Driving change: editing genomes

Genome editing, CRISPR, and gene drives have become hot topics. While I was working on a number of conceptual and normative questions, I had the opportunity of getting involved with topic of genome editing right at the moment when the early developments burst into the next phase and I am happy to tell you more about this part of my work.

It was in 2010, as I tried to understand zinc fingers. As a philosopher and ethicist working in the lab of George Church at Harvard Medical School, I had to learn how genome editing works and, at that time, that meant understanding what zinc finger constructs are useful for. Shortly thereafter, as I just got the clue to zinc fingers, the lab discussed something new and probably better, the TALENs as tools for optimizing genome editing. As a philosopher I’m not making these constructs, but in order to reflect upon lab experiments and the effects of potential applications, I must be able to follow the lab discussions. Neither zinc fingers nor TALENs are easy stuff for non-biologists. In 2011 when the lab discussions on the strengths and weaknesses of zinc fingers vs TALENs were ongoing, ‘CRISPR’ popped up. This time, my efforts to understand the biology and the technology really paid off: CRISPR is here to stay as a high precision tool for genome editing. The impact of CRISPR can be compared with that of genome sequencing and with the invention of PCR. While CRISPR enables high precision cutting of a sequence, the addition of a guide-RNA – Cas9, with newer guides being developed – allows the insertion of new sequences, i.e. the ‘cut and paste’ editing of any genome in any cell or organism.

This new technique raises new questions, not only direct and practical ones on study design, lab protocols and biosafety, but also in the humanities, including philosophy and ethics. It is a typical technology that calls for conceptual and normative inquiry. What does it mean to change organisms and how far should we go? These questions suddenly got an extra dimension as Kevin Esvelt, from the Church lab at the Wyss Institute in Harvard, combined the CRISPR-Cas9 system with the mechanism of a driving ‘selfish’ gene – and although both systems occur in nature, their combination is a real invention. The resulting “gene drives” allow for the rapid spread of the CRISPR-based alterations in any population of sexually reproducing organisms and thereby enable making changes in ecosystems.

Very big questions arise: what are potential benefits and how do they relate to the risks? Can we reliably calculate large-scale ecosystem effects? Are these GMOs and do current regulations apply? How about biosafety and biosecurity? These are matters of global importance, but how can they be regulated, taking all interests into account? With the Synthetic Biology Policy Group of the Program on Emerging Technologies at MIT ( http://poet.mit.edu ), I am involved in trying to find answers and in discussing new models of planning and governance with policymakers and regulators. On 29 January 2016, we had a first meeting with the US Office of Science and Technology Policy at the White House.

Editing the Genome : Over the last four years, scientists have discovered a simple and powerful method for altering genes. This will have massive implications for all of us as it raises the possibility of easily changing thegenetic code in animals, plants and ourselves. The potential for good is enormous. The ethical challenges are profound. Professor Matthew Cobb explores the brave new world of CRISPR gene editing.
BBC Radio, Discovery, March 2016. Two parts (both 27 mins, MP3) http://www.bbc.co.uk/programmes/p03kzwd8, http://www.bbc.co.uk/programmes/p03lqvnf

Editing Life: http://www.bbc.co.uk/programmes/b06zr3zj BBC Radio, February 2016 (28 mins, MP3)

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