A Framework for Tomorrow’s Pathogen Research

Final Report


Ravindra Gupta

Ameenah Gurib-Fakim

Shahid Jameel

David Relman


Jesse Bloom

Filippa Lentzos

February 2024


Amman, B.R., C.G. Albariño, B H. Bird, L. Nyakarahuka, T.K. Sealy, S. Balinandi, A.J. Schuh et al. 2015. “A Recently Discovered Pathogenic Paramyxovirus, Sosuga Virus, is Present in Rousettus aegyptiacus Fruit Bats at Multiple Locations in Uganda.” Journal of Wildlife Diseases 51 (3): 774-779. LINK

Byers, K.B. and A.L. Harding. 2006. “Laboratory-associated Infections.” In Biological Safety: Principles and Practices. 5th Edition, edited by Dawn P. Wooley and Karen B. Byers, 59-94. ASM Press. LINK

Bandyopadhyah, A.S., J. Garaon, K. Seib, and W.A. Orenstein. 2015. “Polio vaccination: past, present and future.” Future Microbiology. 10 (5). LINK

Beitzel, B.F., S.R. Radoshitzky, N.D. Paola, J.M. Brannan, D. Kimmel, K. Caviness, V. Soloveva et al. 2021. “On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization.” Viruses 13 (10): 2010. LINK

Blacksell, S.D., S. Dhawan, M. Kusumoto, K.K. Le, K. Summermatter, J. O’Keefe, J.P. Kozlovac et al. 2023. “Laboratory-acquired infections and pathogen escapes worldwide between 2000 and 2021: a scoping review.” The Lancet Microbe. Advance online publication. LINK

(Bulletin) Bulletin of the Atomic Scientists. 2023. Pathogens Project. Chicago: Bulletin of the Atomic Scientists. LINK

Cai, Y., C. Ye, B. Cheng, A. Nogales, M. Iwasaki, S. Yu, K. Cooper et al. 2020. “A Lassa Fever Live-Attenuated Vaccine Based on Codon Deoptimization of the Viral Glycoprotein Gene.” mBio 11 (1). LINK

Cao, Y., F. Jian, J. Wang, Y. Yu, W. Song, A. Yisimayi, J. Wang et al. 2023. “Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution.” Nature 614: 521–529. LINK

Carlson, C.J., G.F. Albery, C. Merow, C.H. Trisos, C.M. Zipfel, E.A. Eskew, K.J. Olival, N. Ross, and S. Bansal. 2022. “Climate change increases cross-species viral transmission risk.” Nature 607: 555–562. LINK

Carus, W.S. 2002. Bioterrorism and Biocrimes: The Illicit Use of Biological Agents Since 1900. Fredonia Books. LINK

Casagrande, R. and D. Greene. 2022. Gryphon Staff Outline a Framework for Assessing Benefits of Human Pathogen Research. Gryphon Scientific.

Cello, J., A.V. Paul, and E. Wimmer. 2002. “Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template.” Science  297 (5538): 1016-18. LINK

Cui, Q. and W. Huang. 2023. “Application of Pseudotyped Viruses.” In Pseudotyped Viruses. Advances in Experimental Medicine and Biology, edited by Y. Wang. Springer. LINK

Evans, D. G. 1966. “Wilson Smith. 1897-1965.” Biographical Memoirs of Fellows of the Royal Society 12: 478–87. LINK

Evans, N. G., M. Lipsitch, and M. Levinson. 2015. “The Ethics of Biosafety Considerations in Gain-of-Function Research Resulting in the Creation of Potential Pandemic Pathogens.” Journal of Medical Ethics 41 (11): 901–908. LINK

Eyal, N., J. Kimmelman, L.G. Holtzman, and M. Lipsitch. 2019. “Regulating impact on bystanders in clinical trials: An unsettled frontier.” Clinical Trials 16 (5): 450-54. LINK

Fathi, A., C. Dahlke, and M.M. Addo. 2019. “Recombinant vesticular stomatitis virus vector vaccines for WHO blueprint priority pathogens.” Human Vaccine 15 (10): 2269-85. LINK

Fink, G.R., R. Atlas, W.E. Barkley, R.J. Collier, S.E. Cozzens, R. Faden, D.R. Franz et al. 2004. Biotechnology Research in an Age of Terrorism. Washington, DC: The National Academies Press. LINK

Fenner, F. 1993. “Smallpox: emergence, global spread, and eradication.” History and Philosophy of the Life Sciences 15 (3): 397-420. LINK

Flynn, J. M., N. Samant, G. Schneider-Nachum, D.T. Barkan, N.K. Yilmaz, C.A. Schiffer, S.A. Moquin, D Dovala, and D.N.A. Bolon. 2022. “Comprehensive fitness landscape of SARS-CoV-2 Mpro reveals insights into viral resistance mechanisms.”  eLife 11: e77433. LINK

Fonseca, C., J. Pettitt, A. Woollard, A. Rutherford, W. Bickmore, A. Ferguson-Smith, and L. D. Hurst. 2023. “People with more extreme attitudes towards science have self-confidence in their understanding of science, even if this is not justified.” PLoS Biol 21 (1): e3001915. LINK

Gilbert, N. 2022. “Climate change will force new animal encounters—and boost viral outbreaks.” Nature, April 28. LINK

Greene, D., K. Brink, M. Salm, C. Hoffmann, S. Evans, and M. Palmer. 2023. The Biorisk Management Casebook: Insights Into Contemporary Practices: Stanford Digital Repository. LINK

Gross, L., E. Lhomme, C. Pasin, L. Richert, R. Thiebaut. 2018. “Ebola vaccine development: Systematic review of pre-clinical and clinical studies, and meta-analysis of determinants of antibody response variability after vaccination.” International Journal of Infectious Diseases 74: 83-96. LINK

Guillemin, J. 2005. Biological Weapons: From the invention of state-sponsored programs to contemporary bioterrorism. Columbia University Press. LINK

Gutnik, D., P. Evseev, K. Miroshnikov, and M. Shneider. 2023. “Using AlphaFold Predictions in Viral Research.” Current Issues in Molecular Biology 45 (4): 3705-32. LINK

Halfmann, P., J.H. Kim, H. Ebihara, T. Noda, G. Neumann, H. Feldmann, and Y. Kawaoka. 2008. “Generation of biologically contained Ebola viruses.” Proceedings of the National Academy of Sciences 105 (4): 1129-33. LINK

Hannemann, H. 2020. “Viral replicons as valuable tools for drug discovery.” Drug Discovery Today 25 (6): 1026-1033. LINK

Herfst, S., C.K.P. Mok, J.M.A. van den Brand, S. van der Vliet, M.E. Rosu, M.I. Spronken, Z. Yang et al. 2018. “Human Clade A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets.”  mSphere 3 (1):  e00405-17. LINK

(HHS) US Department of Health and Human Services. 2017. Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens. US Department of Health and Human Services. LINK

Hoenen, T., A. Groseth, F. de Kok-Mercado, J.H. Kuhn, V. and Wahl-Jensen. 2011 “Minigenomes, transcription and replication competent virus-like particles and beyond: reverse genetics systems for filoviruses and other negative stranded hemorrhagic fever viruses.” Antiviral Research 91 (2): 195-208. LINK

Hope-Hailey, V., S. Gustafsson, G. Abbey, V. Robinson, and C. McCartney. 2014. Cultivating trustworthy leaders. Chartered Institute of Personnel and Development. LINK

(IAP) The Interacademy Partnership. 2005. IAP Statement on Biosecurity. The Interacademy Partnership. LINK

Inglesby, T., A. Cicero, M. Hopkins, M. Lipsitch, and D. Relman. 2023.  Response to OSTP RFI on Policies for Oversight of DURC and P3CO Framework. Johns Hopkins Center for Health Security. LINK

Inglesby, T.V. and D. Relman. 2016. “How likely is it that biological agents will be used deliberately to cause widespread harm?” EMBO reports 17 (2): 127-130. LINK

Ismi, D.P., R. Pulungan, and  Afiahayati. 2022. “Deep learning for protein secondary structure prediction: Pre and post-AlphaFold.” Computational and Structural Biotechnology Journal 20: 6271-6286. LINK

Jackson, S.S., L.E. Sumner, C.H. Garnier, C. Basham, L.T. Sun, P.L. Simone, D.S. Gardner, and R.J. Casagrande. 2019. “The accelerating pace of biotech democratization.” Nature Biotechnology 37: 1403–1408. LINK

Johnson, B.A., X. Xie, A.L. Bailey, B. Kavleram, K.G. Lokugamage, A. Muruato, J. Zou et al. 2021. “Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis.” Nature 591: 293–299. LINK

Jones, B. 2022. The Changing Political Geography of COVID-19 Over the Last Two Years. Pew Research Center. LINK

Kennedy, B. and A. Tyson. 2023. Americans’ Trust in Scientists, Positive Views of Science Continue to Decline. Pew Research Center. LINK

Kimman, T. G., E. Smit, and M.R. Klein. 2008. “Evidence-Based Biosafety: a Review of the Principles and Effectiveness of Microbiological Containment Measures.” Clinical Microbiology Reviews 21 (3): 403–425. LINK

Klotz, L. and E. Sylvester. 2012. “The unacceptable risks of a man-made pandemic.” Bulletin of the Atomic Scientists, August 7. LINK

Koblentz, G.D., B. Earnhardt, J. Rodgers, F. Lentzos, M. Ameneiros, R. Houser, and H. Wingo. 2023. Global BioLabs Report 2023. King’s College London and Scharr School of Policy and Government George Mason University. LINK

Lentzos, F., ed. 2016. Biological Threats in the 21st Century: The Politics, People, Science and Historical Roots. Imperial College Press. LINK

Lentzos, F. and C. McLeish. 2021. “Chemical and biological security threats.” In SIPRI Yearbook 2021: Armaments, Disarmament and International Security. Oxford University Press. LINK

Lentzos, F. and U. Jakob. 2022. “Chemical, biological and health security threats.” In SIPRI Yearbook 2022: Armaments, Disarmament and International Security. Oxford University Press. LINK

Lentzos, F. and U. Jakob. 2023. “Chemical, biological and health security threats.” In SIPRI Yearbook 2023: Armaments, Disarmament and International Security. Oxford University Press. LINK

Linster, M., S. van Boheemen, M. de Graaf, E.J.A. Schrauwen, P. Lexmond, B. Manz, T.M. Bestebroer et al. 2014. “Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus.” Cell 157 (2): 329-339. LINK

Lipsitch M and T.V. Inglesby. 2014. “Moratorium on research intended to create novel potential pandemic pathogens.” mBio 5 (6): e02366-14. LINK

Lipsitch, M. 2016. “Comment on ‘Gain-of-Function Research and the Relevance to Clinical Practice.’” The Journal of Infectious Diseases 214 (8): 1284–1285. LINK

Lipsitch, M. 2018. “Why Do Exceptionally Dangerous Gain-of-Function Experiments in Influenza?” In Influenza Virus. Methods in Molecular Biology, edited by Y. Yamauchi, 589-608. New York, NY: Humana Press. LINK

Mayer, R.C., J.H.  Davis, and F.D. Schoorman. 1995. “An Integrative Model of Organizational Trust.” The Academy of Management Review 20 (3): 709–34. LINK

Mejlgaard, N., L.M. Bouter, G. Gaskell, P. Kavouras, N. Allum, A. Bendtsen, C.A. Charitidis et al. 2020. “Research integrity: nine ways to move from talk to walk” Nature 586: 358-360. LINK

Michaud, C.M. 2009. “Global Burden of Infectious Diseases.” In Encyclopedia of Microbiology. 3rd Edition, edited by Moselio Schaechter, 444-454. Academic Press. LINK

Mumma, J. M., F.T. Durso, A.N. Ferguson, C.L. Gipson, L. Casanova, K. Erukunuakpor, C.S. Kraft et al. 2018.  “Human Factors Risk Analyses of a Doffing Protocol for Ebola-Level Personal Protective Equipment: Mapping Errors to Contamination.” Clinical Infectious Diseases 66 (6): 950–958. LINK

Murray, C.J.L.., A. D. Lopez, B. Chin, D. Feehan, and K. H. Hill. 2006. “Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918-20 pandemic: a quantitative analysis.” The Lancet 368 (9554): 2211-18. LINK

(NIH) National Institutes of Health. n.d. Research Involving Enhanced Potential Pandemic Pathogens. National Institutes of Health. LINK

Noyce, R.S., S. Lederman, and D.H. Evans. “Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments.”  PLoS ONE 13 (1): e0188453. LINK

(NSABB) National Science Advisory Board for Biosecurity. 2023. Proposed Biosecurity Oversight Framework for the Future of Science. National Science Advisory Board. LINK

Palmer, M.J., F. Fukuyama, and D.A. Relman. 2015. “Science Governance. A more systematic approach to biological risk.” Science 350 (6267): 1471-3. LINK

Racaniello, V.R. and D. Baltimore. 1981. “Cloned poliovirus complementary DNA is infectious in mammalian cells.” Science 214 (4523): 916-19. LINK

Radoshitzky SR, V. Soloveva, D. Gharaibeh, J.H. Kuhn, and S. Bavari. 2018. “Retrovirus-Based Surrogate Systems for BSL-2 High-Throughput Screening of Antivirals Targeting BSL-3/4 Hemorrhagic Fever-Causing Viruses.” In Hemorrhagic Fever Viruses. Methods Molecular Biology, edited by M. Salvato. LINK

Relman, D.A. 2014. “‘Inconvenient Truths’ in the Pursuit of Scientific Knowledge and Public Health.” The Journal of Infectious Diseases 209 (2). LINK

Rimmer, M. 2018. “How Smallpox Claimed Its Final Victim.” BBC News, Aug. 9. LINK

Ritterson, R., and R. Casagrande. 2017. “Basic Scholarship in Biosafety is Critically Needed to Reduce Risk of Laboratory Accidents.” mSphere 2 (2). LINK

Rotblat J. 1999. “A hippocratic oath for scientists.” Science 286 (5444):1475. LINK

Sandbrink, J.B. 2023. “Artificial intelligence and biological misuse: Differentiating risks of language models and biological design tools.” arXiv. LINK

Spreeuwenberg P, M. Kroneman, J. Paget. 2018 “Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic.” American Journal Epidemiology 187 (12): 2561-2567. LINK

Starr, T. N., A.J. Greaney, A. Addetia, W.W. Hannon, M.C. Choudhary, A.S. Dingens, J.Z. Li, and J.D. Bloom. 2021 “Prospective mapping of viral mutations that escape antibodies used to treat COVID-19.” Science (371) 6531: 850-854. LINK

Starr, T.N., N. Czudnochowski, Z. Liu, F. Zatta, Y. Park, A. Addetia, D. Pinto, et al. 2021. “SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape.” Nature 597: 97–102. LINK

Starr, T. N., S.K. Zepeda, A.C. Walls, A.J. Greaney, S. Alkhovsky, D. Veesler, and J.D. Bloom. 2022. “ACE2 binding is an ancestral and evolvable trait of sarbecoviruses.” Nature 603: 913-918. LINK

Steeds, K., Y. Hall, G.S. Slack, S. Longet, T. Strecker, S.K. Fehling, E. Wright et al. 2020 “Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies.” Scientific Reports 10 (14289). LINK

Steinbruner, J. E.D. Harris, N. Gallagher, and S.M. Okutani. 2007. Controlling Dangerous Pathogens: A Prototype Protective Oversight System. College Park, MD: The Center for International and Security Studies at Maryland. LINK

Thorpe, C. 2004. “Violence and the Scientific Vocation.” Theory, Culture & Society 21 (3): 61. LINK

Tran, Thi Nhu Thao, F. Labroussaa, N. Ebert, P. V’kovski, H. Stalder, J. Portmann, J. Kelly et al. 2020.“Rapid Reconstruction of SARS-CoV-2 using a synthetic genomics platform.” Nature 582: 561-565. LINK

Trimpert, J., K. Dietert, T. Firsching, N. Ebert, T. Tran, D. Vladimirova, S. Kaufer, et al. 2021. “Development of safe and highly protective live-attenuated SARS-CoV-2 vaccine candidates by genome recoding.” Cell Reports 36 (5): 109493. LINK

US Government. 2012. United States Government Policy for Oversight of Life Sciences Dual Use Research of Concern. US Government. LINK

Versini, R., S. Sritharan, B.A. Fas, T. Tubiana, S.Z. Aimeur, J. Henri, M. Erard, O. Nüsse et al. 2024. “A Perspective on the Prospective Use of AI in Protein Structure Prediction.” Journal of Chemical Information and Modeling 64 (1): 26-41. LINK

Wallace, J., P. Goldsmith-Pinkham, and J.L. Schwartz. 2023. “Excess Death Rates for Republican and Democratic Registered Voters in Florida and Ohio During the COVID-19 Pandemic.” JAMA Internal Medicine 183 (9): 916-923. LINK

Watson, O. J., G. Barnsley, J. Toor, A.B. Hogan, P. Winskill, and A.C. Ghani. 2022. “Global Impact of the first year of COVID-19 vaccination: a mathematical modelling study.” The Lancet Infectious Diseases 22 (9): 1293-1302. LINK

Wenigenrath, J., L. Kolesnikova, T. Hoenen, E. Mittler, and S. Becker. 2010. “Establishment and application of an infectious virus-like particle system for Marburg virus.” Journal of General Virology 91 (5). LINK

Wheelis, M, L. Rózsa, and M. Dando, eds. 2006. Deadly Cultures: Biological weapons since 1945. Harvard University Press. LINK

(WHO) World Health Organization. 2004. WHO SARS International Reference and Verification Laboratory Network: Policy and Procedures in the Inter-Epidemic Period. World Health Organization. LINK

(WHO) World Health Organization. 2020. Laboratory biosafety manual. 4th ed. World Health Organization. LINK

(WHO) World Health Organization. 2022 Global guidance framework for the responsible use of the life sciences: mitigating biorisks and governing dual-use research. World Health Organization. LINK

(WHO) World Health Organization. 2023. Measles. World Health Organization. LINK

(WHO) World Health Organization. n.d.a History of the Measles Vaccine. World Health Organization. LINK

(WHO) World Health Organization. n.d.b Joint External Evaluation. World Health Organization. LINK

Wilkinson, A.L., K Zaman, M. Hoque, C.F. Estivariz, C.C. Burns, J.L. Konopka-Anstadt, B.A. Mainou et al.  2023 “Immunogenicity of novel oral poliovirus vaccine type 2 administered concomitantly with bivalent oral poliovirus vaccine: an open-label, non-inferiority, randomised, controlled trial.” The Lancet Infectious Diseases 23 (9): 1062-71. LINK

Wyneken, H.L., A.A. Cerles, K.N. Kim, C. Heren, E.J. Reuter, C. McCarty, K. Chen et al. 2023a. “Rate of Splashes When Opening Microfuge Tubes with Various Methods.” Applied Biosafety 28 (2). LINK

Wyneken, H., K.N. Kim, A.A. Cerles, C. Heren, S. Bowman, E.J. Reuter, C. McCarty et al. 2023b. “Frequency of Leaks from Conical Centrifuge Tubes.” Applied Biosafety. Advanced online publication. LINK

X. Xie, A. Muruato, K.G. Lokugamage, K. Narayanan, X.  Zhang, J. Zou, J. Liu et al. 2020. “An Infectious cDNA Clone of SARS-CoV-2.” Cell Host Microbe 27 (5): 841-848. LINK

Yen, H, C. Liang, C. Wu, H.L. Forrest, A. Ferguson, K. Choy, J. Jones et al. 2011. “Hemagglutinin–neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets.” Proceedings of the National Academy of Sciences 108 (34): 14264-14269. LINK

Young, A. 2023. Pandora’s Gamble: Lab Leaks, Pandemics, and a World at Risk. Nashville: Center Street. LINK

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