-target effects. Professor Feng Zhang and colleagues report in Science that modifying three amino acids in Cas9, the enzyme that 'cuts'  DNA during modification, reduced off-target effects to undetectable levels.

The modified protein, which the researchers have named 'enhanced' S. pyogenes Cas9 (eSpCas9), is now being made available to researchers worldwide.

'Many of the safety concerns [about genome editing] are related to off-target effects,' said Professor Zhang. 'We hope the development of eSpCas9 will help address some of those concerns, but we certainly don't see this as a magic bullet. The field is advancing at a rapid pace, and there is still a lot to learn before we can consider applying this technology for clinical use.'

SOURCES & REFERENCES
STAT | 02 December 2015
 
Science News | 03 December 2015
 
Scientific American | 03 December 2015
 
The National Academies of Science, Engineering & Medicine | 03 December 2015
 
Nature News | 02 December 2015
 
New York Times | 03 December 2015
 
The Guardian | 03 December 2015
 

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