Scientists plan to build human genome from scratch

June 6, 2016

Efficiency trends in DNA sequencing (green) and synthesis of double-stranded DNA (dsDNA, blue) and single-stranded DNA (ssDNA, red) over the past ~35 years. The disruptive improvement in sequencing and ssDNA (oligonucleotides) synthesis technologies has improved from multiplex and miniaturization technologies in high-throughput DNA sequencing and oligo microarray technologies, respectively. (credit: Jef D. Boeke et al./Science)

Leading genomics experts have announced Genome Project-write (HGP-write), which aims to synthesize entire genomes of humans and other species from chemical components and get them to function in living cells.

As explained in Science, the goal of HGP-write is to reduce the costs of engineering large genomes, including a human genome, and to develop an ethical framework for genome-scale engineering and transformative medical applications.

Impacts expected on human health, energy, agriculture, chemicals, and bioremediation

HGP-write will build on the knowledge gained by The Human Genome Project (HGP-read), especially in genomic-based discovery, diagnostics, and therapeutics. But while the Human Genome Project “read” DNA to understand its code, HGP-write will use the cellular machinery provided by nature to “write” code, constructing vast DNA chains.

The goal is to launch HGP-write in 2016 with $100 million in committed support from public, private, philanthropic, industry, and academic sources globally. Autodesk has already contributed a leadership gift of $250,000 to seed the planning and launch of HGP-write.

According to the authors of the Science commentary, although “…sequencing, analyzing and editing DNA continues to advance at breakneck pace, the capability to construct DNA sequences in cells is mostly limited to a small number of short segments, restricting the ability to manipulate and understand biological systems.”

Exponential improvements in genome engineering

The new effort is expected to lead to a massive amount of information connecting the sequence of nucleotide bases in DNA with their physiological properties and functions, and it promises to have a significant impact on human health and other critical areas such as energy, agriculture, chemicals, and bioremediation, according to the organizers.

HGP-write will be implemented through a new, independent nonprofit organization, the Center of Excellence for Engineering Biology as an open, international, multi-disciplinary research project.*

“This grand challenge is more ambitious and more focused on understanding the practical applications than the original Human Genome Project,” said George Church, Ph.D., Robert Winthrop Professor of Genetics at Harvard Medical School. “Exponential improvements in genome engineering technologies and functional testing provide an opportunity to deepen the understanding of our genetic blueprint and use this knowledge to address many of the global problems facing humanity.”

Another goal is development of new genomics analysis, design, synthesis, assembly and testing technologies, with the goal of making them more affordable and widely available. “Writing DNA code is the future of science and medicine, but our technical capabilities remain limited,” said Andrew Hessel, Distinguished Researcher, Bio/Nano Research Group, Autodesk, who will head a multidisciplinary team exploring computer-aided design and manufacturing for biotechnology and nanotechnology R&D.

“HGP-write will require research and development on a grand scale, and this effort will help to push our current technical limits by several orders of magnitude,” he said.

The HGP-write project developed from a series of meetings held over the last several years, including a closed-door meeting held May 10 in Boston, which brought together a diverse group of 130 participants from many different countries, including biologists, ethicists, engineers, plus representatives from industry, law and government.

* The Genome Project-write (HGP-write) will be an open, international research project led by a multi-disciplinary group of scientific leaders who plan to oversee a reduction in the costs of engineering and testing large genomes, including a human genome, in cell lines more than 1,000-fold within ten years. 

To ensure public engagement and transparency, HGP-write will include mechanisms to encourage public discourse around the emerging HGP-write capabilities. The Woodrow Wilson Center for International Scholars will help to lead such efforts for HGP-write.

Principals are:

  • Jef Boeke, Ph.D., Director, Institute for Systems Genetics, Professor, Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center. Dr. Boeke is a leader of the Synthetic Yeast Project (Sc2.0), which seeks to create living yeast cells with entirely redesigned chromosomes by 2017.
  • George Church, Ph.D., Robert Winthrop Professor of Genetics at Harvard Medical School, Core Faculty Member at the Wyss Institute for Biologically Inspired Engineering at Harvard University, Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT), and Senior Associate Faculty member at the Broad Institute. Among the leaders of the original HGP-read, Dr. Church currently heads an effort to create a version of the bacteria E.coli with a redesigned genome.
  • Andrew Hessel, Distinguished Researcher, Bio/Nano Research Group, Autodesk. He spearheads a multidisciplinary team exploring computer-aided design and manufacturing for biotechnology and nanotechnology R&D.
  • Nancy J Kelley, J.D., M.P.P., President & CEO, Nancy J Kelley & Associates, formerly Founding Executive Director, New York Genome Center. She is lead executive of HGP-write and the related Center of Excellence for Engineering Biology.

Abstract of The Genome Project–Write

The Human Genome Project (“HGP-read”) nominally completed in 2004 aimed to sequence the human genome and improve technology, cost, and quality of DNA sequencing (12). It was biology’s first genome-scale project, and at the time was considered controversial by some. Now it is recognized as one of the great feats of exploration, one that has revolutionized science and medicine.

Although sequencing, analyzing, and editing DNA continue to advance at breakneck pace, the capability to construct DNA sequences in cells is mostly limited to a small number of short segments, restricting the ability to manipulate and understand biological systems. Further understanding of genetic blueprints could come from construction of large, gigabase (Gb)–sized animal and plant genomes, including the human genome, which would in turn drive development of tools and methods to facilitate large-scale synthesis and editing of genomes. To this end, we propose the Human Genome Project–Write (HGP-write).