‘Human Genome Project–Write’: Experts propose building synthetic human genome

Leading figures in synthetic biology have proposed a project to build large genomes from scratch, including human genomes, and test them in cell lines. Called the Human Genome Project–Write, the proposal is the outcome of a meeting at Harvard University, which was recently criticized for being too secretive. Writing in Science, the meeting attendees emphasize the importance of establishing an ethical framework for genome-scale engineering.

 

Dr. Samuel Deutsch, Head of DNA Synthesis and Assembly, DOE Joint Genome Institute (webpage):

Expertise: DNA synthesis and assembly, pathway refactoring, genotype to phenotype modeling.

“The ambitious goal of the Human Genome Project-Write is to build and deploy a fully synthetic human genome in human cell lines within 10 years. Accomplishing such a milestone will require transformative advances in DNA synthesis technologies relative to current state-of-the-art.

“The most ambitious genome synthesis project to date is Sc 2.0, an international collaboration to build a fully synthetic yeast strain that has been in the works for over 5 years. Relative to Sc2.0, HGP-write is 200x larger and includes a much higher proportion of difficult-to-synthesize ‘low complexity’ DNA.

“An additional challenge, is that in higher eukaryotes genetic information is functionally coded not only by DNA but as chromatin, a complex association of DNA and proteins that are modified epigenetically to carefully regulate genome function.

“Despite these challenges, a coordinated initiative such as the one proposed, is likely to drive the technological advances required. For HGP-write, the immediate applications and necessary intermediate milestones are not clear but the authors do suggest some very compelling potential applications such as synthesizing discrete genomic regions to help model human diseases or making more robust cell lines for the production of biologics (commonly used by the pharmaceutical industry), which would have clear societal benefits.

“It is very important to make a clear distinction between synthesizing a human genome in somatic cell lines as is proposed, and modifying human germline cells that could be hereditably transmitted, which is not in the scope of this project. Nevertheless, all technology that could be potentially used to modify human genomes needs to proceed in the context of open and transparent dialogue with many societal stakeholders, and under a regulatory framework that governs how such technology can be used in a safe and ethically acceptable manner.

“The authors propose that a percentage of all funding raised for this project be dedicated to ethical, legal and social issues. This is not only advisable but also essential. By starting a broad, transparent and inclusive conversation early on, both the scientific community and society in general will be better positioned to address the societal implications of HGP-write as the technology comes of age.”

 

Dr. Megan J. Palmer, Senior Research Scholar and William J. Perry Fellow in International Security, Center for International Security and Cooperation (CISAC), Stanford University (webpage):

Expertise: Societal aspects of biotechnology; biotechnology policy and practices; biological safety, security, and governance

“The Human Genome Project Write (HGP-Write), positioned as the logical extension of the Human Genome Project (HGP-Read) has already stirred public controversy over the closed, invitation-only nature of the meeting held to develop the vision and generate the Science article. The Perspective attempts to address concerns by foregrounding the need for an “ethical framework” alongside technology development. The authors state that the project “will require continual public involvement and consideration of the ethical, legal and societal implications (ELSI) from the start”. Moreover, they advocate going beyond an ELSI approach (the term used to describe the approach in HGP-Read) and adopting a “responsible innovation” approach. This approach would involve “identifying common goals important to scientists and the wider public through timely and detailed consultation among diverse stakeholders”.

“It’s admirable that the authors state a need for an early, ongoing and participatory approach to the societal aspects of their work. However, it’s not clear how such work will proceed. To use their own language – how they will go from observation to action? Confusion about transparency in the early stages of the project demonstrates that the main challenge in developing an ethical framework often lies in its implementation.

“The current review of the US Coordinated Framework for the Regulation of Biotechnology Products illustrates some of the complexities of conducting nuanced public deliberations. Even with a framework in place, the process to determine whether a new technology is “desirable” “effective” or “safe” is contentious and takes years. Such a process becomes even more complex on an international stage, as shown by the ongoing debates within the UN Convention on Biological Diversity and the UN Biological Weapons Convention, which will both have bearing upon this effort’s goals, such as equitable benefits sharing.

“There are nascent efforts to conduct experiments and develop expertise in responsible innovation, but we have a long ways to go. The capacity to build genomes may bring new benefits, risks and understanding of our human makeup. But the grand challenge of such a project is not in synthesizing human genomes – it’s in synthesizing humility within our human scientific endeavors.”

 

Dr. Keith Tyo, Assistant Professor of Chemical and Biological Engineering, Northwestern University (webpage):

Expertise: Synthetic biology, protein engineering, metabolic engineering, global health.

“Human Genome Project-Write is a worthy goal.  I respect the scientists’ transparency and sensitivity to the ethical implications of the work.  Compared to something like the Manhattan project, HGP-Write is plotting a much better trajectory from a societal standpoint.

“What made HGP-Read successful was the appearance of a private sequencing effort that innovated the process.  It would be wise to create the opportunity for such a situation here.

“Within the 10-year timeline, even if whole genome synthesis is not possible, the use of very large DNA strands (>100 kb) to edit and reconfigure larger swaths of a genome would have important implications on human health and environmental sustainability.  These developments may not be ready for wide-spread use in 10 years, but proof-of-concept is feasible.”

 

 

Declared interests (see GENeS register of interests policy):

Megan J. Palmer: I previously served at the Deputy Director of Policy and Practices for the multi-university NSF Synthetic Biology Engineering Research Center where I interacted with many of the authors involved in this effort.

No further interests declared.

 

Reference:

‘The Genome Project-Write’ by Boeke et al., published in Science on Thursday, June 2, 2016

 

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