New Plan to Synthesize the Human Genome Emphasizes Transparency, Known Unknowns

Thirteen years after the completion of the Human Genome Project, scientists have announced the next major DNA agenda item: Human Genome Project-Write. While the focus of the original HGP was to identify and map the genes of human genome — and subsequently revolutionized science and medicine — HGP-Write is supposed to drive down the cost of genomic engineering while creating the framework to build and deploy a fully synthetic human genome in human cell lines within the next 10 years.

But reducing the cost of engineering and testing genomes, while scientifically advantageous, presents a problem: How do you ensure ethical engineering? While the vast majority of genetic engineering efforts are focused on things that are very good for us — growing transplantable human organs, engineering cancer resistance into therapeutic cell lines — the situation could head in a mad scientist, super-strong toddler direction pretty quickly.

Exactly how things could become unethical and what exactly is unethical is another question. For example, human germline modification, the practice of deliberating changing the genes passed to children, is currently banned in 40 countries. But how ethical it is to genetically modify a human embryo is still debated worldwide by scientists, ethicists, and legal experts.

The 25 scientists spearheading HGP-Write don’t have the answer to what exactly the ethical guidelines need to be — but they do have a first person understanding of the public’s fear of worse case scenarios. In May the same team of scientists came under scrutiny for a meeting they held to discuss how to synthesize an entire human genome. They purposefully did not invite the media, a step they said they took to allow everyone to “speak freely and candidly.” Meanwhile, the public saw the words “talk privately” and began to fret about our eventual genetically-created overlords. It’s uncertain how much of this proposal was written after the backlash, but it certainly screams a different tune than secret meeting.

“As human genome-scale synthesis appears increasingly feasible, a coordinated scientific effort to understand, discuss, and apply large-genome engineering technologies is timely,” they write in Science. “HGP-write will require public involvement and consideration of ethical, legal, and social implications from the start.”

The emphasis here is on “public involvement and consideration.” There are no ethical guidelines specific to HGP-write yet. This is what the researchers are starting with:

1. Identify the common goals between scientists and the wider public.
2. See if the “diverse stakeholders” are okay with those goals.
3. Have an open dialogue about those goals.
4. Make sure that informed consent comes with any use of organic material — with an emphasis on being informed to what exactly will be done with DNA and cells.
5. The highest biosafety standards will guide all project work and inform the design process.
6. The highest biosafety standards will guide all project work and inform the design process.And that’s basically step one. Existing stem cell research guidelines
7. The highest biosafety standards will guide all project work and inform the design process.And that’s basically step one. Existing stem cell research guidelines will likely serve as a blueprint, but because national and international genetics laws and regulations differ HGP-write has the freedom (or the curse) to start from scratch. They are going to want to get cooking with those — the goal is to reduce the costs of genetic engineering and testing by over 1,000-fold

“An expectation of HGP-write will be to catalyze a sharp price drop as new technology development occurs apace with advancement of the project,” they write. “Extreme cost-reduction is feasible, as demonstration by the $1,000 genome grant program as well as sharing of CRISPR tools from over 80 labs through addgene.org.”

While HGP-write kicks on in 2016 and is expected to spur a series of smaller projects that will output shorter DNA segments, ultimately the team expects that support from HGP-write will lead to the creation of a complete synthetic human genome within the next 15 to 20 years. Broad and transparent conversation is needed now, so that scientists can manipulate and understand gene regulation and the evolutionary process behind that in the future.