25 years after the Human Genome Project was initiated, scientists have announced Phase 2: the Human Genome Project – Write. The announcement, published in the journal Science last week, proposes the ambitious goal of synthesizing the entire human genome, all 3 billion base pairs of DNA, from scratch within 10 years. A tall order considering the practical limit for chemical DNA synthesis is currently only 200 base pairs. For larger segments, many smaller pieces must be connected together.
Improvements in technique
But development of technology often happens as a result of necessity. Since the launch of the human genome project, the cost of DNA sequencing has decreased dramatically such that it is now possible to sequence an entire human genome for close to $1000.
The authors of this paper hope that such an ambitious DNA synthesis goal will drive the field to make the necessary advancements and decrease the overall cost of synthesis by 1000-fold within the 10 year period.
Breaking it down
The proposed project would proceed in stages beginning with several pilot projects such as:
1) Synthesizing whole genes complete with coding and non-coding segments
2) Synthesizing whole chromosomes
3) Synthesizing chunks of DNA containing all genes required for a specific cell function.
These pilot projects alone could vastly increase our understanding of cell biology and certain diseases.
But given the significant advances made in gene editing technologies such as CRISPR, is it ever really necessary to synthesize DNA from scratch?
“That depends on your point of view and your goal,” says Jef Boeke, Professor of the New York University School of Medicine and lead author on the paper. “If your goal is to make a systematic type of change genome wide, and the feature you are changing is randomly dispersed, then yes, full genome synthesis would be the most effective way.”
Ethical concerns
Reactions to the project announcement have been mixed – excitement for this new chapter of scientific discovery, tempered by concerns of the things it may lead to.
Then again, such ambitious projects usually garner mixed reviews. Many were against sequencing the human genome, worried about discrimination based on genetics. This led to the Genetic Information Non-discrimination Act, a federal law that protects Americans from being treated unfairly because of differences in their DNA that may affect their health.
The advancement of gene editing technologies such as CRISPR has led to a proposed moratorium on the editing of inherited genes.
“I don’t think we should, or even can, impede the progress of science, but it is equally important to discuss the intent and develop policies that surround the use of information coming from the project,” says Mark Poznansky, President and CEO of Ontario Genomics.
One worry with full genome synthesis is that it may lead to designer babies with no real biological parents, but the authors are prepared to put in safeguards including removing the synthetic cell’s ability to reproduce.
“To avoid doubt, we absolutely are not planning to make humans with synthetic genomes!” stresses Boeke.
Measure of success
Instead, synthetic DNA success will initially be gauged by measuring the cell growth rate and RNA expression profile – sensitive methods to measure “human-ness”.
“If the genome integration is done in an induced pluripotent stem cell, the cells can also be assessed for their ability to form differentiated progeny,” explains Boeke.
And although the human genome is touted as the ultimate goal, other organisms like crop plants of infectious agents are also on the list.
“This project is terrifically exciting and has the potential to provide extremely important knowledge,” says Poznansky.
