A team led by New York University’s Jef Boeke, Harvard’s George Church, and Andrew Hessel of the California-based commercial design studio Autodesk Research has published its proposal to synthesize entire genomes from scratch, including those of humans. Called the “Human Genome Project-Write” (the authors refer to the original HGP as Human Genome Project-Read), the initiative could take 10 years and a minimum of $100 million just to get started, the researchers reported on June 2 in Science.
The proposal is to string together synthetically made DNA and shape from it a human genome able to power a cell in a dish. But the idea — which essentially aims to develop technologies that reduce the cost of DNA synthesis — has not met with universal excitement among researchers.
“My first thought was ‘so what,’” Martin Fussenegger, a synthetic biologist at the Swiss Federal Institute of Technology in Zurich comments, “I personally think this will happen naturally. It’s just a matter of price at the end.” Others think that the project should be delayed until its leaders can win broader support for the idea. In an e-mail sent to reporters, synthetic biologist Drew Endy, at Stanford University in California, and religion scholar Laurie Zoloth, at Northwestern University in Evanston, Illinois, say that the HGP-write team has not properly justified its aims, and that the project should be abandoned. “We are still waiting for a serious public debate with participation from a broad range of people,” they say.
“There was a lot of confusion about what was going on”, says Tom Ellis, a synthetic biologist at Imperial College London, who attended the invitation-only meeting at Harvard University in May, when HGP-write was first aired to more than 100 scientists, entrepreneurs, lawyers and ethicists. The three-page announcement of HGP-write fills in some detail. It notes that current technologies are both too expensive and too primitive to synthesize the 3-billion-base-pair human genome. The team calls for a series of pilot projects, including synthesizing much shorter segments of the genome and making slimmed-down chromosomes to do specific tasks, to make its eventual goal doable. The whole project should require less than $3 billion (the price of the publicly funded Human Genome Project), the researchers say.
However, cheaper DNA synthesis isn’t the only thing that stands in the way of writing a human genome that could function inside a cell. There are currently no methods for inserting very large pieces of DNA into a mammalian cell and making them function normally, and researchers have little clue how to design a complex genome that has anything more than trivial changes to an existing one.
Researchers also worry that commercial bodies such as DNA-synthesis companies may stake a claim on the project. Therefore they prefer the project stays an open, publicly funded initiative. Boeke would prefer that there be no intellectual-property restrictions on the products of HGP-write, as is the case with his 270,000bp synthetic yeast genome project reported in 2014. But, he says, the “chances are good” that companies involved in HGP-write will be granted such rights “to get the job done”. To allow wider access, the effort may establish patent pools to allow users to easily license the fruits of the project, he adds.
The creators of HGP-write say their goal is to raise $100 million toward synthesizing a human genome inside of 10 years, but only in a lab dish. The synthetic cells will be engineered to make reproduction impossible. “We’re not trying to make an army of clones or start a new era of eugenics. That is not the plan.”, Boeke says. ”The purpose of this project is to develop and test large genomes in cells, and that is where it stops,” says Nancy Kelley, a fundraiser who is among the authors of the paper and is described as the “lead executive” of the project. The effort so far, including two planning meetings, has been paid for with a $250,000 grant from the software company Autodesk to an organization called the Center of Excellence for Engineering Biology, which Kelley runs.
Read more: Boeke, J. D. et al., “The Genome Project–Write”, Science, Jun 2016, DOI: 10.1126/science.aaf6850
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