Spotlight: Scientists propose ambitious project to synthesize human genome

A group of leading scientists on Thursday proposed the launch of an ambitious follow-up to the 13-year, 3-billion-U.S.-dollar Human Genome Project (HGP), including creating a fully synthetic human genome within 10 years.

Called Human Genome Project-Write (HGP-write), the proposal by genome research pioneers such as Jef Boeke and George Church was first revealed two weeks ago, when a "secret" meeting at Harvard University on this topic triggered debate in the life science community.

TIME TO WRITE HUMAN GENOME

The original Human Genome Project only aimed to read DNA's 3 billion pairs, but Boeke, Church and colleagues declared in the prestigious U.S. journal Science that now is the time to beyond that to "write" them via chemical synthesis.

They argued that the original HGP, which ended nominally completed in 2004, was also once considered controversial by some but now "recognized as one of the great feats of exploration, one that has revolutionized science and medicine."

According to these scientists, although technology for sequencing DNA continues to advance rapidly, 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-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," the scientists said.

"To this end, we propose the Human Genome Project-Write (HGP-write)," they wrote. "HGP-write will require public involvement and consideration of ethical, legal, and social implications from the start."

HGP-WRITE GOALS

The group said they planned to launch HGP-write in 2016 with 100 million dollars in committed support, from public, private, philanthropic, industry, and academic sources from around the world.

Total project costs, they said, are difficult to estimate, but would likely be less than the three billion dollars spent by the original HGP.

The primary goal of the proposed follow-up, according to the scientists, is to reduce the costs of building and testing large genomes, defined as having 0.1 to 100 billion base pairs, in cell lines by over 1000-fold within 10 years.

This will include whole-genome engineering of human cell lines and other organisms of agricultural and public health significance, or those needed to interpret human biological functions -- gene regulation, genetic diseases, and evolutionary processes, for example.

"This goal is necessarily ambitious, since building a human genome at today's prices would cost more than" the original HGP, they said.

This effort should begin with "stepping stone" projects that will focus on a fraction of the genome, typically one percent, they said.

The potential applications include growing transplantable human organs; engineering immunity to viruses in cell lines via genome-wide recoding; engineering cancer resistance into new therapeutic cell lines; and accelerating high-productivity, cost-efficient vaccine and pharmaceutical development using human cells and organoids.

ETHICAL ISSUES

In 2010, genome research pioneer Craig Venter had succeeded in synthesizing the genome of a bacteria known as Mycoplasma mycoides, which consists of 1.08 million base pairs.

In 2014, an international team of scientists, led by Jef Boeke of the Langone Medical Centre at New York University, achieved another milestone by synthesizing one of the 16 chromosomes for yeast.

But not everyone was in favor of the proposal of synthesizing a human genome.

Stanford University scientist Drew Endy and Northwestern University bioethicist Laurie Zoloth, who were the first to reveal the "secret" Harvard meeting, slammed the project as raising ethical issues and moral implications.

"For example, would it be OK to sequence and then synthesize Einstein's genome?" they asked in an article. "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?"

While calling it a "milestone," Samuel Deutsch of the the U.S. Department of Energy Joint Genome Institute, emphasized that 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.

"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," Deutsch said. Endit