1. The Lemon-Relman Report Lecture No. 16

2. 1. Outline The Lemon-Relman Report –Slides 2 - 7 The Recommendations –Slides 8 - 11 Assessing Relevant Scientific Developments –Slides 12 -20

3. 2. The Lemon-Relman Report (i) “…the committee has worked in the shadows of the…Fink report. However, there is a clear difference….Our focus has been on the advances in the life sciences and related and convergent technologies that are likely to alter the biological threat spectrum over the next 5 to 10 years. To a greater extent [also] we have attempted to take a global perspective…”

4. 3. The Lemon-Relman Report (ii) “…the biological agent used in the postal attacks was anthrax, a ‘classic’ choice of those intent on waging biological warfare…and the the biodefense research priorities… evolved subsequently with a nearly exclusive focus on well-recognised, ‘traditional’ biowarfare agents. Such a focus is dangerously narrow…”

5. 4. The Lemon-Relman Report (iii) “…The committee’s charge has been to examine current trends and future objectives of research in the life sciences that may enable the development of a new generation of future biological threats….While this has been far from easy…several conclusions stand out with startling clarity…”

6. 5. The Lemon-Relman Report (iv) “First, the future is now. Even in the short time since the creation of the committee, we have seen the phenomenon of RNA interference capture the collective consciousness of the life science community….Similarly ‘synthetic biology’, an approach embraced… by few at the time the committee was formed, has…been promoted to the cover of one of the most widely read scientific journals…”

7. 6. The Lemon-Relman Report (v) “…This leads to the second conclusion, that the task of surveying current technology trends in order to anticipate what new threats may face us down the road will be never ending. This report, published in early 2006, will in some respects be out of date by 2007.”

8. 7. The Lemon-Relman Report (vi) “…it is increasingly important that life scientists… take every possible step to ensure that…their work [is] not exploited in a malevolent fashion.…This will require that those working in the life sciences achieve a much greater appreciation of the dangers than that now held by most and a greater willingness to shoulder this responsibility. A new ethos is required, and it must be achieved on a global scale…”

9. 8. The Recommendations (i) “1. The committee endorses and affirms policies that, to the maximum extent possible, promote the free and open exchange of information in the life sciences. 2. The committee recommends adopting a broader perspective on the ‘threat spectrum’.”

10. 9. The Recommendations (ii) “3. The committee recommends strengthening and enhancing the scientific and technical expertise within and across the security communities. 4. The committee recommends the adoption and promotion of a common culture of awareness and a shared sense of responsibility within the global community of life scientists. 5. The committee recommends strengthening…public health… and existing response and recovery capabilities.”

11. 10. The Recommendations (iii) “2a. Recognize the limitations inherent in any agent-specific threat list and consider the intrinsic properties of pathogens and toxins that render them a threat and how such properties have been or could be manipulated by evolving technologies.”

12. 11. The Recommendations (iv) “2b. Adopt a broadened awareness of threats beyond the classical ‘select agents’ and other pathogenic organisms and toxins, so as to include, for example, approaches for disrupting host homeostatic and defense systems and for creating synthetic organisms.”

13. 12. Assessing Relevant Scientific Developments (i) Structure of the Report –Chapter 1. Framing the Issue –Chapter 2. Global Drivers and Trajectories of Advanced Life Sciences Technologies –3. Advances in Technologies with Relevance to Biology: The Future Landscape –4. Conclusions and Recommendations

14. 13. Assessing Relevant Scientific Developments (ii) “…this chapter (1) highlights technologies likely to have obvious or high-impact near- term consequences; (2) illustrates the general principles by which technological growth alters the nature of future biological threats; and, (3) highlights how and why some technologies are complementary or synergistic in bolstering defense against future threats while also enhancing or altering the nature of future threats.”

15. 14. Assessing Relevant Scientific Developments (iii) “1. Acquisition of novel biological or molecular diversity –“…Technologies in this category include those dedicated toward DNA synthesis; the generation of new chemical diversity (i.e. through combinatorial chemistry); those that create novel DNA molecules (from genes to genomes) using directed in vitro molecular evolution (e.g. ‘DNA shuffling’); and those that amplify or simply collect previously uncharacterized sequences (genomes) directly from nature (i.e. bioprospecting)…”

16. 15. Assessing Relevant Scientific Developments (iv) 2. Directed design –“These are technologies that involve deliberate efforts to generate novel but predetermined and specific biological or molecular diversity….Example include but are not limited to rational, structure-aided design of small-molecule ligands; the genetic engineering of viruses or microbes, and, the emerging field of ‘synthetic biology’.”

17. 16. Assessing Relevant Scientific Developments (v) “With the complete genetic sequencing of the H1N1influenza virus…some have questioned whether these studies should have been published in the open literature given concerns that terrorists could, in theory, use the information to reconstruct the 1918 flu virus…”

18. 17. Assessing Relevant Scientific Developments (vi) 3. Understanding and manipulation of biological systems. –“Examples include, ‘systems biology’; gene silencing (e.g., RNA interference); the generation of novel binding (affinity) reagents; technologies focused on developmental programs (e.g.,embryonic stem cells); genomics and genomic medicine; the study of modulators of homeostatic systems; bioinformatics; and advanced network theory.”

19. 18. Assessing Relevant Scientific Developments (vii) “…The quest to identify the molecular circuits and control systems in each specialized cell type in the body, and to understand the perturbations that give rise to disease, is a dominant research theme in contemporary biology….Burgeoning knowledge about the composition and regulation of homeostatic molecular circuits…epitomizes the dual-use dilemma created by rapid advances in systems biology…”

20. 19. Assessing Relevant Scientific Developments (viii) “A greater understanding of how small molecules and naturally occurring bioregulatory peptides function in higher organisms will open up novel opportunities to design agents - for good or bad - that target particular physiological systems and processes, such as the brain and the immune system, in very precise ways…”

21. 20. Assessing Relevant Scientific Developments (ix) 4. Production, delivery, and ‘packaging’ –“These are technologies driven by efforts in the pharmaceutical, agriculture, and healthcare sectors to improve capabilities for producing, reengineering, or delivering biological or biology- derived products and miniaturizing these processes. Examples include…aerosol technology, microencapsulation, microfluids/microfabrication; nanotechnology; and gene theraphy technology…”

22. Sample Questions 1.Give a brief overview of the structure of the Lemon-Relman report and of its main argument. How do you evaluate the validity of this argument? 2. Do you agree with the authors of the Lemon-Relman report’s authors that life scientists should achieve a much greater appreciation of the dangers and how a greater willingness to shoulder their responsibilities? 3. Should the 1918 Spanish Influenza Pandemic Virus has reconstructed? 4. What are the four groups of technologies listed in the Lemon-Relman Report? Discuss one of these in detail and analyse the potential misuse that could arise from developments in this particular group of technologies.

23. References (Slide 2) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=1 http://books.nap.edu/openbook.php?record_id=11567&page=1 (Slide 3) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=R7 http://books.nap.edu/openbook.php?record_id=11567&page=R7 (Slide 4) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=R8 http://books.nap.edu/openbook.php?record_id=11567&page=R8

24. (Slide 4) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=R8http://books.nap.edu/openbook.php?record_id=11567&page=R8 (Slide 5) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=R8http://books.nap.edu/openbook.php?record_id=11567&page=R8 (Slide 6) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=R8http://books.nap.edu/openbook.php?record_id=11567&page=R8 (Slide 7) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=R9http://books.nap.edu/openbook.php?record_id=11567&page=R9 (Slide 8) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=6http://books.nap.edu/openbook.php?record_id=11567&page=6

25. (Slide 9) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=216 http://books.nap.edu/openbook.php?record_id=11567&page=216 (Slide 10) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=216 http://books.nap.edu/openbook.php?record_id=11567&page=216 (Slide 11) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=217 http://books.nap.edu/openbook.php?record_id=11567&page=217 (Slide 12) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://www.nap.edu/catalog.php?record_id=11567 http://www.nap.edu/catalog.php?record_id=11567

26. (Slide 13) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page= 139 http://books.nap.edu/openbook.php?record_id=11567&page= 139 (Slide 14) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page= 140 http://books.nap.edu/openbook.php?record_id=11567&page= 140 (Slide 15) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page= 140 http://books.nap.edu/openbook.php?record_id=11567&page= 140

27. (Slide 16) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=1 64 http://books.nap.edu/openbook.php?record_id=11567&page=1 64 Tumpey, T.M., Basler, C. F., Aguilar, P. V., Zeng, H., Solórzano, A., Swayne, D. E., Cox, N. J., Katz, J. M., Taubenberger, J. K., Palese, P., García-Sastre, A., (2005) Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus, Science, 310(5745). pp. 77-80. Available from http://www.sciencemag.org/cgi/content/abstract/310/5745/77 http://www.sciencemag.org/cgi/content/abstract/310/5745/77 (Slide 17) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=1 41 http://books.nap.edu/openbook.php?record_id=11567&page=1 41

28. (Slide 18) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=178 http://books.nap.edu/openbook.php?record_id=11567&page=178 (Slide 19) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=180 http://books.nap.edu/openbook.php?record_id=11567&page=180 (Slide 20) National Research Council (2006) Globalization, Biosecurity, and the Future of the Life Sciences, Washington, D.C.: National Academy Press. Available from http://books.nap.edu/openbook.php?record_id=11567&page=140 http://books.nap.edu/openbook.php?record_id=11567&page=140