The good, bad and unknown outcomes in gene editing

Earlier in 2019, a more rapid and detailed analysis tool for gene editing experiments was introduced-  CRISPresso2. CRIPSresso is a tool that will project accurate outcomes of potential gene edits in the context of research and experimentation. As tools like these continue to improve, the advances will cut down continually on research time for the public and private sector- gaining a more rapid stride in the direction of prolific gene editing. 

At the same time these advances are happening, there are projects ongoing at DARPA- specifically the Safe Genes project, that is focused entirely on defining and mitigating or stopping harmful risks in gene editing. In order to understand what happens across generations in terms of tracking gene edits or detecting them or stopping them, DARPA is working with top U.S. universities to establish and study what a synthetic biology production pipeline would look like. 

It will be interesting to see the pace of these trajectories- that of the private and public sector to secure gene editing superiority, establish low-risk edits that can be implemented in a large-scale, and the ability for our society to understand and adapt to a new reality of the big small world of our genetics and personalized medicine. 

Here are the three main categories outlined, based on the materials and goals of these programs and comments from DARPA speakers:

Good

These are all of the best, most sought after outcomes of gene editing- to improve our quality of life and cure the incurable diseases, reducing pain and suffering around the world. 

• Safeguarding against disease or eradicating genetically inherited disease that has no current cure. 

• Mapping an individual's genetic makeup and applying insights to lifestyle choices and diet in the form of preventative care. 

• The ability for A.I. to help rapidly create insights from genetic data, a game-changing moment in personalized medicine.

Bad

Could include malicious attempts to change the local genetic makeup of animal populations and plant life to produce deleterious effects.

• Nefarious gene drives to kill crops.

• Genetically engineering an invasive insect species to carry a disease to infect people or livestock.

• Sharp biological inequality between classes due to expensive, private editing services. 

• Unethical or high risk edits that produce off-target mutations in unborn babies, children or adults.

Many of these outcomes are very hard to achieve. Gene drives are thwarted by biological diversity. While these can work in local mosquito populations to combat disease, there does not appear to be a current-day capability to drive malicious DNA through a genetically diverse population.

In terms of highly accurate genetic editing that is proven and regulated- these services would likely start in the private sector and be extremely expensive. Although the possibility may exist in the future for genetically altered babies with safeguards built in against inherited disease, the realistic cost of those services could introduce another layer of inequality- genetic inequality. Unknown

This is what worries experts in the field the most. The unpredictable, unintended consequences of a gene edit. This is arguably the real danger and one which the Safe Genes project aims to shed the most light on. 

• Off-target mutations that occur as a direct result of a risky gene edit.

• The arrival of black-market gene-edit shops that offer risky gene editing, exploiting people by offering cheap services.

• The occurrence of "genetic fraud", i.e. impersonating someone or masking genetic information.

• Unintended ecological impacts resulting from a past gene edit that adversely impact animal populations or local ecosystems.

The only way to deal with the unknown is to go out there and do as much experimentation as possible to arrive at these scenarios in the lab. Once there is a repeatable design process in place for genetic editing or new synthetic biological organism production, you can understand how things could go wrong. 

Unsurprisingly, there is another fascinating Synthetic Biology project ongoing at DARPA called Living Foundries- this is where the mechanics and design process is getting formulated for the future of production-level novel molecules. What DAPRA is working on right now is the ability to have a "foundry" that can be requested to produce novel molecules, on-demand, for an eclectic variety of purposes ranging from internal medicine to aircraft coatings.  

This is something that will be, much longer down the road, a completely integrated part of us and our physical world. The path the commercialization of something like this is very far off into the future- much like the way the early emergency communications network for the defense department became the internet today.