It is four years since the Second International Summit on Human Genome Editing. There, the birth of two genome-edited twins was announced by Dr He Jiankui to resounding shock across the scientific community (see BioNews 1029). Given that the Third International Summit was originally intended to take place this month, it seems an apt time to survey the current landscape of human genome editing. To this end, the Progress Educational Trust (PET) recently arranged a lineup of key figures at the vanguard of different aspects of genome editing, who presented their opinions and current research. In particular, these experts addressed two questions – where are we now, and what happens next?

The event weaved a mix of regulation, policy, science, law and ethics – all areas that must be considered to answer questions as broad as those proposed in the title. The discussion was chaired jointly by PET's director Sarah Norcross and chair of trustees Professor Robin Lovell-Badge (Professor Lovell-Badge also chairs the planning committee for the Third International Summit).

The first expert consulted was the co-lead of the World Health Organisation's (WHO) global health ethics and governance unit, Katherine Littler, who oversaw three Human Genome Editing reports produced by the WHO (see BioNews 1103). Littler gave an insight into the global regulatory landscape surrounding human genome editing, and the challenge of trying to regulate an emerging technology internationally. Surprising to me was Littler's exploration of the need for self-governance within science, even to the extent of whistleblowing, to manage genome editing.

Littler highlighted the WHO's registry of human genome editing trials, which seeks to avoid surprises like Dr He's research, and also suggested a similar registry for 'basic' genome editing studies. Fundamentally, I agree with this, but I question whether something like this would be willingly adopted by researchers. Science is often conducted in a cloud of secrecy, given the highly competitive nature of research funding, and those who don't want their ideas revealed to all by a registry may be driven underground.

I am left feeling that it will be up to individual states and even individual researchers to manage whether or how they use genome editing, and that if a nation chooses to ignore whatever mandates or treaties are developed, then little will come of it.

Next to speak was Professor Kathy Niakan, director of the Centre for Trophoblast Research at the University of Cambridge. Professor Niakan presented the audience with a deft overview of the landscape of genome editing approaches as they stand. I think the key focus for many viewers here, and myself, is data from Professor Niakan and others concerning off-target effects.

Any excitement that I may have had that there had been leaps and bounds in this area was rapidly quashed. Professor Niakan painted a picture similar to that which we saw a year or two ago – germline genome editing results all to easily in off-target mutations, large chromosomal rearrangements, and mosaicism. This is grim in terms of clinical viability, and reminds us that much more basic research is needed before we can consider using CRISPR to edit the human germline in the clinic.

Continuing the basic science theme was Professor Wolf Reik, founding director of the Cambridge Institute of Science at Altos Labs. Professor Reik gave a concise look at the epigenome, the non-heritable chemical changes made to the genome capable of directing gene expression, and the fact we can now edit it, providing control of this process. I am struck by the number and complexity of available approaches for epigenome editing that have already emerged, and even more surprised that they are already showing promise in animal models for addressing conditions such as Fragile X syndrome.

As Professor Reik spoke, I wondered if epigenome editing holds the potential to see broader use than genome editing. It seems to have more potential given its potentially transient and reversible nature, and the diversity of its possible applications. However, it may well come with its own host of complexities, something I wish Professor Reik had done more to acknowledge.

The event then pivoted away from basic science and towards the ethical and legal realms with Professor Hank Greely, director of the Centre for Law and the Biosciences at Stanford University, and author of books including 'CRISPR People: the science and ethics of editing humans' (see BioNews 1097). Professor Greely took a somewhat more pragmatic and refreshing viewpoint versus previous speakers, questioning if our reverence of genome editing is truly necessary, and even wondering why we treat the human germline like the Ark of the Covenant.

Professor Greely started by offering some grounding perspective, convinced that there is little need for germline genome editing given the existence of preimplantation genetic diagnosis (PGD). He did, however, concede that certain compelling use-cases exist, albeit rare, such as two autosomal recessive parents wanting to have biological children.

Professor Greely also delved into the realities of genome editing being used for that darkest of words, 'improvement', which to me is very much part of the 'what happens next' part of the public's mind. He advocated a rational approach, and reasoned that the practicalities of improving humans are far harder than scaremongers would like to have you believe. I found myself agreeing.

Closing the talks was Nick Meade, joint interim CEO of Genetic Alliance UK, who gave insight into genome editing from a rare disease perspective. As he pointed out, most single gene disorders – likely the first to be treated by genome editing (whether somatic or germline) – are, by their very, nature rare. Something Meade highlighted was that more than 1000 rare disease conditions have PGD approval in the UK – far more than have available treatments. I wondered if, even in a hypothetical world where germline genome editing was safe and efficient, companies would feel the commercial desire to invest in it.

The question of equity and access for genome editing treatments came up, as might be expected. Meade provided insight into the difficulties patients can already have accessing already existing and established treatments, to say nothing of novel genome editing treatments.

As talks concluded, I was struck by the breadth of topics covered and the amount of knowledge shared in two hours. The event finished with a considerable Q&A session. An audience member asked whether Professor Niakan could realistically see germline genome editing being used in clinics, to which the answer was – somewhat unsurprisingly – not in its current form.

Others delved deeper into the landscape surrounding the international regulation of genome editing. How do we encourage education, engagement and empowerment, in countries where state media is the only option? Littler suggested that this is worth attempting, by engaging with relevant authorities in these countries.

I came away from the event with a sense that where we are now still at the very early stages of the journey for human genome editing, and that what happens next is increasingly complex. However, I would urge you to use PET's film of the event (due to appear in a future edition of BioNews) as a resource to form your own opinion on where genome editing currently stands, and is heading. The event surveyed the state of genome editing from a uniquely broad range of perspectives.

PET is grateful to Cambridge Reproduction, the Anne McLaren Memorial Trust Fund and the Association of Reproductive and Clinical Scientists for supporting this event.