Nearly 200 experts in genetics and bioengineering will be attending a meeting in New York City this week, to discuss a project that will create much debate over issues of ethicality and legality. The project is an effort to synthesise DNA, including human DNA.

Researchers say they will start the ambitious and controversial plan with simpler organisms, such as microbes and plants, but hope to ultimately create strands of human genetic code synthetically.

Jef Boeke, director of the Institute for Systems Genetics at NYU School of Medicine, said that incorporation of synthesised DNA into mammalian or even human cells, could happen within four to five years.

A follow-up to the Human Genome Project

The project named Genome Project-write (GP-write) is expected to cost USD100 million to research, engineer, and test living systems of model organisms, including the human genome.

It is framed as a follow-up to the Human Genome Project (HGP), which began in 2003 and ended last year, mapping out the entire human genetic code.

“HGP allowed us to read the genome, but we still don’t completely understand it,” said Nancy Kelly, the coordinator of GP-write.

The intention of GP-write is to provide a better fundamental understanding of how nucleotides work together. Using synthesised genomes has pragmatic and theoretical implications – it could lead to lower cost and higher quality of DNA synthesis as well as discoveries about DNA assembly in cells and the ability to test many DNA variations.

“If you do that, you gain a much deeper understanding of how a complicated apparatus goes,” Boeke said.

GP-write’s results could provide many medical possibilities

One of the things that GP-Write intends to address is the understanding of an “ultrasafe cell line”.

“[Cell lines] have been cultured in dishes in labs for decades. But you can’t engineer the genomes – the tools for doing that are quite crude, relatively speaking,” Boeke explains.

When the cells get infected with a virus drug production gets completely shut down. A synthetic cell that lacks the unnecessary genetic material could be virus-resistant, consistently producing useful drugs to treat disease.

The understanding of how nucleotides work could also lead to stem cell therapy that eliminates the risk of infecting the patient with another disease, or create a line of microorganisms that could help humans generate some amino acids that are usually obtained from food.

“Getting big pieces of DNA efficiently into mammalian cells, engineering them rapidly, these will be major challenges,” Boeke said. Cost is also a factor to be considered.

Yeast chromosome almost fully synthesised

Boeke led a research that attempted to synthesise the yeast chromosome. The paper was published in March and saw the synthesis of five more of the 16 chromosomes that make up the genome of yeast. The first time synthesis was done was in 2014.

The human genome is much more complex than the yeast genome and “obviously the details of writing a human genome will be different, but some of the things we learned should feed into GP-write,” said Boeke.

Other scientists agreed, calling the paper “the quintessential first step toward creating a synthetic organism.” The success of the project meant that a “designer genome” could be constructed. But some scientists are not quite sure.

Secret meeting provoked controversy

Experts involved intended to portray the project as an open international collaboration designed to further understand genome science.

“I think articulation of our plan not to start right off synthesising a full human genome tomorrow was helpful. We have a four-to five-year period where there can be plenty of time for debate about the wisdom of that, whether resources should be put in that direction or in another,” Boeke said.

“We want to hear what people have to say,” he added.

But GP-write provoked controversy after its first large meet-up last year that was conducted virtually in secret when a select group of invite-only experts held talks behind closed doors.

“Given that human genome synthesis is a technology that can completely redefine the core of what now joins all of humanity together as a species, we argue that discussions of making such capacities real… should not take place without open and advance consideration of whether it is morally right to proceed,” wrote medical ethicist Laurie Zoloth from Northwestern University and synthetic biologist Drew Endy of Stanford University.

However, the GP-write team has not shown signs of stopping anytime soon, and perhaps after next week, a more transparent discussion will come to light, regarding the applications, ethics and logistics behind the project. MIMS

Read more:
Are we over-propagandising genetic research?
FDA approves sale of genetic tests for disease risk
Human knockouts: A way to decipher why some drugs work, while others fail