GP-write and the Future of Biology

Imagine going to the airport, but instead of walking through – or waiting in – long and tedious security lines, you could walk through a hallway that looks like a terrarium. No lines or waiting. Just a lush, indoor garden. But these plants aren’t something you can find in your neighbor’s yard – their genes have been redesigned to act as sensors, and the plants will change color if someone walks past with explosives.

The Genome Project Write (GP-write) got off to a rocky start last year when it held a “secret” meeting that prohibited journalists. News of the event leaked, and the press quickly turned to fears of designer babies and Frankenstein-like creations. This year, organizers of the meeting learned from the 2016 debacle. Not only did they invite journalists, but they also highlighted work by researchers like June Medford, whose plants research could lead to advancements like the security garden above.

Jef Boeke, one of the lead authors of the GP-write Grand Challenge, emphasized that this project was not just about writing the human genome. “The notion that we could write a human genome is simultaneously thrilling to some and not so thrilling to others,” Boeke told the group. “We recognize that this will take a lot of discussion.”

Boeke explained that the GP-write project will focus on the genomes of cells, and the researchers involved are not trying to produce an organism. He added that this work could be used to solve problems associated with climate change and the environment, invasive species, pathogens, and food insecurity.

To learn more about why this project is important, I spoke with genetics researcher, John Min, about what GP-write is and what it could accomplish. Min is not directly involved with GP-write, but he works with George Church, another one of the lead authors of the project.

Min explained, “We aren’t currently capable of making DNA as long as human chromosomes – we can’t make that from scratch in the laboratory. In this case, they’ll use CRISPR to make very specific cuts in the genome of an existing cell, and either use synthesized DNA to replace whole chunks or add new functionality in.”

He added, “An area of potentially exciting research with this new project is to create a human cell immune to all known viruses. If we can create this in the lab, then we can start to consider how to apply it to people around the world. Or we can use it to build an antibody library against all known viruses. Right now, tackling such a project is completely unaffordable – the costs are just too astronomic.”

But costs aren’t the only reason GP-write is hugely ambitious. It’s also incredibly challenging science. To achieve the objectives mentioned above, scientists will synthesize, from basic chemicals, the building blocks of life. Synthesizing a genome involves slowly editing out tiny segments of genes and replacing them with the new chemical version. Then researchers study each edit to determine what, if anything, changed for the organism involved. Then they repeat this for every single known gene. It is a tedious, time-consuming process, rife with errors and failures that send scientists back to the drawing board over and over, until they finally get just one gene right. On top of that, Min explained, it’s not clear how to tell when a project transitions from editing a cell, to synthesizing it. “How many edits can you make to an organism’s genome before you can say you’ve synthesized it?” he asked.

Clyde Hutchison, working with Craig Venter, recently came closest to answering that question. He and Venter’s team published the first paper depicting attempts to synthesize a simple bacterial genome. The project involved understanding which genes were essential, which genes were inessential, and discovering that some genes are “quasi-essential.” In the process, they uncovered “149 genes with unknown biological functions, suggesting the presence of undiscovered functions that are essential for life.”

This discovery tells us two things. First, it shows just how enormous the GP-write project is. To find 149 unknown genes in simple bacteria offers just a taste of how complicated the genomes of more advanced organisms will be. Kris Saha, Assistant Professor of Biomedical Engineering at the University of Wisconsin-Madison, explained this to the Genetic Experts News Service:

“The evolutionary leap between a bacterial cell, which does not have a nucleus, and a human cell is enormous. The human genome is organized differently and is much more complex. […] We don’t entirely understand how the genome is organized inside of a typical human cell. So given the heroic effort that was needed to make a synthetic bacterial cell, a similar if not more intense effort will be required – even to make a simple mammalian or eukaryotic cell, let alone a human cell.”

Second, this discovery gives us a clue as to how much more GP-write could tell us about how biology and the human body work. If we can uncover unknown functions within DNA, how many diseases could we eliminate? Could we cure aging? Could we increase our energy levels? Could we boost our immunities? Are there risks we need to prepare for?

The best assumption for that last question is: yes.

“Safety is one of our top priorities,” said Church at the event’s press conference, which included other leaders of the project. They said they expect safeguards to be engineered into research “from the get-go,” and part of the review process would include assessments of whether research within the project could be developed to have both positive or negative outcomes, known as Dual Use Research of Concern (DURC)

The meeting included roughly 250 people from 10 countries with backgrounds in science, ethics, law, government, and more. In general, the energy at the conference was one of excitement about the possibilities that GP-write could unleash.

“This project not only changes the way the world works, but it changes the way we work in the world,” said GP-write lead author Nancy J. Kelley.