The ability to sequence and edit human DNA has revolutionized biomedicine. Now a new consortium wants to take the next step and build human genomes from scratch.
The Human Genome Project was one of the great scientific moonshots of the last century. Mapping the entirety of our DNA took thousands of researchers from across the globe 13 years and nearly $3 billion, but the benefits have been enormous.
The project has revolutionized our understanding of the genetic basis of disease and driven rapid advances in the technology needed to read and interpret our DNA. The cost of sequencing an entire human genome has plummeted from around a million dollars in 2008 to just a few hundred dollars today.
The ability to not only read but also build human genomes from scratch could bring more fundamental breakthroughs. And now the world's largest medical charity, the Wellcome Trust, is providing £10 million ($13.6 million) in funding to kickstart the Synthetic Human Genome Project (SynHG).
“The ability to synthesize large genomes, including genomes for human cells, may transform our understanding of genome biology and profoundly alter the horizons of biotechnology and medicine,” Jason Chin from the University of Oxford, who will lead the project, said in a statement.
The project builds on a steady stream of advances in DNA synthesis in recent years. Chin himself led a team that synthesized the entire genome of the bacteria E. coli in 2019. And in 2023, an international consortium completed the first synthetic genome of yeast—a significantly more complex organism that is closer in evolutionary terms to humans.
At this stage, the SynHG project is focused on developing foundational tools and methods, and the organizers admit it will likely take decades to synthesize an entire human genome. For now, the goal is to build a single human chromosome—one of the 46 tightly wound bundles of DNA that make up the human genome—in the next 5 to 10 years.
While gene editing makes it possible to tinker with existing genetic instructions, synthesis would make it possible to build larger stretches of DNA from scratch. Those kinds of capabilities could lead to breakthroughs in our understanding of disease and open the prospect of new therapies based on designer cell or even designer tissues and organs.
"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,” Matthew Hurles, director of the Wellcome Sanger Institute in the UK, told The BBC.
Much of our existing knowledge of the genome is restricted to the roughly 2 percent that codes for specific proteins, with the other 98 percent of “non-coding” DNA still largely a mystery. Being able to build the entire sequence from scratch could help us understand the genome’s “dark matter,” Julian Sale, from the UK’s Medical Research Council Laboratory of Molecular Biology, told The Guardian.
The project is controversial though. There are fears the same technology could be put to more ethically questionable uses. These could include new bioweapons, genetically enhanced humans, or even strange new organisms that incorporate some human DNA, geneticist Bill Earnshaw, from Edinburgh University, told The BBC.
"The genie is out of the bottle," he said. "We could have a set of restrictions now, but if an organization who has access to appropriate machinery decided to start synthesizing anything, I don't think we could stop them"
In an attempt to head off these concerns, SynHG will also have a social-science program designed to map out potential risks and how to deal with them. One particular issue it will focus on is the fact that genomic research is currently skewed towards people of European ancestry, which could limit broader applicability.
Fortunately, given the huge technical challenge ahead, there is likely plenty of time to map out the potential pitfalls. And if the project is successful, it could spark a second great revolution in genetics likely to do more good than harm.
