1. Synthetic Biology: Unique Challenges for Public Policy Kelly Drinkwater kdrinkwa@mit.edu Research Group of Kenneth Oye, MIT BioBuilder Workshop, July 25, 2013

2. What bio-ethical issues are generally addressed in HS biology? Cloning Genetically modified crops (moral, environmental) Genetic testing and privacy Human subjects ethics...can we go farther?

3. Synthetic Biology's Challenge: Regulation without stifling innovation Environmental safety Security / bio-terrorism Intellectual property rights iGEM Following: Discuss how to integrate these into your classrooms Handout available & please email with questions!

4. SynthBio products pose new risks to the environment Algae raceway pond (Biofuels) Algal bloom near Cornwall Tarball from Deepwater Horizon oil spill

5. ...heard of these folks?

6. Who's regulating this thing?! Not part of my mandate!

7. Current environmental regulations are a patchwork EPA: "Toxic Substances or Pesticides" USDA: "Plant Pests" FDA: "Food, drugs, or animal feed" Lab research is covered by NIH Guidelines, like all recombinant DNA work Medical applications are better regulated (FDA & other countries' equivalents)

8. Current environmental regulations are a patchwork EPA: "Toxic Substances or Pesticides" USDA: "Plant Pests" FDA: "Food, drugs, or animal feed" Lab research is covered by NIH Guidelines, like all recombinant DNA work Medical applications are better regulated (FDA & other countries' equivalents) Theme: Not regulating genetic information as information

9. What counts as an environmental harm? Changes to ecosystem services, such as:  Carbon/nitrogen cycling  Arability  Recreational value Changes to species composition of an ecosystem Not well defined, and partly a philosophical question

10. What makes a synthetic bug likely to cause harms? Fitness / survival Evolution / mutation / genetic instability Horizontal gene transfer

11. Fitness: Will the bug outcompete native species? Assumption: Genetic modifications impose a metabolic burden. Modified organism will be less fit than the wild-type and will not compete. Reality: Some applications require a highly fit organism! Even if the organism may be less fit, the assumption has not been rigorously tested.

12. Evolution / Instability: Will the bug change out from under us? Assumption: Mutations and evolution can be ignored on the bench-top scale. Reality: Mutations and evolution cannot be ignored on the industrial scale. Will the organism change its genotype or phenotype? Will mutations inactivate any safety features?

13. Horizontal Gene Transfer: Will inserted genes escape? Assumption: HGT is rare, and nearly impossible between organisms not closely related. Reality: HGT is far more common than we thought even 10-15 years ago, and occurs even across kingdoms! Archaea to Bacteria Fungus to AnimalBacteria to Animal

14. "Recruitment of genetic elements to ensembles that cause harm" Fitness / SurvivalEvolution / Instability Horizontal Gene Transfer

15. Security, Bio-Warfare, Bio-Terror Legacy laws: Select Agent List, Australia Group Guidelines Voluntary screening of DNA synthesis orders Dual Use Research of Concern

16. Legacy rules outlaw organisms, not information United States Select Agent List Australia Group Guidelines "No organisms from this list of nasty pathogens..."...or "genetic elements associated with the pathogenicity of those organisms." No clear guidance on what that means (and what about dangerous sequences from other species?) Organism-based rather than information-based regulations

17. Screening: "The Guardian started it" "The DNA sequence of smallpox, as well as other potentially dangerous pathogens such as poliovirus and 1918 flu are freely available in online public databases. So to build a virus from scratch, a terrorist would simply order consecutive lengths of DNA along the sequence and glue them together in the correct order. This is beyond the skills and equipment of the kitchen chemist, but could be achieved by a well- funded terrorist with access to a basic lab and PhD-level personnel."

18. "Clearly this should not be possible!" Lots of conferences HHS issues screening guidance Companies voluntarily screen customers and orders; information- based regulation! (But now we have bench- top DNA synthesizers...) Voluntary screening by DNA synthesis providers

19. Dual Use Research of Concern (DURC) Research for peaceful purposes, which could also be used for nefarious ends Covers many fields: nuclear, cybersecurity, bio Examples...

20. Spanish Flu and Mousepox

21. H5N1 (Avian) Flu: Fouchier and Kawaoka

22. Controversy: Safer to keep it secret? Should the research be done at all? In many cases, the peaceful justifications are weak. If the research is done, should it be published? Who decides?

23. Patents and IP: The Anti-Commons Problem More IP Protection More Free Use Certainty Uncertainty ANTI-COMMONS

24. Why is Anti-Commons a problem in synthetic biology? One product might use dozens or hundreds of parts, all owned by different people Some parts are free, some are proprietary, some are uncertain Many parts may be covered by over-broad patents... but who wants to challenge? Laws about gene patentability are in flux (many genes of interest are not made free by Myriad decision)

25. Work with iGEM Safety Committee Ensure participant safety Model safety practices for an international audience Encourage students to discuss broader implications Instill a culture of responsibility

26. Why is iGEM important to policymakers? Massive diffusion of technical skills; should be managed A chance to model proactive, not reactive, risk management A test-bed for real regulatory issues

27. To sum up... Synthetic biology presents interesting new challenges and risks in many different areas Regulators and others are actively working to address those risks and attack uncertainties Hopefully this will be interesting to your students!

28. Discussion: How can this be integrated into the classroom? Formats for discussion: Debate, Four Corners, current events writing? Others? How could this integrate with BioBuilder and with existing course content? How could this integrate across disciplines? (Environmental Science, History, Civics / Government?)