The Origins, Risks, and Prevention of Emerging Diseases Patient Zero: The Origins, Risks, and Prevention of Emerging Diseases by Andrew E. Lyman-Buttler The International School of Minnesota, Eden Prairie, MN Based on the Radiolab episode “Patient Zero” with animations from HHMI Holiday Lectures

Learning Objectives Explain how the molecular clock can act as a “tape measure” of evolution. Describe how emergent diseases can spread into human populations. Evaluate the effects of social and cultural factors in the transmission and understanding of disease. Explain how the molecular biology of HIV allows it to infect target cells. Discuss the mechanisms of viral recombination, and explain its role in the emergence of new diseases. Describe one strategy for the prevention of new pandemics. Outline the steps of the HIV reproductive cycle.

Part I – An Emerging Disease A new and deadly disease has emerged, causing symptoms unlike anything ever seen before… As a class, list all the possible causes of disease. Some diseases are transmissible from person to person. List all the ways this might happen. Epidemiologists can’t do controlled experiments on human subjects (i.e., purposefully exposing people to suspected disease-causing agents). How can they determine the cause of a disease? How can they figure out whether it’s transmissible? If it is, how can they determine the mode of transmission?

An emerging pandemic… Play Audio 1 0:00 to 6:04 http://www.radiolab.org/2011/nov/14/aids/ An emerging pandemic… “Patient Zero” audio file available at http://www.radiolab.org/2011/nov/14/aids/ Network diagram courtesy of FMS - Sentinel Visualizer, http://www.fmsasg.com, used with permission.

HIV reproductive cycle View the following animation (4:52) from the Howard Hughes Medical Institute that shows how HIV infects a cell and replicates itself using reverse transcriptase and the host's cellular machinery: http://www.hhmi.org/biointeractive/disease/hiv_life_cycle.html

The molecular clock Play Audio 2 6:04 to 10:04 Figure 26.20 Dating the origin of HIV-1 M with a molecular clock

Part II – Spillover How does the molecular clock allow us to determine the approximate time of origin of a virus? What other viral infections have you heard of that can infect other animals in addition to humans? Why do you think these viruses are so alarming to public health officials?

Spillover of influenza View the following video lecture clip (1:18) on the origins of influenza virus strains. http://media.hhmi.org/hl/99Lect4.html?start=29:02&end=30:21

Play Audio 3 10:04 to 15:02 Spillover of HIV

Part III – Why Then? How was the world changing in 1908? How might these conditions be relevant to the spread of an infectious disease?

Recombination Play Audio 4 15:02 to 24:20 Scanning electron micrograph of HIV-1 (in green) budding from cultured lymphocyte. Multiple round bumps on cell surface represent sites of assembly and budding of virions.

Recombination (example based on influenza virus) View the following animation (3:05) from the Howard Hughes Medical Institute that shows how two different strains of influenza can infect a single cell to produce a new third strain of influenza: http://www.hhmi.org/biointeractive/disease/recombination.html

Part IV – Prevention How can non-human animals provide a pathway for new viruses to enter the human population? Consider the emergence of a pandemic, from the first spillover event to worldwide transmission. Where are the points at which we could stop the spread of the disease? Which point would be easiest?

Preventing the next pandemic Play Audio 5 24:20 to end Preventing the next pandemic

You should now be able to: Explain how the molecular clock can act as a “tape measure” of evolution. Describe how emergent diseases can spread into human populations. Evaluate the effects of social and cultural factors in the transmission and understanding of disease. Explain how the molecular biology of HIV allows it to infect target cells. Discuss the mechanisms of viral recombination, and explain its role in the emergence of new diseases. Describe one strategy for the prevention of new pandemics. Outline the steps of the HIV reproductive cycle.

References/Media Credits: Abumrad, J., and Krulwich, R. "Patient Zero: The Cell That Started a Pandemic." Radiolab. 14 November 2011. WNYC. http://www.radiolab.org/2011/nov/14/aids/ Social network diagram (Slide 4): FMS - Sentinel Visualizer, http://www.fmsasg.com, used with permission. Howard Hughes Medical Institute 2007 Holiday Lectures: AIDS: Evolution of an Epidemic. DVD. Howard Hughes Medical Institute 1999 Holiday Lectures: 2000 And Beyond: Confronting the Microbe Menace. DVD. Diagram on Slide 7 & phylogeny on Slide 10: Hillis, David. "The Unexpected Practical Applications of Evolutionary Biology." National Association of Biology Teachers Conference. Hyatt Regency Hotel, Dallas, TX. 2 November 2012. Lecture. Used with permission. Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocyte: C. Goldsmith, CDC. http://phil.cdc.gov/phil/details.asp?pid=10000 Africa 1908 map (Slide 11): Hemispheres Antique Maps & Prints. From Rand McNally's Indexed Atlas of the World, 1908. http://www.betzmaps.com Slide 15 images: Global Viral Forecasting Initiative: http://globalviral.org/