Life drawing

A new project aims to synthesise a human chromosome

The tools developed along the way could revolutionise medicine

Jul 03, 2025 02:10 PM

WHEN THE first draft of the DNA sequence that makes up the human genome was unveiled in 2000, America’s president at the time, Bill Clinton, announced that humankind was “learning the language with which God created life”. His assessment was a little quick off the mark. For one thing, the full sequence would not be completed until 2022. For another, whereas scientists can use sequencing tools to read DNA, and CRISPR technology to make small edits, actually writing the genomic language has proved trickier.

The Synthetic Human Genome, or SynHG, a project launched on June 26th, aims to change that. Funded partly by Wellcome, a charity, and including members from a handful of British universities, its goal is to develop the tools needed to create a human chromosome from scratch. Jason Chin, who is based at the University of Oxford, is the project’s lead. He believes its work will help scientists understand better how the sequence of a gene affects its function inside a living cell.

Geneticists have long dreamed of such power. The first synthetic gene was created in the 1970s, and the field has advanced since then. The genomes of the bacteria Mycoplasma genitalium, Mycoplasma mycoides and Escherichia coli were synthesised in 2008, 2010 and 2019, respectively. Attempts to recreate the genome of baker’s yeast, an organism genetically much closer to animals than bacteria, have been ongoing since 2006. A paper published in January 2025 announced the last of its 16 chromosomes had been synthesised.

At the same time, giant artificial-intelligence (AI) models, fed on growing troves of genomic data, promise to help guide DNA design. In February the Arc Institute in Palo Alto released Evo 2, a generative AI model, capable of devising new genomes based on short DNA sequences it is given as prompts. Then on June 25th Google DeepMind, an AI lab, launched AlphaGenome, a deep-learning model that can predict how small genetic changes will affect cell function. Hani Goodarzi, one of the scientists at Arc who developed Evo 2, says that the two models could, when combined, allow scientists to produce new designs for human DNA that would enable specific cellular functions.

It is a tantalising vision. If it comes to pass, biologists would be able to predict and test the effect of any change to the genome. Cell therapies, in which healthy or engineered cells are injected into people’s bodies to fix a genetic disease or a faltering liver or heart, could be designed to react only with the intended tissues, making them safer and more efficient. Cells, tissues or organs could also have their DNA redesigned ahead of a transplant to make them impervious to viruses.

The most daunting challenge is scale. DNA is made up of building-block molecules known as nucleotides, which each contain one of four chemicals known as bases. In the double-stranded DNA helix, the bases bond together into base pairs. Scientists build the strands individually, one nucleotide at a time, before bringing the strands together. This process reliably creates small bits of DNA, but longer stretches (made by combining short ones) are more difficult and costly to produce accurately. The largest completed synthetic genome so far—that of yeast—is 12m base pairs (bp) long. The smallest human chromosome—number 21—measures 45m bp.

Cost is another issue, says George Church, a biologist at Harvard University who has tweaked E. coli genomes to avoid viral infection and is hoping to do the same with pigs (he is the co-founder of eGenesis, a company that rears gene-edited pigs for organ harvesting). He estimates that synthesising an entire human chromosome may cost more than $20m.

Finding ways to overcome such challenges is exactly what Dr Chin hopes to achieve (his own cost estimate is closer to $650,000). For all his ambition, though, it is not clear that building genomes will ever become routine. Gene editing may become a cheaper and more reliable alternative to full-blown synthesis. CRISPR techniques are now capable of making several simultaneous edits to a given chunk of genome, and new alternatives are allowing ever-longer stands of DNA to be edited.

Then there is the question of ethics. Hank Greely, a lawyer and bioethics expert at Stanford University, believes that testing whether a synthetic human chromosome functions normally would require putting it into babies, which would be illegal in most countries, including Britain. Dr Chin stresses he has no plans to do this, and points out that a programme within SynHG called Care-full Synthesis will investigate the ethical dimensions of human synthetic genome research.

Even the production of a human chromosome in a Petri dish would be a significant achievement—confirmation that scientists had learned not just to read the language of life, but to write it. ■