Notes on Engineering Health, May 2020

A Short History of Genetic Engineering in the Time Of Covid-19

From the 1950s when the double helix structure of DNA was unveiled to the CRISPR editors of the past few years, progress toward being able to engineer biology consistently and at high fidelity has been constant. Our ability to treat biology as an engineering discipline may even be reaching the point where it can be tasked with solving problems such as the current coronavirus pandemic. 

The ability to read DNA—uncovering its structure (1953), discovering restriction enzymes (1968), developing Sanger sequencing (1977) and sequencing the first human chromosome (1999), next generation sequencing (2010s)—and write it—creating recombinant DNA (1972),  creating the first transgenic animal (1981), developing the polymerase chain reaction (1983), cloning the first mammal (1996), approving the first gene-targeted drug therapy (2001)—have progressed in parallel.

The last decade started with the creation of the first synthetic life form by Craig Venter and his team. The genome of this microorganism was neither evolved or born but entirely engineered. This milestone and the ones that followed launched the field of synthetic systems. Engineered life forms help deepen our understanding of biology—what is necessary and what isn’t? First these techniques lacked precision, then they lacked usability (while precision increased over time, achieving scale was still not possible). The advent of the CRISPR technique to edit genes (2012) by the team of Jennifer Doudna at Berkeley (and others) solved many hurdles. The new, lower bar to modify genes precisely and at scale opened two revolutionary tracks. The first, and the more exciting one for most, was the possibility to rewrite the genetic information in patients’s cells directly. This fresh new take on gene therapy is still in its infancy but shows tremendous therapeutic promise.

The second track is to generalize Venter’s approach to synthetic systems not only to create new life forms, but to generate new disease models, new metabolic pathways, and new drug targets. These synthetic systems can be designed to test virtually any biological hypothesis. A recent system aims to build a fully functional yeast-based synthetic genomics platform to genetically reconstruct diverse RNA viruses, including members of the Coronaviridae family. Thanks to this tool, researchers are able to rapidly functionally characterize SARS-CoV-2 evolution in real time, target the right epitopes and inch closer to a resolution to this health crisis and the ones to come. 

Jonathan Friedlander, PhD & Geoffrey W. Smith