Scientists are contemplating fabricating a human genome, spurring intrigue and concern in the life-sciences community.
Scientists are contemplating the fabrication of a human genome, meaning they would use chemicals to manufacture all the DNA contained in human chromosomes.
The prospect is spurring intrigue and concern in the life-sciences community, because it might be possible, such as through cloning, to use a synthetic genome to create people without parents.
While the project is still in the idea phase, and involves efforts to improve DNA synthesis in general, it was discussed at a closed-door meeting Tuesday at Harvard Medical School in Boston. The nearly 150 attendees were told not to contact the media or to tweet during the meeting.
Organizers said the project could have a big scientific payoff and would be a follow-up to the original Human Genome Project, which was aimed at reading the sequence of the 3 billion chemical letters in the DNA blueprint of human life. The new project, by contrast, would involve not reading, but rather writing the human genome: synthesizing all 3 billion units from chemicals.
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Such an attempt would raise numerous ethical issues. Could scientists create humans with certain kinds of traits, perhaps people born and bred to be soldiers? Or might it be possible to make copies of specific people?
“Would it be OK to sequence and then synthesize Einstein’s genome?” Drew Endy, a bioengineer at Stanford University, and Laurie Zoloth, a bioethicist at Northwestern University, wrote in an essay criticizing the proposed project. “If so, how many Einstein genomes would it be OK to make and install in cells, and who would get to make and control these cells?”
Endy, though invited, said he did not attend the Harvard meeting because it was not being opened to enough people and was not giving enough thought to the ethical implications of the work.
George Church, a professor of genetics at Harvard Medical School and one of the organizers of the proposed project, said the characterization was a misunderstanding, and that the project was aimed more generally at improving the ability to synthesize long strands of DNA, which could be applied to various types of animals, plants and microbes.
“They’re painting a picture which I don’t think represents the project,” Church said.
He said the meeting was closed to the media, and people were asked not to tweet because the project organizers, in an attempt to be transparent, had submitted a paper to a scientific journal. They were therefore not supposed to discuss the idea publicly before publication. He and other organizers said ethical aspects have been amply discussed since the beginning.
The project was initially called HGP2: The Human Genome Synthesis Project, with HGP referring to the Human Genome Project. An invitation to the meeting at Harvard said the primary goal “would be to synthesize a complete human genome in a cell line within a period of ten years.”
But by the time the meeting was held, the name had been changed to “HGP-Write: Testing Large Synthetic Genomes in Cells.”
The project does not yet have funding, Church said, though various companies and foundations would be invited to contribute, and some have indicated interest. The federal government will also be asked. A spokeswoman for the National Institutes of Health declined to comment, saying the project was in too early a stage.
Besides Church, the organizers include Jef Boeke, director of the institute for systems genetics at NYU Langone Medical Center, and Andrew Hessel, a self-described futurist who works at the Bay Area software company Autodesk and who first proposed such a project in 2012.
Scientists and companies can change the DNA in cells, for example, by adding foreign genes or changing the letters in existing genes. This technique is routinely used to make drugs, such as insulin for diabetes, inside genetically modified cells, and to make genetically modified crops. Scientists are debating the ethics of new technology that might allow genetic changes to be made in embryos.
But synthesizing a gene, or an entire genome, would provide the opportunity to make even more extensive changes in DNA.
For instance, companies are using organisms such as yeast to make complex chemicals, such as flavorings and fragrances. That requires adding not just one gene to the yeast, for example to make insulin, but numerous genes to create an entire chemical production process within the cell. With that much tinkering, it can be easier to synthesize the DNA from scratch.
Synthesizing DNA remains difficult and error-prone. Existing techniques can reliably make strands that are only about 200 base-pairs long, with the base pairs being the chemical units in DNA. A single gene can be hundreds or thousands of base-pairs long. To synthesize one of those, multiple 200-unit segments have to be spliced together.
But the cost and capabilities are rapidly improving. Endy of Stanford, who is a co-founder of a DNA synthesis company, Gen9, said the cost of synthesizing genes has plummeted from $4 per base pair in 2003 to 3 cents. But even at that rate, the cost for 3 billion letters would be $90 million. He said that if costs continued to decline at the same pace, that figure could reach $100,000 in 20 years.
Craig Venter, a genetic scientist and entrepreneur, synthesized a bacterial genome consisting of about 1 million base pairs. The synthetic genome was inserted into a cell and took control of that cell. While his first synthetic genome was mainly a copy of an existing genome, Venter and colleagues this year synthesized a more original bacterial genome, about 500,000 base-pairs long.
Boeke is leading an international consortium that is synthesizing the genome of yeast, which consists of about 12 million base pairs. The scientists are making changes, such as deleting stretches of DNA that do not have any function, in an attempt to make a more streamlined and stable genome.
But the human genome is more than 200 times as large as that of yeast and it is not clear if such a synthesis would be feasible.
Jeremy Minshull, chief executive of DNA 2.0, a DNA-synthesis company, questioned if the effort would be worth it.
“Our ability to understand what to build is so far behind what we can build,” said Minshull, who was invited to the meeting at Harvard but did not attend. “I just don’t think that being able to make more and more and more and cheaper and cheaper and cheaper is going to get us the understanding we need.’’