Written by Luke Alphey, The Pirbright Institute
While “I know it when I see it” is good enough for many purposes, a broadly recognised definition is important for framing debates, not least about regulation and in the context of public engagement.
The NAS 2016 report “Gene drives on the horizon” reviewed the origin and use of the term and concluded that it is essentially synonymous with “selfish DNA”. From my personal perspective, the concept seems to have arisen from “meiotic drive” and similar naturally-occurring genetic systems, then perhaps became synonymous with “synthetic gene drives” – with a lot of excitement over the potential of engineered transposons, for example, though their star has waned considerably in recent years – and has now moved to something a little more all-encompassing including both natural and synthetic systems.
However, with the increasing prominence of endonuclease-based ‘homing’ drives, especially CRISPR/Cas9-based ones, the meaning seemed to be drifting again, to refer only to low-invasion-threshold, self-sustaining CRISPR/Cas9 homing drives. This could lead to the much greater diversity of natural and synthetic gene drives being overlooked, particularly by non-specialists. Stakeholders and publics might also assume that the various risks, benefits and issues associated with synthetic homing drives apply equally to all gene drives. These issues were discussed, for example at the Gene Drive Research Forum (Montreal, 2018), leading to the conclusion that it is important to emphasise the diversity of gene drives.
To complicate things further, “gene drive” sometimes refers to a phenomenon – the process of gene drive, i.e. of biased inheritance favouring one allele or sequence over another – and sometimes to the material object, e.g. gene, that leads to that phenomenon. Finally, gene drives may not always drive, i.e. may only lead to the phenomenon of gene drive under certain circumstances.
Recognising that it would be helpful for all concerned to have some standardisation around these terms – not just “gene drive” but ancillary terms like “high-threshold”, “localised”, and so on, the Foundation for the National Institutes of Health (FNIH) – one of the co-organisers of the Montreal meeting - set out to find a consensus view. FNIH, and Stephanie James in particular, have been well-regarded coordinators and facilitators of genetic control developments, including gene drive, for many years.
This effort led to the recent publication “Standardizing the definition of gene drive” which tries to provide some definitions. One complication in writing the paper, more specifically the supplementary tables of definitions, was what to include. Everyone gives a new name to their specific implementation, no matter how small or large the difference from the prior art! This is not a criticism – I have done the same myself – but it does make it difficult to know which terms will persist and which will not.
While some concepts, such as “population suppression” or “underdominance” seem relatively timeless, terms that are closer to brand names for specific implementations may not. On the other hand, the sterile insect technique (SIT), which is in that category, is still going strong after more than 50 years, far longer than the gene drive field has existed in any recognisable form, so who knows!
While I hope the paper is useful for providing some common language for discussion, and perhaps also as an entry point for students and others trying to get to grips with the jargon in the field, I’m sure it’s not going to be the last word. The intention is for the paper to be housed on the GeneConvene Virtual Institute website; the core definition is here, where interested parties can indicate support for a common definition and provide comment on the current version.
The publication “Standardizing the definition of gene drive” is available at the journal PNAS.