1. To CRISPR or not to CRISPR? Group 2 Ethics of technology and science: Seminar II

2. CRISPR/Cas is an adaptive immune system in prokaryotes A CRISPR/Cas system has been developed as a genetic tool for precise gene modifications: –Deletions and insertions Widely used as tool in research in both eukaryotes and prokaryotes Easy design, easy execution and can be used on many different sequences Background

3. Setting the scene: –More knowledge about gene and gene function than a few years ago –Delivery vehicle for editing in developed cells is available –In vitro fertilization techniques already in place Unknown “off-target” effects and unknown long-term “on- target” effects Use the system to change the inherited human genetic material? Y. Wu, D. Liang, Y. Wang, M. Bai, W.i Tang, S. Bao, Z. Yan, D. Li, J. Li Correction of a Genetic Disease in Mouse via Use of CRISPR-Cas9 Cell Stem Cell 2013, 13(6):659-662.

4. “Should we develop the CRISPR method on humans to cure disease, knowing that it could be used for other things?” The problem

5. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution Stop

6. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead +: Glory, career opportunity, scientific esteem - : Increase competition & targeted by opponents, big responsibility, risk of failure & possible negative legacy Proceed with caution Stop Solution 1 – ”Go Ahead”

7. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead +: Glory, career opportunity, scientific esteem - : Increase competition & targeted by opponents, big responsibility, risk of failure & possible negative legacy +: Prestige & increase funding -: Risk of bad PR & costly legal issues Proceed with caution Stop Solution 1 – ”Go Ahead”

8. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead +: Glory, career opportunity, scientific esteem - : Increase competition & targeted by opponents, big responsibility, risk of failure & possible negative legacy +: Prestige & increase funding -: Risk of bad PR & costly legal issues +: Possible huge revenue +/-: Good/Bad PR -: Costly legal issues, patent cost Proceed with caution Stop Solution 1 – ”Go Ahead”

9. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead +: Glory, career opportunity, scientific esteem - : Increase competition & targeted by opponents, big responsibility, risk of failure & possible negative legacy +: Prestige & increase funding -: Risk of bad PR & costly legal issues +: Possible huge revenue +/-: Good/Bad PR -: Costly legal issues, patent cost +: Eradicate genetic diseases +/-: “Designer babies”, unpredictable effects on society, long term effects unknown -: Identity issues, loss of diversity Proceed with caution Stop Solution 1 – ”Go Ahead”

10. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead +: Glory, career opportunity, scientific esteem - : Increase competition & targeted by opponents, big responsibility, risk of failure & possible negative legacy +: Prestige & increase funding -: Risk of bad PR & costly legal issues +: Possible huge revenue +/-: Good/Bad PR -: Costly legal issues, patent cost +: Eradicate genetic diseases +/-: “Designer babies”, unpredictable effects on society, long term effects unknown -: Identity issues, loss of diversity -: Angry Proceed with caution Stop Solution 1 – ”Go Ahead”

11. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution +: Possible recognition & esteem, discovery of important side effect/issues, “clean conscience” -: Might get scooped, time consuming legal ‘stuff’ Stop Solution 2 – ”Proceed with caution”

12. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution +: Possible recognition & esteem, discovery of important side effect/issues, “clean conscience” -: Might get scooped, time consuming legal ‘stuff’ +: Less risk of legal issues -: Less prestige, perhaps less funding (less risk & less benefit) Stop Solution 2 – ”Proceed with caution”

13. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution +: Possible recognition & esteem, discovery of important side effect/issues, “clean conscience” -: Might get scooped, time consuming legal ‘stuff’ +: Less risk of legal issues -: Less prestige, perhaps less funding (less risk & less benefit) +: Profit, better / more reliable product -: Delays, less profit than solution 1, more regulations Stop Solution 2 – ”Proceed with caution”

14. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution +: Possible recognition & esteem, discovery of important side effect/issues, “clean conscience” -: Might get scooped, time consuming legal ‘stuff’ +: Less risk of legal issues -: Less prestige, perhaps less funding (less risk & less benefit) +: Profit, better / more reliable product -: Delays, less profit than solution 1, more regulations +: More effective treatment, more informed public, legislation might prevent “designer babies” -: Delayed application of method Stop Solution 2 – ”Proceed with caution”

15. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution +: Possible recognition & esteem, discovery of important side effect/issues, “clean conscience” -: Might get scooped, time consuming legal ‘stuff’ +: Less risk of legal issues -: Less prestige, perhaps less funding (less risk & less benefit) +: Profit, better / more reliable product -: Delays, less profit than solution 1, more regulations +: More effective treatment, more informed public, legislation might prevent “designer babies” -: Delayed application of method -: Still angry Stop Solution 2 – ”Proceed with caution”

16. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution Stop +: “Very clean conscience”, no risk of adverse effects -: No glory, less career opportunities, lose influence over develop- ment of field Solution 3 – ”I just can’t go on...”

17. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution Stop +: “Very clean conscience”, no risk of adverse effects -: No glory, less career opportunities, lose influence over develop- ment of field +: No legal issues -: Missed opportunity, loss of funding / PR / prestige Solution 3 – ”I just can’t go on...”

18. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution Stop +: “Very clean conscience”, no risk of adverse effects -: No glory, less career opportunities, lose influence over develop- ment of field +: No legal issues -: Missed opportunity, loss of funding / PR / prestige +: No legal risk -: No revenue from CRISPR Solution 3 – ”I just can’t go on...”

19. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution Stop +: “Very clean conscience”, no risk of adverse effects -: No glory, less career opportunities, lose influence over develop- ment of field +: No legal issues -: Missed opportunity, loss of funding / PR / prestige +: No legal risk -: No revenue from CRISPR +: Slower progress but eventual eradication of genetic diseases -: Public will lose researcher’s voice of reason Solution 3 – ”I just can’t go on...”

20. Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead Proceed with caution Stop +: “Very clean conscience”, no risk of adverse effects -: No glory, less career opportunities, lose influence over develop- ment of field +: No legal issues -: Missed opportunity, loss of funding / PR / prestige +: No legal risk -: No revenue from CRISPR +: Slower progress but eventual eradication of genetic diseases -: Public will lose researcher’s voice of reason -: Angry, but about something else Solution 3 – ”I just can’t go on...”

21. So …. What? Solutions & Consequences Interested Parties ResearcherUniversityCompany (associated with researcher) Users/PublicReligious Organ. Solutions Go ahead +: Glory, career opportunity, scientific esteem - : Increase competition & targeted by opponents, big responsibility, risk of failure & possible negative legacy +: Prestige & increase funding -: Risk of bad PR & costly legal issues +: Possible huge revenue +/-: Good/Bad PR -: Costly legal issues, patent cost +: Eradicate genetic diseases +/-: “Designer babies”, unpredictable effects on society, long term effects unknown -: Identity issues, loss of diversity -: Angry Proceed with caution +: Possible recognition & esteem, discovery of important side effect/issues, “clean conscience” -: Might get scooped, time consuming legal ‘stuff’ +: Less risk of legal issues -: Less prestige, perhaps less funding (less risk & less benefit) +: Profit, better / more reliable product -: Delays, less profit than solution 1, more regulations +: More effective treatment, more informed public, legislation might prevent “designer babies” -: Delayed application of method -: Still angry Stop +: “Very clean conscience”, no risk of adverse effects -: No glory, less career opportunities, lose influence over develop- ment of field +: No legal issues -: Missed opportunity, loss of funding / PR / prestige +: No legal risk -: No revenue from CRISPR +: Slower progress but eventual eradication of genetic diseases -: Public will lose researcher’s voice of reason -: Angry, but about something else