Synthetic Human Genome project launched in the UK

The creation of synthetic human genomes is being investigated in a £10 million Wellcome funded project.

The project Synthetic Human Genome (SynHG) is a collaboration between five UK universities, seeking to create a toolkit that will enable the synthesis of the first synthetic human chromosome – accounting for approximately two percent of a human's total DNA – within the next five to ten years. The practical and scientific elements of the project will be coupled with investigations of the socio-ethical implications.

'The ability to synthesise large genomes, including genomes for human cells, may transform our understanding of genome biology and profoundly alter the horizons of biotechnology and medicine,' said Professor Jason Chin from the Ellison Institute of Technology and the University of Oxford. 'With SynHG we are building the tools to make large genome synthesis a reality, and at the same time we are pro-actively engaging in the social, ethical, economic and policy questions that may arise as the tools and technologies advance.'

The Human Genome Project published a rough draft of human reference genome in 2000 (see BioNews 64) and a final draft in 2003 (see BioNews 204), but there remained gaps in the human genome sequence which were only filled during later years (see BioNews 943, 1056 and 1086). A draft version of the complete human genome sequence was published in 2021 (see BioNews 1098) and a final version was published in 2022 (see BioNews 1140), followed by a comprehensive gene-function map (see BioNews 1147) and by further work sequencing the Y chromosome (see BioNews 1204). SynHG seeks to build on this earlier work, to gain deeper insight into how changes in DNA affect humans.

'Synthesising human genomes is a logical next step after what has been achieved to date with sequencing and editing human genomes,' Sarah Norcross, director of PET (the Progress Educational Trust) said. 'There are two important nuances to add. First, we must recognise that this sort of work is not without controversy, and that it is vital for researchers and the public to be in communication with one another. Second, we must not forget ongoing work in genome sequencing and genome editing, which remains vital.'

While the human DNA sequence can be read, the function of a large proportion of our DNA remains mysterious. The purpose of many coding regions of DNA has been discovered, but these are surrounded by large sequences whose function remains unclear.

'Building DNA from scratch allows us to test out how DNA really works and test out new theories, because currently we can only really do that by tweaking DNA in DNA that already exists in living systems,' Professor Matthew Hurles, director of the Wellcome Sanger Institute, told the BBC.

The project raises ethical and social considerations that will be addressed from the outset through work headed by Joy Zhang, professor of sociology at the University of Kent. This branch of the project, entitled 'Care-full Synthesis', will investigate societal perceptions of genome synthesis research.

'The public must have a clear understanding of what this research entails, while researchers and funders must have a thoroughgoing understanding of where the public wants to go with this science,' Norcross explained. 'We are therefore extremely pleased to see that a dedicated social science programme has been incorporated into this work at the outset.'

To date, genomic studies have not been representative of the full range of human genomic diversity, instead favouring people with European ancestry (see BioNews 1207 and 1293). 'Care-full Synthesis' will seek to address this shortcoming by conducting empirical studies across Africa, Asia and the Americas, while also investigating how science policy can accommodate diverse regional and community perspectives.